Pharmacology - II (PV Publication)

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PU Dr. Madan Kaushik
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BOOKS
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4 Text Book of
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JATE
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PHARMACOLOGY-II
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Strictly As Per Syllabus Prescribed for B.Pharmacy
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Semester- by Pharmacy Council ef India, New Delhi
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IKAS AND COMPANY (MEDICAL PUBLISHER5)

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SIxEAMPLRA, JALANDHAR CIT-144 00S (PUNIAB). INDLA
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0106
ND-227. CIT-144 0aS (PUNAB). INDA
TANDA ROAD. JALANDHAR
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CnON:ND 226. TAMDA ROAD. LALANDHAR CITY-144 008 (PUNUAS). INDIA
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oss1-4054738, s0S2798, C34785-4545
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cER CARE: Fer aty quenes. piease centact-0S4756-14148 B00RS

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A Text Book of
PHARMACOLOGY-II
Strictdly As Per Syllabus Prescribed forB.Pharmacy
Semester-V by Pharmacy Council of India, New Delhi
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Dr. Madan Kaushik
Professor, (Pharmacology)
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AVIPS- School of Pharmacy.
Shobhit University, Gangho,
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Sharnpur, Uttar Pardesh
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SVIKAS AND COMPANY MEDICAURUBLISHER5
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YouTube - Study Pharmacy
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An Imprint of
Preface to the First Edition
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S.VIKAS AND COMPANY (MEDICAL PUBLISHERS) A Text book of Pharmacology, Vol-I provides comprehensive and concise concept of
ADMIN: ND-106, BIKRAMPURA, JALANDHAR CITY-144 008 (PUNJAB), INDA Pharmacology. The major thrust has been to make the book more students friendly, catering to
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SALES: ND-227, TANDA ROAD, JALANDHAR CITY-344 008 (PUNUAB), INDIA
PRODUCTION:ND-226, TANDA ROAD, JALANDHAR Cm-144 00B (PUNIAB), INDA the recommendation of Pharmacy Council of India. For under-graduate teaching in
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PHONE:0181-4es44, 509Ns, 0%4716* Pharmacology, each chapler in this book is self-contained and serve as a dual teaching function
cUSTOMER CARE:Fer any eueles, ple ase centact-094784-1414
EMAIL:ok to highlight the basic concepts and to relate them to Pharmacology. Topics have been explained
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Onlire Shog : www.pvbooks.h
according to the PCI syllabus, avoiding unnecessary details as per the requirement and
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structure of question paper. Diagrammatically mechanism of drug have been fully

incorporated to make the concept clear in a more refined way. The substantial amount of
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@Copyrights Reserved
information is added particular in all major topics. Itis hoped that book is useful not only for the
Al ights reserved. No part of this publication may
pharmacy and those appearing in various entrance examinations of the medical profession, but
be reproduced or used in any form or by any means
will serve asa good resource in clinical practice also. An exclusive pattern as detailed below has
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photographic, electronic or mechanical including
photocopying. recording, taping or informalion becn introduced.
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storage and retreval systema-without the written Introducing the chapter
permission of the publishers
Definition, classification, mechanism of action, pharmacological action, Adverse effect,
Indication, contraindication, uses, dose, ADME and brand name of drugs.
IsBN 97815-43343-31-1 Bioassay concept
Detailed and comprehensive subject matter wilh well labeled diagrams.
Provides a well rounded and comprehensive approach to PharmacyY
TradeMark No. 1350444
Review Questions- the backbone of the book containing MCQ, Long short answer questions
appended at the end of each chapter
Edition 2019
Major P'oints have been highlighted for a quickreview of core concepts.
This bookis also useful for other medical students. The students can easily carrier begins in
medical profession withA Test Book of Pharmacology-Vol-II
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PRICE:525/
I have no words to express my gratitude to my beloved parents for their inspiration and
blessings in writing this Project. I am immensely thankful to Chancellor Shri Kunwar Shekhar
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Mustrators:Apkritl Jain
Vijendra Shobhit University, Pro-Vice Chancellor Professor Ranjeet Singh, Shobhit University,
Printed and bound In India
Chancellor Charnjeet Singh Channi, CT University, Professor S. P. Bhardwaj, Professor Ishwer
By Rahul Art & Press Pal Kaushik, Professor Ajay Bansal and Professor Sanjeev Kalra, who have been sources of
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Exclusively marketed and distribuled by PV books motivation and encouragement in this work of writing. Thanks are also to my energetic and
For sale only in Indla, Nepal, Bangladesh, Sri Lanka
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dynamic publishers Sh. P.K. Jain and Mr. Vikas Jain of MsS. Vikas & Company for bringing
and UA.E. out the quality based book wel in time. Any suggestion for further improvement of this book
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will be highly appreciated.

The publishers make no represenlatlon, express Or
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information
implied with regard to the accurecy of the
May, 2019
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contained In this book and cannot accept legal

responsiblity for any errors or omissions. Dr. Madan Kaushik
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CONTENTS
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Chapter 6 Bioassay 337-358

Chapter 1 Pharmacolo8y of Dnugs Acting on Cardio Vascular System 1-83
6.1 Bioassay 337, 6.2 Types of bioassay 339, 6.3 Bioassay of insulin
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1.1 Introduction to hemodynamic 2, 12 electrophysiology of heart 5,
343, 6.4 Biological assay of oxytocin 345, 6.5 Biological assay for
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1.3 Cardiotonics 8, Pharmacology of cardiac glycoside 9,

Pharmacological actions of cardiac glycosides 10, Toxic effects of vasopressor activity348, 6.6 Bioassay of adrenocorticotrophic hormone
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cardiac glycosides 12, 1.4 Antihypertension 17, Pharmacology of 349, 6.7 Bioassay of gonadotrophin 351, 6.8 Bioassay of d-tubocurarine
352, 6.9 Bioassay of digitalis 353, 6.10 Bioassay of histamine 354
antihypertensive agents 19, Angiotension converting inhibitors 19,
Angiotensin blockers 29, 1.5 Anti anginals 43, 1.6 Anti arrhythmic Index (i)-ii)
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drugs 51, 1.7 Hypolipidaemics 69
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Chapter 2 Drug Affecting on Hematopoietic Systems 84-137
2.1 Drug used in the therapy of shock 85, 2.2 Haematinics 91, 2.3
Coagulants 102, 2.4 Anti coagulants 107, 2.5 Antiplatelet drugs 115,
2.6 Fibrinolytics 120, 2.7 Plasma expanders 124
Chapter 3 Pharmacology of Drugs Acting on Urinary System 138-172
3.1 Diuretics 138, 3.2 Anti diuretics 159
Chapter 4 Autocoids and Related Drugs 173-257
4.1 Introduction to autacoids 174, 4.2 Histamine 175, 4.3 Histmine
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antagonist/antihistaminics 179, 4.4. Serotonin (5-ht) and their
antagonists 191, 4.5 Prostaglandins thromboxanes and leukotrienes
199, 4.5.1 Thromboxanes 207, 4.5.2 Leukotrienes 207, 4.6 Angiotensin
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210, 4.7 Bradykinin212, 4.7.1 Bradykinin antagonists 215, 4.8 Substance
p 215, 4.9 Non-steroidal anti-inflammatory agents (NSAID) 218, 4.10
Gout and anti-gout drugs 237, 4.11 Antirheumatic drugs 241
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Chapter 5 Pharmacology of Drugs Acting on Endocrine System 258-336
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5.1 Basic concepts in endocrine pharmacology 259, 5.1.2 Pancreas 263,
5.3 Growth hormones analogues and their inhibitors 265, 5.3 Prolactin
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269, 54 Thyroid and antithyroid drugs 272, 5.5 Hormones regulating

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plasma calcium level282, 5.6 Hormones regulating parathormone 284,
5.7 Hormornes regulating calcitonin 285, 5.8 Hormones regulating
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vitamin-d 287, 5.9 Insulin 289, 5.9.1 Diabetes mellitus 290, 5.10 Oral
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hypoglycaemic drugs 294, 5.11 Gucagon 303, 5.12 Aderno
corticotrophin hormones 305, 5.13 Corticosteroids 309, 5.14 Androgen
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and anabolic steroids 314, 5.15 Drugs acting on the uterus 324, 5.16
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Uterine relaxants 328
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SAARS
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No alai aitgntiasnaioiy ngnt
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1 PHARMACOLOGY OF DRUGS ACTING
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CHAPTER ON CARDIO VASCULAR
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INTRODUCING THE CHARTER
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Introduction to hemodynamie
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Electrophysiology of heart
Drugs used in congestive heart failure
Anti-hypertensive drugs
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Anti-anginal drugs
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Anti-arrhythmic drugs
Anti-hyperlipidemic drugs
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KEY WORDSD
Action potential : The action potential is generated by electrolytes. The Na", K* and Ca
Ri plays role in the diferent phase and generate cardiac impulse. The magnitude for ventricular
muscle = about 105 mV i.e., going from about 85 mV to + 20 mV): his abrupt change in
membrane potential corresponds to the "spike" Depolarization duration = about 02 seronls
for atrial muscle & about 0.3 seconds for ventricular muscle
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Conduction: The condution of Velocity is the atrial/ventricular muscle fibers: 0.3-0.5 inelers
per second. The specialized fibers for action polential propagation through the heart (eg
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Purkinje fibers): 0.02-4 m per second.
ardiotonics These are the drugs which lend to increase the efficiency of contraction of the
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heart muscles.
Antihypertension: The drugs uscd in the treatment of hypertension are called
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antihypertensive drugs. These drugs act by reducing the cardiac output or reucing the total
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peripheral resistance without correcting the cause.
Antianginal These are the drugs used in the treatment of angina pectoris. These drugs
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prevent terminate attacks of angina pectoris.

Anii arhythmie These are the drugs used to correct an abnormal cardiac rhythm. Cardiac
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arrhythmias occur as a result of defective impulse conduçtion

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Hypolipidaemic: These are drugs which lower the level of lipids and lipoprolcins in bloond.
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P A Text Book of Pharmacolog9y- Pharmacology of Drugs Acting on Cardio Vascular System
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HINTRODUengNERNEMODYNAMIC
Blood moves within vessels because the force venous blood is squeezed toward the heart-the only diection the valves will permit
that drives flow is greater than the resistance
toward the heart.
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Now. The force that drives blood flow is
the pressure gradient between two points in a
vessel. Blood will flow from the point where pressure
is higher toward the point where
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pressure is lower. Resistance to flow is determined by the diameter i"gt " Right atrlum
and length of the vessel i i 2 Ljo*i
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and by blood viscosity. The pharmacologic viewpoint,

the mostimportant determinant of i Nz7 120
resistance is vessel diameter. The the vessel is larger smaller 122jT
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the resistance. Accordingly, Central veins
when vessels dilate, resistance declines, causing blood flow to
increase-and when vessels
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constrict, resistance rises, causing blood flow to decline. To maintain adequate.low

when "71013d
arteries S
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resistance rises, blood pressure must rise as wel.
Pressuregradient sitsesi-ias Muscular2i Bloodpressure. a as ib a:) ttieie

Lower
Higher t, iri, n
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pressure pressure
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Flow v
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t'it:"1ag-2 lurt s'n
40 7:dssldt isto:i
slts.i) i eit Venules Arterioles il oliit
Resistance:
Vessel diameter. 2 1.22
Vessel length
Blood viscosity . 1
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Fig.1.1. Distribution of the pressure within the systemic cireulation **
"i, .Fig 1.2 Range of biood presser in vascular system
isii itndi ca!1s *
2ofri: 2
Pressure is highest when blood leaves the left ventricle, falls to only 18 mm IHg as blood cxits
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capillaries, and reaches negative values within the right atrium. The pressure falls Regulation of Cardiac Output: In the average adult, cardiac output is about 5 L/minute
progressively as blood moves through the systemic circulation. (The Pressure is 120 mm Hg Hence, every minute-he-heart-pumps-the-equivatent- of-alt-the-blogd in the body. In this
when blood enters the aorla, 30 mm Hg when blood enters capillaries, and only 18 mm Hg section, we consiier the major factors that determine how much blood the heart pumps.
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when blood leaves capillaries, and then drops to negative values (0 to -5 mm Hg) in the Determinants of Cardiac Output: The basic equation for cardiac outpht is:
right atrium, (Negative atrial pressure is generated by-expansion of the chest during CO-HR«SV
inspiration.)
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where CO is candiac output, HR is heart rate, and SV is stroke voleme. According to the
The pressure is only 18 mm Hg when blood leaves capillaries, we must ask, "How does
equation, an inctease in HR or SV_will increase CO, wherea a decrease in HR or SV will
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blond get back to the héart In addition lo the small pressure head in venules, three
decrease CO. Fot the average person, heart rate is about 70 beats/minkute and stroke volume
merhanisms help ensure venous return. First, the negative pressure in the right atrium helps
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is about 70 mL. NMuliplying these, we get 4.9 L/minutethe average talue for CO.
"suck" blood constriction of smoolh muscle in the venous waN increases yenous pressure,
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FMeart Rate: Heat rate is controlled primarily by the autonomic neirveus system (ANS). Rate
which helps drive blood toward the heart. Third, and mpst importantly, the combination of
is increased by jhe sympathetic branch acting through betaj:adrenergic receptors in the
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venous valves and skeletal muscle contraction constitutes an auxiliary "venous pump. The
sinoatrial (SA) Åode. Rate is decreased by the parasympathetic branch acting through
vens are equipped with a system of one-way valves. When skeletal muscles contract the
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muscarinic receptors in the SA node. Parasympathetig impulses reach the heart through the
vagus nerve
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Pharmacology of Drugs Acting on Cardlo Vascular System
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PU A Text Book of Pharmacology-l
12ELECTROPESTOLOGYOF HRARD
Soke Volume: Stroke volume is determined largely by three factors: (1) myocardial
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contractility, (2) cardiac afterload, and (3) cardiac preload. Myocardial cotractility defind
is There are three types of cardiac muscle
as the force with which the ventricles contract. Contractility is determined primarily by the contraction duration
A. Atrial muscle-similar to skeletal muscle but with a longer
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degree of cardiac dilation, which in turn is determined by the amount of venous return. The contraction duralion
importance of venous return in regulating contractility and SV is discussed separately later. B. Ventricular muscle-similar to skeletal muscle but with a longer
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contractile fibers, hence

In addition to regulation by venous return, contractility can be increased by the sympathetic C. Specialized muscle of the cardiac conducting system-few
cardiac electrical excitation
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nervoussystem, acting through betaradrenergic receptors in the myocardium. limited contractility: important because of their central role in
-90 mV for normal cardiac muscle and -90 ta -100
The Resting membrane potential is -85 to
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Preload: Preload is formally defined as the amount of tension (stretch) applied to a muscle (
before contraction. In the heart, stretch is determined by ventricular filling pressure) thát is, mV for specialized conducting fibers, e.g. bundle of His, AV nodal fibers
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the force of venous return: the greater the filling pressure is, the more the ventricles will
Ation polential: The action potential of cardiac muscle cell is shown in figure 14 whichis
stretch. Cardiac paoad can ,be expressed as either end-dinstolic volume or end-diastolic generated by electrolytes. The Na, K* and Ca** plays role in a different phase and
pressureAs discussed later, an increase in preload will increase SV, whereas a decrease in generate cardiac impulse. The magnitude for ventricular muscle = about 105 mV (i.e., goin
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preload will reduce SV Frequently, the terms preload and force of venous return are used from about -85 mV to + 20 mV): this abrupt change in membrane potential corresponds to
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interchangeably-although they are not truly equivalent. =
the "spike; Depolarization duration about 02 seconds for alrial muscle & about 0.3 seconds
erload: It is formally defined as the lond against wkich a muscle exerts its force (ie., the for ventricular muscle.
load a muscle must overcome in order to contract). For the heart, afterload is the arterial
This process occurs in four Phases
pressure that the left ventricle must overcome to eject blood. If afterload increases, the SV is
Phase 0, rapid depolarization. It occurs when the membrane potential reaches a critical firin
decrease. Conversely, if afterload falls, SV is rised. Cardiac afterload is determined primarily
threshold (about -60 mV) the entry of Na* ions are inside the cell, inside current of becomes
by the degree of peripheral resistance, which in turn is determined by constriction and
large enough to produce a regenerative depolarization. They are therefore closed during the
dilation of arterioles. That is, when arterioles constrict, peripheral resistance rises, causing
plateau of the action potential and initiation of another action potential until the membrane
AP (afterload) to rise as well. Conversely, when arterioles dilate, peripheral resistance falls,
repolarises.
causing AP to decline.
nteau
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phase: extends the duration of the action potential significantly (3-15 times) rclative
the action potential duration of skeletal muscle. The
to lons and the myocardial action
potential:
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BA nede Asepee
"Fast" response component- due to activation of fast sodium
channels: At normal resting
membrane potentials, activation of sodium channels involves a large number of
channes
opening in a synchronous manner. A large number of rapidly and synchronously
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opening
channels results in a significant inward sodium current which
ndnedl prdays is the basis for typically rapid
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conduction & action potential propagation through the heart
Puntnj fbers
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Fig13 Electrophysiology of Heart
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Feanner
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PVA Text Book of Pharmacology-ll Pharmabologyot Drugis Acting oh Cádio Vascular System
Contract. The SA node is located in the upper wall of the right atrium. It is composed
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of odal tissue that has characteristics of both muscle and nervous tisue.
Sty 2: AV Node Impulse Conduction' The atrioventricular (AV) node lies on the right side of
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Rapld Ma nhux he partition that divides the atria, ncar the bottomof the right atrium. When the impulses
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hrough scos bu 1
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. from the SA node reach the AV node, they are delayed.for ehout tenth of a second. This
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channels remein open and
um TMP t
delay allows atria to contract and empty their conténts into,the ventricles prior to ventricle
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contraction.
Ne Cae channels 1
Sep 3: AV Bundle Impulse Conduction: The impulses are then sent down the atrioventricular
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bundle, This bundle of fibers branches off into two bundles and the impulses are carried
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down thecenter of the heart to theleft and right vehtricles.
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Stey4: Purkinje Fibers Impulse Conduction" At-the base óf the heart, the atrioventricular
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1i TIME ,t it'" " ""t
: Pse Phase0 bundles start to divide further into Purkinje fibers. When the impulses reach these fibers
PhsA"PheneR "" Phase 3
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} 11-i: l "g
ihey ürigger the musclé fiberš in the'vehtriclès tö oritaE The right Véniride'sends blóodto
the lungs via the pulmonary artery. The left ventricle pumps blood to the aorta. iteon
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cFK K
Eonduction: The conduction'of vétócity'is tië itriat/vehiticuta miuisilé titbes 6tos heters
ig 1.4 A Systematic presentation: The role of electrolytes is in the Electrophysiology of heart. per second. The specialized ibers for actiónipotential propagation' thouw the' hëartqeg&
Purkinje fibers): 0.02-4 m per secohd. yisaols i t instnnå tenm ei &lh rnthgaqo[ o
s :Partial repolarisafion.It ocurs when the Na current is inactivated.
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Eicitability: The uniqie chaaieriste'öf tardiae musclé àctiort fotentlat the plhhéNäde
çurrent. Calcium ie the maintenance of thé pótenitiäl'át a"'positvë evel The plhteat' hesi 8r skw
hase 2 Ca plays a role in the plategu, the results from an inward Ce
V channcls show a pattern of activation and inactivation qualitatively similar tp,sodium
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sodium/calcium channels that remain open "tor" ševeral "huhdred'inilišeökids" the
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channels, but with a much slower ime course
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1.,
repolarisation is produced by:thë closing of the fast sbdiurh arld-slow sodiuh/cáhkium
irile gls it ebtrtzs
se 3: Repolarisation, the Ca,current is inactivated and a delayed qutwardly rectifying K
current activates, causing outward K° current. This is augmented by another K.current
channels and opening of the potasiuin hanrels. The prolomgéd depoiárisátióif enalesthat
the absolute refractory peridd (ARP) of the heart inuscde tëlls is.rèlatively loager ihäw thatof
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which is activated by high intraçellular Ca2* concentrations, [Ca2] during the plateau, and other muscle colls. This prolonged ARP resulls in the fact that the heart muscle cell can never
3 *9ut Ji*98Tt5 1:075 efi 1 fen
somclimes also by other K currents." *Y221i
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be tetanised important as for normal pumping action of the ieartrequires some diastole to
*
ase
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the pacemaker, potential is gradual depolarisation during.diastple.Cells, in,the SA
4
efractory Period:Definitiopu, Ths,amounti of time follawing.an actioaipotentalrduring
node have a greater background,gonductance. to Na1than do atrijalgr.ventricular, myorytes,
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leáding to a greater background inward. urrenthese,elsctrolytFenerate,thePLER hich the normal erdis,impulse.sannot.estethePqawienelxsrsint iwustizia
eitsiziCi drad taiunsid a o zu1ssi Lwinb
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which areeen in the electrocardiogram. This is the absolue refractory period sff c3qur
normal absolute refractory perjot025:0.3 secondsirtsdod ali yvng arksaT SGEI
Iie The impulse generation in four steps.
eneration: Duration
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St 1: Pacemaker Impulse Generation: The first step of cardiac conduction is impulse all a tdrsdnudzil o mot>ient a gnraiiwi muitlin uds bice ei 1
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generation. The sinoatrial (SA) nodefalso referred to as the pacemaker of the heart) contracts, iesrp ei thtl io d buiqny erirsl vrin ritw teilaiib) voig xui uiniuine rizub
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generating nerve impulses that travel throughout the heart wall. This causes both atria to
*1ml; si'8tai h wuq Lo»rteildides aw tul odt no oits i quin dios
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Telegram - Study S.vPharmacy
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Pharmacology of Drugs Acting on Cardio Vascular System
VA Toxt Book of Pharmacology-
glycosides (i) digitoxin
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Digitalis purpurea contains three
are sirmlar M chemical composition.
(i) gitovin (ii) gitalin.
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of cardiac
classification is bascd on Source
Atrlal Fiber Classification of cardiac glycosides : The
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Ventricular Fbers
Purkinje FIbers slycosides
(Digoxin), Gitoxin, Citalin
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Digitalislanta
(Digitoxin), Gitoxin, Digoxin
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Digitais purpura
(Stropanthin
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ERP Stropanthus gratus
Stropanthus kombe (Stropanthin G) (Ouabian)
100
gNa Urginca (Scila) Proscillaridin
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gcat Thevetia neriifolia (nut) Thevetin
g
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Convallaria majalis Convallotoxin
Bufo rulgaris Bufotoxin
Relative refractory period: The cardinc muscle may be excited, but with greater difficulty
than normal. PHARMACOLOGY OF CARDIAC GLYCOSIDE
inotropic
Mechanism of action: The mechanism whereby cardiac glycosides cause positive
a
Durstio: approximately 0.05 seconds (adds somewhat to the absolute refractory period)
Pharmacological effeetive refractive period (ERP) which is the minimum interval between effect and electrophysiologic changes is stil not completely clear. Several mechanisms have
two propagation APs is most important. It is closely related to the AP (ADP). An action been proposed, but the most widely accepted involves the ability of cardiac glycosides
to
potential duration (ADP). An AP can be evoked in fast channel fibers even before complete inhibit the membrane bound Na+-K+-ATPase pump responsible for Na+-Kr exchange
repolarization ie. ERP/ADr is« 1; while in slow channel fbers ERP/ADP is less >1. Anti
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arrhythmic drugs increase ERP/ADIP ratio. Cardiae Gycosdes
Atrial refractory period (absolute refractory - 0.15 seconds; relative refractory 0.03
seconds) - shorter than ventricular refractory period. As a consequence, atrial contraction
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rates may be significantly higher than ventricular contraction rates.
13 CARDIOTONICS (USED IN GHE

-
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Cardiotonics are the drugs which tend to increase the eficiency of contraction of the Ta
comE
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heart muscles. The example is of digitalis which is cardiac glycoside used as cardiotonic.
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Digitalis is the most commonly used drug as a cardiac glycoside. It is obtained from the
dred leaves of a biennial herb Digitalis purpurea. Tie common name of this plant is fox glote, in
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1542 Fuchs gave its botanical name Digitalis purpurea.
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Fig.1.5 Mechanism of sction

It is said that william withering a physician of Birmingham-England learnt thata
The process of membrane depolarization / repolarization is controlled by the movement of
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decoction containing fox glove (digitalis) with other herbs prepared by an old lady is capable
three cations, Na, Cas2, and K°, in and out of the cell. At the resting stage, the concentration
of curing dropsy. He tried extract of fox glove alone and found it effective in some cases. In
of Na is high on the outside. On membrane depolarization sodium luxes-in
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20th century its effect on the heart was established digitalis purpurea and digitalis lanata plants leading to an
immediate elevation of the action potential. Elevatod intracellular Na* triggers the
influx of
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wcV alipu) AText'Book bf Pharmacology- Pharmacology of Drugs Acting on Cardio Vascular System 11
free of Ca that occurs more
slowly. The higher intracellular [Ca-] 5) Diuresis : The majór eftect of digitalis in oedema is diuresis due to decrease in venous
K. The reestablishment results in the efflux of
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of the action potential occurs later pressure which passes the oedema luid into blood circulation cause diuresis, also
K exchange. by the reverse of the Na
inhibits reabsorption ot sodium..:
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The Na* 7 K exchange requires

energy which is provided by an enzyme Na--K*-ATPase. 6) Coronary. circulation :, Digitalis cause no direct effect on coronary blood flow, an
Cardiac glycosides are proposed to inhibit
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this enzyme with a net result of reduced sodium improvement in coronary Dow occurs secondary to the improved cardiac output.i 3
change with potassium that leaves increased intracellular Na*. This

Digitalis in therapeutic doses, do not affect the clotting time of
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results in increased n Effgct on blood cloting :
intracellular [Ca]. Elevated intracellular calcium
concentration triggers.a series of blood.
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intracellular biochemical events that ultimately result in an

myocardial contraction or a positive inotropic effect.
increase in the force of the 8) Vagal and extravagal effect: Digitalis in small doses cause cardiac slowing due to vagal
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stimulation in large doses, it is due to prolagation of refractory period. ubr,ahzww
PHARMACoLOGICAL ACTIONS OF CARDIAC GLYCOSIDES 9) Effect on the vomiting center: Digitalis is administered orally.. intramuscularly, or
vascular system intravenously, in many individuals produce nausea and vomiting as vomiting center in
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Ation en cardio (CvS): s.
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the brain is stimulated by the action of digitalis:"n
Cardiac glycoside (digitalis) increases the strength and speed of myocardial contraction .m
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10) Effect on conduction system :Digitalis depresses the conduction system by, direct
due to which cardiac output is increased. In normal individual small doses of digitalis do not
action. The refractory period is elongated and the conduction rate is slowed. This effect is
prducc any significant change in cardiac output, mean arterial pressure and stroke volume u ith dli
produced as an increáse in P R interval in ECG (electrocardiogram).
may be increased.
11) lonic effect:
In congestive cardiac, failure, the heart rate is increased. Digitalis increase oxygen
Sodium: The sodium ions are retained in the body with a failing heart. The sodium ions
cwnsumption of heart to normal. It does not increase energy production by cardiac muscles it are mobilized and eliminated by digitalisation. Digitalis' is inhibits sodium ions
improres energy utilization. The digitalized heart can do more work with less energy, due to
which efficiency of the heart improves.
-
Fnergy production: Digitalis do not increase encrgy production by the cardiac muscles it
reabsorption in renal tubules, and are excreted in the urine.
Calcium: Calcium ions increases the force of contraction of the heart. Excss of calcium
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increases its energy utilization, there is a conversion of chemical energy into mechanical 'ions (Cat* ions) concentration is leads to cardiac arrest in systole: Digitalis increases the
force of contraction by increasing the amount of calcium ini the cardiac tissuè. "The
energy. The digitalised heart can do the same work with less energy or more zwork with the same
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cuorgy consuption. It is because of this usefut efect, digitalis is calld as ardinc tonie' or
n töxicity
of digitalis is increased with the calcium'ionis (Ca** ions) which leads to cardiac
Cardiotonic. arrest in systole. Speciat care should be taken, calciumi préparatión šhould not be adinistered in
unl the troatment of indioviduat uwith cardiac glycosides. ia iei hiv g*wyoh.qust
pressure : The eftect of digitalis depends on the initial stafe of blood circulation. If
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2)Blood
Pötasšiuint Digitalis in therapëütic doses increasë pótaišsturt iptake! Toxic doses léads
blood presure is low, it is raised to normal. The nomal blood press
ure
is not raised.
sto potisšium depletión ifroi"thé"héart By the' loss'of potassiuni Tonš'by diuresis
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There is no hypertension as normal blood pressure is not raisèd. In ventricular stroke,
pressure falls. (produced by potent diuretics) can induce digitalis toxicity increase
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systolic blood pressure may rise whereas diastolic blood

12) Cóhdiètiön systém: Diitalis deipressés thie cbniduétiön' system directly. The refräctory
Cardiac size : In normal heart, digitalis decreases, the size of heart due to which cardiac
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31
period is elongated and conduction rate is decreased. Conductioh' throughi 'AV. node is
out put is decreased. Digitalis in cardiac failure and normal heart it decreases heart size,
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gradually in heart failure it returns the size of the heart to normal,.it. Ti ta enaq i
udepresedby both vegal and éxtra vegal actioris: This effect is therapeutically useful.
13 Bifraéardiae' icttbi Ažtot'ont kidnéy "Digitátis "tn' ëongésirvë' cdrdiác'ikure
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raised
4) Venous P'ressure : Digitalis cause decrease in the venous pressure which has been
effect is produced due to increase in cardiacout 6edematoüš'patiéhts, catise"'dhüresis "this'is'idueto detrédséd vënöus pressürë" which
in case of congestive heart failure: This
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liigiu u viinai) T1ulii sr.ibnt>ot tts isuor

put and decreased plasma volume produced diureis. it
by aii ie
tili 'sis sn i
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13
Pharmacology of Drugs Acting on Cardio Vascular
Systom
PUA Text Book of Pharmacology-l
eosinophilia. Digitalis crosses
effects are skin rash,
Other toxic effects: The other side
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shifts edema fluid into the blood circulation and improves renal circulation resulting in 8)
delivery.
increased excretion of sodium ion (Nat) and water. placental barrier and may lead to premature
one of them. There is no
and digitalis is also
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cardioglycosides are toxic substances
14) Action on Gastro intestinal tract: Digitalis in toxic doses may produce diarrhoea, tis clear that
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nausea and vomiting which may be due to stimulation of chemo receptor trigger zone cardiac glycoside which is non toxic.
large
small doses and large effect wilh
(CTZ). It is adequately absorbed from the smal intestines, eliminated slowly Digitalis like other drugs produces less effect with
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through
administered with saturating quantity to produce its eftect
kidneys so likely to produce cumulative toxicity if repeatedly administered for prolong doses. Digitalis must be taken digitalis
to know that patient has
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geriod. therapeutically. In digitalis therapy it becomes necessary

slowly excreted so it may produce The cumulative effect
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Subeutaneous, intramuscular injections of digitalis is unreliable, it may produce earlier or otherwise. Digitalis is
iritation, effects.
swelling and abscess. So glycosides are administered orally or intravenously. (toxicity). The only contra indication of digitalis is its toxic
TOXIeEFFECTS OF CARDIAC GLYCOSIDES

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B
Cardiac toxicity: Digitalis produces cardiac arrhythmias due to the disturbance in
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impulse formation or in impulse conduction or both. Cardiac arrhythmias like atrial Normal heart
tachycardia, ventricular tachycardia, ventricular flutter, ventricular fibrillation occur. Increasing dose
of digitallis In CHF
The disorder of impulse formation is due to ectopic pacemaker activity which shows
multi focal extra systole followed by partial or complete A.V. blockade.
A Hypokalemia : There is loss of potassium ion (K*) whicth increases digihalis toxicity. In
congestive cardiac failure patients, there is edema formation due to increased sodium ion CHF
(Nat) retention. There is potassium ion loss in urine which precipitates the cardiac
toxicity.
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3) ECG changes: The cardiac glycosides cause shortening of Q-T intervals, inversion Filing pressure
of T
waves, and lengthening of P.R. intervals. Fig. 1.6 Digitalis tends to shift the curve toward normal.
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4oxic effects on eyes : Digitalis produce visual disturbances like blurred vision and Relation between heart fallure and cardiac output In normal hoart.
colour defects, colour vision, appearance of dancing and flickening dots.
USES OF
DJGITALIS
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5) Neurological toxicity: Digitalis and cardiac glycosides produces drowsiness, headache,
fatigue and vertigo. Some patients feels tingling and numbness in lips, tips of nose, ears and face ATUsed in congestive heart failure.
2)Used to control arrhythmias like atrial fibrillation, atrial flutter, paroxysmal atrial
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(cheeks). There occur confusion and psychotic
behaviour in patients on cardiac glycoside
therapy. tachycardia.
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6 Blood coagulation effect: Digitalis is likely to produce thrombo embolic complications as DICOXIN: Digoxin occurs as colourless white crystalline powder slightly soluble in water.
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it increases coagubility of blood. Its molecular formula is C41H64O14 It is a digitalis precparation used as cardiac glycoside. It
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7)Gastro intestinal tract toxicity: Digitalis produce vomiting nausea

and diarrhoea (rare) is obtained from leaves of plant digitalis lanata.
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Gastro intestinal toxicity occurs prior to cardiac toxicity
due to which anorexia and
vomiting are common symptoms of toxicity. It is therefore necessary
to distinguish that
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vomiting is due to cardiac failure or toxicity of digitalis.

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14
PU AText Book of Pharmacology-
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Mechanism of action: Pharmacology of Drugs Acting on Cardio Vascular System
Digoxin inhibits the TPatient, should take salt restricted,

sodium potassium adenosine (sodium restricted) diet during therapy.or.as
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calcium available for triphosphatase (AT Pase) advised.
contractile proteins, and makes more
force of contraction. which increase cardiac
output, by increasing
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Fig.1.5 the : Patient to inform difficulty in breathing, edema, weight gain, loss;.of ,appetitej
tations headache, yellow vision, blurred vision, skin rash to the treating goctor
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.
Congestive heart failure, cardiogenic
:
shock, atrial flutter, atrial

a ueinitsht
atrial fibrillation. tachycardia, To store drugs in a cool place, airtight containers, protect from heat and light, keep out
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*
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Dosage. of reach of children.
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Adult: Initially 0.25 to 1.5 mg daily orally. Treatment overdose : Discontinue digoxin, give potassium administer antidote of digoxin:
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digoxin immune FAB.
Maintenance dose:0.25 to 0.5 mg
daily.
DIGITOXIN is a digitalis preparation. it occurs as awhite powder insoluble in water. Its
Child: Initially 10 to 20 mg per.kg. t
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body weight 6 hourly. molecular formula is C41H6413t is used as a cardiac glycoside cardiotonic, It is rapidly
Maintenance dose : 10 to 20mg per kg
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body weight in single or divided doses. and completely absorbed in stomach, duodenum and in jejunum. It is obtained from leaves
Contraindications : Hypersensitivity; of digitalis purpurea, digitalis lanata.
ventricular tachycardia, renal disease, AVi block,
pregnancy, lactation, hypokalemia,
respiratory distress. Mechanism of action : Digitoxin inhibits sodium, potassium, Adenosine triphosphatase
e effects : Blurred vision, diplopia, colour vision defect, green yellow (ATPase) and makes more calcium available for contractile proteins which increase cardiac
halos; heádache,
drowsiness, confusion, fatigue, depression, disorientation, output
vomiting, nausea: anorexia,
hypotension, diarrhea and abdominal pain. Indications: Congestive heart failure, atrial Autter, atrial tachycardia, atrial fibrilation.
T'harmacokinctics :Orally onset action 30 minutes to 2 hours, peak concentration Dosage: Adult and child age 12 years and above, orally 1.2 to 1.6 mg per day in divided
6'hours,
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duration of action 3 to 4.days. Plasma half life 35 to 36 hours, excreted in-urine, crosses doses. Maintenance dose of 0.05 to 0.3 mg daily. Child 1 to 2 year age 004 mg per kg weight
placental barrier. daily above age 2 year 0.03 mg per kg OD.
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Drugs inleractions May cause hypokalemia, diuretics, corticosteroids, carbenicillin,
: Contraindications: Hypersensitivity, hypokalemia, pregnancy, lactation, hepatic disease
A.V. block, ventricular tachycardia, elderly.
amphotericm B. Increased bradycardia with Beta adrenergic blockers, antidysrythmics
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Side effects: Vomiting nausea, diarrhoea, loss of appetite, headache, confusion,
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irand names 1ut1'
Digoxin: Tablet, Injection, Cardioxin, Sangoxin, L'anoxin, Dixin, Digox
disorientation, fatigue, depression, blurred vision, yellow green halos, diplopia,
0.25mg tablets, Injection 0.25mg per ml.
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hypotension, bradycardia, muscular weakness.
Availability : Tablet Lanoxin (digoxin) 0.25 mg. tablet Cardioxin (digoxin) 0.25mg. Injection
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Pharmacokineties: Oraly onsef action 'i hour poák concentraiion 4 to 12 Hours, serun 'half
Dixin containing 0.5 mg Digoxin. Syrup digoxin 1.5 mg/30 mi iianati:
*tu,.iu
"
i itdg*ionn saiiima trh

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life 4 to 9 days, metaboliízed in liver, excreted in urine.
P'rcautions for patient
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Drug interactions: Decrease the level of digitoxin with thyroid drugs. Toxicity occurs with
P'atient should not to discontinue drug suddenly.
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diuretics, quinidine and thioamines.
Patient should not take any other medicine, with treatment. To take only
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recommended or prescribed medicine in correct dosage.

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17
PU A Text Book of Pharmacology-l Pharmacology of Drugs Acting on Cardio Vascular System
gas tro intestinal tract. The action of

Treatment of overdose :Discontinue drug, to administer digoxin immune FAB, potassium,
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intravenous route because it is poorly absorbed from the
can be used in
monitor ECG. quabain is similar to digitalis the action is quick but of a short duration,
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DIGOXIN IMMUNE FAB: It is used as an antidote in digoxin, digitoxin over dose toxicity. emergency.
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an increase
Mechanism of action: Mechanism of action, nhibits the Na-K-ATpase membrane pump, resulting in
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in intracellular sodium and calcium concentrations. Increased intracellular concentrations of
Digoxin immune FAB do not allow digoxin to bind to the sites of action and reverse digoxin
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toxicity. calcium may promote activation of contractile proteins (e.g, actin, myosin). Quabain also
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Indications: Digoxin or digitoxin toxicity. acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization,
shortening the action potential duration, and decreasing the maximal diastolic potential.
Dosage: Digozin torieity.
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Indication: It is indicated that for the treatment of atrial fibrillation and futter and heart
Adult: For unknown ingested amount give iv 800 mg. If dose taken is known; Dose ingested
failure
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(mg) serum digoxin concentration 5.6 weight of the patient in kgs (divided by) 1000.
Digitozin tozicity: Dose ingested (mg.) serum digitoxin concentration 0.56 weight of patient Jsés: It is a cardiac glycoside similar to digitoxin.It is used to treat congestive heart failure.
It is used in the treatment of supraventricular arrhythmias due to reentry mechanisms, and
in kg 100, administer calculated dose intravenously.
to control ventricular rate in the treatment of chronic atrial fibrillation.
Contraindications: Hypersensitivity, mild digoxin toxicity, children, pregnancy, lactation.
Side effects : Facial swelling, redness, rapid respiration rate, low cardiac output, atrial
fibrillation. 14ANTIHMRERTENSTON
The drugs used in the treatment of hypertension are called antihypertensive drugs.
Pharmacokinetics: Excreted in the urine.
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These drugs acts by reducing the cardiac output or reducing the total peripheral resistance
1) To administer after diluting 40 mg in 4 ml water for injection may further dilute with
without correcting the cause.
normal saline. Use a clear solution.
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Hypertension is a disease characterized by abnormal high blood pressure. Normal B.P
2 To evaluate therapeutic response, correction of digitoxin toxicity investigate digoxine
120/80 mm Hg is considered normal in adults.
level 0.5 to 2 mg per mi, digitoxin level 9 to 25 mg per ml.
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Primary or essential hypertension: is hypertension for
3 To advice patient to report, chills, fever, itching, swelling, dyspnea, urticaria, skin rash to which the exact cause is not
known.
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the treating doctor.
(in Secondary hypertension: Hypertension may be
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due to renal, endocrine or vascular

disease.
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Squill contains cardiac glycosides. The bulb of Drimia maritima. Drimia indica (kunth)
plant contains cardioglycosides. The action of squill is quick than digitalis and can
Hypertension is harmful irrespective of the cause.
It may lead to degenerative
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be given changes
to patients who cannot tolerate digitalis. It produces gastrice irritation on retinal tissue, coronary, renal tissues. Antihypertensive
drugs are used in the treatment of
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so it is rarely used at
present. hypertension.
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STROPHANTHUS: The important gycoside of strophanthus

is g strophanthin called as
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quabain. It is obtained from the plant strophanthus
gratus. It is administered through
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18 PV A Text Book of Pharmacoloay-
PHARMACOLOGY OF ANTIHYPERTENSIVE AGENTS
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ANGIOTENSION CONVERTING INHIBITORS
Blood Pressure
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angiotensin-converting enzyme (ACE),
LISINOPRIL: It is a potent, competitive inhibitor of
(AT).
of angiotensin-I (ATi) to angiotensin-II
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the enzyme responsible for the conversion

the renin-angiotensin-aldosterone
ATii regulates blood pressure and is a key component of
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Casification anti-hyperension system (RAAS).
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which arise from

Mechanism of action: ACE has two functionally active domains, N and C
to and inhibit the activity of both domains,
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tandem gene duplication. ACE inhibitors bind
inhibitory activity against the C-domain. It is one of
but have a much greater affinity for and
ACE inhibitors that are not a prodrug competes with anti for binding to ACE and
the few
ATu. Decreasing ATa levels in the body
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c
inhibits and enzymatic proteolysis of ATI to
Angio tension Calciwm chanmel Angiotensin tAT p Adrenerge
pressure by inhibiting the pressor effects of ATa as described in the
blockers decreases blood
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conrersion enzyme blockers Dlockers
inhibitors Verapamil (o Propranolol
cH) Metoprolol pharmacology section above. Lisinopril also causes an increase in plasma renin activity
Lisinopril ) Dltsazem
(un)
Gi) Irbesarlan
(ii) Ateno likely due to a loss of feedback inhibition mediated by ATa
on the release of renin and/or
Gi) Ramipr Nifedipine Ciin Candesarian
(iv) Labeta
(u) Captopn () Amlodipine
(o) Felodipine
(D)
potassium
Losartan
(v). Carvedilol stimulation of reflex mechanisms via baroreceptors.
() Enalaprnl
(p) Nitrendipine v.Telmisartan,
to) Perindopri
(vi) Fosinopril,
Anglotensinogen
Renin
a Adrenergic Vasodilators Central Diuretics 1-PA Angiotensinl

blockers Arteriolar sympatholytics Thiazides: Catheosin G Chymase ACE
Prazosn Clonidine Hydrochlorothiari Cathepsin G Inhibitors
yaiazine e
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Terazosin Doxazosin Minoxidi GD Methyldopa
Fhentolamine Diazoxide Chlorthalidone, Angiotensin I
Indapamide
Phenoxybenzamine Arterolar + Denous:
High ceilin
Sodium Agrceptor AT receptor ARBs
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Furosemide, etc.
nitroprusside K+ Sparing
Spironolactone, Vasodilation Vasoconstriction
Amiloride Inhibition of cell growth Sympathetic Activation
Apoptosis Cell growth
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Sodium and fuld retention
Drugs decrease the blood pressure
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ACE inhibitor
Fig. 1.7 ACE Inhibitors act on Angiotensin converting enzyme. Lisinopril is example of
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Pharmacokinetics: It has an oral bioavailability of 25 percent 4 percent, which is unaffected

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by food. The accumulation half-life averages 12.6 hours despite a terminal serum
half-life of
approximately 40 hours. Steady state is attained after two daily doses (every 24 hours) in
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Lisinopril
healthy volunteers. The drug is not metabolized but is eliminated via the kidneys.
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probably undergoes glomerular filtration, tubular secretion, and tubular reabsorption.
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PU A Text Book of Pharmacology-! Pharmacology of Drugs Acting on Cardio Vascular System
Indication: It is indicated for the treatment of hypertension and symptomatic congestive Uses: It is used for the treatment of essential or renovascular hypertension and symptomatic
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heart failure. It may be used in conjunction with thrombolytic agents, aspirin and/or p- congestive heart failure It may be used alone or in combination with thiazide diuretics.
blockers to inmprove survival in hemodynamically stable individuals following myocardial Brand Name: Act Enalapril Tab 4 mg. oral, Enalapril tab 8 mg. oral.
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infaretion. It may be used to slow the progression of renal disease in hypertensive patients
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with diabetes mellitus and microalbuminuria or overt nephropathy.

PErINDOPRL: It is a nonsulfhydryl prodrug that belongs to the angiotensin-converting
Uses: It used to treat hypertension and symptomatic congestive heart failure to improve
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Survival in certain individuals following myocardial infarction, and to prevent progression enzyme (ACE) inhibitor class of medications.
Mechanism of action: The active metabolite of perindopril, is Perindoprilat which competes
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of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or

overt nephropathy. with AT for binding to ACE and inhibits and enzymatic proteolysis of ATi to AT
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Brand Name Act Lisinopril tab 20 mg. oral, Lisinopril 5 mg oral. Decreasing ATa levels in the body decreases blood pressure by inhibiting the pressor efects
of ATu as described in the Pharmacology section above. Perindopril also causes an increase
RAMIPRIL: It is an inactive prodrug that is converted to ramiprilat in the liver, the main in plasma renin activity likely due to a loss of feedback inhibition mediated by ATu on the
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site of activation, and kidneys. It confers blood pressure lowing effects by antagonizing the release of renin and/or stimulation of reflex mechanisms via baroreceptors.
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effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics,
water and electrolyte balance. The extent of absorption is at least 50-60%. food decreases the Pharmacokineties: It is rapidly metabolized in the liver its active metabolite, orally is rapidly
rate of absorption from the GI tract without affecting the extent of absorption. The absolute absorbed with peak plasma concentrations occurring at approximately 1 hour and are
bioavailabilities of ramipril and ramiprilat were 28% and 44%, respectively, when oral attained 3 to 7 hours. The absolute oral biaavailability is about 75%. It is approximately 30 to
administration was compared to intravenous administration. 50% of systemically available which is hydrolyzed to its active metabolite, perindoprilat,
Brand name: Act Ramipril 5 mg Capsule, Altace 5 mg Capsule Oral, which has a mean the bioavaidability of about 25%. The presence of food in the
gastrointestinal tract does not affect the rate or extent of absorption of perindopril but
CAPTOPRIL It is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE), reduces bioavailability of perindoprilat by about 35%. It is only 4 to 12% of the dose
the enzyme responsible for the conversion of angiotensin-I (AT) to angiotensin-1I (AT). ATn recovered unchanged in the urine.
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regulates blood pressure and is a key component of the renin-angiotensin-aldosterone Uses : It is used to treat mild to moderate essential hyperternsion, mild to moderate
system (RAAS). It is used in the treatment of hypertension. congestive heart failure, and to reduce the cardiovascular risk of individuals with
Brand name: Bci Captopril Tablets 50 mg. oral, Capoten 100mg/1 Tablet oral, hypertension or post-myocardial infarction and stable coronary disease.
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Brand Name: Aceon tab 8 mg. oral.
ENALAPRIL It is a potent, competitive inhibitor of ACE, the enzyme responsible for the
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conversion of angiotensin-1 (AT) to angiotensin-1I1 (ATn). ATn regulates blood pressure and FOSINOPRIL : It is a phosphinic acid-containing ester prodrug that belongs o the
is a key component of the renin-angiotensin-aldosterone system (RAAS). Is affinity for ACE angiotensin-converting enzyme (ACE) inhibitor class of medications.
Ph
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is approximately 200,000 times greater than that of ATI and 300-1000 times greater than that Mechanism of action: Fosinoprilat, the active metabolite of fosinopril, competes with ATI
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enalapril. It is a lipid-soluble and relatively inactive prodrug with good oral absorption (60
for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII
to 70%), a rapid peak plasma concentration (1 hour) and rapid clearance (undetectable by 4
levels in the body decreases blood pressure by inhibiting the pressor eífects of ATII.
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hours) by de-esterification in the liver to a primary active diacid metabolite, enalaprilat.
Fosinoprilat also causes an increase in plasma renin activity likely due to a loss of feedback
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The peak plasma concentrations occur 2 to 4 hours after oral administration. The
elimination thereafter is biphasic, with an initial phase which reflects renal filtration inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisnms
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(elimination half-life 2 to 6 hours) and a subsequent prolonged phase (elimination half-life via baroreceptors.
36 hours). Pharmacokinetics: The primary site of absorption is the proximal small intestine
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(duodenum/jejunum). It is rapidly and completely hydrolyzed to principle active

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Pharmatology of Drugs Acting on Cardio Vascular System
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A Tex Book of Pharmacology
metabobte. tosinoprilat. This hydrolysis orcurs in the gastrointestinal mucosa and liver. The Chronic coronary insufficiency, angina pectoris, hypertension, atrial flutter,
planma pratein binding is >95%. It is approvimately hall of the absorbed dose is excreted in
ications:
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fibrilltion
atrial
pregnancy, hepatic injury,
the urine and the remainder is eacnted in the feces Contraindications Sick sinus syndrome, cardiovascular shock,
:
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lactation, chikdren with precautions, congestive heart taiure
ts h uve to treat mild to moderate hyertension, as an
adjunct in the treatment of
ankle oedema, hypotension, constipation,
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oyrestive hoart failure, and to slow the rate of progression of renal disease in hypertensive Side effects: Headache, nausea, fatigue, flushing,
weakness.
imdivdua with diabetes melitus and microalbuminuria or overt nephropathy. anxiety, depression, insomnia, confusion,
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peak plasma
tiared name, losinopril tab 10 mg oral, Monopril tab 10 mg/1 oral. Pharmacokinetics: Orally onset action variable, and metabolized in liver the
duration of action 18 to 24
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4 hours, half life IV 4 minute orally 3 to 7 hours,

ntM 71ANNEL BLOCKER concentration to
3
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The main group of medicines is to inhibit calcium ion mediated channel
action of this hours and excretd through urine.
quinidine, decreased effect of
Drug interactions Increase hypotension with prazosin,
:
nwand urrent act as calcium antagonist effet on smooth vascular muscles of coronary
arteries due to which myocardial blood flow is increased. lithium, neurotovicity is increased with carbamazepine.
dose 480 mg per day,
Dosage: Adult orally 40 to 80 mg three to four times a day maximum
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7RAPAMI It has a marked antiarrhythmic drug due to its antagonistic effect on the
if desired effect not obtained further 5 mg after
not to exceed 480 mg/day. IV: mg initially,
5
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smth vascular muscles of the coronarices the myocardial blood flow is increased. verapamil
5 to 10 minutes, child to 5 years 2 to mg
1 3 LV. age of child 6 to 14 years 2.5 to 5 mg only as
reduos workioad on the heart by reducing the oxygen requirement of the myocandium and
by dereasing pernpheral resistance. Its molerular formula is C27H39CL NO4 onset dose.
Vasopten, Veramil, Verap 40mg
Brand Names: Verapamil: Tablet Injection, Calaptin,
hanism ef action : inhibits calcium ion flow across cell membrane during cardiac
It
Calan tab. 120mg. oral, Calan SR tub.
8Omg. 120mg. 240mg tablets, Injection 5ng per 2ml.
deplaization, proxducs relaxation of coronary vascular smooth muscles, dilates coronary 160 mg. Covera-liS 240 mg.oral
calcium
arteries, dilates peripheral arteries and decrease SA. inhibits voltage-dependent
It
Treatment of overdose Administer atropine for AV. block, for hypotension give
:
channes. Secifically, its effect on L-type caleium channels in the heart causes a reduction in
blood pressure. vasopressors.
iomotropy and chronotropy, thus reducing heart rate and
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pressure with
P-gp Inhibltors Verapamil DILTIAZEM: It is a potent coronary dilator. It produces modest fall in blood
Cell
reflex cardiac effect occurs. It is a calcium channel
membran no change in heart rate, with large doses
Cytotoxie
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Drug blocker drg
cardiac
cytoplasm DiMusion A Mechanism of action: It inhibits calcium ion flow across cell membrane during
Nucleus
relaxation of coronary artery smooth muscles, due to which
depolarization, produce etfect of
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coronary arteries dilatation occurs, also dilates peripheral arteries
PGlycoprotein
to coronary
Indications: Hypertension, atrial flutter, atrial fibrillation, angina pectoris due
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insufficiency.
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time before meals,

Dosage :Adult orally 30 mg 2 to 4 times a day, before meals, at bed
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Drugbndug per kg body weight over
Sile on 120 mg twice daily. Adult IV 0.25 mg
P-Gycoprotein slowly increase dose 60 mg to
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2 to 3 minutes slowly.
to the function as an energy syndrome. Use with
Children pregnancy, bradycardia, sick sinus
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Fig 1.6 The transmembrane proleins G"-glycoprotein's is believed Contraindications :
congestive heart failure.

independent etfiua punyp or drug transporter. precautions in pregnancy, lactation children, hypotension,
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Telegram - Study Pharmacy Puw
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25
Vascular System
Text Book of Pharmacology-l
Pharmacology of Drugs Acting on Cardio
PUA decreased effect of
nifedipine with
Cimetidine increases nifedipine level,
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Drug interactions :
oedema, flushing, dizziness, depression, insomnia,
Side effects : Headache, skin rash, ankle quinidine syngergism with Beta
blockers.
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weakness, tremors, drowsiness. chronic stable angina.
concentration 2 to 3 Uses:It is used to treat hypertension and 120 mg per day.
Pharmacokinetics : Orally onset action 30 to 60 minutes, peak plasma
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day, maximum dose of

excreted in urine, excreted in breast Dosage : Adult :5 to 20 mg three times a
renal
hours, plasma half life 4 to 9 hours metabolized in liver, hypotension, pregnancy lactation, children,
Contraindications: Hypersensitivity,
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milk.
Calcigard, Cardipin, Depin,
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theophylline level disease.

Drag interactions : Elevate serum digoxin cyclosporin, Tablets, Cardilet, Calblc,
Angigem, Channel, Dilgard, Icidil Brand names: Nifedipine: Capsules, Cap 10ng
5 mg capsule oral, Adalat
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-
Brand names: Diltiazem: Tablet Dicard, Dilcor, Cardem, capsules. Adalat

Cap. Act Diltiazem T 240 mg-,Apo Nicardia, Nifelat, Smg, 10mg, 20mg
30mg, 60mg 90mg tablets. Act Diltiazem CD 180 mg
oral, Adalat Cap 5mg. oral. stable angina,
Diltiaz Tab 30mg. of vasospastic angina, chronic
Uses: It is used for the management for left ventricular
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Raynaud's phenomenon. It is used as a first line agent
with short hypertension, and
NIFEDIPINE :It is a vasodilator and antianginal drug having rapid onset action (long-acting agents).
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increase in hypertrophy and isolated systolic hypertension
duration of action. It causes dilatation of coronary blood vessels and cause
coronary blood flow. It causes fall in systolic and diastolic blood pressure and cause
reflex Precautions for patient
tachycardia. Patient should not crush, chew, or break capsules.
limited tea, coffee and to take salt
Mechanism of action: It decreases arterial smooth muscle contractility and subsequent Patient should not take alcohol, avoid smoking, take
vasoconstriction by inhibiting the influx of calium ions through L-type calcium
channels. restricted diet.
common may occur.
Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound To change position slowly, orthostatic hypotension that is
recommended medicinecs.
calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated
MLCK
Patient should not take any medicines other than the
catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in To report for vomiting, nausea, headache, oedema to the doctor.
for hypotension,
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muscle contraction. Signal amplification is achieved by calcium-induced calcium release Overdose treatment : Atropine sulphate for AV block, vasopressor
from the sarcoplasmic reticulum through ryanodine receptors. Defibrillation.
A second proposed mechanism for the drug's vasodilatory effects involves pH-dependent
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inhibition of calcium influx via inhibition of smooth muscle carbonic anhydrase.
AMLODIPINE: It is a calcium channel blocker drug. It is a long-acting 1,4-dihydropyridine
Indications: Hypertension, ongestive heart failure, vasospastic angina, acute myocardial calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing
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infarction, migraine. voltage-gated L-type calcium channels in their inactive conformation. It inhibiting the infhux
:
Side effects Headache, fatigue, drowsiness, anxiety, depression, weakness, insomnia, of calcium in smooth muscle cells,
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nervousness, blurred vision, edema, vomiting, nausea, dry mouth, gastric upset, polyurea,
Mechanism of action : Inhibition of the initial infux of calcium decreases the contractile
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skin rash, hair loss, sexual weakness, cough, fever, tachycardia, nasal stiffness.
activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of
Pharmacokinetics : Well absorbed orally, onset action 20 minutes, peak concentraton 1 to 6
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amlodipine result in an overall decrease in blood pressure.
hour, serum half life 2 to 5 hours, Its protoens binding is 92-98%. Its hepatic metabolismis
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viacytochrome P450 system. Predominantly is metabolized by CYP3AS, but also by CYP1A2 Indications :It is useful in hypertension, chronic stable angina and vasospastic angina.
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and CYP2A6 isozymes. It is extensively metabolized to highly water-soluble, inactive Contraindications : Hypersensitivity, hypotension, pregnancy lactation, renal disease,
metabolites accounting for 60 to 804o of the dose excreted in the urine. children, elderly.
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Side effects :Hypotension, edema, vomiting, nausea, syncope, abdominal cramps, anorexia,
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polyurea, skin rash, urticaria, hair loss, depression, insomnia, anxiety, headache and malaise.
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VA Tert Book of Pharmecology-l
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26 Pharmacology of Drugs Acting on Cardio Vascular Systen
blocker with marked vasodilator action It
TNage is an
Adult 5 to 10 mg daily NITRENDIPINE: t is a calcium channel blockers in that it
Phamatokinetics differs from other calcium channel
effective antihypertensive agent and
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Peak concentration 6 to 9 hours, plasma half life 30 to 50 hours,
mildly natriuretic, rather than sodium
metaboliznd in liver and excreted in urine. does not reduce glomerular filtration rate and is
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F'revautions for patient retentive
with
ion-control gating mechanisms, and/or interfering
Mechanism of action: It inhibits the
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P'atient should not crush, chew, or break capsules. it inhibits the influx of extracellular
the release of calcium from the sarcoplasmic reticulum,
Tatient should not take aleohol, avoid smoking, take limited tea, coffee and to take salt cell membranes. The decrease in
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calcium acoss the myocardial and vascular smooth muscle
restricted diet. processes of thee myocardial smooth muscle cells,
contractile
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intracellular calcium inhibits the

To change position slowly, orthostatic hypotension that is common may occur. arteries, increased oxygen delivery to the
causing dilation of the coronary and systemic
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Patient should not take any medicines other than the recommended medicines. blood pressure,
myocardial tissue, decreased totall peripheral resistance, decreased systemic
To reort for vomiting. nausea, headache, ocdema to the doctor.
and decreased afterload.
verdese treatment: Atropine sulphate for AV block, vasopressor for hypotension,
treatment of mild to moderate hypertension
Indication: It is indicated for the
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Ifibrillation. Hypotension, Nausea, Edema, Headache, Dizziness,
Flushing, Palpitation,
side effect:
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trug, interactions Increased effect of digitalis, theophyllin, prazocin. Paraesthesia, Gastrointestinal disturbances
Fatigue,
trand Names cardiac
Amlodipine Tab Amlong, Espin, Esdil, Esam, Eslo, S Num lo 2.5mg
interaction: Beta-blockers: Synergistic action, reverses depression of
Drug
Smg, 10mg tablets, Tab Amlip, Amloz, Amtas, Amlopress, Amlosun, Defidin. Theophylline, phenytoin: Increases
function. Quinidine: Plasma levels of quinidine reduced.
erdee therapy Atropine for Av block, vasopressor for hypotension, diuretics, plasma levels of nitrendipine.
defibrillation, IV calcium. Increased to 20 mg twice daily if required.
Dose: Starts with 5 to 20mg once daily.
It is used alone or with an angiotensin-converting enzyme inhíbitor, to treat
Uses:
oirN: 1t is a long-acting 1,4-dihydropyridine calcium channel blocker. It is a new hypertension, chronic stable angina pectoris, and prinzmeta's variant angina.
antihyypertensive drug requires once daily dose. It is suitable for mild to moderate
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hyywrtension.
PADRENERGIC BLOCKERS
of action:
Mechanism Inhibition of the initial influx of calcium decreases the contractile antiarrhythmic drugs. It is a mild antihypertensive
Propranol: It has been discussed under
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The vasodilatory effects of
activity of arterial smooth muscle cells and results in vasodilation. drug and do not significantly lower blood pressure in normotensives
indications, dosage,
felodipine result in an overall decrease in blood pressure.
side effects, same as mentioned at page number
tndcations: Hypertension. antianginal drugs. It is antihypertensive drug and is
Atenolol: It has been discussed under
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If required other
Adult 5 mg daily maintenance dose 5 to 10 mg once daily. given in single daily dose. Adult dose: orally 50 mg to
100 mg daily.
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antihypertensive drug may be added. It is an antihypertensive drug. It is used for treatment of mild
to moderate
toprolol:
hypertension dosage: Adult orally 100 to 200 mg in two divided doses daily.
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Cotraindications: Hypersensitivity, pregnancy, lactation, elderly, children.

ide ctfects Ocdema, Aushing, headache, palpitaiton, dizziness, dry mouth, nausea. beta blockers. It is used in all types (all grades) of
Labetalol: Its action is faster than pure
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hypertension. It has been used L.V. for rapid blood pressure reduction.
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is used to treat mild to moderate essential hypertension.
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competitively block adrenergic stimulation of p-receptors

Felogard tab, Renedil, Plendil 2.5mg, 5mg, 10mg tablets, Cardif
BrAd Names tab, It is to
Mechanism of action:
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within the myocardium (ßl-receptors)JcAMP/pkA and within bronchial and vascular
Nitrepen tab. smooth muscle. This causes
smooth muscle (2-receptors), and al-receptors within vascular
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A Text Book of Pharmacology-! System
via its alpha
systemic vascular resistance
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decrease in systemic arterial blood pressure and systemic vascular resistance without a and myocardial oxygen demand. It also decreases
substantial reduction in resting heart rate, cardiac output, or stroke volume, apparently adrenergic receptor blocking properties.
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because of its combined a and p-adrenergic blocking activity. Labetalol reduces blood
pressure without reflex tachycardia, reduce elevated plasma renins,
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Indications : Mild to moderate hypertension. Severe hypertension G.V). Vasomotor center
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volume Cardiac Output
Dozage: Adult oraly for hypertension : 100 mg twice a day may increase dose after 2 to 3
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days to 200 mg bid. Renin

ng
:
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Hypertensive crisis TV infusion 200 mg per 200 ml dextrose 5% run infusion at 2 ml per Preload
minute, stop or discontinue infusion when desired response achieved. Ang
BP-COx TPVR
Aldosteron
Contraindications: Hypersensitivity, sinus bradycardia, bronchial asthma, pregnancy, Vascular
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lactation, diabetes, elderly hepatic disease, renal disease. Smooth
Cells
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Side effects : Sore throat, visual change, double vision, dry eyes, vomiting, nausea, skin TPVR
rash, urticaria, fever, thrombocytopenia, impotence, ejachulation failure, drowsiness, Total Peripheral Vascular Resistance (TPVR)
headache, catatonia, depression, nightmares, lethargy, chest pain, postural hypotension,
bradycardia. Fig. 1.9 effect of drug in AT receptor
Pharmacokinetics:Onset action hour to 2 hours, peak plasma concentration 2 to 4 hours, Carvedilol and its metabolite BM-910228 (a less potent beta blocker, but more potent
duration of action 8 to 12 hours. IV onset action 5 minutes peak concentration 15 minutes antioxidant) have been shown to restore the inotropic responsiveness to Caž* in OH° free
duration 2 to 4 hours. Plasma half life 6 to 8 hours. Metabolized by liver, excreted in urine, radical-treated myocardium. Carvedilol and its metabolites also prevent OH radical-
croSses placental barrier, excreted in breast milk. induced decrease in sarcoplasmic reticulum Ca-ATPase activity. Therefore, carvedälol and
Drug interactions: Decrease effect of labetalol by thyroid preparations, indomethacin, its metabolites may be beneficial in chronic heart failure by preventing free radical damage
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theophyllin, 1idocaine, increased hypotension with diuretics, antihypertensives. Indication: It is used in hypertension and congestive heart failure.
Brand names: Labetalol: Tablet, Capsule, Injection, Lobet, Normadate 50mg, 10mg, Dose: The dose for hypertension is initialy 6.25 mg twice daily, if tolerated increase dose
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200mg Capsule, tablets Injection 50mg per ml. after 14 days to 125 mg twice daily. In congetstive heart failure dose is 3.125 mg twice daily,
Precautions for patient raise to 6.25 mg after two weeks. The side effects, contra indication are similar to labelalol.
Patient should take salt restricted diet, not to consume alcohol, avoid smoking Brand name : Tab Carvetrend, Carvil 3.125, 6.25, 12.5 and 25 mg carvedilol tablets.
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Not to take any other medicine unless advised by the treating doctor. Uses: It exerts antihypertensive effect partly by reducing total peripheral resistance and
Ph
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Not to discontinue drug abruptly, taper dose for one to two weeks then stop taking vasodilation by blocking alpha one adreno receptors.
treatment.
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Take medicine dose at bed time to prevent postural hypotension.

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CARVEDILOL: is a non-selective beta blocker indicated in the treatment of mild to ANGIOTENSIN (AT1 RECEPTOR) BLOCKERS
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moderate congestive heart failure (CHE), It blocks beta-1 and beta2 adrenergic receptors as VALSARTAN: It is an angiotensin-receptor blocker (ARB) that may be used to treat a
well as the alpha-1 adrenergic receptors.
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variety of cardiac conditions including hypertension, diabetic nephropathy and heart failure.
Mechanism of action: It inhibits p adreno receptors mediated compensatory mechanism. It Mechanism of action: It inhibits the binding of angiotensin II to AT1, which is found in
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is beta-adrenergic receptor blocking ability decreases the heart rate, myocardial contractility,
many tissues such as vascular smooth muscle and the adrenal glands. This effectively
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30
PA Text Book of Pharmacology-
inhibits the AT1-mediated vasoconstrictive and aldosterone-secreting conditions including hypertension, diabetic
effects of angiotensin Indication: It is used to treat a variety of cardiac
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lI and results in a decrease in vascular resistance antagonizing the renin-
and blood pressure. nephropathy and heart failure. Its lowers blood pressure by
angiotensin-aldosterone system (RAAS).
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CassikalRAS
Brand Name: Act Valsartan 160 mg Act Valsartan 80 mg. Diovan 40 mg.
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IRBESARTAN: The drug act on angiotensin antagonist.

II
Angiotensinogen system, angiotensin I is converted by
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Mechanism of action: The renin-angiotensin
the
angiotensin-converting enzyme (ACE) to form angiotensin TI. Angiotensin stimulates
Renin II
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cortex to synthesize and secrete aldosterone, which decreases the exCretion of

adrenal
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tetrazole derivative and
Angiotensin 1
ACE2 sodium and increases the excretion of potassium. It is a nonpeptide
of angiotensin II to the
an angiotensin II antagonist that selectively blocks the binding
Anglotensin (1-9) effects of aldosterone.
ATi receptor promotes vasodilation and decreases the
ACE inhibitors ACE
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ACE lt is indicated for the treatment of hypertension, as well as diabetic nephropathy
Indication:
in patients with type 2
with an elevated serum creatinine and proteinuria (>300 mg/day)
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Angiotensin II
ACE2
diabetes and hypertension. It is also used as a second line agent in the treatment of
AT receptor Angiotensin (1-7)
blockers congestive heart failure.
lightheadedness, upset stomach, diarrhea, heartburn, or tiredness
Side effect Dizziness,
AT Mas)
ATa Pharmacokinetics: It is rapid and complete with an
average absolute bioavailability of 60-
80%. Food has no affect on bioavailability. The volume of distribution
is 53 to 93 L. The
(primarily albumin and al-acid
proteins binding is 90% bound to serum proteins
Neurotoxicity Neuroprotection metabolized
glycoprotein) with negligible binding to cellular components of blood. It is is
and oxidation. It is excreted by both biliary and renal routes.
Fig. 1.10 drug act on AT receptor via glucuronide conjugation
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for the treatmentof hypertension. It is used as a second line agent in
aldosterone Uses: It is used mainly
I is sclective for AT1 and has virtually no affinity for AT2. Inhibition of the treatment of congestive heart failure.
kidneys while decreasing8
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sccretion may inhibit sodium and water reabsorption in the
4-hydroxy valsartan, has Brand name: Act Irbesartan 75, 150, 300 mg. oral, Aprovel 75 mg.
potassium excretion. The primary metabolite of valsartan, valeryl
no pharmacological activity. blocker (ARB) that may be used alone or
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'harmacokinetics: Absolute bioavailability 23% with high variability. The volume of CANDESARTAN: It is an angiotensin-receptor
orally as the prodrug, candesartan
-979% bound to serum with other agents to treat hypertension. It is administered
distribution is 17 L (low tissue distribution). The proteins binding 94
Ph
Ph
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rapidly converted to its active metabolite, candesartan, during absorption
It excreted largely as unchanged drug (80%). It is 83% ilexetil, which is
proteins, primarily serum albumin. is antagonizing the renin-angiotensin-
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lowers blood pressure by

13 % is excreted in urine, primarily as in the gastrointestinal tract. It
of absorbed valsartan is excreted in feces and aldosterone system (RAAS). It competes with angiotensin
II for binding to the type-1
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unchanged drug. pressure increasing effects of
angiotensin II receptor (ATI) subtype and prevents the blood
effecls: Headache, dizziness, lightheadedness, tiredness, flu symptoms, upper
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Side
angiotensin Il.
runny or stuffy nose, sneezing, sore
respiratory infection, diarrhea, cold symptoms (cough,
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oral.
Brand Name: Act Candesartan 8,32 mg.oral, Atacand 32 mg
throat).
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System
VA Text Book of Pharmacology- mitogen-activated kinase and
Pls Kinase
rom intracellular stores, activation of
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LOSARTAN : I's longer acting metabolite Jower the blood pressure by antagonizing the pathways and subsequent vasoconstriction. inhibiting dIA-Teceptor
renin-angiolensin-aldosterone sy'stem (RAAS). t is an angiotensin-receptor blocker (ARB) pharmacological effects by
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hypertension. It competes with harmacological action: It produces its and prostate results in muscie
that may be used alone or with other agents to treat receptors in the vasculature benign
activation. Inhibition of these in symptomatic
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(AT1) subtype and prevents

angiotensin 1 for binding to the type-1 angiotensin I receptor improved urinary outflow
I1. relaxation, decreased blood pressure and
the blood pressure increasing effects of angiotensin
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prostatic hyperplasia. treatment of
50,100 mg. oral, Cozaar 50 mng. (BPH). It is used in the
Brand name: Act Losartan Uses: It is used to treat the benign
prostatic hyperplasia adrenaline on
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the action of
It works by blocking
hypertension and prostate enlargement.
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TELMISARTAN: It is an angiotensin II receptor antagonist (ARB) which used in
is the vessel walls.
smooth muscle of the bladder and the blood
treatment of hypertension. Its bind to the angiotensin bype (AT)
11 1
receptors with high
1,2,5 mg tab usually maintained
dose 2 to 10 mg
Brand name: Hytrin olyster,
II on vascular smooth muscle,
affinity, causing inhibition of the action of angiotensin
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ultimately leading to a reduction in arterial blood pressure. selectively antagonises
postsynapuc d
DOXAZOsIN: It is a quinazoline-derivative that hypertension and in the
Brand name: Act Telmisartan 40 80 mg. Kinzalmono 80 mg.
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to mild to moderate
adrenergic receptors. It may be used (BPH). The ar-Receptors mediate
hyperplasia
management of symptomatic benign prostatic of the
muscle cells. It is a selective inhibitor
a ADRENERGIC BLOCKERS contraction and hypertrophic growth of smooth
Its antagonism action leads to smooth muscle
TRAZOSIN: TERAZOSIN, DOXAZOSIN PHENTOLAMINE PHENOXYBENZAMINE alphal subtype alpha
of adrenergic receptors.
hypertension and
relaxation in the peripheral vasculature and
prostate gland. It used to treat
rRAZOSIN: It is a selective a--adrenergic receptor antagonist having ai, aa selective ratio
1000:1. It isa selective inhibitor of the alphal subtype of alpha adrenergic
receptors. In the benign prostatic hyperplasia.
agonist)-induced contractions. XL 4mg tab. Doxazosin mesylate
human prostate, Prazosin antagonizes phenylephrine (alphal Brand Name: Cardura 8mg tab. Cardura
However, dilates arterioles more than vaints.
on
Mechanism of action: It acts by inhibiting the postsynaptic alpha (1)-adrenoceptors
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VASODILATORS ARTERIOLAR:
vascular smooth muscle. It inhibits the vasooonstrictor effect of circulating and
locally clinically is hydralazine. This
HYDRALAZINE: It is direct acting vasodilator that is used
released catecholamines (epinephrine and norepinephrine), resulting in peripheral heart failure. It is used occasionally
drug is used in the treatment of hypertension and
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Vasodilation. (although rarely alone) in the treatment of arterial
hypertension. It is not first-line therapy
a beta-blocker and diuretic to
Uees: It is used to treat hypertension and benign prostatic hyperplasia. Its antagonism effect for arterial hypertension. It is often used in conjunction with
renal sodium retention,
which leads to smooth muscde relaxation in the peripheral vasculature and prostate gland.
It
attenuate the baroreceptor-mediated reflex tachycardia and
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is used in conjunction with cardiac glycosides and diuretics in the management of severe respectively.
it appears to have
Mechanisnm of action: The mechanism of action is not entirely clear and
Ph
Ph
Ph
congestive heart failure. It is used alone or in combination with P-blockers in the
the vascular smooth muscle. First, hydralazine causes smooth
preoperative management of signs and symptoms of pheochromocytoma. multiple, direct effects on
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K*-channels. It also may

Brand Name: Minipress 5 mg Capsule, Prazosin-1 Tab 1mg
muscle hyperpolarization quite likely through the opening of
reticulum. This
inhibit IP'-induced release of calcium from the smooth nmuscle sarcoplasmic
ar
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TERAZOSIN: It is the first a-receptor antagonist to demonstrate selectivity for the aia* calcium combines with calmodulin to activate myosin light chain kinase, which
induces
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reoptor. tlhe vascular

contraction. Finally, hydralazine stimulates the formation of nitric oxide by
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Mechanism of action: Alphar-Receptors are 7-transmembrane domain receptors coupled to endothelium, leading to cGMP-mediated vasodilation.
G proteins, Gqn. Activation of ateceplors activates Gyproteins, which results in
ac
intracellular stimulation of phospholipases C, Az and D. This results in mobilization of

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PU A Text Book of Pharmacology-l
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P'hamacokinetics: It is readily absorbed
liver and peak blood concentrations from the gastrointestinal tract
and metabolized in ATP, adenosine triphosphatase; CaM, calmodulin; cAMP, cyclic adenosine monophosphate;
are reached in 1 hour. The
approximately 1: 30 hour; however, hydralazine plasma half-life is also
CCB, calcium channel blocker; cGMP, cyclic guanosine monophosphate; CPI-17, protein
y
and is slowly removed from these exhibits a high affinity for vascular
muscle G1P,
sites. Only a
unchanged, with the major portion undergoing small percentage of hydralazine is exCreted kinase C-potentiated inhibitory protein of 17 kDa; GMP, Guanosine monophosphate;
PDE,
guanosine triphosphate; MLCK, myosin light chain kinase; NO, nitric oxide;
Ph
Ph
Ph
acetylation in urine.
Side effect: Headache, anorexia, nausea,
dizziness, and sweating. Less frequently phosphodiesterase; pGCase, particulate guanylyl cyclase; PGI prostacyclin; PKC. protein
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cncountered effects include nasal congestion,

hypotension, and depression. Tolerance to flushing. tremors, cramps, postural kinase C; PKG-1, type 1 protein kinase G; sGC, soluble guanylyl cyclase.
these effects may develop, especially if the initial
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dosage is gradually increased. Long-term Pharmacokinetics: It is absorbed 90% from the GI tract. It does not bind to plasma proteins.
administration of hydralazine in large doses, may
cause a syndrome resembling lupus erythematosus, It is approximately 90% of the administered drug is metabolized, prodominantly by
r
particularly in slow acetylators.

Dose: It is usually administered three or conjugation with glucuronic acid at the N-oxide position in the pyrimidine ring, but also by
four times daily, preferably starting with an
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individual dose of 12.5 to 25 mg. A lower dose (10 mg) conversion to more polar products. Known metabolites exert much less pharmacologic effect
may be used if there are side effects.
Uses: The direct acting vasodilator that is than minoxidil itsclf. The half life is 4.2 hours. It is excreted through urine.
used clinically is hydralazine. It used in the
treatment of hypertension and heart failure. Side effect: The common side effects include burning or irritation of the eye, itching, redness
c
c
MINOXIDiL.: It is a potent direct-acting peripheral vasodilator (vasodilator or irritation at the treated area, and unwanted hair growth elsewhere on the body.
agents) that Exacerbation of hair loss/alopecia has been reported. Severe allergic reactions may include
y
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reduces peripheral resistance and produces a fall in blood pressure.
rash, hives, itching, difficulty breathing, tightness in the chest, swelling of the mouth, face,
Merhanisn of action: It is thought to promote the survival of human dermal lips, or tongue, chest pain, diziness, fainting, tachycardia, headache, sudden and
papillary cells
(DPCs) or hair cells by activating both extracellular signal-regulated
kinase (ERK) and Akt unexplained weight gain, or swelling of the hands and fect.norTemporary hair loss is a
and by preventing cell death by increasing the ratio of BCI2/Bax. common side effect of minoxidil treatment.
inoxidil may stimulate
the growtih of human hairs by prolonging anagen through these proliferative
and anti- Uses: It is used for the treatment of severe hypertension and in the topical treatment
apoptotic elfects on DPCs. Minoxidil acts by opening adenosine triphosphate-sensitive
(regrowth) of androgenic alopecia in males and females and stabilisation of hair loss in
potassium channels in vascular smooth muscle cells. This vasodilation may also improve the patients with androgenic alopecia.
viability of hair cells or hair folicles.
Brand Name: Loniten tab 10 mg. oral. Loniten 10mg. oral
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Minoxid
cCBs
inecidn
DIAZOXIDE: It is A benzothiadiazine derivative that is a peripheral vasodilator used for
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hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide
Ca Co
Ca Ce"-CaM AMP group. It is Thiazides like diazoxide also inhibit sodium ion transport across the renal
copmie tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. It
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ATP
"
M MLCK Actin myosin eross bridge act as a antihypoglycemic, diazoxide inhibits insulin release from the pancreas, probably by
7LCMyosin
Phosphate 7- Png and contraction
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Ph
Ph
opening potassium channels in the beta cell membrane.
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CPI-17
Uses: It is used parentally to treat hypertensive emergencies. It is also used to treat
MP OTp hypoglycemia secondary to insulinoma.
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POE Brand name: Hyperstat 300mg20 ml injection, 1lyperstat Inj 15mg/ml, Proglycem capsule
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Natiuretie 100 mg, Proglycem Susp 50mg/ml.

lon channal
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Fig. 1.11 Vascular smooth muscle contractile regulation
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PV A Text Book of Pharmacology-ll System
and peripheral
ARTERIOLAR+VENOUS: METHYLDOPA: It is an alpha-2 adrenergic agonist
that has both central
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sODIUM NITROPRUSSIDE: It serves as a source of nitric oxide, a potent peripheral nervous system effects. alpha-adrenergic receptors, lcacung
inhibitory
vasodilator that afects both arterioles and venules (venules more than arterioles). It is more Mcchanism of action: It stimulates the central blood pressure.
Ph
Ph
Ph
peripheral resistance, and
active on veins than on arteries
o a reduction in sympathetic tone, total both central and periplheral
ha
as the inhibition
of
Mechanism of action: It is activated to NO, it activates guanylate cyclase in vascular smooth Keduction in plasma renin activity, as well contribute to the arugs
may also
orepinephrine and serotonin production,
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rpuscle and increases intracellular production of cGMP. cGMP stimulates calcium movement of action. This is done
major mechanism
from the cytoplasm to the endoplasmic reticulum and reduces calcium available to bind wíh annhypertensive effect, although this is not a dihydroxyphenylalanine (DOPA)Ahe
r
decarboxylation of
calmodulin. This eventually leads to vascular smooth muscle relaxation and vessel through the inhibition of the precursor of
5-hydroxytryptophan (5-HTP)-the
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dilatation. Fig. precursor of norepinephrine-and of
Indication: It is indicated for immediate reduction of blood pressure of patients in serotonin-in the CNS and in most peripheral tissues.
agent.
hypertensive crises, reduce bleeding during surgery, and for the treatment of acute Uses: Its primary clinical use is an antihypertensive 2504al,
Aldomet Tab 250nng, Medimet
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congestive heart failure. Brand Name: Aldomet Ester HCi Inj 250 mg.,
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Uses: It is used to Prevent bleeding during surgery, acute congestive heart failure, Methyldopa 125mg
hypertension
and used for the treatment of
Brand Name: Nipride Solution 25 mg, Nipride Rtu Injection, solution 0.5 mg/1mL, Sodiumn DIURETICS: These are the drugs increased the urine output
Nitroprusside for Injection 25 mg/ml. hypertension
odourless, tasteless, white glistenin8

CENTRAL SYMPATHOLYTIC THIAZIDES : (HYDRO FLUMETHIAZIDE): It is an It
powder. It is slightly soluble in water. It is a thiazide diuretic.
CLONIDINE: It is an imidazoline-derivative hypotensive agent is a centrally-acting a crystals or crystalline
decreases the reabsorption of electrolytes by the proximal part of the distal tubules and
adrenergic agonist. It crosses the blood-brain barrier and acts in the hypothalamus to induce water. It does not change lhe
increases excretion of sodium, potassium and chloride ions and
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a decrease in blood pressure. administered by mouth. Its molecular
body's acid base balance. it is rapidly absorbed when
Mechanism of action: It is an a-adrenergic agent that acts specifically on arreceptors. az
formula is CgHsF3N304S2
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receptors regulate a number of signalings pathways mediated by multiple G proteins, Gai.
Gaa and G & alphas. Stimulation of azrreceptors mediates effects such as inhibition of O=
aderylyl cyclase, stimulation of phospholipase D, stimulation of mitogen-activated protein
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kinases, stimulation of K* currents and inhibition of Ca* currents. Three G-protein coupled NH2SO2-
arTeceptor subtypes have been identified: a Gz8, and azc.
Ph
Ph
Ph
Uses: It is used in prophylaxis of vascular migraine headaches, treatment of severe CF3
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dysmenorhea, It is used in the management of nicotine dependence, topical use to reduce

Structural formula of Hydroflumethiazide
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intraocular pressure in the treatment of open-angle and secondary glaucoma and
hemorrhagic glaucoma associated with hypertension, and in the treatment of attention- diuretic. It decreases the
Mechanism of action: Hydroflumethiazide is a thiazide
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deficit hyperactivity disorder (ADHD). It also exhibits some peripheral activity. of tubules, loop of Henle. It increases excretion
reabsorption of electrolytes, by proximal part
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It does not change acid base
Brand name: Catapres tab.0.220mg. of sodium, chloride, potassium and water from the body.
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balance of the human body.

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PU A Text Book of Pharmacology-l System
Pharmacology of Drugs Actlng on Cardio Vascular
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Indications:Hypertension,oedema polyurea, uremia,
Side effects: Drowsiness,
depression, headache, weakness fatigue,
Dosage:ypertension Adult : 25 mg to 50 mg, once blurred vision, rash, urticaria, alopecia,
or twice daily. nausea, vomiting, hepatitis, cramps, pancreatitis,
anemia, irregular
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Ocdema:Adult: 25 mg to 100 mg. once or twice increased, leukopenia,
daily. increased serum creatinine, blood urea nitrogen
Contraindications: Hypersensitivity, pregnancy, pulse, hypotension palpitation.
lactation, hypokalemia, anuria.
Ph
Ph
Ph
Side effects : Weakness, head ache, fatigue, concentrations 4 hours. Plasma half
polyuria, nausea vomiting uremia, pancreatitis, Pharmacokinetics On set action 2 hour, Peak plasma
:
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blurred vision, anemia, rash, urticaria, blurred by kidneys, crosses placenta, enters breast milk.
vision, hypotension, palpilation. life 6 to 15 hours excreted
antidiabetics anticoagulants, decreases absorption of
hamacokinetics : On set action 1 to 2 hours, diuresis is maintained
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6 to 12 hours. Peak Drug interactions Decreases effect of
:
diuretics.
plasma concentration 4 hours, plasma half life 15 colestipol, cholestyramine. It increases efect of loop
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hours, metabolised by kidneys, excreted in

the urine, enters brcast milk, crosses the placenta. Aquazide, Xenia, Hydride, Bsidrex 12.5mg
Brand names: Hydrochlorothiazide Tablets
:
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Drug Interactions : Increased effect of loop diuretics, 25mg and 50mg tablets.
decreases effect of antidiabetic drugs,
thick ascending limb of
anticoagulants. CHLORTHALIDONE :It acts as diuretic It acts on distal tubule and
There is increased excretion of sodium, potassium, chloride, magnesium
loop of Henle.
c
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100 mg tablets.
YDROCHLOROTHIAZIDE : It is available as a white crystalline odourless bicarbonate and water. It is available as 15mg 50mg,
y
y
powder with
bitter taste. It acts as a thiazide diuretic. It is slightly soluble in water.
It acts on distal tubules
and cortical thick ascending limb of loop of Henle by
increasing excretion of sodium
chloride, potassium and water. Its molecular formula is C7 Hg CI Ng O4S2 NH
-OH
O
NH2SO2 NH
C SO,NH
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C
(Structural formula of Hydrochlorothiazide)
Structure of Chlorthalidone
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thick ascending
Mechanism of action : Hydrochlorthiazide acts on distal tubule, Cortical thick ascending Mechanism of action : The drug Chlorthalidone acts on distal tubule and
of sodium, potassium, chloride,
loop of Henie by increasing the excretion of sodium, chloride, potassium and water. Useful limb of the loop of Henle by increasing excretion
diuresis.
bicarbonates and magnesium. It is used in Hypertension, Ocdema, CHF and
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in oedema, hypertension.
:Hypertension, edema, congestive cardiac failure, nephrotic syndrom.
Indications Indications
Ph
Ph
Ph
Hypertension, edema, congestive heart failure, diuresis, edema in mg daily.
corticosteroid therapy. Dosage: Adult: Orally 25mg to 200 mg per day. Then 100
ha
Dasage Oedema: Adult: mg to 100 mg per day Children : age 6 month and above orally Child:by mouth 2 mg per kg body weight.
ar
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mellitus,
22 mg per kg body weight in divided doses. Contraindications: Hypersensitivity, hypokalemia, pregnancy, lactation, diabetes
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lypertension: Adult 25 mg to 50 mg daily. elderly, hyperlipidemia, anuria.

impotence, nausea, vomiting
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Conttaindications : Hypersensitivity, anuria, hypomagnesmia, renal decompen-sation, Side effects: Headache, fatigue, weakness, polyuria, uremia,
hyperglycaemia,
pregnancy, lactation, hypokalemia, gout. cramps, gastro intestinal irritation, rash, urticaria, hepatitis, blurred vision,
ac
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PV A Text Book of Pharmacology-! System
increased blood urea nitrogen, serum creatinine, irregular puise, postural hypotension, HIGH CEILING DIURATIC with the
absorption of electrolytes
y
palpitation, hypokalemia, volume depletion. It is a loop diuretic which reduce the
FrOSEMIDE :
henle. The furosimide increase

loop of
Phamacokinetics: On set action 2 hour, peak concentration 6 hour, plasma half life 36 help of proximal and distal renal tubules and
Ph
Ph
Ph
a result of this
water excretion is also
hours, excreted by kidneys, crosses placenta, enters breast milk. excretion of sodium potassium and chloride ion as when given by mouth.
absorbed
ha
Drug interactions: Chlorthalidone decreases effect of antidiabetics, anticoagulants, antigout increased. The acid base balance is not changed. It is rapidly the doseo
augs. is intense diuresis which last for four to six hours. It is given by mouth in
There
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tor
mg once to three times a day. It is also administered orally
to hypertensive patients
Brand names: Chlorthialidone : Tablet Hythalton, Clothalton, 15mg, 100mg 40
administered intravenously.
r
moderate hypertension. In cerebral oedema it is

Cure of mild to
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INDAPAMIDE: It acts on proximal section of distal renal tubule and loop of Henle by Ttsmolecular formula is C12 H11 CIN2 O5S.
inhibiting reabsorption of sodium. It block calcium channel and vasodilation is caused. It is ÇOOH
available as 1.25mg, 15 mg tablets. -NH-CH2
c
c
Mechanism of action : Indapamide acts on pordimal part of distal renal tubule and thick
NH2SO2-
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y
ascending loop of Henle by inhibiting reabsorption of sodium, chloride ions. It acts by direct
vasodilation caused by blocking of calcium channel used in oedema, hypertension.
Structural formula Furosimide
Indications: Indapamide is useful in the treatment of Hypertension, diuresis, edema in chloride
Mechanism of action : The drug furosimide inhibits reabsorption of sodium and
congestive cardiac failure. in oedema,
ions at proximal and distal tubules, and in the loop of Henle. The drug is used
Dosage: Adult: For Edema :25 mg daily, dose may be increased to 5 mg if needed, to be CHF and Hyperension treatment.
taken early morning as oral dose.
Indications : Hypertension, pulmonary oedema, oedema in congestive heart failure, cerebral
For Hypertension : Adult: 125 mg to 5 mg per day for 8 weeks duration.
oedema, toxaemia of pregnancy, renal disease, nephrotic syndrom.
Contraindications Hypersensitivity, anuria, hepatic coma, pregnancy lactation, Dosage : Adult 20 mg to 80 mg single dose, if the results are not satisfactory, then 20 to 40
dehydration, hypokalemia, renal disease.
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mg after 6 hours, maximum upto 600 mg can be administered.
Side effects Hyperglycaemia, hypokalemia, polyuria, nocturia, impotence,
Children: 2mg per kg body weight, then 1.2 mg per kg body (infant to 12 year age) Wait 6
hypomagnesemia, headache, fatigue, weakness, depression, nausea, vomiting, anorexi
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hours after the previus dose maximum upto 40mg per day.
cramps, dry mouth, abdomina' pain, constipation, rash, postural hypotension, palpitation,
blurred vision, sinusitis. Contraindictions Hypersensitivity, anuria, hypovoluemia, lactation, pregnancy,
hypokalemia, malnutrition, diarrhoea, renal failure.
Pharmacokineties: Administered by mouth, onset action 1 hour, duration of action 36
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hours, excreted in urine, plasma half life 18 hours. Side effects: Chest pain, ECG changes, loss of hearing, blurred vision, Head ache, weakness,
vertigo, paresthesias, hypokalemia, metabolic alkalosis, hypocalcaemia, hypomagnesemia,
Ph
Ph
Ph
Drug Interactions : It decreases effect of antidiabetics drugs, anticoagulants, decrease
hyperglycaemia, anemia, rash, pruritis urticaria, sweating, stevens johnson syndrome.
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absorption cholestyramine. The effect of indapamide is decreased

by drugs indomethacin,
and Non steroid antiinflammatory drugs. Pharmacokinetics:Peak plasma concentration atained in 1 hour with oral dose of 80 mg.
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Brand names: Indapamide: Tablet Perifer, Lorvas, Diurix, Indicontin, Plasma half ife 30 minutes, in patient with liver disease, renal failure plasma half life may be
Divret, 1.5mg, 2.5mg
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tablets 20 hours, excreted in urine, breast milk, crosses placenta.

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Drug Interactions: Decrease effect of furosemide with indomethacin, metolazone. There is
increased ototoxicity with aminoglcosides, vancomycin.
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42 PU A Toxt Book of Pharmacology-ll Pharmacology of Drugs Acting on Cardio Vascular System
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of action is 24 hours. It is
Brand Naimes: Frusimide: Tablet and injection Lasix, Frusemix, Tebemid, Lasiride, orally and its effect/action begins after 2 hour and duration
hydrochlorthiazide 50mg.
Injection Frusix. It is available as tablet Lasix, 40 mg, Inj Lasix 10 mg per 2 ml ampoule. available as tablet containing amiloride hydrochloride 5 mg, with
y
increased to 20
Usual dose for, adult is amiloride 5mg to 10 milligrams, orally dose may be
milligrams daily if needed. Its molecular formula is Cghi9 Clh N7 O:2H20
Ph
Ph
Ph
K+ SPARING DIURATIC
Structural Formula:
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sPiRONOLACTONE: It is a potassium sparing diuretic. It is a buff coloured odourless

powder. It is very slightly soluble in water. It is usually administered by mouth. It increases cO.NH.C.NH
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retention of sodium and excretion of ptassium by acting on the distal part of the distal
C
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tubules. The excretion of sodium is increased and excretion of potassium is decreased' It is a

inhibitor of natural corticosteroid harmone aldosteron. It is effective when given by íouth to H2N NH2 HCI:2H20
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patients on a low salt diet. If aldosteron output is low it is ineffective. It is effective in the NH2
treatment of hypertension, edema due to CCE, female hirsutism, nephrotic syndrome. It is
available as 25mg, 100mg tablets. Its molecular formula is C24 H32 O4S. Mechanism of action : It acts primarily on the proximal distal tubule by an increase of
c
c
sodium, chloride ions and water. It cause increase in retention of potassium.
Mcchanism of action: The drug spironolactone is a potassium sparing diuretic. It competes
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Dosage : Adult 5 mg to 10mg orally, daily.
with aldosterone at receptors site in the distal tubule resulting in increase of sodium,
chloride ions and water. It makes retention of potassium phosphate. It is useful in oedema, Indications: Oedema, mild to moderate hypertension, congestive cardiac fajlure, nephrotic
syndrome.
CHF, hypertcnsion and cirrhosis of liver.
Contraindications: Hypersensitivity, renal failure, hyperkalemia, pregnancy, lactation,
ndicotions:Hypertension, edema of CHF (congestive heart failure) Hypokalemia,
diabetes, hepatic dysfunction.
Dosage: Adult: 25mg to 200 mg daily in single or divided doses orally.
Side effects : Abdominal distension, anorexia, nausea, vomiting, constipation, dryness of
Child:1 to 2 mg per kg body weight, in equal two doses. mouth, weakness, muscle cramps, postural hypotension, rashes, confusion, pruritis and
pregnancy, dehydration,
Contraindications: Hypersensitivity, anuria, hypokalemia, visual disturbances.
lactation, renal disease. Pharmacokinetics : When oral dose of 20 mg administered peak plasma concentration is
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effects are:
Side effects : Prolong use in young patients may cause hirsutism. The other side attained with in 2 to 3 hours. Serum half life 6 hours and excreted unchanged in urine.
irregular
metabolic acidosis, hyperkalemia, hyponatremia, impotence, 8ynecomastia, Drug interactions : Increased effect of antihypertensive drugs, the diuretic effect is reduced
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menses, hirsutism, deepening voice, ammenorrhea, headache, confusion, drowsiness,
ataxia,
with NSAID'S.
rash, urticaria, cramps, nausea, vomiting, anorexia, gastritis
Brand names: Amiloride : Tablet Biduret, Amilochlor, Biduret-L
Tharmacokinetics: On set action 24 hours, peak concentration 48 to 72 hours, metabolized
in
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crosses placenta.
liver, excreted urine,
in
1.5 ANTLANGINALS
Ph
Ph
Ph
effect of antihypertensives
Drug interactions: Decrease effect of anticoagulants, increased Antianginal are the drugs used in the treatment of angina pectoris. These drugs prevent
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(antihypertensives) digitalis, lithium.

terminate attacks of angina pectoris.
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25mg, 100mg.
BRAND NAMES: Spironolactone: Tablet Aldactide, Aldactone
Angina pectoris is a disease results from anoxia of the cardiac muscles, it is
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characterized by pain in chest (pain syndrome), sternal pain radiates down the left shoulder
diuretic. It acts on the distal part of the
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AMILORIDE (Amiloride hydrochloride): It is a mild and arm. Two main forms of angina are:
It increase excretion of sodium, chloride and decrease the excretion of
distal lubule.
ac
yellow crystalline powder soluble in water. It is administered

potassium. It is an odourless,
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Text Book of Pharmacology-!
Pharmacology of Drugs Acting on Cardio Vascular Systom
( Classical angina: The attacks occurs during emotions, exercise, eating, coitus and subside
when more or increascd energy demand is withdrawn and is relieved on taking rest due to
y
Angina pectoris is a pain syndrome results from anoxia of the cardiac muscles. Myocarata
decreased myocardial workload. It is known as stable angina.
anoxia may be due to number of factors.
Ph
Ph
Ph
ANGINA
Blood flow heknownobstruction of coronary vessels due to thrombosis or spasm of the vessels is
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uimonen hrough rtery as ischaemic anoxia.

arterles ls restricted
by atheroma 2.Myocardia anoxia due to anaemic conditions is anaemic anoxia.
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en coronay 3.Myocardial anoxia in oxygen demand of the myocardium not met by increase in
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P lassic
Anaina coronary blood flow is called as functional anoxia.
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Cireumflex 4. The coronary circulation insuficiency cause strain on health and function of the heart,
branch of
Varlant Atheroma et coronary and leads to substernal pain which radiates down the left shoulder and arm.
Angina artery
Nitrates are converted to nitrites in the body only nitrite ion is effective as coronary
5.
c
c
Atery wall
Anterlor descending vasodilator.
branch of let
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y
coronary artery Patches of PHARMACoLOGICAL ACTIONS.OF NITRATES AND NITRITES
atheroma within
Sectlon of
coronanyaney theartery
lining Action on eyes: These drugs dilate intraocular blood vessels. Intraocular pressure may be
of increased.
Fig. 1.11 Comparision between classic and variant angina
Action on blood vessels : All blood vessels are not equally effected. Vasodilatation is
causcd
(n Variant angina (Prinzmeta's angina). In this angina attack occurs during sleep (rest) and in coronary, cutaneous and cerebral blood vessels. Blood flow is increased, there is decrease
in blood pressure. These drugs produce direct
is unpredictable. This form of angina is uncommon form and is said unstable angina. relaxant action on arteries, veins and
capillaries without involvement of autonomic nerves.
Aclion on smooth muscles: The drugs nitrates and nitrites
CLASSIFICATION OF ANTIANGINAL DRUGS produce relaxation of smooth
St
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muscles of intestines, uterus, ureter and biliary tract, bronchi and esophagus.
Aetion on haemoglobin : Nitrites convert blood haemoglobin to methemoglobin.
Methemoglobin formed combines with the cyanides to form non toxic cyanmethemoglobin.
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Others
TrimetazidineOx
Nitrates Beta blockers Calcium channel Potassium The nitrites are useful in cyanide poisoning treatment.
channel
a) Glyoeryl. Trinitrate (GTN) Propranolol blockes
yfedrine Amylnitrite Alenolol Verapamil Peners ide effects/Adverse effects of Nitrates, Nitrites
y
y
Dilüazem Nicorandi
Nitroglycerine, Metoprolol Pinacddil, The main side effects of nitrites are hypotension,
b) Isosorbide dinitrate (sublingual
Nifedipine, headache, flushing of face, dizziness,
Cromakaim fainting due to fall in blood pressure.
Ph
Ph
Ph
Felodipne,
route) Amlodipine
Isosorbide Mono nitrate
GLYCERYL TRINITRATE (GTN), (C3H(NO3}3
ha
Erythrityl Tetra nitrate AND NITROGLYCERINE

It is a volatile liquid absorbed on the inert
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matrix of tablet and is rendered non explosive and
is used sub lingually (sub lingual route)
when attack is terminating.
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Drugs dilate the Blood vessel

Nitroglycerine is readily absorbed from skin and a
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cutaneous application has effect for 4 to 6
hours. The tablets should be stored in tightly closed glass
containers (not in plastic containers)
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46 U A Text Book of Phamacology-!l
collapse. Postural hypotension
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otherwise drug may be evaporated. The tablet may be crushed under the teeth and may spread Drug interactions Alcohol may cause severe hypotension and
occurs with antihypertensives, antidepressants.
over buccal mucosa. Sublingual spray formulation has been marketed which acts more reduced. Prophylactic 0.5
rapidly. Dosage: Acute attack (adul), 0.5 mg every 3 minutes when pain is
y
mg to be sucked or chewed not to be swallowed.
CH2.O.NO2 Nitroject, Angised,
Brand names: Glyceryl Trinitrate Nitroglycerin: Tablet Top Nitro,
Ph
Ph
Ph
CH.O.NO2 per 10mi.
Angispan, Nitrocontin, Nitrogard 2.6mg, 6.4mg, 0.5mg tablets, Injection 5mg
CHO.NO
ha
sweet odour. amyl

Glyceryl Trinitrate: C Hs N,O, AMYL NITRITE: It is a clear, yellow volatile inflammable liquid with
ar
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forms an explosive mixture with air or oxygen. it is very inflammable and it should
nitrite
Mechanism of action: Nitrites, organic nitrates, nitroso compounds, nitrogeh oxide it is rapidly absorbed after
r
GC, not be used where it may be ignited. it is used as inhalations.

containing substances (including nitroprusside) can lead to NO formation -NO activates onset is immediate and action last for 4 to 10 minutes. amyl nitrate
ma
ma
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(PDE), reduces breakdown of inhalation, and the action
activates PKG, Modulates àctivities of Phosphodiesterase is used in the treatment of angina pectoris and
cyanide poisoning. it is available as 0.1 to 0.3
cGMP and cAMP in endothelial cells and smooth muscles ml amyl nitrite pearls
Endothelial cells muscles dilates coronary blood
Mechanism of action: Amyl nitrite relaxes vascular smooth
Nivates
c
c
converts haemoglobin to
L vessels, decreases ventricular and diastolic blood pressure. It
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methemoglobin which binds cyanide to form non toxic cyanmethemoglobin.
Guanytyl cyclase" GuanyyM eyclese Indications: Acute angina pectoris, cyanide poisoning.
1 to 6 inhalations from one
POE -sildenfail Dosage: Adult Angina pectoris: Inhalations 0.18 to 0.3 ml,
GMP
GTP cGMP
capsule may repeat after 3 to 5 minutes.
15 seconds until preparation of sodium
Cyanide poisoning: Adult inhalations 0.3 ml in
MLCR
Myosin-dC - MyosinC-PO MyosinC nitrite infusion is ready.
pregnancy, lactation,
Contraindications: Hypersensitivity, severe anaemia, hypertension
Actin -
Relaxation
Contraction children, head injury, cerebral haemorrhage.
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weak-ness, flushing,
cell and smooth muscle shows the
relaxation efect Side effects: Vomiting, nausea, abdominal pain, headache, syncope,
Fig.1.12 Drug act on endothelial
pallor, hemolytic anaemia muscle twitching.
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cGMP would activate PKG which Pharmacokinetics: By inhalations onset action 30 seconds, duration
3 to 5 minutes, serum
In smooth muscles, NO
mediated increase in intracellular calcium ion
chain (MLK) and reduced liver, excreted in urine.
of myosin light half life 1 to 7 minutes. Metabolized in
leads to reduced phosphorylation alcohol, Beta blocker, anti hypertensives.
Vasodilation (Vasorelaxation) Drug interactions: Increased hypotension with
y
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concentration in the cytosolol. cardiac surgery.
coronary vasospasm, hypertension during Precautions for patients
Adications: Unstable angina,
Ph
Ph
Ph
cardiomyopathy.
haemorrhage hypertrophic Medicine may explode in presence of naked flame.
Contraindications: Head injury, cerebral sweating palpitation,
ha
flushing, of children in a secure place.

headache, To keep medicines, inhalers out of reach
effects Weakness, throbbing orthostatic hypotension may ocur.
i position,
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ar
To rise slowly from sitting, lying record of
methaemoglobinaemia. half inhalation and after taking dose. To keep
3 to 6 minutes, serum take several deep breaths during
rm
to 2 minutes, peak blood level To

Pharmacokinetics: Onset action 1 angina attacks.
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Metabolized by liver.
life 2 minutes,
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A Tert Book of Pharmacology-! Pharmacology of Drugs Acting on Cardio Vascular System 9
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ISOSoRBIDE DINITRATE: It is a white crystalline powder, sparingly soluble in water. It is Drug interactions Increased hypotension with drugs antihypertensives, tricyclic
solid and can be used sublingually at the time of attack, as well as orally for chronic antidepressants, alcohol, calcium channel blockers, severe hypotension and collapse.
y
prophylaxis of exertional and vasospastic angina. The day's last dose gives before 6 pm to Brand names: Isosorbide 5 Mononitrate: Tablet Anginex, Angitrit, Angicor, Isocor,
prevent nitrate level to fall during sleep at night. Isomin, Monit, Zinit, 10mg, 20mg, 40mg tablets.
Ph
Ph
Ph
Mechanism of action: It decreases preload, afterload which causes decrease in left ERYTHRITYL TETRA NITRATE: It is long acting nitrate used, its action lasts for 4 to6
ha
ventricular, diastolic blood pressure, reduces cardiac oxygen demand. hours. it is used as prophylaxis in the treatment of angina pectoris. its sustained release
Indications: Chronic stable angina pectoris, prophylactic treatment of pain in angina preparation for oral use are available to give dose 2 to 3 times a day. available as tablet
ar
ar
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pectoris, coronary insufficiency and CHF cardilate, 5, 15 mg tablets.
r
Dosage : Adult orally 5 mg to 10 mg sublingualy for quiek reliet, prophylaxis 5 to 10 mg 3 to

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4 times a day. BBLOCKERS
Contraindications: Hypersensitivity, severe anaemia, increased intra cranial pressure, PROTRANOLOL
cerebral haemorrhage, pregnancy lactation, children. It is indicated in hypertension, angina pectoris it decreases heart rate, cardiac output and
c
c
Side effects : Postural hypotension, tachycardia, collapse, vomiting, nausea, pallor, skin torce of contraction. When administered orally it cause gradual fall in blood pressure in
y
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rash, sweating syncope, flushing. headache, weakness. ypertensives, brings no change in normotensives.
Pharmacokinetics: Orally onset action 15 to 30 minutes sublingually onset action 2.to 5 PROPRANOLOL: It is a prototype of the beta-adrenergic receptor antagonists. It is a
minutes, duration of action 6 to 10 hours, half life 40 minutes, metabolized in liver excreted competitive, nonselective beta-blocker without intrinsic sympathomimetic activity.
in urine. Mechanism of action: It competes with sympathomimetic neurotransmitters such as
Drug interactions Increased effect occurs with Beta blockers, alcohol antihypertensives, catecholamines for binding at pradrenergic receptors in the heart, the Pr-adrenergic
tricyclic antidepressants, severe hypotension may occur. receptors is G proteins couple receptor which regulate through adenyleyclase. The
Brand names: Isosorbide Dinitrate : Tablet, Capsules Cardicap, Sorbitrate, Isordil, propranolol act as antagonist the results in a reduction in resting heart rate, cardiac output,
Cardicap Dinospray 25mg, 40mg, 10mg, 5mg tablets. systolic and diastolic blood pressure, and reflex orthostatic hypotension.
Uses: It used non-cardioselective beta-adrenergic
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DINOSPRAY: Isosorbide dinitrate spray 200 metered doses. antagonist. It is used in the treatment or
prevention of many disorders including acute myocardial infarction,
arrhythmias, angina
pectoris, hypertension, hypertensive emergencies,
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ISOSORBIDE 5 MONONITRATE: It is more active and longer acting drug than isosorbide hyperthyroidism, migraine,
pheochromocytoma, menopause and anxiety.
dinitrate. It is effective in classical and variant angina pectoris. It postpones ECG changes of
Brand name: Apo Propranolol Tab 10mg,
ischaemia. Detensol Tab 10mg, Hemangeol 2 mg/ml
y
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solution.
Indications:Prophylaxis of angina pectoris, hypertension, CHF (congestive heart failure)
Ph
Ph
Ph
Dosage: Adult: orally 20 mg 2 to 3 times a day.
ATENOLOL: It is a cardio selective Beta
ha
Contraindications: Hypotension, pregnancy, lactation, elder person's with precautions. blocker drug having higher lipid solubility. Its
antihypertensive effect persists for at least 24
Side effects: Palpitation, sweating, fushing, dizziness, weakness, throbbing headache, hours, so once daily dose is sufficient for Beta
ar
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blocking and antihypertensive effect.
pallor skin rash, hypotension. It is most commonly used (drug) Beta blocker for
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hypertnesion and angina. It cause no effect on

lipid profile, have no or minor adverse on
Pharmocokinetics: Duration of action 6 to 8 hours plasma half life 4 to 6 hours, metabolized central nervous system. It decreases heart rate,
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in liver excreted in urine decrease oxygen consumption in the
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50
PA Text Book of Pharmacology- Pharmacology of Drugs Acting on Cardio Vascular System
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myocardium. Higher dose decrease renin aldosterone angiotensin system and inhibits Beta 2 Precautions for Patient
receptors in bronchial system. restricted diet.
Not to consume alcohol, avoid smoking, take salt
Hpertension angina pestoris, myocardial infarction taper dose over one to two weeks.
y
Indications: Patient should not discontinue drug abruptly,
Dosage: Adult orally 50 mg to 100 mg once daily dose. Patient should take fat free diet to control weight.
Ph
Ph
Ph
Hypersensitivity cardiac failure, heart block, use with precautions in swelling in legs, night cough to the doctor
Containdications: To report fever, sore throat, depression,
ha
pregnancy, lactation, diabetes mellitus, asthma. immediately.

memory loss, lethargy, strange dreams, vomitin CALCIUM CHANNEL BLOCKERSs
ide effects: Depression, insomnia,
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arms and
nausea, skin rash, fever, alopeca, burning eyes, dyspnea, agranulocytosis, cold
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AMLODIPINE, FELODIPINE have been

legs, hypotension. VERAPAMIL, DILTIAZEM, NIFEDIPINE,
anti-hypertension drug5
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2 to 4 hours, serum half
Phanacokinetics : Orally onset action varies, peak concentration discussed in page no. 22-25 Chapter-1
life 6 to 7hour, excreted in urine.
verapamil
Drug interaction: Indomethacin reduced antihypertensive effect of atenol with OTHER DRUGS
myocardial metabolism and improves
c
c
preipitation of heart failure. OxYFEDRINE: Oxyfedrine is helpful to improve
Atenova, Atpark, Atenex, Atekind,
y
y
BRAND NAMES: Atenolol: Tablet Atacardil, Aten, hypoxia.
coronary insufficiency.
25mg, 50mg, 100mg. Indications: Angina pectoris, myocardial infarction,
Beta 1,
is the prototype of cardio selective times a day.
METOPROLOL : It is an antihypertensive drug. It Dosage: Adult: 8 to mg
24 three
Beta blocking effects.
blockers. It lowers blood pressure by Contraindications : Hypersensitivity, pregnancy.
myocardial infarction.
Mild to moderate hypertension, angina pectoris acute mg per Side effects: Transient impairment of taste.
Indications:
two divided doses i.e. 50 mg bid. Child: 1 to 5 Brand Names: Oxyphedrine: Tablet ldamin 8mg
24mg tablets.
Dosage: Adult 100 mg to 200 mg in from metabolic consequences of ischaemia.
divided doses. TRIMETAZIDINE: It protects the ischaemic cell
kg body weight in two disease, sinus of ischaemia.
chronic pulmonary obstructive Trimetazidine prevents electro physiological
manifestations
Contraindications : Bronchial asthma, disease, heart failure.
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diabetes, renal disease, hepatic disease, angina pectoris.
bradycardia, pregnancy, lactation, headache, confusion, vomiting
Indications: Ischaemic heart
Hypotension, nightmares, insomnia, anxiety, eyes, dyspnea, Dosage: Adult: 20 mg three times a day.
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Side effects: skin, sore throat, burning lactation, elderly.
rash, urticaria, dry Contraindications: Hypersensitivity, pregnancy,
nausea, dry mouth, skin agranulocytosis.
bronchospasm, eosinophilia, concentration 2 to 4 hours, Side effects: Vomiting nausea.
oral dose varies, peak MR, Carvidin, Metagard,
Themidin, Tetaz, Trigard,
y
y
Pharmacokinetics: Onset action with metabolized in liver, excreted in
urine, Brand names: Tablet Cardimax
to 4 hours, duration 13 to 19 hours Trivedon, Trizidine 20mg, 35mg,
60mg tablets.
Ph
Ph
Ph
plasna half life 3
breast milk. decreased
crosses placenta, enters in methyldopa, praxosin, reserpine, ANTIARRHYTHMICDRUGS
ha
Increases hypotension with sympathomimetic drugs. H6 sequence

Drug interactions: indomethacin, any change from the normal
ar
ar
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metoprolol with Starpress, (UNTRODCTION: The term "arrhythmia" refers
to
antihypertensive effect of Metapro, Metolar, too fast, too slowly, or erratically
Betaloc, Lopresor, electrical impulses may happen
rm
names: Metoprolol: Tablet electrical impulses The

Brand too fast, too slowly, or erratically.
ma
ma
ma
Zoticus, 25mg, 50mg
100mg causing the heart to beat
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Pharmacolog9y of Drugs Acting on Cardio Vascular System 53
V A Toxt Book af Pharmacology-!
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or AD is startca
Anti arhythmic drugs are the drugs used to correct an abnormal cardiac rhyihm. ) Early after Depolarization: Here, premature secondary depolarization
during phase 3 (repolarization) of an action potential. There may have

multiple early ADS.
Cardiac arrhythmias ocur as a result of defective impulse conduction. Arrhythmia is the
y
disturbance or irregularity in cardiac rhythm. (i) Delayed after Depolarization : It starts after attaining the resting membrane
potential lo
Ph
Ph
Ph
depolarization threshold potential and initiatea
produce a secondary which reaches to
Single premature action potential. As an action potential is needed
to trigger ADs,
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chanisms of inducing cardiac arrhythmias: arrhythmias based on these ADs are termed as "triggered arrhythmas." Examples
are extra
Mechanical injury, ischaemía, stretching, neurogenic and drug influences, electrolyte and pH
ar
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systoles, tachycardia, coupled beats, etc.
imbalance can cause arrhythmias by the following ways. () Conduction block (i) Enhanced
r
Re-Entry: Normally, a cardiac impulse travels through the entire extent of the ventricies
an
Facemaker activity Gi) Fractšonation of impulse (iv) After depolarizations and (v) Reentry.
ventricular muscle is at that time refractory
ma
ma
ma
ma
finds no place else to go because all parts of the
Conduction Block: Due to ischemia, injury or drugs' infuence, the conduction of impuse
and can not conduct the impulse further.
through the automatic or specialised tissues may be blocked. Among them the partial or
Therefore, that impulse dies and the heart waits for a new impulse to generate in the S.A.
complete A.v. block is most commonly found.
node. Due to decrease in conduction velocity of impulse or shorter refractory period of the
c
c
Enhanced Pacemaker Activity: In the automatic or even in non-automatic ordinary fibres a
muscle, an impulse may Re-circulate in the heart and cause repetitive activation without
y
y
pathological condition may lead to increase in the slope of phase 4 depolarization to cause
generation of a new impulse. It is termed as "Re-entrant arrhythmia."
sinus tachycardia, atrial fluter, or atrial and ventricular extra systoles (tachycardia).
Fractionation of Impulse : When the atrial ERP is brief and not homogenous (may be due to
vegal over-activity), an impulse generated early in diastole (premature depolarization) gets
conducted iregularly over the atrium, ie, it moves rapidly through the fibres which have
completely recovered due to short ERP, slowly through the fibres which are partially
recovered due to long ERP, and not at all through those still refractory. It leads to atrial
fibrillation. The atrial fibrillation is commonly found in dilated atria (mitral stenosis), Refractory
area
because the number of sustained impulses is directly propotional to the mass of tissue.
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St
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St
After-depolarizations (AD): Sometime, a normal AP may be followed by a premature
secondary depolarization started before completion of the APD. This secondary
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Fig. 1.14 Re-entry of an impulse with new conduction velocity around the opening ring of venacava
depolarization is termed as after-depolarization. It is of two types early and delayed AD.
When a premature impulse with low conduction velocity is temporarily blocked in one
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direction by refractory tissue a one way transit around an obstacle (natural orifices in heart,
VUT infracted myocardium, junction of a branched Purkinje fibre and ventricular fibre, etc.) is
Ph
Ph
Ph
produced.
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As the impulse reaches its original spot, the spot is found recovered. The impulse then Re
ar
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enters to the same path and follows it repeatedly to produce recurrent activation of the
adjacent myocardium.
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The re-entry of impulses may cause atrial futter, paroxysmal supraventricular (atrial or A.v.
ma
ma
ma
nodal) tachycardia, or ventricular tachycardia. For re-entry to occur, the
Fig 1.13 Two type of after-depolarization (A Early and B-delay in nonautomatic cardiac fibre path length of the
ac
circuit should be greater than the wave length (ERXP conduction velocity) of the impulse.
Pie- K
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54 PV A Toxt Book of Phamacology-!l
propagation
(Na+) channels in the neuronal cell membrane that
are responsible for signal
No change n and
Prolonged Shorlene postsynaptic neuron will not depolarize
kanzation repolerization poarzation
With sufficient blockage the membrane of the
y
Mid Na Marked N will thus fail to transmit an action potential.
Channel biock anaesthesia, insect bites,
hlock
Indications Peripheral nerve block, epidural, spinal, surgical
Ph
Ph
Ph
:
minor burns, cystoscopy, painful cystitis.

ha
Contraindications : Hypersensitivty, child below 12 years of age, elderly, hepatic
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Class IC impairment, pregnancy.
Class iA Class 18
constriction of the pupils of eyes,
Side effects: Vomiting, nausea, blurred vision, tinnitus,
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necrosis, cardiac arrest,

Fig 1.15 Phase of action potential anaphylaxis, status asthamticus, urticaria, rash, edema, tissue
shivering, drowsiness, loss
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ma
ma
ma
to treat abnormal heart rhythms resulting
hypotension, fetal bradycardia, myocardial depression, tremors,
linition:(Anti-arrhythmic are drugs that are used
of consciousness, convulsions, disorientation.
from irregular electrical activity of the heart. The classification of drugs is as under: hours, plasma half
Pharmacokinects: Onset action 4 to 17 minutes, duration of action 3 to 6
The anti-arrhythmic drug are clasified on the basis of mechanism 90 minutes, half life is increased in
c
c
life by i.v. injection is about 13 minutes by 1M injection
placenta, excreted in urine.
liver disease. It is metabolised by liver, crosses
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Antiarhyhmic Agents
Drug interactions: It decreases the action of lidocaine. Lidocaine with
other drugs like
phenothiazine cause hypertension.
Membrane B-adrenoceptor Durgs Causing Ca-Channel
blockersmil MAOr's tricyclic antidepressants,
stablizing blockers prolong epolarization venous route 50 to
agents 0) Propranolol ) Amiodarone Verapamil Dosage: Varies by route of anaesthesia. Lidocaine may be given by intra
8rebylium Ditiazem 1 to 3mg/minute
100mg alimentary bolus, followed by 20 to 40mg every 10 to 20 minutes or
) Acebutolot
CHi)Esmolol otalol
infusion.
phase 'O Marked phase "O antiarrhythmia
Minimal Phase O oderate
depressors [prolong depressors INo Uses: It is used as a local anesthetic and cardiac depressant. It is used as an
depressors Shoren
repolarization and
re polarization and effect on repola
slow conduction (1+
stow conduction (2 +)| rization and sow agent.
Quinidine conduction (3+ to 4 Tray
Brand name: 2% Lidocaine Hydrochloride Injection USP, AgonEaze, Amniocentesis
6)
0 udocaine
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4n Procainamide (i) Encainide
in) Phenytoin (ii) Flecainide Atelocollagen Implant 3% intradermal. Injection
(n) Mexileline (i) Disopyramidee
() Indecainide 1%, Arthrogram Tray 1% liquid 1.
Civ) Monicizine
Civ) Tocainide 2%, 30ml,
iLorcainide
Propafenone Gesicaine (Lignocaine hydrochloride) 30ml vial. Gesicaine with adrenaline
hydrochloride
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Xylocaine, xylocaine with adrenaline xylocaine heavy 5% (contains ligocaine
53.5mg+Dextrose 75mg, used for spinal anaesthesia for surgery.)
and slow conduction
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MINIMAL rHASE O DEPRESSORS: It is shorten depolarization It is an antiepileptic drug which is useful in the
PHENYTOIN (Diphenylhydantoin):
motor cortex where
Ph
Ph
Ph
cardiac depressant used as an treatment of epilepsy. The primary site of action appears to be the
1LIDOCAINE: (LIGNOCAINE): It is a local anesthetic and stem centers
spread of seizure activity is inhibited. It reduces the maximal activity brain
of
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are more intense and its effects more prolonged than those
antiarrhythmia agent. Its actions responsible for the tonic phase of tonic-clonic (grand mal) seizures. Phenytoin acts to
than that of bupivacaine or prilocaine.
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of procaine but its duration of action is shorter dampen the unwanted, runaway brain activity seen in seizure
by reducing electrical
neuronal membrane by inhibiting the ionic fluxes
rm
Mechanisnm of action: It is stabilizes the

anesthetic conductance among brain cells.
of impulses thereby effecting local
required for the initiation and conduction
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ma
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conduction in neurons by blocking the fast voltage gated sodium
action. It alters signal
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S7
PUA Text Book of Pharmacology-l Pharmacology of Drugs Acting on Cardio Vascular System
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is also a anti-
variety of seizures. It
Mechanism of action: It acts on sodium channels on the neuronal cell membrane and Uses: It is anticonvulsant that is used in a wide
limiting the spread of seizure activity and reducing seizure propagation. It promotes sodium arrhythmic and a muscle relaxant.
antidysrhythmic drug, used
MEXILETINE: It is mexiletine is a lidocaine analogue and act as
y
efflux from neurons. It tends to stabilize the threshold against hyperexcitability caused by
excessive stimulation or environmental changes capable of reducing membrane sodium orally.
Ph
Ph
Ph
gradient. This includes the reduction of post-tetanic potentiation at synapses. Loss of post required for the initíation and
Mechanisn of action :It inhibits the inward sodium current potential, IPhase 0. It
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tetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. conduction of impulses, thus reducing the rate of rise of the action
Refer. Fig. 4.16. chapter 4 pharmacology-I
reduced sodium current by inhibiting sodium channels. It decreases the
achieves this
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Pharmacokinetic: effective refractory period (ERP) in Purkinje fibers in the heart.
The decrease in ERP is of
which results in an
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lesser magnitude than the decrease in action potential duration (APD),

Absorption It is well absorbed orally and its
resting membrane potential or
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ma
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increase in the ERP/APD ratio. It does not significantly affect
Bioavailability is -85% (but varies depending on the manufacture) pressure,
sinus node automaticity, left ventricular function, systolic arterial blood
Food influences absorption
atrioventricular (AV) conduction velocity, or QRS or QT intervals It increases electrical
volume of distribution: 0.5-1.0L/kg stimulation threshold of ventricle, his purkinje system, which stabilizes cardiac membrane.
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c
Distribution .The
Indications:Ventricular tachycardia, during cardiac surgery.
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Protein binding Itis highly protein bound: 90%
Metabolism Hydroxylated in the liver by a saturable enzyme system Zero-order kinetics Contraindications :Hyptersensitivity, cardiogenic shock, pregnancy, lactation, liver disease,
after enzymes are saturated, and first-order before. myasthenia gravis.
Elimination Enhances its own elimination through enzyme induction Side effects : Vomiting, nausea, diarrhoca, anorexia, dry mouth, hepatitis, altered taste,
gastro intestinal bleeding, blurred vision, hearing loss, tinnitus, dizziness, headache,
After administration, most of the drug is excreted in the bile as inactive
confusion, tremors, convulsions, weakrness, change sleep pattern, hypotension, syncope,
metabolites which are then reabsorbed from the intestine and excreted in the
urine
cardiogenic shock, skin rash, dry skin, alopecia, edema, fever, decreased libido.
Pharmoacokinetics :Orally peak 2 to 3 hours, plasma half life 12 hour, metabolized by liver,
Half life Mean plasma half-life is 22 hours
excreted by kidneys, excreted in breast milk.
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Drug interactions : The action of mexilitine decrease by cimetidine, smoking decreases
Adverse effect: Rash (5% to 109% ), Gum hypertrophy, Ataxia, nystagmus, slurred speech, action of drug. Metoclopramide increase action of mexiletine.
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confusion, Drug-induced lupus, agranulocytosis, aplastic anemia, hepatitis and :
Dosage Adult: orally Loading dose 400 mg then 200 mg after 8 hours then same dose of
anticonvulsant hypersensitivity syndrome. 200 mg after next 8 hours.
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Drug interaction: Phenytoin is an inducer of the hepatic cytochrome P450 microsomal
Brand names: Mexiletine: Capsule Mexitil 50mg, 150mg, Injection Mexitil 250mg per
isoenzymes It is metabolised primarily by CYP2C9 major) and CYP2C19 (minor), thus 10ml vial.
Ph
Ph
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several drugs may inhibit or induce the metabolism of phenytoin such as amiodarone
Treatment of overdose : Injection diazepam for convulsions, injection dopa-mine for
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Cincreased level), erythromycin (increased level), fluconazole (increased level, rifampicin

(decreased level), folate supplements (decreased leve!) and fluoroquinolones (decreased circulatory depression, monitor ECG, medical oxygen inhalations.
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level).
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Dose: Dilantin 25 mg, 100 mg cap, 100 mg/4 ml oral, suspension, 100 mg/2 ml ini; Epsolin TOCAINIDE: It is a primary amine analog of lidocaine with antiarhythmic properties
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100 mg tab, 100mg/2 ml inij; Epton 50, 100 mg tab, 25 mg/mi syr, Fentoin-ER 100 mg useful in the treatment of ventricular arrhythmias. It is an antiarrhythmic agent which exerts
extended release cap. a potential- and frequency-dependent block of sodium channels.
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PV A Text Book of Pharmacology-
Mechanisn of action :It acts on sodium channels on the neuronal cell membrane, limiting Pharmacological actions and myocardial
occurs due to vagolytic (Atropine like effect)
Cardiac efect: The effects
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the spread of seizure activity and reducing seizure propagation. It binds preferentially to the influx and destroys ectopic pacemaker
depressant action. Quinidine reduces the sodium
inactive state of the sodium channels. The anti-arrhythmic actions are mediated through
Ph
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Ph
effects on sodium channels in Purkinje fibers. activity.
The threshold of an
Excitability:Quinidine decreases the excitability of the cardiac tissue.
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Indication: It is indicated for the treatment of documented ventricular arrhythmias, such as

impulse to initiate cardiac activity is increased due to
which a weak ectopic impulse becomes
sustained ventricular tachycardia, that, in the judgment of the physician, are life-threateing
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ineffective.
Tharmacokinetics : Its oral administration, the bioavailability approaches 100 percent, and is cardiac
depresses entry of calcium ions (Cat*) into
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unaffected by food. It is approximately 10 percent bound to plasma protein. The iverage Cardiac contractility: Quinidine is
effect on heart due to this cardiac contractility
plasma half-life in patients is approximately 15 hours. May be prolonged up to 35 hours in muscles and exert negative inotropic
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patients with severe renal function impairment. It is excreted in urine. decreased.
the rate of conduction in heart muscles. It
Brand name: Tonocard Tab 400 mg8 Conduction velocity: Quinidine slows down
decreases conduction velocity of cardiac muscles.
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administration produce fall in blood
MODERATE PHASEO DEPRESSORS No cfect on repolarization and slow conduction (3+4) Blood pressure: Quinidine in oral doses or intravenous
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fall in blood pressure is due to diminished peripheral sympathetic action and
pressure This
QUINIDINE SULPHATE of quinidine on arteriolar smooth muscles. There is dilatation of
direct relaxant action
The drug quinidine began to use in the treatment of
cardiac arrhythmias with the
of atrial arteries.
observations of 'wenckebach' in 1914. Frey' in 1918 used quinidine in the treatment refractory period of the cardiac muscles. This
which is a natural Refractory period: Quinidine prolongs the
fibrillation and found it very effective. Quinidine is an isomer quinine
of
effect is produced by depressing potassium ion (K*) eflux during repolarisation. During
alkaloid occurs in cinchona bark. stimuli and heart rate is
refractory period the heart does not respond to weak and premature
H.CH
slowed down.
H
depolarisation by depressing sodium ion (Nat)
Depolarisation: Quinidine slows the rate of
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Quinidine prolong the depolarisation repolarisation cycle. The rate at which
HSO,2 into the cell.
cardiac contractions occur is decreased.
administered intravenously cause hypotension (fall in
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Blood pressure: Quinidine when
blood pressure).
skeletal muscles: It has also an antimalarial,
Quinidine Sulphate): C4oHsoN4Og5:2H20o Skeletal muscles: Quinidine relaxes the
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antipyretic and oxytocic action. If cardiac output is low, quinidine
returns it to normal and if
Molecular weight: 782.9 cardiac output is normal it makes no change.
Ph
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Ph
membrane, limiting
Mechanism of action: It acts on sodium channels on the neuronal cell cause convulsions due to its adverse effect on the
cntral nervous system (CNS): Quinidine
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seizure propagation. The antiarrhythmic actions

and reducing
the spread of seizure activity also act on the central nervous system.
sodium channels in Purkinje fibers. It may
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are mediated through effects on use cause cinchonism characterised by
the rapid (IKT) and slow (lKs) components of the delayed Cinchonism: Quinidine in higher doses or prolong
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slow inward calcium current (ICa), blurred vision, hearing loss.

ATP-sensitive giddiness, tinnitus,
potassium rectifier current (IKI), the ight headedness,
potassium rectifier current, the inward administered orally cause, vomiting,
nausea,
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tract effect: Quinidine when
potassium channel (IKATP) and
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to. Sastro intestinal tract.
diarrhoea, as it causes irritation to gastro intestinal
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61
Pharmacology of Druge Acting on Cardlo Vascutar System
VA Text Book of Pharmecology-l
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membrane by
hdications: Atrial fibrillation, paroxysmal atrial tachycardia, premature ventricular Mechanism of action: It is sodium channel blocker. It stabilizes the neuronal
of impulses thereby
contractions. inhibiting the ionic fluxes required for the initiation and conduction
muscles to electrical
Dosage :Atrial fibrillation/flutter. effecting local anesthetic action. It depresses the excitability of cardiac
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stimulation, slows conduction in atrium bundle and ventricle.
Adult: Orally 200mg three to four times a day maximum dose 4 gms per day. Initially give tachycardia.
Ph
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test dose. Usual dose : 200mg to 300mg three to four times a day. Indications: Atrial fibrillation, ventricular tachycardia, paroxsmal atrial
500mg every 4 to 6 hourly.
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Child: Orally 6mg per kg body weight per day in three or four equal divided doses. Dosage: Atria fibrillation: Adult:1 to 1.25 gm maintenance dose
kg body
Phefnecokinetics: Orally onset action 1/2 hour, peak concentration 5 to 6 hours, serum half Ventricular tachycardia: Adult orally 1gm, maintenance dose 50mg per
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fe 6 to 7 hours duration of action 8 hours, metabolized in liver. excreted unchanged by weight/day in equal doses every 3 to 4 hourly.
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pregnancy,
kidneya Contraindications: Hypersensitivity, myasthenia gravis, severe heart block,
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lactation, renal disease, liver disease, respiratory depression, children.
Drug interactions: Increased effects of digoxin, warfarin. drugs like cimetidine. thiazides,
headache, dizziness,
antacids propranolol increase effect of quinidine. the effect of quinidine is decreased with Side effects: Vomiting, nausea, anorexia, diarrhoea, hepatomegaly,
anaemia,
drugs like barbiturates, rifampin, phenytoin, nifedipine. restlessness, confusion, irritability, psychosis, skin rash, urticaria, edema hemolytic
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Contraindications : Myasthenia gravis, hypersensitiily, severe heart block, hypotension, agranulocytosis.
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1 to 2 hours. duration of action 3 hours,
lactation, paediatric elderily reduce dose. Quinidine Sulphate (C4oHsoN4OgS, 2H20) Pharmacokinetics: Orally peak concentration
plasma half life 3 hours. Metabolized in liver, excreted in urine.
Staeeffects: The side effects of quinidine are: Cinchonism, blurred vision, diturbed colour
vision, hearing loss, vomiting, nausea, diarrhoea, hepatotoxicity, hypotension, bradycardia, Drug interactions : Increased effect of procainamide with cimetidine, barbiturates decrease
effect of procainamide. Toxicity is increased with other antidysrhythmic drugs.
skin rash, urticaria, angioedema, swelling, hemolytic anemia,
respiratory depression,
thrombocytopenia, agranulocytosis, headache, confusion, restlessness, syncope, irritability. :
Brand names: Procainamide Tablet Pronestyl 250mg, Injection Pronestyl 100mg per
ml.
Brand names: Quinidine : Tablet Quinidine, Natcardine Quininga 100mg, 200mg
300mg tablets
DISOPYRAMIDE: It is a lass I anti-arrhythmic agent (one that interferes directly with the
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Treatment overdose of quinidine : Administer dopamine for circulatory depression,
diazepamfor convulsions, oxygen inhalations ECG. depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent)
with a depressant action on the heart similar to that of guanidine.
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PROCAINAMIDE HYDRoCHLORIDE : Procainamide is an amide derivative of local Mechanism of action: It is a type 1A antiarrhythmic drug lie, similar to procainamide and
anaesthetic procaine. It is found to have antiarrhythmic action. It is safe for intravenous use quinidine). It inhibits the fast sodium channels. In animal studies Disopyramide decreases
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and is safer than quinidine and has quick action. the rate of diastolic depolarization (phase 4) in cells with augmented automaticity, decreases
the upstroke velocity (phase 0) and increases the action potential duration of normal cardiac
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cells, decreases the disparity in refractoriness between infarcted and adjacent normally
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coNH.CHCH;NICHs}2
perfused myocardium, and has no effect on alpha- or beta-adrenergic receptors.
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HCI Indications: It is used for the treatment of documented ventricular arrhythmias, such as
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sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias. It is a

ClassI a antiarrhythmic drug.
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NH2
Pharmacokinetics: It is completely absorbed. The proteins binding is 50-60%. It
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Procainamridle (C13 H22 CI N3 )

metabolized in liver The half life is 6.7 hours (range 4-10 hours). It is excreted 50% of a giver
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63
62 VA Toxt Book of Pharmecology-!
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effective in a wide range of ventricular
dose of disopyramide is excreted in the urine as the unchanged drug, about 20% as the FLECAINIDE: It is a potent anti-arrhythmia agent,
mono-N-dealkylated metabolite and 10% as the other metabolites. and atrial arrhythmias and tachycardias.
channels on the neuronal cell membrane, limiting
Uses: it is used in arhythmic It also possesses some anticholinengic and local anesthetic Mechanism of action: It acts on sodium
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actions
properties. the spread of seizure activity and reducing seizure propagation. The antiarrhythmic
anesthetic
channels in Purkinje fibers. It has local
Ph
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Brand name: Norpace cap.150 mg. oral. Norpace CR 150 mg are mediated through effects on sodium
(Class 1) group of antiarrhythmic agents;
it
activity and belongs to the membrane stabilizing
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MORICIZINE: It is an antiarrhythmia agent used primarily for ventricular rhythm of the IC class of antiarrhythmic.
has electrophysiologic effects characteristic
is 40%. It is
It is completely absorbed orally, The proteins binding
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disturbances.
Pharmacokinetics:
Mechanisn of action: Moricizine works by inhibiting the rapid inward sodiuní current metabolized in liver and excreted in urine.
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across myocardial cell membranes. specially it is used for the prevention of paroxysmal
Uses: It is used antiarrhythmic agent
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Indication: n is used to treat irregular heartbeats (arrhythmias) and maintain a normal atrioventricular nodal reentrant
supraventricular tachycardias PSVT), including
supraventricular tachycardias.
heart rate. tachycardia, atrioventricular reentrant tachycardia and other
rhamnacokinetics: It is well absorbed; absorption is complete within 2 to 3 hours. Brand Name: Flecainide Acetate tab. 100mg/1 oral, Tambocor 50 mg. oral
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approximately 38%.
Significant first-pass metabolism results in an absolute bioavailability of
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not affect the extent
Administration within 30 minutes after a meal slows the rate, but does INDECAINIDE: It is a rarely used antidysrhythmic.
Indecainide has local anesthetic
of absorption, although peak plasma concentrations are
reduced. The volume of distribution (Class 1) group of antiarrhythmic agents; it
activity and belongs to the membrane stabilizing
95%. It is metabolized in liver. It is excreted IC class of antiarrhythmics. It acts on
is 300 L. The proteins binding are approximately has electrophysiologic effects characteristic of the
in the urine. on the neuronal cell membrane, limiting the spread of seizure activity and
sodium channels
to maintain a normal heart are mediated through effects on
Uses: It is used to treat irregular heartbeats (arrhythmias) and reducing seizure propagation. The antiarrhythmic actions
It used for treatment of life-threatening dysrhythmias
rate. sodium channels in Purkinje fibers. is
Brand name: Ethmozine 250 mg and sustained ventricular tachycardia
and slow conduction 3-4)

MARKED PHASE O DEPRESSOR: (NO effeet on repolarization
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LORCAINIDE: It is a new type-1 antiarrhythmic drug that
is well absorbed orally, with
compounds known as administration. It is metabolized
ENCAINIDE : This compound belongs to the class of organic bioavailability increasing with both dose and continued
anilide group in which the require dosage reduction.
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containing an liver disease will
benzanilides. These are aromatic compounds patients through the liver, and patients with significant
benzene ring. It increased death rates in norlorcainide, whose activity is similar to that of
carboxamide group is substituted with a The drug has an active metabolite, levels of
abnormalities after a recent heart attack. 26 hours instead of 8 for the parent compound. The
who had asymptomatic heart rhythm lorcainide but whose half-life is
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long half-life of the
to voltage gated sodium this metabolite are nearly twice those of lorcainide at steady state. The
Mechanism of action: It is a sodium channel blocker, binding
fluxes required for the lorcainide require that a given dose be
inhibiting the ionic metabolite and the changing bioavailability of
Ph
Ph
Ph
channels. It stabilizes the neuronal membrane
by
excitability is depressed and the administered for week for the maximum effect to be demonstrated.
Ventricular 1
initiation and conduction of impulses.
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increased during diastole.

stimulation threshold of the ventricle is
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irregular
was used for management of
Uses: It is used as antiarrhythmic agent which
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flutter, ventricular tachycardia, and ventricular

heartbeats, such as atrial fibrillation, atrial
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fibrillation. Oral.
irand name: Encainide hydrochloride (25 mg/1.
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PU A Text Book of Pharmacology- Pharmacology of Drugs Acting on Cardlo Vascular System 65
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PROPAFENONE: It is an antiarrhythmia agent that is particularly effective in ventricular Migraine: Adult: 80 mg daily or in divided doses 40 mg bd.
arrhythmias. It also has weak beta-blocking activity. Angina: Adult orally 80 mg to 320 mg, 80 mg four times a day.
Mechanism of action: The electrophysiological effect of propafenone manifests itself in a
Dysrhythrmias : Adult 10 to 30 mg tid. or four times a day.
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reduction of upstroke velodty (Phase 0) of the monophasic action potential. In Purkinje Contraindications: Hyptersensitivity, cardiac failure, sinus bradycardia, congestive heart
fibers, and to a lesser extent myocardial fibers, It reduces the fast inward current carried by
Ph
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tailure, with precautions in diabetes, pregnancy, lactation, renal disease, hypotensi0n,
zodium ions, which is responsible for the drugs antiarrhythmic actions. Diastolic excitability myasthenia gravis, hepatic disease, congestive heart failure.
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threshold is increased and effective refractory period prolonged. It reduces spontaneous

Side effects: Swelling on face, skin rash, fever, hyperglycemia, sore throat, dryness of eyes,
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automaticity and depresses triggered activity.
blurred vision, decreased libido, vomiting, diarrhoea, night mares, forgetfulness, muscle
Phamacokinetics: t is completely absorbed oral administration (90%). Systemic
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fatigue, bad dreams, dry mouth, hepatomegaly.

bioavailability ranges from 5 to 50%, due to significant first-pass metabolism. The volume of
Pharmacokinetics: Onset action 30 minute, peak concentration 1 to 1% hour, duration of
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distribution is 250 L The proteins binding is 97%. Approximately 50% of propafenone
action 6-12 hours, plasma half life 3 to 5 hours, metaboloised in liver, crosses placenta, blood
metabolites are excreted in the urine
brain barrier, excreted in breast milk, wine.
Uses: It is used to prolong the time to recurrence of paroxysmal atrial fibrillation/flutter
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Drug interactions : Propranolol with adrenaline develops hypterension, bradycardia.
(PAF) assoiated with disabling symptoms in patients without structural heart disease. Also
Increased hypotension with quinidine, haloperidol
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used for the treatment of life-threatening documented ventricular arrhythmias, such as
sustained ventricular tachycardia. Brand names: Propranolol Tablet Ciplar, Prop, Ciplar, Betacap, Betabloc, Inderal,
Corbeta 10mg, 20mg, 40mg, 80mg tablets.
ACEBUTOLOL: It is a cardioselective beta-adrenergic antagonist with little effect on
BADRENORECEPTOR BLOCKERS
the bronchial receptors. The drug has stabilizing and quinidine-like effects on cardiac
PROPRANOLOL: It is an colourless white powder with a bitter taste. It acts as adrenergic rhythm as well as weak inherent sympathomimetic action.
beta blocker. It molecular formula is C16H22CINO2. It is antihypertensive drug. Refer anti
Mechanism of action: It is a selective ß1-receptor antagonist. Activation of p1-receptors by
hypertension
epinephrine increases the heart rate and the blood pressure, and the heart consumes more
oxygen. It blocks these receptors, lowering the heart rate and blood pressure. This drug then
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OH
CHs has the reverse effect of epinephrine. In addition, beta blockers prevent the release of renin,
t CH CHa NH
CHs which is a hormone produced by the kidneys which leads to constriction of blood vessels
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Indications: It is indicated for the management of hypertension and ventricular premature
beats in adults
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Pharmacokinetics: It is well absorbed from the Gl tract with an absolute bioavailability of
approximately 40% for the parent compound. The proteins binding is 28%. It is extensive
Ph
Ph
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Propranokol Hyarochioride first-pass hepatic biotransformation (primarily to diacetolol). It is elimination via
renal
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Mechanism of action: It decreases heart rate, cardiac output and force of contraction. Blood excretion is approximately 30% to 40% and by non-renal mechanisms 50% to 60%,
which
pressure is lowered in hypertensives, produce no effect on normotensives includes excretion into the bile and direct passage through the intestinal wall.
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Indications Hyptertension, angina pectoris, migraine, aniely, tachycardia, fallot letrology
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Dosage
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Hypertension: Adult orally 40 mg twice daily or 80 mg once daily.
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A Toxt Book of Pharmacology Pharmacology of Drugs Acting on Cardio Vascular System
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Brand name: Acbutolol 400mg. oral, Monitan 100mg. Pharamacokinetics : Orally, peak concentration 2 to 10 hours plasma half life 3 to 8 weeks.
ESMOLOL: Esmolol is an ultrashort acting beta one blocker. it is short acting drug having Metabolized by liver, excreted in urine.
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quick action b, blocker iv. administration is very effective in atrial fibrillation. esmolol slows Drug interaction Increased anticoagulant effect with warfarin, Bradycardia with Beta
:
conduction of AV node decrease heart rate decrease oxygen consumption in myocardium.
Ph
Ph
Ph
blocker, calcium channel blockers.
Mechanism of action: It is similar to other beta-blockers, esmolol blocks the agonistic effect Brand names: Amiodarone: Tablet, Injection, Amiodar, Duron, Panaron, Tachyza,
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- of the sympathetic neurotransmiters by competing for receptor binding sites Cardarone 100mg, 200mg tablets, Injection 150mg per ml.
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Indications : Supraventricular tachycardia, hypertension. Treatment over dose: Dopamine injection for irculatory depression, diazepam for
Dosage: Supra ventricular tachycardia (SvT) Adult initial dose, loading dose 500 mcgs per convulsion, oxygen respiration.
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kg body wveight per minute, maintenance dose 50 mcg per kg per minute for four/minutes,
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maximum dose 300 meg per kg per minute. :
BRETYLIUM This drug was introduced in 1960's and used as antihypertensive. Due to its
Contraindications: Cardiogenic shock, hypersensitivity, cardiac failure, use with precaution adverse effects it is not put in use now a days.
in hypotension. pregnancy, lactation, diabetes, renal disease children.
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Side effects Headache, confusion, anxiety, depression, fatigue, hypotension, OCALCIUM CHANNEL BLOCKERS
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bronchospasm, vomitins, nausea, heart burn, chest pain, shortness of breath, skin rash, dry The main action of this group of medicines is to inhibit calcium ion mediated channel
skin, alopecia, oedema, constipation, bloating. inward current act as calcium antagonist effect on smooth vascular muscles of coronary
Pharmacokinetics : Onset action rapid, duration short, plasma half life 9 minutes, arteries due to which myocardial blood flow is increased.
2 metabolized by liver, excreted in urine. VERAPAMIL: Verapamil has a marked antiarrhythmic drug. due to its antagonistic effect
Drug interactions: Increased effect with disopyramide, increased level of esmolol with on the smooth vascular muscles of the coronaries the myocardial blood flow is increased.
morphine. verapamil reduces work load on the heart by reducing. oxygen requirement of the
Brand Names: Esmolol: Injection Esocard, Neotach, Miniblock 100mg. 250mg per
10ml. myocardium and by decreasing peripheral resistance. its molecular formula is cz7h39cln204
Treatment of overdose: Discontinue drug therapy.

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AMIODARONE: It is an long acting antiarrhythmic drug. it elongate duration of action HeCHa.
. CH CH-N
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potential duration and effective refractory period in atria. HC.
Indications: Severe ventricular tachycardia, atrial flutter atrial
fibrillation.
per day for to 3
1
weeks, then 600 to 800 mg daily for one
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Dosage: Adult: 800 to 1600 mg OCH OCHs
efective dose 200
month, then 200mg three times a day for one week, maintain minimum OCH
Ph
Ph
Ph
mg daily. IV: initially 150 mg over 10 minutes, slow IV.
Verapamil Hydrochioride
Hyptersensitivity, lactation, pregnancy, bradycardia, electrolyte
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Contraindications Mechanism of action

imbalance, goitre, A.V. block.
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hepatotoxicity, Varapamil inhibits calcium ion flow across cell membrane during cardiac
nausea, anorexia, diarrhoea,
Side effects: Microdeposits in cornea, vomiting,
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depolarization, produces relaxation of coronary vascular smooth muscles, dilates coronary

bradycardia, skin rash, alopecia,
headache, tremors, fatigue, ataxia, insomnia, hypotension,
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arteries, dilates peripheral arteries, decrease SA. SV node conduction.
leg pains, weakness
discolouration of skin (blue, gray) abnormal taste, edema, flushing,
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U A Toxt Book of Phamacology-! 59
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Jdications: Chronic coronary insufficiency, angina pectoris, hypertension, atrial flutter, concentralion 2 to s
atrial fibrillation. namacokinelics : Orally onset action 30 to 60 minutes, peak plasma in breast
nours, plasma half life 4 to 9 hours metabolized in liver, excreted in urine, excreted
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Dosage: Adult orally 40 to 80 mg three to four times a day maximum dose 480 mg per day, milk.
not to exceed 480 mg/day. IV: 5 mg initially, if desired effect not obtained further 5 mg after
Ph
Ph
Ph
Drug interactions: Elevate serum digoxin cyclosporin, theophyliline leve
5 to 10 minutes, child 1 to 5 years 2 to 3 mg L.V, age of child 6 to 14 years 2.5 to 5 mg only as
Brand names: Diltiazem: Tablet Dicard, Dilcor, Cardem, Angigem, Channel, Dilgard,
ha
onset dose.
Icidil 30mg, 60mg. 90mg tablets.
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Contraindications: Sick sinus syndrome, cardiovascular shock, pregnancy, hepatic injury,
lactation, children with precautions, congostive heart failure. Treatment overdose : Give atropine for A.V. block, for hypotension give vasopressor.
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Sjde effects : Headache, nausea, fatigue, flushing, ankle oedema, hypotension, constipation,
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17HYPOHLPIDAEMICS
anxietydepression, insomnia, confusion, weakness
Pharmacokinetics:Orally onset action variable, peak plasma concentration 3 to 4 hours, half Introduction: Hypolipidaemic are drugs which lowers the level of lipids and lipoproteins in
life IV 4 minute orally 3 to 7 hours duration of action 18 to 24 hours, blood.
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Lipids : Lipids are the free fatty acid fractions present in blood. Lipids are insoluble in water,
Drug interactions: Increase hypotension with prazosin, quinidine, decreased efect of
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lithium, neurotoxicity is increased with carbamazepine. soluble in alcohol, ether chloroform, and other solvents. Lipids are stored in the body serve
the purpose of energy storage as energy reserve. Various kinds of lipids are cholesterol, fatty
Brand names: Verapamil : Tablet, Injetion, Calaptin, Vasopten, Veramil, Verap 40mg
acids, neutral fat, phospholips and triglycerides. Total lipids in serum are 400 to 800 mg per
80mg, 120mg 240mg tablets, Injection 5mg per 2ml.
dl, cholesterol 150 to 250mg/dl fatty acids 9 to 15 mg per litre, neutral fats 0 to 200 mg/dl
Treatment of overdose: Administer atropine for AV. block, for hypotension give phospholipids 150 to 380 mg/dl, triglycerides 10 to 190 mg/dl.
vasopressors.
Lipoproteins : Lipoproteins are synthesized in liver contains different amountss of
triglycerides, cholesterol, phospholipids and protein and are classified according to their
DILTIAZEM: Diltiazem is a potent coronary diator. it produces modest fall in blood density and composition as high density ipoprotein, low density lipoproteins, very low
pressure with no change in heart rate, with large doses reflex cardiac effect ocurs. it is a density lipoproteins.
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calcium channel blocker drug.
Mechanism of action : Diliazem inhibits calcium ion flow across cell membrane during TYPES
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PIRCHOLESTROLEMIA
cardiac depolarization, produce effect of relaxation of coronary artery smooth muscles, due uPOPROTEIN UPASE
LDL ECEPTORAPOB EXTRA
to which coronary arteries dilatation occurs, also dilates peripheral arteries. APOI NCEPTOR
ALeoeOTN ca
LVvE APOE
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ATC
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Cholesterol
Indications: Hypertension, atrial flutter, atrial fibrillation, angina pectoris due to coronary DEFICENC
CoA
insufficiency chylomicron
HMG COA
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APOLIPOPROTEINEMIA chylomikron nDL
Dosage: Adult orally 30 mg 2 to 4 times a day, before meals, at bed time before meals, B100 B4 UN INTESTINAL emnent
CeLL Acetoacetyl CoA
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slowly increase dose 60 mg to 120 mg twice daily. Adult IV 0.25 mg per kg body weight over acetyl CeA
LCAT
2 to 3 minutes slowly. EYE
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Contraindications : Children, pregnancy, bradycardia, sick sinus syndrome. Use with

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precautions in pregnancy, lactation children, hypotension, congestive heart failure.

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Side effects: Headache, skin rash, ankle oedema, flushing, dizziness, Fig. 1.16 process of TG and cholesterol
depression, insomnia,
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weakness, tremors, drowsiness.

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The food consumed in the form of cholesterol and TG.
It is absorption in intestine, Taken by Contraindications Hypersensitivity, pregnancy, lactation, liver disease use with
lactels. The lactels cholesterol and TG taken through
thoracic duct to blood vesicle with help precautions in hypotension, visual disorders, children, electrolyte imbalance.
of chylomicrone. In blood vesicle The TG
converted into Fatty acid and glycerol in blood
Side effects: Muscle cramps, myalgia, myositis, skin rash, pruritis, head ache, tremors,
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vesicle with the help of lipoproteins lipase. The fatty
acid taken up by adipose cell and gets nausea,constipation, heart burn, pain abdomen, liver dysfunction, blurred vision.
converted to the TG again. Remanant chylomicrone enter in the liver.
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The liver is secreted
TG and cholesterol into blood vesscle and as VLDS. This TG Pharmacokinetics: Lovastatin is metabolised, excreted in urine, orally peak plasma
again metabolized in blood
2 to 4 hour, plasma half life 3 to 4 hou, crosses placenta, excreted in breast
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vesscle by LPL. Thus now VLDL changes to IDL The IDL is taken back concentrtion
to liver which
converted to LDL containing cholesterol and distributed to various milk.
tissues. The HDL carries
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cholesterol from periphery to liver. The cholesterol is excreted in bile in the free , Drug interactions: Increased bleeding when administered with warfarin, in presence of
forí of bile
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acid. The bile salt undergo enterohepatic circulation. propranolol there is decreased antihyperlipidemic efect.
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The Hypolipidaemic drugs have played an important role in the treatment Brand names: Lovastatin: Tablet Lipistat, Aztatin, Lovex, Pro HDL, Lovalip,
as these drugs
prevents cardiovascular disease decreasing the accelerated atherosclerosis in Lovadac, Lostatin 10mg, 20mg tablets.
hyperlipidaemic patients.
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The drugs are classified as under: SIMVASTATIN: It is twice as potent as lovastatin. It is antihyperlipidemic drug. It is
administered orally as an cholesterol lowering agent.
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CLASSIFIGATioNHYPOLIRDAEMIG DRUGS
Mechanism of action : It inhibits Hydroxymethyl glutaryl coenzyme A (HMG-CoA)
reductase enzyme and decrease synthesis of cholesterol.
Indication: Primary hyper cholesterolemia, coronary artery disease.
(HMG CoA) Bile acid sequestrants Fibric acid Others:
reductase inhibitors (Resins) derivatives Dosage: Adult: Initial dose 5 to 10 mg oraly as a single dose in the evening not to exceed40
Ci) Cholestyramin (W
G)Ezetimibe
(i)Lovastatin Bezafibrate
Gi)Clofibrate (i) Guglipid. mg per day.
(i) Simvastatin (id Colestipol
(ii)Pravastatin i)Fenofibrate Contraindication Hypersensitivity, pregnancy, lactation, liver disease. Use with
iv)Atorvasta tin v) Gemfibrozil
(v) Rosuvastatin
precautions in alcoholism, hypotension, electrolyte imbalance, seizure disorder
(uncontrolled).
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Side effects: Muscle cramps, myalgia, myositis; headache, tremors, vertigo, peripheral
HYDROxY neuropathy, lens opacity, skin rash, alopecia, pruritis, constipation, nausea, diarrhoea, heart
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METHYL GLUTARYL COENZYME A (HMG COA) REDUCTASE
INHIBITORS. burn, abdominal pain, Iliver dysfunction, pancreatitis.
Pharmacokinetics: Metabolized in liver, orally, peak concentration 1 to 2 hours, excreted in
LOVASTATIN: It is the first statin that was clinically used orally act as cholesterol lowering
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agent. bile, faeces.
Drug Interactions: Increased effect of warfarin, increased serum level of digoxin.
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ehanism of action: Lovastatin inhibits hydroxy methyl glutaryl coenzyme. A reductase
enzyme and reduces synthesis of cholesterol. Brand names: Simvastatin: Tablets, Simlo, Simlip, Biosim, Starstat, Simvo, Zosta, SVT,
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Simcard, Simvin 5mg, 10mg, 20mg, 40mg tablets.

dcation: Hyperlipidemia, Hypercholesterolemia, Hypertriglyceridemia.
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Dusage: Orally 20 mg daily, may increase dose 20 to 80 mg per day in single or divided
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dose not to exceed 80 mg per day, dose adjustment may be made according to the PRAVASTATIN: It is an antilipidemic drug it is a competitive inhibitor of HMG-C
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improvement noted. The patient be adviced to cholesterol free diet. reductose. It is administered orally.
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Mechanism of action : Pravastatin inhibits HMG-CoA reductase enzyme which decreases Brand names: Atorvastatim : Tablet Aztor, Alt vas, Astin, Dipolip, Atorva,
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cholesterol synthesis. Lipwas, Liporest, 5mg, 10Omg, 20mg, 40mg tablets.
Indications: Primary hypercholesterolemia type Ila, ITb, Atherosclerosis, Hyperlipidemia.
Dosage : Adult orally 10 to 20 mg in the evening, maximum dose, 40mg per day. Eiderly ROSOVASTATIN : This is the latest statin and is most potent. It is the two times noe
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require less dose (lower dose). effective than atorvastatin. The effect of Rosuvastalin 10mg is equal to 20mg
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Contraindications : Hypersensitivity, pregnancy, lactation, liver disease. atorvastatin. It acts as antihyperlipidemic drug
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Mechanism of action : It inhibits HMG-CoA reductase enzyme which reduce synthesis
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Side effects: Muscle cramps, myositis, myalgia, skin rash, nausea, constipation, dyspepsia,
heart burn, liver dysfunction, pain abdomen. common cold, cough, lens opacity, headache, cholesterol.
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psychic disturbances. Indications :Primary hypercholesterolaemia, mixed dyslipidaermia.
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20Omg, daily.
Pharmacokinetics: Metabolized by liver, peak concentration 1 to 2 hour excreted in urine, Dosage : Adult orally 10mg daily, start with 5mg daily increase dose up to
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feces, breat milk, crosses placenta. Maximum daily dose is 40mg the dose adjustment after initial dose, may be increased
Drug interactions: Increased effect of warfarin. In the presence of niacin, cyclosporine, an interval of 4 weeks.
erythromycin there is increased risk for myopathy. Contraindications :Hypersensitivity, pregnancy, lactation, liver disease, kidney disease
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Uses: It is use with precautions in electrolyte imbalance, hypotension, liver disease, Side effects :Headache, dizziness, nausea, constipation, abdominal pain, myalgia, skin rash,
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alcoholism, trauma, seizure disorders. pruritis, liver dysfunction.
Brand names:Pravastatin: Tablet Pravator, Prastatin 10mg, 20mg tablets. Pharmacokinetics : Metabolized in liver, excreted in urine, plasma half 1ife 18 to 24 hours.
Drug interactions ncreased effect of warfarin, increase serum level of digoxin, oral
ATORVASTATIN: This newer statin is more potent. It has highest low density lipoproteins contraceptives.
cholesterol lowering capacity. It acts as antihyperlipidemic. Brand names: Rosuvastatin :
Tablet Rovanel, Rovalip, Novastat, Fortius, Rostar,
Mechanism of action :It inhibits HMG-COA reductase enzyme which reduces synthesis of Rozucor, Zyrova 5mg, 10mg, 20mg teblets.
cholesterol. Use of Statins:
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Indications:Primaryn hypercholesterolaemia, hyperlipidaemia. The statins, lovastatin, simvastatin, pravastatin, atorvastatin, rosuvastalin are the choice
Dosage : Adults orally 10 mg daily. Maximum dose is 80mg per day. The dose may be of drugs for primary hyperlipidacmia with raised low density lipoprotein and total
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increased slowly at intervals of 2 to 4 weeks. choelsterol level with or without raised triglyceride level.
Contraindications Hypersensitivity, pregnancy, lactation, liver disease. Use with ci) The statins have reduced rate of mortality and morbidity due to raised low density
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precautions: Alcoholism, trauma, hypotension, electrolyte imbalance, past liver disease, lipoprotein and cholesterol. These are effective in coronary artery disease, ischaemic
severe metabolic disorders. disease.
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Side effects :Headache, myaligia, liver dysfunction, dyspepsia, skin rash, pruritis, alopecia. i)Statins are choice of drugs for dyslipidaemia in diabetic patients
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Pharmacokinetics :Metabolized in liver, excreted in urine, plasma half life is 14 hours. Onset
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action orally 1 hour.
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Drug interactions : Atorvastatin increase effect of warfarin, increase serum level of digoxin,
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oral contraceptives increases level of atorvastatin with erythromycin, intraconazole.
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74
VA Text Book of Pharmacology- Pharmacology of Druga Acting on Cardio Vascular System
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The statins has been introduced in medicine field 1980's. colestipol available).
Dosage: Adult orally 2 to 8 tablets, 2 tablets 6 hourly daily. (tablet gm
in 1
These drugs are best tolerated,
with mast efficacy. A dose dependent effect is
scen with all statin. All the statin produce Maximum dose 15gm per day.
peak low density lipoprotein and cholesterol lowering effect
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lactation, bleeding
Adverse Effects of Statins
after 1 to 2 weeks of therapy. Contraindications: Hypersensitivity, biliary obstruction, pregnancy,
disorder, children.
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Notable side effects of statins are, headache, bowel upset, nausea,
sleep disturbances. Side effects: Constipation, nausea, vomiting peptic ulcer, abdominal pain, decreased
Liver damage is rare as the statins are mctabolised by liver, There may
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rise in serum vitamin A DK, bleeding

transminase orur. Drug's side effects as fever, skin rash, tremors are rare
Tharmacokinetics : Orally : excreted in feces.
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tetracyclines, iron,
Drug interactions : Reduces action of digitalis, warfarin, folic acid,
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I1. BILE ACID SEQUESTRANTS:

Cholestyramine and Colestipol are drugs indirectly corticosteroids, phenobartitone, fat soluble vitamins.
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increase hepatic metabolism of cholesterol to bile acids, with that intermediate density of
lipoproteins (IDL) and low density lipoproteins (LDL) is reduced where as very low density
lipoproteins (VLDL) density is increased. These drugs have poor patient acceptability.
uFIBRICACID DERIVATIVES
i) CLOFIBRATE: Among fibric acid derivatives, clofibrate was used
as hypolipidaemic
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This drug is
drug. Later on it was observed clinically that it does not prevent atherosclerosis.
CHOLESTRAMINE: The Cholestramine is an antilipemic drug
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not used now.
Mechanism of action It combine with bile acids to form insoluble complex which is
: an antilipemic drug. It lowers
(ii) GEMFIBROZIL: The fibric acid derivative gemfibrozil is
synthesis of
excreted through feces, loss of bile acids lowers choelsterol level. plasma triglyceride level by increasing breakdown and suppressing hepatic
Tdications: Primary hypercholesterolemia, diarrhoea caused by excess bile acid. triglycerides. It is effective in hyperlipoproteinemia and in the raised level of blood
:
Dosage: Adult Orally 4 grams at bed time before evening meals, not to exceed 32 grams cholesterol.
(VLDL),
per day. Mechanism of action : It inhibits biosynthesis of very low densily lipoproteins
Child: Orally 240 mg kg body weight in equal three doses, with food or drink decrease triglycerides, increase high density lipoproteins (HDL).
to taken half
Available as 4gm packet containing cholestramine. Dosage: Adult: Orally 600 mg twice daily usual daily dose is 1200 mg dose be
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Sortraindications: Hypersensitivity, biliary obstruction, pregnancy, lactation, children. hour
before meals
Side effects: Skin rash, irritation perianal area, joint pain, headache, drowsiness, vertigo,
ndications: Hyperlipidemia, lipoprotein abnormalities (resistant to diet alone).
Side effects: Vomiting nausea, diarrhoea, pain abdomen, skin rash, urticaria, anaemia
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innitus, vomiting. peptic ulcers.
eosinophilia, dizziness blurred vision, taste perversion, impotence, head ache.
Jharmacokinetics: Orally, excreted in feces, peak effct in two weeks.
ontra indication : Hypersensitivity, liver disease, gall bladder disease, preg-nanc
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Dg interactions : Decrease absorption of warfarin, digitalis, tetracyclines, iron. lactation children
COLESTIrOL: It is an antilipemic drug. It acts after absorption combines with bile acids to Pharmacokinetics: Orally peak concentration 1 to 2 hours, metabolized by liver, plasma hi
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form insoluble complex which is excreted through feces, loss of bile acids lowers cholesterol life1 to 2 hour, excreted in urine.
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level.
Drug interactions: Increase effect of oral coagulants.
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Mechanism of action: Colestipol absorbs and combines with bile acids to form insoluble
Brand names: Gemfibrozil: Capsules, Tablets, Normolip, Lopid, Gempar, Lipizem,|
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complexes, excreted through feces. It losses the bile acids to lower cholesterol level. Lipizyl, Triglyd, Losterol 300mg, 600mg, 900mg capsules
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Indications: Primary hypercholesterolemia, digitalis toxicity.
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Cardio Vascular System
Pharmacology of Drugs Acting on
PV.AText Book of Pharmacology-
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Precautions for patient. decreased libido,
urticaria, hematuria,
Precautions for patients fever, skin rash,
To report to doctor/nurse for
1. To advice patient not to break, crush or chew capsules. impotence, abdominal pain. measures for birth
take precautionary
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2. Patient should not skip dose, not to take double dose
To use birth control
measures, during treatment,
3 To take low fat diet, avoid smoking, not to consume alcohol, to do regular physical
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control. toxicity may result.
exercise. should not skip dose/miss dose,
not to take double dose
Patient capsule, take dose with
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break or chew
4. To report to doctor//nurse if nausea, diarrhoea vomiting, fever, chills, sore throat whole, not to crush,
To swallow capsule as a
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occurs.
meals.
Caid BEZAFTBRATE : It acts as antilipidemic drug. It suppreses endogenous chslesterol
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synthesis cause increase low density lipoproteins (LDL) which leads to lower plasma DRUGS
Iv.OTHER HYPOLIPIDAEMIC
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cholesterol. It is sencond generation fibric acid derivative used in mixed hyperlipidaemias synthesis in liver or
not inhibit cholesterol
EZETIMIDE : This ezetimide is new drug, it does of intestines and check
Indications:Hyperlipidaemia type ITb, 1, Tv, V 5ype acts localized on borders
increase bile acid excretion. Ezetimide delivery of intestinal cholesterol to
Dosage :Adult: Orally 200 mg three times a day with food. cholesterol which leads to a decrease in
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absorption of
Contraindications: Hypersensitivity, pregnancy, lactation, gall bladder diseae, hepatic
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liver.
disease, renal impairment, nephrotic syndrome. sitosterolemia.
Indications: Primary hypercholesterolemia, Homozygous
Side effects : Reversible alopecia, skin rash, vomiting, nausea, head ache, diarrhoea, Dosage: Adult 10mg orally daily.
myalgia, decreased libido, gastrointes tinal upset, blurred vision. pregnancy, lactation, carcinogenesis, hepatic
Contraindications Hypersensitivity,
Brand names: Bezafibrate : Tablet Beza xl, Bezalip, Globez, 200mg, 400mg tablets.
insufficiency.
v. FENOFIBRATE: It is a lipid lowering drug, posessing a prominant action on serum
Side effects : Reversible hepatic dysfunction, myositis (rarely).
triglycerides. It reduces uric acid level, by increasing the urinary excretion of uric acid.
Phamacokinetics :Excreted in feces, plasma half life 22 hours.
Mechanism of action : It inhibits biosynthesis of low density and very low density
lipoproteins responsibie for triglyceride, increases excretion of neutral sterols Ezetimide when used alone act as a weak hypocholesterolaemic drug. So it may be uscd
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alone in mild hypercholesterolaemia when statin is contra indicated. The combination of this
Indication:7ypeIla, IMb, I1, v, V hyperlipidemia resistant to diet.
drug ezetimide with low dose of statin is found more effective in lowering. Low density
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Dosage :Adult: orally, 200mg one capsule daily with meals.
lipoproteins (LDL) cholesterol (Ezetimide + Simvastatin).
Contraindications :Hypersensitivity, renal disease, hepatic disorder, pregnancy, lactation, Brand names: Ezetimide: Tablet Zetica, Lipezet, Zetica, Ezta, Ezibloc, Zeteze, 10mg
peptic ulcers, biliary cirrhosis.
tablets.
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Side effects : Vomiting, nausea, drowsiness, hepatitis, bleeding hepatomegaly, weight gain,
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leukopenia, anaemia, eosinophlia alopecia, polyphagia, myalgia.
POLICOSANOL:It is a new cholesterol lowering drug.
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Pharmacokinetics:Plasma half life 20 hours, excreted in urine.

Drug interactions: Decreased effect of fenofibrate with rifampin, increased effect of insulin,
Dosage:Adult orally 10 to 20 mg daily. Policosanol improves lipid profile in patient with
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type I hypocholesterolemia. It is contraindicated in pregnancy, lactation, children. This drug
sulfonylureas, oral anticoagulants.
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has side effects: Headache, insomnia, dizziness, somnolence, asthenia.

Brand names: Fenofibrate :Caps, Stanlip, Finate, Trichek, Fibral, Lipicard, 160mg
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200mg, Capsule, Tablets. Brand names: Policosanol: Tablet Zetanol, Cosanol, Garlee, Smg, 10mg. 20mg tablets.
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78 Pharmacology of Drugs Acting on Cardlo Vascular System
FU A TextBook of Phammacology-1
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GUGULIPID : This drug is used in Ayurveda. It
is obtained from gum guggal whichis Q.6. What are Anti hypertensive drug?
effectively used in lowering plasma cholesterol and pressure of an individual. The
triglycerides. It is very well tolerated Ans. Hypertension is a disease characterized by abnormal high blood
when given orally. guglip tablet 25 mg three times a day for 15 30 drugs used in the treatment of hypertension, that reduce the increased blood
pressure to
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to days. rarely diarrhoea
may occur as side effect, to patient. Patient is advised to take low fat diet, to normal blood pressure are called antihypertensive drugs.
avoid fried
foods with treatment.
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Q7. What are vasodilator drugs?
NICOTINIC ACID: Nicotinic acid (Niacin) is a B group vitamin. It Ans. The vasodilator are drugs that cause dilatation of blood vessels
; eg, verapamil produce
lowers plasma
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cholesterol and triglyceride levels when given in large doses. Triglyceride level is lowered coronary vasodilatation.
more than cholesterol. Nicotinic acid reduce synthesis of very low density lipoproteins in
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Q8. What are Anti anginal drugs?
liver by inhibiting triglycerides formation. The adverse or side effects are nausea, yomiting Ans. The drugs used in the treatment of Angina pectoris are called as anti anginal drugs. Angina
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fushing, hoat, itchings, liver dysfunction, jaundice are side effects. Dosage Initiaí dose 100
: pectoris is a condition or disease results from anoxia of the cardiac muscles characterized by
pain in chest, sternal pain that radiates down the left shoulder and arm. Eg. antianginal drug
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mg orally three times a day, then gradually increase to 2 to 6 gm per day in three divided
doses after meals. The higher doses are not tolerated by 50 to 60 percent patients. Its use is are glyceryl trinitrate, propranalol.
restricted to high risk cases. 99. What is Tetrology of Fallot?
Ans. It is congenital disease having cardiac anomaly having four defects (Tetra means four) ()
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Pulmonic stenosis ið ventricular septal defect (iið Position of the Aorta (v) Right ventricular
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REVIEW QUESTIIONS hypertrophy.
It is characterized with symptoms in infants cyanosis, hypoxia when child cries. There is
difficulty in feeding there is no weight gain, mal development, clubbing of fingers and toes.
SHORT ANSWER QUESTIONS Treatment is palliative surgical procedure of child at the age of 4 to 5 years. Tetrology of fallot is
Q.1. What are cardiotonics? also called fallot syndrome, blue baby Ginfant borne with cyanosis caused by a congenital heart
Ans. The cardiotonics are the drugs which tends to increased the efficiency of contraction of the anomaly).
heart muscles, example: Digitalis. Q.10. Explain The Determinants of Cardiac Output
Q.2. What is a disease dropsy? Ans. The basic equation for cardiac output is:
Ans. Dropsy is a disease means an abnormal accmulation of clear watery fuid in a body tissue o CO-HRxSv
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cavity as in joints, a fallopiarn tube, the abdomen, or in the gall bladder. Dropsy is also called as where CO is cardiac output, HR is heart rate, and SV is stroke volume. According to the
hydrops. equation, an increase in HR or SV will increase CO, whereas a decrease in HR or SV will
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0.3. What is the harmful effect of Digoxin on the eyes? decrease CO. For the average person, heart rate is about 70 beats/minute and stroke volume is
about 70 mL. Multiplying these, we get 4.9 L/minute-the average value for COo.
Ans. Digoxin produce visual disturbances like blurred vision, diplopia and green yellow halos,
occurs colour vision defect.
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Q.11 Define Cardiac Preload?
04. Nane the cardiac glycosides obtained from the leaves of digitalis purpurca, digitalis lanta?
Ans. The name of cardiac glycosides obtained from the dried leaves of digitalis purpurea is
(i) Ans. It is formally defined as the amount of tension (stretch) applied to a muscle before contraction.
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Digitoxin (i) Gitoxin Gii) Gitalin, and from Digitalis lanta, the glycosides obtained are () In the heart, stretch is determined by ventricular filing pressure, that is, the force of venous
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Digoxin (i) Digitoxin (ii) Gitoxin. return:the greater filling pressure is, the more the ventricles will stretch. Cardiac preoad can be
expressed as either end-diastolic volume or end-diastolic pressure. As discussed later, an increase in
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Q.5. What are Anti arrhythmic drugs?
preload will increase SV, whereas a decrease in preload will reduce SV. Frequently, the
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Ans. Anti arrhythmic drugs are the drug used to correct an abnormal cardiac rhythm. For example terms preload and force of venous returm are used interchangeably-although they are not tru
Quinidine, Procainamide act as antiarrhythmic drugs.
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equivalent.
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PV A Text Book of Phamacology-l Pharmacology of Drugs Acting on Cardio Vascular System
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Q.12. Define cardíac Afterload
Ans. t is formally defined as the load against which a muscle exerts its force (i.e., the load a 9Write the toxic effects of cardiac glycosides Refer.1.3
must overcome in order to contract). For the heart, afterload is
muscle
2 etine anti-hypertension drugs, classify them, Write the pharmacology of captoprl N
the arterial pressure that the left contraindication and use of verapamil
ventricle must overcome to cject blood. Common sense tells us that, plainRefer the mechanism of action, side effects, indication,
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if afterload increases, SV
will decrease. Conversely, if afterload falls, SV will rise. Cardiac afterload
is determined
4
primarily by the degree of peripheral resistance, which in turm is the role of p adrenergie blockers in hypertension write the pharmacology ot propranol.
escribe
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determined by constriction
and dilation of arterioles. That is, when arterioles constrict, peripheral resistance Refer 1
rises, causing
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AP (afterload) to rise as well. Comversely, when arterioles dilate, peripheral resistancé

falls, 9Explain anti-anginals, classify them, write the pharmacology of slyceryl trinitrate Bgrer 1
causing AP to decline. Q8. Describe the anti arhythmic drugs elassify them write the pharmacology of quinidine sulphate:
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Q.13. Pacemaker Impulse Generation Refer 1.6
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Ans. The first step of cardiac conduction is impulse generation. The sinoatrial (SA) 09. Describe the mechanism of action, adverse effect, indication, dose and brand name of esnmolol
node(also referred
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to as the pacemaker of the heart) contracts, generating nerve impulses that travel Refer 1.
throughout
the heart wall. This causes both atria to contract. The SA node is located in the upper wall Hypolipidaemic, Classify them, write the pharmacology of lovastatin Refer 1.7
right atrium. It is composed of nodal tissue that has characteristics of both muscle and
of the
nervous
Define
Q.11. Explain the Pharmacology
tissue. of clofibrate Refer 1.7
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Q12. Describe the mechanism of action, side effect and atenolol Refer
Q.14. Explain the mechanism of carvedilol 1.
A3Write a note on management of Hypertension Refer 14
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Ans. It inhibits ß adreno receptors mediated compensatory mechanism. It is beta-adrenergic receptor
blocking ability decreases the heart rate, myocardial contractility, and myocardial oxygen
demand. It also decreases systemic vascular resistance via its alpha adrenergic receptor MULTIPLE CHOICE QUESTIONS
blocking
properties. 0.1 The non-glycoside positive inotropic drug is:
Q.15. Describe the esmolol a) Digoxin b) Strophantin K
Ans. Esmolol is an ultrashort acting beta one blocker. It is short acting drug having quick action p ) Dobutamine d) Digitoxin
blocker iv. administration is very effective in atrial fibrillation. It slows conduction 0.2. Sugar molecules in the structure of glycosides influence:
of AV node
decrease heart rate decrease oxygen consumption in myocardium. a) Cardiotonic action b) Pharmacokinetic properties
Q.16. What is calcium channel blockers
Toxic properties
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d) All of the above
Ans. The main action of this group of medicines is to inhibit calcium ion mediated channel inward Q.3 Aglycone is essential for
current act as calcium antagonist effect on smooth vascular muscles of coronary arteries a) Plasma protein binding
due to b) Half-life
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which myocardial blood flow is increased
c) Cardiotonic action
d) Metabolism
Q.17. Define hypolipidaemics Q4. Choose the derivative of the plant
Foxglove (Digitalis):
Ans. Hypolipidaemic are drugs which lowers the level of lipids and lipoproteins in blood a) Digoxin
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b) Strophantin K
Q.18. Explain the side effect of fenofibrate c) Dobutamine
d) Amrinone
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Ans. These are Vomiting, nausea, drowsiness, hepatitis, bleeding hepatomegaly, Q.5. All of the following statements
weight gain, regarding cardiac glycosides are true EXCEPT:
leukopenia, anaemia, eosinophilia alopecia, polyphagia, myalgia.
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a) Digoxin is a mild inotrope
LONGANSWER QUESTIONS b) Digoxin increases vagal tone

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) Digoxin has a longer half-life
than digitoxin
1.Describe the Electrophysiology of heart, write the role of PQRST Rfer 1.2.
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d) Digoxin acts by inhibiting the Na+/K+ ATPase

02 Kplain the pharmacology of cardiac glycoside Refer. 1.3
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PU A Text Book of Pharmacology- Pharmacology of Drugs Acting on Cardlo Vascular Systemn
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Q.6. The most candiae manifeslation of glycosides intoxication is: Q.17This drug is a Class II antiarrhythmic drug:
a) Atrioventricular junctional rhythm b) Second-degree atrioventricular blockade a) Flecainide b) Propranolol
Ventricular tachycardia d) All the above c)Lidocaine d) Verapamil
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Q.7. The manifestations of glycosides intoxication are: Q18. This drug is a Class III antiarrhythmic drug
a) Visual changes b) Ventricular tachyarthythmias a) Flecainide b) Sotalol
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Gastrointestinal disturbances d) All the above )Lidocaine d) Verapamil
Os. For digitalis-induced arrhythmias the following drug is favored: Q.19This drug prolongs repolarízation:
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a) Verapamil b) Amiodarone a) Flecainide b) Sotalol
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Lidocaine d) Propanolol c) Lidocaine d) Verapamil
Q.20 Which of the following nitrates and nitrite dugs are long-acting?
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Q.9. In very severe digitalis intoxication the best choice is to use:

a) Lidocaine b) Digibind (Digoxin immune fab) a) Nitroglycerin, sublingual
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Oral potassium supplementatinn d) Reducing the dose of the drug b) Isosorbide dinitrate, sublingual dsordil, Sorbitrate)
Q.10. This drug is a selective beta-1 agonist: Amyl nitrite, inhalant (Aspirols, Vaporole)
a) Digoxin b) Dobutamine d) Sustac
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c
)Amrinone d Dopamine Q.21Which of the following nitrates and nitrite drugs is a short-acting drug8
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Q.11.Tolerance to this inotropic drug develops after a few days a) Nitroglycerin, 25% ointment ONitrol)
a) Amrinone b) Amiodarone b) Nitroglycerin, oral sustained -release (Nitrong)
Dobutamine d) Adenosine )Amyl nitrite, inhalant (Aspirols, Vaporole)

Q.12.This drug inhibits breakdown of cAMP in vascular smooth muscle: d) Sustac
Q.22. Which of the following nitrates and nitrite drugs is used for prevention of angina
b) Dobutamine attack?
a) Digoxin
c) Amrinone d Dopamine a) Nitroglycerin, 2% ointrment (Nitrol)
state and b) Nitroglycerin, oral sustained -release (Nitrong)
Q.13. This drug is useful for treating heart failure because it increases the inotropic
reduces afterload: c)Isosorbide mononitrate Ismo)
a) Amiodarone b) Amrinone d) All of the above
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Propano d) Enalapr ANSWERS
Q.14.This drug is a Class IA antiarrhythmic drug
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ali b) Proj 5C 6D
1C 2B 4A
Topamil 11C 12C
7D 8C B 105
Q.15.This drug is a Class IC antiarrhythmic drug: 18.B
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13B 14D 15C 16A 17B
a) Flecainide
19B 20D 21 22
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c)Lidocaine
Q.16This drug is a Class IC antiarrhythmic drug
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a) Flerainide
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c)Lidocaine
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Telegram - Study Pharmacy 2
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Drugs Affecting on Hematopoletic Systems
2
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DRUGS AFFECTING ON INTHEDEHRAPYOE SHOCK
21 DRUGUSED the cardiovascular system fails to perfuse
tissues
HEMATOPOIETIC SYSTEMS Shock is a condition in which
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CHAPTER circulatory system, and/or volume
adequately blood. It is due to impaired cardiac pump,
Inadequate tissue perfusion can result
in:
can lead to compromised blood flow to tissues.
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impairment of cellular metabolism -
generalized cellular hypoxia (starvation) widespread
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INTRODUCING THE CHAPTER tissue damage organ failure death
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Cells switch from aerobic to anaerobic metabolism lactic acid
production Cell function
& fluids seep in & out of
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Drugs used in the therapy of shock ceases & swells membrane becomes more permeable electrolytes
death
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Hematinics cell Na+/K+ pump impaired mitochondria damage cell
Coagulants
Anticoagulants. hypoxia due to reduced oxygen
Definition: Shock is defined as a state of cellular and tissue
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Fibrinolytics This most
utilization.
delivery and/or increased oxygen consumption or inadequate oxygen
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(ie, reduced
commonly occurs when there is circulatory failure manifest as hypotension
Anti-platelet drugs
Plasma volume expanders "Undifferentiated shock" refers to the situation where shock is
tisswe perfusion).
recognized, but the cause is unclear. While patients often have a combination of more than
KEY WORDS one form of shock (multifactorial shock), four classes of shock are recognized,
Shock : It is defined as a state of cellular and tissue hypoxia due to reduced oxygen
delivery and/or increased oxygen consumption or inadequate oxygen utilization. This most
commonly occurs when there is circulatory failure manifest as hypotension
Haematinics: These are substances required in the formation of blood and are used for treatment of
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anaemias. Distributive
(n Cardiogenic 1) Hypovolemic IV). Obstrnuctive
Coagulants : These are the drugs which promotes lotting. These drugs are used in haemorrhagic Septic shock
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Cardiomyopathic Hemorrhagic P'ulmonary vascular
states. Systemic inflammatoryy
Anti-coagulants: These are the drugs which prohibit (check, prevent) the process of clotting Tesponse syndrome Arhythmic Nonhemorrhagic Mechanical,
(SIRS)
Mechanical Combined
Anti-platelet drugs : These are drugs which interfere with platelet function and are used as
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Neurogenic shock
prophylaxis of thromboembolic disorders.
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Anaphylactic shock
O Fibrinolytic These are the drugs used to decompose thrombi or clot to recanalize obstructed blood
:
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Drug and toxin-induced

vessels mainly coronary artery. These drugs decompose the clot by activating the natural fibrinolytic
shock
system.
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Plasma expanders : These are the agents usually a high molecular weight dextran which is
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administered intravenously to increase the decreased plasma volume.

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FUA Text Book of Pharmacology-l
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in systolic as well
DRUG UsED IN THE TREATMENT OF SHOCK receptors. At High dose or rapid iv. infusion produces marked increase
receptors in blood vessels),
as diastolic B.P. (as the number of a receptors are more than 2
The following drug are frequently used for the treatment of shock such as Adrenalin, concentration is
which is followed by a fall in the mean B.P. (because when the epinephrine
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Norepinephrine, Epinephrine, Hydrocortisone, Levophed, Dobutamine,
remain attached on more sensitive
Methylprednisolone, Dexamethasone, Decadron, Dobutrex, Cortef, Dexamethasone reduced by degradation, rest of the amount
Pa receptors). This is called as biphasic response of epinephrine on blood
pressure.
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intensol, Adrenacl, Medrol, Adrenalin chloride, Albumin human, Depo-medrol, Isuprel, effect is
Smooth Muscle: The GIT of smooth muscle is relaxed by epinephrine. This
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Dexpak taperpak, Medrol dosepak, Phenylephrine and De-sone la

the membrane of
mediated by both ai and p2 receptors on effectors cells and azreceptors on
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K* efflux and
para sympathetic nerve endings. The ajreceptor activation causes increase in
: It stimulates both the alpha- and beta- adrenergic system, causes
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EPINEPHRINE cytosolic
thereby hyperpolarization of the muscle cell. Ba receptor activation increases
systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates another
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concentration of cAMP. Then cAMP stimulates protein kinase A which stimulates
bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay the this leads to dephosporylation and inactivation of myosin
enzyme. After 2-3 such steps
absorption of local anesthetics. Its pharmacological effects depend on the concentration and of
light chain (MLC). Stimulation of presynaptic a receptors renders inhibition of release
the type and number of available receptors, Generally, it has more affinity for ß receptors.
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neurotransmitter Ach from intramural nerve. These three response combined
excitatory
So, at lower concentration,f effect predominates. But if the number of receptors is nmore in
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cause relaxation of GIT smooth muscles.
an organ (e-g, blood vessels), a higher concentration of epinephrine is produced a
sphincter: Epinephrine usually increases sphincter contraction via ai receptors (by
mediated action.
activation of phospholipase C)
Pharmacological Action
p Respiratory: Bronchial smooth muscle relaxes (a receptors activation -CAMP D.
ieart: The direct receptor mediated actions of epinephrine are positive chronotropic (f
Ulerus: The non-pregnant uterus of human is contracted and pregnant one is relaxed by the
heart rate) and ionotropic (t force of contraction) effect on the heart, increased cardiac
drug. It relaxes detrusor muscle (ß2 receptors) and contracts the trigone and sphinctor
output, myocadical contractility, coronary blood flow and so oxygen consumption by heart.
muscles (a receptors) of the bladder.
The conduction velocity through A-V node, bundle of His, parkinje fibres, atrias and
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ventricular fibres is increased by epinephrine to cause the above responses. Epi - pi recep. Metabolism: It stimulates glycogenolysis (P2 mediated) in liver and muscle, causes
1
Gs - Ad. cycl. f-cAMP 1 PKA -Ca3-channels open [Ca2*]t Ca2
Contraction of myocardial
inhibition of insulin secretion (a mediated) and increases free fatty acids in blood
(P mediated- activation of triglyceride lipase breakdown of triglycerides into free fatty
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calmodulin complex MLCK 1- Phosphorylation of MLC
fibre.] acids and glycerol)
Blood Vessels: Epinephrine mainly acts on small arterioles and precapillary sphincters. It Eye: Mydriasis occurs due to contraction of radial muscles (areceptors) of iris by
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of epinephrine. The intraoccular pressure falls, specially in wide angle glaucoma, due to
also exerts its action, to some extent, on veins and large arteries. It causes constriction
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cutaneous, renal, pulmonary, arterial and venous, and other visceral blood vessels because relaxation of ciliary muscle (a receptors).
of the presence of predominant a receptors. It dilates blood dialates blood vessels of skeletal
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Skeletal Muscle: It does not directly excite skeletal muscle but facilitates neuromuscular
B2 receptors. At
muscles (at low doses), coronary and liver which is mediated by powerful transmission through the activation of a and pareceptors of somatic Moto neurons releasing
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causes vasoconstriction in skeletal muscle. [Epi Parec. Gs Ad. cycl.
higher dose, it Ach rapidly. The twitch tension of white muscle (fast contracting fibres) is increased.
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VSM].
CAMP PKA 1- dephosphorylation of MLC~ relaxation of Whereas that of red muscle (slow fibres) is reduced. Other Pa agonists (eg. salbutamol) may
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Blood Pressure: At lower concentration slow iv infussion or S.C. injection of epinephrine also act similarly.
ac
pareceptors are more sensitive than a

causes fall in peripheral resistance because vascular
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PU A Text Book of Pharmacology-1l Drugs Affecting on Hematopoietic Systems
Uses: It is mainly used to treat patients in vasodilatory shock

states such as septic shock and
CNS: Being polar compound, epinephrine cannot enter into the CNS but restlessness, over dopamine.It is also used as a
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apprehension, headache and tremor may occur due to its secondary to some peripheral neurogenic shock and has shown a survival benefit
vasopressor medication for patients with critical hypotension.
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effects on CNS, skeletal muscles, and intermediary metabolism.
Norad, Vascue,
Brand Name: Nordrin 2 mg (base)/2 ml amp, Adrenor,
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Pharmacokineties: Though epinephrine is absorbed from the GIT, but its bioavailability is
primary activity results from
poor because it is rapidly degraded in the intestinal wall and liver
(by MAO and COMT). DOBUTAMINE: It is a direct-acting inotropic agent whose
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while producing comparatively mild
beta-adrenoceptors of the heart
The absorption from im. inj. site is more rapid than s.c. in site, (due to local stimulation of the
It acts primarily on
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arrhythmogenic, and vasodilative effects.

vasoconstriction). chronotropic, hypertensive,
receptors. It does not cause
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or alpha
0.3 ml, iv. inj. Single-dose beta-1 adrenergic receptors, with little effect on beta-2
Xreparation: Adrenaline inj (BAIF, 280pg/0.1 ml). Dogs-0.1 to does dopamine. It is indicated when
the release of endogenous
norepinephrine, as
vials (1mL)-25; Multi-dose vials (30mL)-1, 10 resulting either írom organic
parenteral p decompensation due to depressed contractility receptors of
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USE:
or from cardiac surgical procedures. It directly stimulates beta-1
heart disease
A.Cardiovascular System: resulting in increasecd
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volume,
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contractility and stroke
the heart to increase myocardial
myocardial infarction or open heart
(a) Cardiac arrest adrenaline cardiac output. It is proposed as a cardiotonic after
(b) Cardiogenic shock- dobutamine, dopamine. surgery.
vasoconstriction or tachycardia. It is
(c)Heart block (A-V block) isoproterenol Uses: It is cardiac stimulant action without evoking
surgery.
proposed as a cardiotonic after myocardial infarction or open heart
2. Anaphylactic reactions:
Hydrochloride, Crdiject 50 mg/4 ml
(a) Acute anaphylactic (or type I hypersensitivity) reaction Adrenaline. Brand name: Dobutamine 12.5mg/ml, Dobutamine
and 250 mg per 20 ml amp, Dobutrex, Dobustat 250 mg vial
3. Miscellaneous uses:
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(a) Used with local anaesthetic to prolong the action adrenaline (vasoconstrictor agent) cortex. Its
HYDROCORTISONE:The main glucocorticoid secreted by the adrenal
(b) Bronchial asthma epinephrine, isoproterenol, salbutamol topically, in the treatment of
synthetic counterpart is used, either as an injection or
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c)As decongestant (allergic rhinitis)epinephrine inflammation, allergy, collagen diseases, asthma, adrenocortical
deficiency, shock, and
(d) Ophthalmic use (to dilate pupil) ephedrine, phenylephrine some neoplastic conditions.
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receptor. After binding the
Mechanism of action: It binds to the cytosolic glucocorticoid
plants and is used translocates itself into the cell nucleus,
NOREPINEPHRINE (LEVARTERENOL): It is also found in receptor the newly formed receptor-ligand complex
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that is secreted (GRE) in the promoter region of
pharmacologically as a sympathomimetic. It is a precursor of epinephrine where it binds to many glucocorticoid response elements
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central and autonomic neurotransmitter. It is the target genes. The DNA bound receptor then interacts
with basic transcription factors,
by the adrenal medulla and is a widespread
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postganglionic sympathetic fibers and of the diffuse causing the increase in expression of specific target genes.
the principal transmitter of most
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inflammatory and pruritic manifestations of

projection system in the brain arising from the locus ceruleus5. Indications: It is indicated for the relief of the
to treat endocrine (hormonal) disorders
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to cause Also used
on both alpha-1 and alpha-2 adrenergic receptors corticosteroid-responsive dermatoses.
Mechanism of action: It acts to many immune and allergic
vasoconstrictor by acting on alpha-adrenergic (adrenal insufficiency, Addisons disease). It is also used treat
vasoconstriction. It functions as a peripheral
ac
of the heart and dilator of coronary

arteries as a .
receptors. It is also an inotropic stimušator

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beta-adrenergic receptors.
result of it's activity at the
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on Hematopolotic Systems
Drugs Affocting
90 PU A Text Book of Pharmacology-
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mg
Brand name: Decadron tab 0.75 mg/1 oral. Dexamethasone
Omega Unidose 10
colitis, and
disorders, such as athritis, lupus, severe psoriasis, severe asthma, ulcerative cardiac stimulant action without
DOBUTREX: It is a beta-1 agonist catecholamine that has myocardial
Crohn's disease. as a cardiotonic after
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evoking vasoconstriction or tachycardia. It is proposed
Uses: Used in allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some
infarction or open heart surgery.
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neoplastic conditions beta-1 receptors of the heart to
AFASSCO 17 Mechanism of action : Dobutamine directhy stimulates
Brand Name: Advanced Hydrocortisone cream 10 mg/ gm,
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stroke volume, resulting in increased cardiac output.

Hydrocortisone, Oint. Anti Itch cream. increase myocardial contractility and
activity results from stimulation of the
It is a direct-acting inotropic agent whose primary
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METHYLPREDNISOLONE: Methylprednisolone and its derivatives, methylprednisolone mild chronotropic,
beta-adrenoceptors of the heart while producing comparatively
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sodium succinate and methylprednisolone acetate, are synthetic glucocorticoids/used as vasodilative effects. Dobutamine acts primarily on beta-
hypertensive, arrhythmogenic, and
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anti-inflammatory or immunosuppressive agents. 1 adrenergic receptors, with little effect on
beta-2 or alpha receptors. It does not cause the
Mechanism of action: Unbound glucocorticoids cross cell membranes and bind wi high release of endogenous norepinephrine, as does
dopamine.
It
affinity to specific cytoplasmic receptors, modifying transcription and protein synthesis. Hydrochloride in
Brand name : Dobutamine 12.5mg/ml 12.5 mg. Iv., Dobutamine
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inhibits leukocyte infiltration at the site of inflammation, interfere with mediators of
Dextrose 200 mg/100mL IV.
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inflammatory response, and suppress humoral immune responses. The antiinflanmmatory
actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, ERELAEMATINIGS
lipocortins, which control the biosynthesis of potent mediators of inflammation such as for the
prostaglandins and leukotrienes. O Haematinics are substances required in the formation of blood and are used
treatment of anaemias. These drugs increase the number of red blood cells and being the
Brand name Depo-Medrol Injection, suspension 40 mg/1ml. IM. normal.
amount of hemoglobin to normal level and above when it is below brings
cells
Anaemia occurs when the balance between production and reduction red blood
of
DEXAMETHASONE: Dexamethasone and its derivatives, dexamethasone sodium
is disturbed
phosphate and dexamethasone acetate, are synthetic glucocorticoids. It is used as anti-
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(a) Due to blood loss
inflammatory or immunosuppressive properties and ability to penetrate the CNS. It is used
6) Impaired red cell formation due to
alone lo nanage cerebral edema and with tobramycin to treat corticosteroid-responsive
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inflammatory ocular conditions. Deficiency of essential factors: Iron, folic acid vitamin B12
Mechanism of action: It is a glucocorticoid agonist. Unbound dexamethasone crosses cell (i) Bone marrow depression, erythropoietin deficiency
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receptors.
membranes and binds with high affinity to spedfic cytoplasmic glucocorticoid (c)Increased destruction of RBCs (Haemolytic anaemia)
This complex binds to DNA elements (glucocorticoid response elements) which results in a
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zon: Iron from the ancient times has been considered an important element for the body.
modification of transcription and, hence, protein synthesis in order to achieve inhibition of
Iron was found to be present in blood in 1713. Iron is an essential body constituent. Total
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leukocyte infiltration at the site of inflammation, interference in the function of mediators of an adult human body is 2.5 to 5 gms. The Greek thought,mars is the god of,
body iron in
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inflammatory response, suppression of humoral immune responses, and reduction in
strength and iron is dedicated to mars, so iron was used for weakness, which is commonly
edema or scar tissue. The antinflammatory actions of dexamethasone are thought to
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of used for anaemia. Blaud prepared his famous pill was known as Blaud's pill that was
involve phospholipase Az inhibitory proteins, lipocortins, which control the biosynthesis
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containing ferrous sulphate and potassium carbonate for the treatment of anaemia.
potent mediators of inflammation such as prostaglandins and leukotrienes.
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93
DrugsAffecting on Hematopoletic Systems
PV A Toxt Book of Phamacology-!
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destruction of red blood
Haemolytic anaemia : It is a condition in which there is increased
germ yeast, dry fruits, dry beans, egE yolk, liver, oyster, the normal quantity ot
Djetary Sources of Iron: Wheat cells. The red cells present are of normal size and contains
Toot vegetables. Medium sourres of iron are meat, chicken, fish, spinach, apple. Milk and
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haemoglobin.
milk products are poor sources of iron. by haemorrhage. In
Tron deficiency anaemia : It is due to inadequate of iron or loss of iron
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pistribution of Iron in body : Iron is an essential body constituent. It is distributed into: less than the normal quantity
this condition the red blood cells are small in size and contain
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Haemoblobin (Hb) 66%

of haemoglobin (hypochromic).
cells) fail to
Iron stores as ferritin and haemosiderin 25% Megaloblastic anaemia : It the condition in which erythrocytes (Red blood
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Myoglobin in musles 3% mature because deficiency of vitamin B12 or folic acid.
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of
Parenchymal iron (in enzymes) 6%
Sickle cell anaemia : In this condition mutant hemoglobin molecule
undergo
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disc
Iron is stored in the body in ferric form in combination with a large protein apoferritin. polymerisation under low oxygen tension, the shape of RBC changes from biconcave
The loss of 100 ml of blood there is loss of 50mg of elemental iron. To raise haemoglobin to elongated sickle like shape.
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level of blood by 1gm about 200 mg of iron is required. Pernicious anaemia It occurs in old people for lack of intrinsic factor essential for
:
the
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Preatment of Anaemia: absorption of vitamin B12. The maturation of RBC in bone marrow becomes disordered,
every severe anaemia treatment when hemoglobin is 20 percent or below due to
1. In lateral and posterior columns of spinal cord deteriorate RBC's, and WBC count is reduced.
any cause, blood transfusion is necessary. There is weakness, tingling and numbers in leg and arms, fever, pallor, anorexia, weight
2. In microcytic anaemia and hypochromic anaemia iron is required specifically to be loss occur. Treated with cyanocobalamine
administered along with iron rich diet.
3. In macrolytic anaemia due to any cause, liver extract vitamin B12, folic acid each 2.2.1pRUGS USED IN ANAEMIA
alone or in combination are used.

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4. In permicous anaemia vitamin B12 is specifically needed for treatment.
5. In all cases of anaemia side by side with the treatment of anaemia, symptomatic
Cyanocobalamine
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Folic Acid Erthropoietin Iron
treatment should be given with dietary supplements.
(Vitamin B12)
Morphologically: Classification of anaemia is as under
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Microcytic anaemia: The size of the Red blood cell is smaller than normal size.
Macrocytic anaemia : The size of the red blood cell is larger than normal. 1.CYANOCOBALAMINE (VITAMIN Bi2
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Microcytic hypochromie anaemia : The size of the red blood cells (RBC) is found smaller Cyanocobalamine is synthesized by microorganisms in intestines of animals, in soil
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than the normal size and the haemoglobin amount is less than the normal value. and water. The vegetarian get vitamin B12 from milk, milk products, nodudated root
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Aplastic anaemia : It is a condition in which there is inadequate red blood cells formation vegetables, legumes. Non vegetarian get this vitamin from food like liver, kidney, fish, eggs
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as a result of degeneration of the bone marrow. RBC's present are of the normal size. and meat muscles which are rich in vitamin B12
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Telegram - Study Pharmacy PU A Text Book of Pharmacology-l Drugs Affecting on Hematopoietic Systems 95
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syndrome, vitamin
Indications : Pernicious anaemia, hemolytic anaemia, malabsorption
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B12 deficiency, hemorrhage renal and hepat disease.
woo-C OH-CHCONH
Dosage:Pernicious anaemia / malabsorption syndrome.
100 to 1000 Hg daily for 2 weeks, then same dose monthly,
Intramuscularly
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Adult:1/M
injection.
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NHOO
Child:100 to 500 mg I/M for 2 weeks then 50 mg IM monthly.

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*H-GR-O*
Maintenance dose 100 to
Vitamin B2 deficiency: Adult IM 30 to 100 Hg for 5 to 10 days.
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200 mg JM monthly.
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: Skin rash, pain at the site of injection, Pulmonary

oedema, Hypokalemia, .
Side effects
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anaphylactic shock, flushing,optic nerve atrophy, diarrhoea.
Tablet
Brand Names: Cyanocobalamine Tablet Carron, Folictin, Polybion capsules,
:
Structure of vitamin Bz (Cyanocoblamin) Optineuron, Capsule Vitone.

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Vitamin B12 is a water soluble vitamin thermostable red crystals. It is naturally Treatment of overdose :Discontinue drug use.
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occuring vitamin which is synthesized by micro organisms, animals including man and
plants take it from them. In 1849 Thomas Addison described a case of anaemia not cured FOLIC ACID: Folic acid occurs as yellow crystals insoluble in water, its sodium salt is
isolated
with iron. This type of anaemia was called as pernicious anaemia which was cured by soluble in water. Chemically folic acid is Pteroyl glutamic acid. Mitchell in 1941
adding liver in diet. The daily requirement of vitamin B12 is 1 to 3 mg. during pregnancy folic acid from spinach and called it folic acid means from leaf. It is also called as vitamin
and lactation 3 to 5 gram. B9.
Dietary sources of folic acid :Spinach, green leafy vegetable, liver, egg,
meat, milk, milk
Cyanocobalamine (Vitamin required for adequate nerve functioning
B12) is
products. The side effects of folic acid are, flushing, bronchospasm.
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carbohydrate and protein metabolism. It is essential for red blood cell formation
(development, normal growth of individual and also in reproduction of cels Mechanism of action:
Folik acid (Vitamin B-9) is required for erythropoiesis, for increase in number of RBC's,|
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Mechanism of action :Cyanocobalamine vitamin B12. Also called Hydroxy cobalamine is
wBC's and platelet formation in megalblastic anaemia. It is useful in pregnancy
required for adequate nerve functioning. It helps in the carbohydrate and proteins
alcoholism, liver diseasetis biochemically inactive, is converted to tetrahydrofolic acid
pabolism. It is required for normal body growth, RBC and cell reproduction.
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and methyltetrahydrofolate by dihydrofolate reductase. These folic acid congeners are
Deoryadenosyl cobalamin is a cofactor needed by the enzyme that acts to convert L-
transported across cells by receptor-nediated endocytosis where they are needed to
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Ph
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methylnalonyl-CoA to succinyl-CoA. This conversion is an important step in the extraction of
maintain normal erythropoiesi. syrduesize_purine and thymidylate nucleic_acids
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energy from proteins and fats. Additionally, succinyl CoA is necessary for the production of
amino acids, me'iyate iRNA, and generate and use formate. Using vitamin
interconvert
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hemoglobin, the substance that carries oxygen in red blood cels.
B12 as a cofactor, foli d Iuulize high homocysteine levels by remethylation of
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L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyi-CoA in the

homocysteine to riuh:ne via nmethionine synthetase.
degradation of propionate, an important biochemical reaction in the metabolism of lipids
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and proteins. Succinyl-CoA is also required for hemoglobin synthesis
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Drugs Affocting on Hematopoletic Systems 7
PU A Text Book of Pharmacology-
appear in folic acid
(i) Weakness, weight loss, sterility, neurological symptoms rarely
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akaddand vitamn in lcobalamns)- deficiency.
NADP NADNH H
Otbereorgans
thdebit ii)There are neural tube defects including spina bifida.
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pdase
Vimh
O.001m/dy Peficiency of folic acid occurs due to:
lactation, rapid growth period and
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Me 1. There is increased body demand in pregnancy,
cobaam noration
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hemolytic anaemia
ydrolou
Thaue
Due to inadequate dietary intake.
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2.
release of folvite Irom liver cells
Deary eaxy 3. In chronic alcoholism, intake of folic acid is poor,
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Erythropowss thymidylate
id late
Eytroytes
DIArtesh and recirculation are interfered.
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phenytoin, oral
4. Prolongtherapy with drugs like phenobarbitone sodium,
2nemaror storage of folic acid.
contraceptives and primidone cause decrease in absorption and
Fig. 21 Metabolism of folic äcid & Vitamin Bia folic acid level. Hydantoins,
c
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Prug interactions: Chloramphenical decreases metho-trexate.
Indications : Megaloblastic anaemia, macrolytic anacmia caused by folic acid deficiency, phenobarbitone increase metabolism of folate. Donot use folic acid with
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liver disease, alcoholism, pregnancy, intestinal obstruction.
LIVER EXTRACT:
NH Liver extract being biological product, it is not stable purified liver preparations
CHNH cONH-CH;CHCOOH contain vitamin B12 crude liver contains folic acid and vitamin B12. The injection of liver
CooH
extract is painful. Due to disadvantages of liver preparation being not so effective the liver
(siructure of Folilc Acid)
extract preparations are not used.
Dosage: Pregnancy: Orally, IM. IV, 08 mg daily ; orally 5mg OD.
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IRON
Megalobiastic anaemia : Adult child Orally. IM, IV Img daily for 4 to 5 days
It is a metallic element found in certain minerals, in nearly all soils, and in mineral waters. it
Macrocytic anaemia : Img daily for 4 to 5 days.
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is an essential constituent of hemoglobin, cytochrome, and other components of respiratory
BRAND NAMES: Folic acid : Tablet Folacid, Folib, Folix, Folson, Folictin, Folinal 5mg folic enzyme systems. its chief functions are in the transport of oxygen to tissue (hemoglobin)
acid tablets. and in cellular oxidation mechanisms. depletion of iron stores may result in iron-deficiency
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Contraindications: Hypersensitivity, uncorrected pernicious anaemia, vitamin B12 anemia.
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deficiency anaemia. Iron absorbed from the intestine is stored as ferritin in intestinal epithelium or transported
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Side effects : Flushing, Bronchospasm, Oral folic acid is non toxic. in plasma as transferrin. erythroid progenitors obtain iron for hemoglobin synthesis from
plasma transferrin coming from the intestine or from recycling of senescent erythrocytes by
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Pharmacokinetics: Orally onset action 15 to 20 minutes peak concentration 30 minutes to 1
macrophages in bone marrow, spleen and liver. iron that is in excess for that required for
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hour, metabolized by liver, excreted in breast milk, excreted in urine.

hemoglobin production is stored in macrophages as ferritin. excess iron is complexed to
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Symptoms of folic acid deficiency:
phosphate and hydroxide to form hemosiderin. these stores can be released from
9Symptoms of deficiency are glositis, enteritis, diarrhoea, steatorrhoea.
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8
PU A Toxt Book of Pharmacology- Drugs Affecting on Hematopoietic Systems
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macrophages in times of need (increased erythropoiesis),
1with ferritin being more soluble
Ferous gluconate: Adult: Orally 200 to 400 mg three times a day.
Child 6 to 12 year age
and readily available compared to the insoluble hemosiderin. orally 300 mg T.I.D. child below 6 year age : 100 mg orally three times a day.
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The most commonly used foms of iron are ferrous sulphate, ferrous gluconate and ferrous entraindications Hypersensitivity, cirrhosis of liver, peptic ulcer disease.
:
fumerate tablets.
Nausea, vomiting, constipation, black and red terry stools, transient
Ph
Ph
Ph
Side effects :
discolouration of teeth, eye

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eruloplasmin Transfemin
(needs cu) ecepio Pharmacokinetics: When administered orally it is excreted in urine, feces, skin, breast milk,
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iron absorption
Macrophage Eyro
gennos
corsses placenta enters in blood stream.
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Hom o Apotransfemin
The structures of different forms of iron salts used

are as under
Feroportin
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Intestinal men Hemoglobin
produclion
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c
Ferous umarate) C4 H2 Fo O4
Sage
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Recent RBCS II. Ferrous sulphate = FeSO4:7 H20
Hephaes Transferrin
INTESTINE
heeds, Cu BLOOD BONE MARROW
IIL.
Fig.22 Process of iron absorption
AERROUs sULPHATE, FERROUS GLUCONATE AND FERROUS FUMARATE HOCH

Mechanisn of action: Oral administration and parenterally given replace iron required for
OH Fo:2 HO
red blood cell development release of energy and oxygen transport. Iron is carried to the HOH
bone marrow by transfer, it is changed into haemoglobin. It is useful in iron deficiency
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anaemia. It is estimated that ferrous sulphate contains 209% elemental iron, ferrous gluonate Ci2 Hz Foo14: 2H20
4, OH
Ferous Guconate
contains 12%, ferrous fumarate contains 33 percent of elemental iron.
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When iron compounds are given by mouth (orally) for treatment of anaemia it may
hdications : Iron deficiency anaemia, Iron deficiency in pregnancy.
take three months for the hemoglobin to reach normal (level) value. Treatment of severe
Desage: Orally 300 to 600 mg per day in divided doses in pregnancy.
anaemia may be continued upto six months. In iron deficiency anaemia iron provides the
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Jron deficiency anaemia : Ferrous fumarate adult 200 mg orally three times a day child 3 Keystone for the arch' for the hemoglobin molecule.
mg per kg weight per day in equal doses thrice daily infant : oraly 10 to 25 mg daily in 3 to
Ph
Ph
Ph
4 doses.
Tosy of Iron/Iron poisoning.
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The ingestion of excess amount of iron cause gastric haemorrhage, circulatory collapse
:
Ferrous sulphate Adult: orally 200 mg to 600 mg per day in equal three divided doses, 8 and
finalty death. Fatal poisoning occurs in children when
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taken iron table by mistake attracted by
hourly. colours of tablets and presume as sweet tablets. In case of considered as toxic,
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treatment of
Child: 6 to 12 years orally 600 mg per day, 200 mg three times a day. poisoning should be started immediately.
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Drug Interactions : Decrease absorption of
iron preparations by antacids, tetracycline,
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vitamin E. In the presence of iron the absorption

of drugs is decreased such as:
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PU A Text Book of Pharmacology-ll 101
100 Drugs Affecting on Hematopoletic Systems
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chloramphenicol, vitamin
penicillamine, methyldopa, levadopa, quinolines. The drugs like Physiological effects of erythropoietin
Cincrease absorption of iron. Erythropoietin is essential to the production of red blood cells
because it is required for
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Brand names: Iron: Capsule, Tablet, Syrup. Autrin, Atofer Z, Carboz, CFE, Dexorange, erythroid progenitor cells in the bone marrow.
survival, proliferation, and differentiation of
receptor for erythropoietin is
Ph
Ph
Ph
Fefol Z, Globac, Glob up, Haemup, Vitcofol capsules, Tablets iron. in the later stages of erythrocyte differentiation, the
downregulated and the hormone no longer necessary for cell survival.
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Precautions for patient
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Patient should not take overdose of iron preparation than prescribed, iron poisoning Low oxygen carrying Kidney increases
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secretion of EPO
)
capacity of blood
may occur.
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Iron preparations will hange stools colour dark green or black. Decreased tissue
Increased EPO
stimulates production
To swallow capsule, tablets of iron as a whole, not to break or crush. OryEenaton of red blood cells
Normal RBC
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Anemla
Keep out of reach to children, attracted by colour children may consume iron tablets LowRBC Effect of Erythropoietin on RBC Numbers
Concentrafon
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by mistake considering it as sweets, poisoning may develop. Concentratfon
After taking iron preparation for 15 minutes atleast donot take rest reclining position Fig, 2.3 Process of Production of RBC
to avoid corrosion of oesophagus. Red blood cells deliver oxygen to all tissues and when red cell numbers are reduced or
To keep iron preparations out of reach of children strictly.
abnormal a condition called anemia - tissues are deprived of
oxygen. anemia can result
destruction of red cells due
Treatment of Overdose : Give eggs, milk until lavage can be done. induce vomiting from broad range
a of problems, for example from hemorrhage,
to autoimmunity, or interference with cell production associated with cancer
Note: There is no substitute of iron salts for one and another. As 300 mg of ferrous fumarate
contains about 100 mg of elemental iron, ferrous sulphate 300 mg contains about 60 mgof chemotherapy. as depicted below, anemia leads to hypoxia within the kidney, which
triggers additional interstitial cells there to start secreting erythropoietin. increased
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iron, ferrous gluconate 300 mg contains about 35mg of elemental iron.
secretion of erythropoietin enhances and accelerates the production of new red blood cells
Note :Several ases of accidental poisoming zwith sugar coated (iron) ferrous sulphate, tablets have
from their progenitors.
been reported in children, twho twere fatally poisoned. Death occured due to ingestion of over dose of
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ferrous sulphate. Poisoning within 5 hours afier ingestion of tablets of ferrous sulphate, have ben PHARMACOLOGY OF ERYTHROPOIETIN (EPO)
reported. It is a growth factor produced in the kidneys that stimulates the production of red blood
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ERYTHROPoIETIN: Erythopoietin is a protein hormone essential to production of red cells. It works by promoting the division and differentiation of committed erythroid
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blood cells (erythrocytes), which themselves deliver oxygen to all tissues in the body. This progenitors in the bone marrow.
hormone is synthesized in the kidney and its secretion is regulated by the amount of
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Mechanism of action: Erythropoietin or exogenous epoetin alfa binds to the erythropoietin

oxygen delivered to that organ. Erythropoietin was one of the first drugs produced through receptor (EPO-R) and activates intracellular signal transduction pathways. Upon binding to
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recombinant DNA technology and is widely used in conditions where red blood cel EPO-R on the surface of erythroid progenitor cels, a conformational change is induced
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production is deficient which brings EPO-R-associated Janus family tyrosine protein kinase 2 JAK2) molecules
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into close proximity. JAK2 molecules are subsequently activated via phosphorylation. The
signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the
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EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors
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102 PU A Text Book of Pharmacology-l
Drugs Affecting on Hematopoietic Systems 103
to activate target genes involved in cell division or differentiation, including the apoptosis Thromboplastin
Tissue platelets
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inhibitor Bc-x. The inhibition of apoptosis by the EPO-activated JAK2/STATS/Bcl-x
pathway is critical in erythroid diferentiation. Via JAK2-mediated tyrosine Calcium
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phosphorylation, erythropoietin and epoetin alfa also activates other intracellular protins Prothrombin Thrombin
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involved in erythroid cell proliferation and survival.

Indications: It is Indicated in adult and paediatric patients for the: Chronic Kidney Disease Fibrinogen Fibrin (clot)
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(CKD).
Thromboplstin is formed due to damage of platelets and tissue. Thrombolplastin in the
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Uses: It is used in following conditions: presence of calcium is converted to prothrombin which in the presence of calcium
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It is used in the treatment of anemia due to Chronic Kidney Disease (CKD) in patients on converted to thrombin. The thrombin activates fibrinogen to form fibrin. The fibrin fromed
dialysis and not on dialysis. enmesh red blood cells and other cellular elements which forms a clot (blood clot)
Acting Drugs (Local Haemostatics
c
c
It is used in the treatment of anemia due to zidovudine in patients with HIV-infection. () Local
It is used in the treatment of anemia due to the effects of concomitant myelosuppressive 0 Adrenaline produces vasoconstriction when applied locally. It increased coagubility
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chemotherapy, and upon initiation, there is a minimum of two additional months of of blood during emotions, stress, and endogenous adrenaline liberation. (ii) Sodium
planned chemotherapy. alginate is obtained from sea weeds algae namely laminaria cloustoni is used as local
It is used in the reduction of allogeneic RBC transfusions in patients undergoing elective, haemostatic. (i) Oxidized cellulose is prepared by the nitrogen dioxide oxidation of
noncardiac, nonvascular surgery. surgical gauze or colton. Its haemostatic action depends upon the formation of artificial
dlot. It is used for the control of haemorrhage in surgical procedures. It is applied dry in the
Brand name: Abseamed Injection, solution, 10000 IU/1.0m, Intravenous; Subcutaneous
form of cotton pads, gauze strips or pledgets. (iv) Gelatin sponge: Gelatin sponge is
2EICOAGULANTS prepared by heating gelatin containing small quantity of formalin, whisking to a porous
foam, freez drying, packed and steriliseed by dry heat. Absorbable gelatin sponge is used as
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Koagulants are the drugs which promotes clotting. These drugs are used in a hemostatic. When applied to bleeding surface a clot is rapidly formed.
Uáemorrhagie states. Coagulation is the process of transforming a liquid into solid, Local haemostaties are also called as styptics.
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especially of the blood and it means blood clotting. Coagulants are classified as
Replacement of Clotting Factors
(9 Local acting : ) Adrenaline (i) Gelatin spongue (ii) Sodium alginate Giv) Oxidised
Transfusion of whole human blood, horse serum which contains thrombin and
cellulose.
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prothrombin, they replace the clotting factors which are deficient. Fresh whole blood or
(i) Replacement of clotting factor: Whole blood transfusion, vitamin K, calcium blood plasma provides all factors required for coagulation and is best treatment/therapy
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Ph
Cin) Antiheparin acting drugs : Protamine, toluidine blue, Hexadimethrine bromide. for deficiency of any clotting factor. Coagulen is prepared from platelets and tissue extracts,
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and vitamin K can induce clotting. Other drugs used to restore haemostasis are
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Mechanism/Process of clotting Vitamin K: It is a fat soluble dietary vitamin required for the synthesis of clotting factors.
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The mechanism of clotting involves the following sequence of reactions Phylloquinone is the major form of vitamin K. It is found in plants. The basic function of
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vitamin K is in the blood clotting process. It is required for formation of prothrombin by
liver. Prothrombin is a normal constituent of blood, when injury occurs it helps cloting of
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blood on contact with air. Vitamin K was called as Koagulation vitamin (Vitamin K). In
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PU A Text Book of Pharmacology-!
Drugs Affecting on HematopoleticSystems
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1939 similar vitamin was prepared 105
from alfa alfa grass and
sardine (sea fish) meals vitamin K was called as vitamin K1,
prepared was labelled as K2, from
prepared and is labelled as vitamin K3. synthetic compounds Side effects: Headache, with large doses brain damage occurs, nausea, skin rash, urticaria,
y
hemolytic anaemia, hyperbilirubinemia.
Pharmacokinetics: It is metabolized in liver, excreted in urine.
Ph
Ph
Ph
PHYTONADIONE (Vitamin
K): Vitamin K1, Phytonadione is Drug Interactions: Decreased action of oral anticoagulant drugs.
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pbtained from plants ie. alfa fat soluble vitamin. It is

alfa grass. It is needed for Brand names: Vitamin K: Tablet Cadisper C, Gystat, Kaplin,Stypindon tabletss
blood clotting.
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Phytonadione drug vitamin K1 is fat soluble Precautions for patient

vitamin which is required for blood
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cdotting, factors I, VIL,
D X factors of blood clotting. To take dietary sources for vitamin K like spinach, tomatoes, coffee, liver, lettuce.
Patient should not take any other medicine than prescribed.
Decarboy
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prothrombin Prothrombln
FIBRINOGEN: The fraction of human plasma fibrinogen is used to control bleeding in
or VIt, IX,X or Vil, Ix, X haemophilia, antihaemophilic globulin (AHG) deficiency.
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LVER
Vitamin KHindependent factors Tissue factors
Plat elet fac tors
PROTROMEIN
Vitamin KK
Factor Xa
Vitamin K
hydroquinone Circulation
epoxide THROMBIN
COAGULATION
FIBRINOGEN FIBRINOGEN
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INSOLUBLE
Plasma protein CLOT
Blocked by oral anticoagulants Many of the clotting factors are proteases
NAD
NADH
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Nicotine adenine dinucleotide
Fig. 2.5. Role of fibrinogen in the process of coagulation
Fig.2.4 Mechanism of action of oral coagulants Dosage: Adult 0.5 gm intravenously
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Indications : Prevention of hemorrhagic disease of new borne, vitamin K malabsorption, Rutin:It is a plant glycoside. It is used to reduce capillary bleeding. It is administered in
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hypoprothrombinemia the dose of 60 mg orally twice to thricea day.
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Available: Tablet Cadisper C containing menadione sodium bisulphite 20 mg, methyl

Dosage: Haemorrhagic disease in new borne : Newnates SC/1M 0.5 to 1mg after birth
hesperidin 40 mg, Rutin 60 mg. vitamin C 100 mg adrenochrome monosemicarbazine
-
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repeat after 6 to 8 hours if required. mg
Img, dibasic calcium phosphate 100
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Hypothrombinemia caused by vitamin K malabsorption. Adult: Orally or intra-muscular 2

ETHAMsYLATE : It is used to reduce capillary bleeding when platelets are adequate. Itis
to 25 mg. Child : by mouth or 1M injection 5 to 10 mg Infants:Oraly or 1M injection 2 mg
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used in the treatment and prevention of capillary bleeding in case of menorrhagia, malena,
Lontraindications : Hypersensitivity, severe liver disease, pregnancy last few weeks)
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hematuria, epistaxis and after tooth extraction, haemoptysis, haematemesis, post abortion,
post partum haemorrhage.
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106 PU A Toxt Book of Pharmacology Drugs Affecting on Hematopoietic Systems 107
Dosage: Adult 250 mg to 500 mg three times a day.
reticuloendothelial system. In large doses, protamine sulfate may also have an
y
Side effects: Headache, nausea, skin rash, independent-however weak-anticoagulant effect.
Hypotension transient with ntravenous
injection.
Action: Protamine sulphate binds heparm by making it ineffective.
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Ph
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Conlraindications: Hypersensitivity, pregnancy,
lactation, actute porphyria. Indications: Antidote for heparin, Heparin overdose.
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Brand names: Ethamsylate: Tablet, Injection

Cosklot, Alstat, Dicynene, Ethaclot, Dosage: Adult and child 1 ml of protamine sulphate neutralize the effect of 1000 1U of
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Ethamstat, Ethasyl, Zylate 250mg, 500nng
tablet, lInjection 250mg per ml. heparin circulating in blood, (Slow IV).
ALCUM
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DOBESILATE: It acts on capillary

walls by regulating the impaired Contraindications :Hypersensitivity, use with care in pregnancy, lactation, children.
physiological functions, it increases permeability
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and decrease resistance, it increases side effects : Vomitting, nausea, loss of appetite, skin rash, urticaria, anaphylaxis,
indirectly lymphatic drainage due to which oedema
is reduced. It opposes the breakdown pulmonary edema, dyspnea hypotension, bradycardia, circulatory collapse.
of collagen and reduces plasma and blood
hyperviscosity improves blood flow in blood
Pharmacokinetics: Onset action (IV injection) 5 minutes, duration of action 2 hour
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circulation and tissues.
excreted in urine.
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Indications: Post thrombic syndrome, treatment of
primary and secondary vericose veins. Brand Names: Protamin : injection Prota, Protamine sulphate, Newtain 50mg per Sml
Dosage: Adult orally 500 mg to 1gm once
daily with meals. For few weeks to several injection per vial.
month according to the disease, treatment/therapy.
Miscellaneous drugs : Congored, antibiotics penicillin and streptomycin, ACTH, and
Contraindications :Hypersensitivity, pregnancy, lactation.
cortisone also induce clotting.
Side effects : Nausea, voimting diarrhoea, skin
rash, fever.
Brand names: Calcium Dobesilate: Capsule Dobest, Dobium,
Caldob, Dobesil 500mg capsules.
Vasoflo, Doxium 500m, 24ANTICOAGULANTS
Anti coagulants are the drugs which prohibit (check, prevent) the process of clotting
Adrenochrome mono semicarbazone
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These anticoagulants are classified as
It reduces capillary fragility, controls
oozing from raw surfaces, micro vessel bleeding.
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Indications: Hematuria, epistaxis, retinal haemorrhage, secondary bleeding
from wounds.
Dosage: Adult 1 to 5 mg orally, or by Intramuscular injection.
USED IN VIvo DRUGS USED IN VITRO
Contraindications : Hypersensitivity. Use with precautions in pregnancy,
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lactation, elder A. Heparin, low molecular weight heparin 1. Sodium citrate
persons. 2. Soduim oxalate
Heparinoidss-Heparan sulphate,
Ph
Ph
Ph
PROTAMINE SULPHATE: It is a heparine antagonist, a low 3. Ethylene diamine
molecular weight protein. It Danaparoid- Ancrod, lepinudin. tetra acetic acid
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is used as antidote for heparin in uncontrolled bleeding. (EDTA

B. Coumarin derivatives:- Dicoumarol, 4. Sodium edetate
Mechanism of action : It binds heparin sodium by making it ineffective
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and is used in warfarin soduim, Ethylbiscoumacetate.
Heparin overdose. It is a highly cationic peptide that binds to either
rm
heparin or low
molecular weight heparin (LMWH) to form a stable ion pair, which Indanediones:-Phenindione, Diphenadione.
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does not have
anticoagulant activity. The ionic complex is then removed and broken
down by the
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109
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108 PV A Text Book of Pharmacologyl well
effective (ineffective). It is
Metabolism: Heparin after oral administration is not
HEÉPARIN Heparin in a mucopoly sacharide.
t cansists.os hexosamine and hexuronic metabolised in liver by an
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absorbed by subcutaneous and intramuscular injections. It is
acid molecules esterified with sulphuric acid, The contents of sulphuric acid esterified is
enzyme called as heparinase. It is excreted in urine.
Ph
Ph
Ph
very high. Heparin carries strong electronegative charge and is the strongest organic acid
present in the body. Kdverse effects (Toxicity) of Heparin
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is most serious complication of

heparin.
Heparin was discovered in 1916 by Mclean in the liver as a powerful anticoagulant. It 1. Due to over dose, danger of bleeding
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name Heparin was named by Howel and Holt in 1918. It was named as Heparin because it Hematuria occurs.
of heparin.
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was obtained from liver. It has been clinically used in 1937 when its sufficient purification 2. There is transient and reversible alopecia on prolong use
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state was achieved. 3. There are allergic and anaphylactic reactions.
doses.
Heparin is also obtained from lungs and intestinal mucosa. Heparin is present in all 4. On long term use of heparin osteoporosis may develop with higher
number of platelets is reduced.
tissues containing mast cells. In mast cells it occurs as a bigger molecule, molecular weight 5. There is occurence of thrombocytopenia due to which
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75000 and is losely bound to the gramular protein. Commercially heparin is produced from such condition low molecular
There may be bleeding from small capillaries. In
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ungs and pig jntestinal mucosa. Heparin is released from mast be stopped because
OX cells during weight heparin are not safe in such patients. All drugs should
anaphylactic shock corticosteroids may be
any drug may cause/develop this condition. Adrenal
Mechanism of action : Heparin prevent clotting both in VTVO and vitro. It does not inhibit administered.
(stops) prothrombin synthesis. Heparin has a strong electronegative charge so due to this it dialysis procedure,
Indications Heparin is used as anticoagulant in transfusian ,and
:
forms a complex with thromboplastin with the help of blood plasma, and inhibit conversion embolic onditions, deep vein thrombosis, open heárt surgery, disseminated
thrombo
of prothrombin to thrombin. The mechanism of action of heparin is ATil-depedent. intravascular clotting syndrome, myocardigtigfarction.
Intrinsic Extrinsic
Dosage: Deep vien thrombosis and myocardial infarction.
U 12
Pathway Pathway hour or deep sub cutaneous injection 25000
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Adult: TV 5000 to 10000 units every 4 to 6
Factor Ka Heparin to 24 hourly.
ProthromblnThrombin
Children 50 to 100 units per kg body weight every 4 to 6 hours.
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Fibrinogen Fibrin Open heart surgery: Adult 1V infusion 150 to 300 U per kg body weight.
Contraindications: Hypersensitivity, bleeding disorders, hemophilia, peptic ulcer disease,
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Clotting severe hypertension, piles, thrombocytopenia, threatened abortion, tuberculosis, chronic
alcoholics, aspirin and other antiplatelet drugs. In case of pregnancy it is clearly indicated if
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Fig. 2.6. Mechanism of action heparin taken near delivery there may be excessive haemorrhage, elderly.
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It acts mainly by accelerating the rate of the neutralization of certain activated coagulation to over dose, transient and reversible alopccia, osteoporosis,
Side effects : Bleeding duenausea,
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factors by antithrombin, but other mechanisms may also be involved. The antithrombotic hypersensitivity, vomiting, cramps,
fever, chills, hepatitis, abdominal hematuria,
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effect of heparin is well correlated to the inhibition of factor Xa. Heparin is not a thrombocytopenia, skin rash, urticaria.
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thrombolytic or fibrinolytic. It prevents progression of existing clots by inhibiting further
clotting. The lysis of existing clots relies on endogenous thrombolytics.
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Systems
Drugs Affocting on Hematopoietic
PV A Toxt Book of Pharmacology-l
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110 surgery, total hip
in hemodialysis hip fracture
Indications : Prevention of vein thrombosis
amacokincties &
peak concentration 5 minutes, duration of action 2 to 6 hours.
TV
replacement.
Subcutaneously onset 20 minute, duration 8 to 12 hours, does not cross placenta, breast
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Dusage: Venous thrombosis prevention
milk not altered, excreted inurine. daily for 1 week.
Adull:Subcutaneous injection 750 anti Xa units twice
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Ph
prug Interactions: Heparin decrease action of corticosteroids, increase action of heparin.
Hemodialysis : IV 2400-4800 anti Xa units predialysis.
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The action of heparin is increased with oral anti coagulants, Asprin salicylates) steroids, 12 days post
750 anti Xa twice daily for 10 to
dextran. Hip fracture surgery : Adult: subcutaneously
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Brand Names: Heparin : Injection : Heploc, Unihep, Caprin, Beparin, Declot, Heparin, operatively.
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thrombocytopenia.
Inhep, Thromboparin 100, s000 IU per ml. Side effects: Hypersensitivity, skin rash,
leukemia, severe
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Trcatment of overdose : Discontinue use of heparin, administer protamine sulphate Contraindications Hypersensitivity to this drug, hemophilia,
hypertension, cardiac disease, purpura.
well absorbed. Peak
HErARINOIDS (Substitutes of Heparin) Pharmacokinetics: Danaparoid when administered subeutaneous is
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hours plasma half life 2 to 3 hours, excreted by kidneys.
These are sulfated polysaccharides having strong negative charges. Their anticoagulant plasma concentration is attained 4
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(Salicylates).
action depends on the degree of esterification with sulphuric acid. Drug Interactions: Increased risk of bleeding with oral coagulants, Aspirin
Heparan sulphate : It is heparine like natural substance found in cell surface and Treatment of over dose Protamine sulphate 1% intravenously.
:
intracellular surface matrix in many tissues. Heparin sulphate is less potent anti coaguant
than heparin. ANCROD It is an enzyme obtained from malayan pit viper toxin. It degrade
:
fibrinogen to
DANAPAROID: Danaparoid is a preparation containing mainly heparan sulphate unstable fibrin which is taken up by reticulo endothelial cells, fibrinogen gets depleted and
obtained from pig, gut mucosa. It is used in cases with heparin induced thrombocytopenia. heparin like effect apparently results. It is administered slowly by infusion 20 per kg in6
It is a low molecular weight heparin it acts as anti coagulant. hours for deep vein thrombosis in patients who develop thrombocytopenia.
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Mechanism of action : It prevents conversion of fibrinogen to fibrin and prothrombin to Brand Name: Orgaran 750 unit Intravenous; Subeutaneous
thrombin. In the coagulation cascade leading to clot formation, factor X and factor II
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requires activation to promote subsequent conversion of fibrinogen to fibrin. The LEPIRUDIN: tis a preparation of hirudin, which is a polypeptide anticoagulatn secreted
mechanism of action of danaparoid resulting in anticoagulant and antithrombic effects by salivary glands of leech which act directly by inhibiting thrombin formation. It is
involves a complex interaction between 2 components, factor Ila and in particular, factor Xa
advised to or recommended to patient with heparin induced thrombocytopenia.
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Via binding to antithrombin and inducing a conformational change. It enhances and
Mechanisn of action: It forms a stable non-covalent complex with alpha-thrombin, thereby
catalyzes the binding of factor Xa to antithrombin, which induces antithrombin-mediated
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Ph
Ph
abolishing its ablity to cleave fibrinogen and initiat the clotting cascade. The inhibition of
inactivation of factor Xa. This leads to inhibition of thrombin generation and subsequently
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thrombin prevents the blood clotting cascade.

thrombus formation. Danaparoid also weakly enhances antithrombin IlIl and heparin
Indication: For the treatment of heparin-induced thrombocytopenia.
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cofactor II inactivation of factor Ia. There is evidence that danaparoid also suppresses the
Brand Names: Refludan powder 50 ng Iml Iv.
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activation of factor IX which, in conjunction with simultaneous inhibition of factor X, may

lead to antithrombic effects
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PVA Text Book of Pharmacology-
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Drugs Affecting on Hematopoletic Systems 113
coUMARIN DERIVATIVES
Warfarln
DICOUMAROL (BISHYDROxY coUMARIN):
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Orally it absorbs slowly. Its metabolism Oxidlzed vit K
reducfase
depends on the dose. It is used alone or with heparin in the treatment of post operative Oxoen Functlonal form
Prohrombin
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Ph
thrombophelebitis and pulmonary embolism. It is used in cononary occlusion. This VitK
Cervoyese
F
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medicine is contraindicated in persons with liver disease, renal function impairment and
Reduced vt K FA
who are bleeding from any case/ disease. First day administer dose 5 mg per kg of body
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Inactive form
weight 200 to 300 mg oraly of bishydroxy coumarin is administered check prothrombin prothrombin
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time if found normal omit the dose or reduce dose. In adult men the maintenance dase is 50 FVIl
FIX
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mg to 75 mg daily. The colour of urine patient may be observed because hematyria may FX
occur which is most common form of bleeding.

Fig. 2.7 Mechanism of action warfarin
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It inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K
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(vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the
OH H
Bishydronycoumain (Dicoumaro Nterminal regions of vitamin K-dependent proteins, this 1imits the gamma-carboxylation
The toxic dose/ fatal dose of bishydroxy coumarin is 40 mg per kg body weight. and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of
Intravenous fatal dose of dicoumarol cause death in animals through damaging liver. It is available vitamin K-dependent coagulation factors It, vIL, IX, and X and anticoagulant proteins C and
S
assolourless crystalline solid insoluble in water. When administered orally it causes Gastro is inhibited. Depression of three of the four vitamin K-dependent coagulation factors
Cfactors 1I, VIL, and X) results in decreased prothrombin levels and a decrease in the amount
ntestinal disturbances.
of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
NARFARIN SODIUM:It is a white crystalline powder soluble in water. The action of
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warfarm is similar to bishydroxy coumarin. It acts as an anticoagulant.
Indications: Post cardiac valve replacement, pulmonary embolism venous thrombosis,
myocardial infarction.
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Contráindication Hypersensitivity, pregnany, lactation, Hepaticdisease, renal
O.Na. CH2f-CH impairment, cerebrovascular haemorrhage, peptic ulcers disease, severe hypertension, used
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Warlartn Sodium (Coumadin Sodum) with precaution in elderly, alcoholism.
Warfarin is used extensively as a rodenticide, because it produces fatal internal bleeding in Dosage : Adult: Orally 10 to 15 mg daily for 3 days monitor prothrombin time daily.
Ph
Ph
Ph
rodents/animals. Side effects : Vomiting, nausea, anorexia, stomatitis, anorexia, hepatitis, hematuria, skin
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Mechanism of action : It interferes indirectly with blood clotting. It depresses hepatic rash, urticaria, fever alopecia, (eucopenia, eosinophilia, haemorrhage).
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synthesis of vitamin K dependent coagulation factors in liver. Pharmacokinetics: Orally onset action 12 to 24 hours peak plasma concentration 1 to 2
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days, duration of action 3 to 5 days metabolised in liver, crosses placenta, excreted in urine.
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Dug Interactions Increased action of warfarin with drugs like, chloramphenicol,
disuliram, metronidazole, sulfonamides, chloral hydrate, phenyl butazone, isoniazid.
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114 A Toxt Book of Pharmacology-l/
Action of warfarin is decreased by drugs like rifampin, barbiturates, griseofulvin oral ANTICOAGULANTS
of ammonium oxalate and four parts of
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contraceptives, estrogens. Double Oxalate : Mixture contains 6 parts 0.8
Use 2 mg per ml of blood i.e. it contains 1.2 mg of ammonium oxalate
Brand names: Warfarin Tablet Warf, Uniwarfin, Sofarin, Img, 2mg, 5mg tablets.
: potassium oxalate.
Ph
Ph
Ph
Used for haemoglobin estimation, blood
Ppsutions for patient mg of potassium oxalate per ml of blood.
leucocyte count, ESR. Double oxalate
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Touse soft bristless tooth brush to avoid gum bleeding. grouping. packed cell volume, RBC count, total
7 be used for blood urea, serum potassium estimation.
mixture cannot
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Avoid use of razors
citrate is used for study E.S.R.
Trisodium Citrate :3.8 % aqueous solution of trisodium
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To avoid smoking, as smoking required increased dose requirement, leading to side

10 to 20 mg per ml of blood is used.
Sodium fluoride: It is used for blood sugar estimation
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effects.
EDTA (Ethyl diamine tetra acetic acid). The dipotassium or disodium salts of EDTA are
For taking treatment for any cause inform the dentists and other physician, doctors for blood study, hemocrit
used in the concentrations of lmg per ml. of blood used
regarding the anticoagulant drug intake. blood.
Anticoagulants and preservatives solutions used as preservative for
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To avoid playing foot ball, hockey, skiing, work with heavy machinery, dangerous citrate and dextrose in
Sterile pyrogen free solutions of sodium citrate or sodium acid
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work that may cause injury.
water for injection are suitable solution for blood preservation.
To take vitamin, mineral rich diet.
Treatment over dose : Administer vitamin is prepared as per
ACD (ACID CITRATE, DEXTROSE SOLUTION): The solution
K.
ETHYL BIScOUMA ACETATE (TROMEXAN) sodium citrate 22 grams, citric acid monohydrate 8 gram dextrose monohydrate for
formula
is a synthetic anticoagulant of the coumarin series. It was synthesized by Link and
Tt 1.V use 24.5 grams, water for injection 1000 ml. The solution is prepared by dissolving
100 ml of whole
his associates in 1942. It is a colourless, crystalline powder. It is soluble in water. It is less above contents in 1000 ml water for injection. Volume for collection of
potent than bishydroxycoumarin. It is rapidly absorbed and rapidly excreted. It has a short human blood is required 15 ml.
The solution is used to prevent coagulation of blood which is collected for blood
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duration of action. It can be administered to patient of thromboembolic disease for long
period. Dose is 600 mg to 900 mg daily in divided doses-orally. When dose is not properly transfusion. Dextrose delays haemolysis of red blood cells or red blood corpuscles. The
other formula is citrate phosphate dextrose solution. Which is required 14 ml for collection
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regulated severe bleeding can occur.
of 100 ml of blood.
IN VITRO ANTICOAGULANTS soDIUM EDETATE: It is used as anticoagulant 2mg in Iml of blood and sodium oxalate
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10mg per ml blood, used in blood taken for laboratory investigations.
These compounds are chelating agents like citrates, oxalates, filuorides, Ethylene
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Ph
Ph
diamine tetra acetic acid (EDTA). These compounds act by removing calcium ions. These
2:5 ANTIPLATELETDRUGS
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are used to make blood suitable for transfusion and in vitro to preserve blood.
Mechanism of action: It is an essential factor of blood coagulation, when anti coagulants Antiplatelet are drugs which interfere with platelet function and are used as prophylaxis of
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like oxalate salts are added to blood calcium oxalate is formed. This calcium oxalate formed thromboembolic disorders. The different drugs act differently to interíere with platelet
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precipitated in an insoluble form, thus blood lacking calecium ions is failed to clot. functions. The important drugs which are used as antiplatelet are:
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6 Aspirin
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Gi) Dipyridamole
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Drugs Affocting on Hematopoletic Systems 117
116 PU AText Book of Pharmacology-
clottin
(id Clopidogrel ndications: Myocardial infarction, prophylactic in increased risk of blood
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coronary, bypas, transluminal angioplasty.
(iv) Ticlopidine
Dosage:Bdult orally 50 to 100 mg daily or as per requirement
Ph
Ph
Ph
(v) Cilostazol
Hypersensitivity,
Platelet disorders, peptic ulcers bleeding disorders,
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The common mechanism of action are shown in figure no ontraindications:

haemophilia, pregnancy, asthma, Gastro intestinal haemorrhage.
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Pleque dlarupbon Side effects:Vomiting, nausea, abdominal pain.
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Drug interactions: Action of anti coagulant is increased.

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Tissuo tacto Colagen Zospirin, Mezoral
WES Brand Names: Aspirin ASA 75g, Aspin, Aspirin, Loprin, Delisprin,
:
75mg, 150mg tablets.

Plateletedhesion
DIPYRIDAMOLE : It is a coronary vasodilator and acts as anti-platelet acting dru8
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andsecretlion
dipyridamole inhibit adenosine uptake which produce coronary vasodilation, increases
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Aspirin COx-1
TXA ADP coronary blood flow and oxygen saturation in coronary tissues. it decreases platelets
aggregation by inhibition of an enzyme phosphodiesterase
Clooidroore
Thrombin Platelel recruitment Mechanism of action It inhibits both adenosine deaminase and phosphodiesterase,
nOOUvduon preventing the degradation of cAMP, an inhibitor of platelet function. This elevation in
CAMPblocks the release of arachidonic acid from membrane phospholipids and reduces
GPIbilla actvation
thromboxane A2 activity, It also directly stimulates the release of prostacyclin, which
Cilostazol
Plotelet ag9regation induces adenylate cyclase activity, thereby raising the intraplatelet concentration of cAMP
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and further inhibiting platelet aggregation
Fig. 2.8 Action of Anti-platelet drugs It inhibits adenosine uptake which produces coronary vasodilation. It cause increase
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oxygen saturation in coronary tissue, increase coronary blood flow. It decreases platelet
SPIRIN: These drugs are also called as antithrombotic drugs. in small doses aspirin
blocks platelet aggregtion by irreversible inhibition of the platelet enzyme cycloxygenase, aggregation by inhibition of enzyme phosphodiesterase. It is useful in the treatment of
Angina pectoris.
prevents formation of thromboxane A2. Aspirin prolongs the bleeding time and the efect
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remains for 5 to 7 days in blood. Aspirin in small dose of 40 mg have an effect on platelet Indications: Coronary insufficiency, prevention of transient ischaemic attacks, prevent
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Ph
Ph
myocardial reinfraction, thromboembolism.xith warfarin.
aggregation. It inhibits the release of adenosine diphosphate from platelets and their
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sticking to each other. the aspirin has no effect on platelet survival time and there adhesion Dosage: Transient ischaemic attack: Adult orally 50mg three times a day, not to exceed 400
mg. Dose to take empty stomach 2 hours before meals.
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to damage vessels walls.
Inhibition of platelet adhesion :Adult : orally 50 to 75 mg four times a day in combinatior
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Mechanism of action : Aspirin blocks para impulses in the central nervous system, it
with Aspirin, or warfarin.
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inhibits rostglandin synthests The antipyretic action is due to vasodilation of peripheral
vessels. It decreases platelet aggregation. Aspirin is acetyl salicylic acid and belong to class Contraindications: Hypersensitivity, hypotension, pregnancy, lactation.
ac
salicylate. It directly and irreversibly inhibits the activity of both types of cyclooxygenase
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(COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and
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thromboxanes from arachidonic acid. )

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1118 PV Drugs Affecting on Hematopoletic Systems
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A Text Book of Pharmacology-l 119
Side effects: Vomiting nausea, anorexia, skin rash, flushing, head ache dizziness, syncope, Side effects: Neutropenia, diarrhoea, skin rash, thrombocytopenia, abdominal pain,
fainting. postural hypotension.
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vomiting, nausea head ache.
Pharmacokinetics: Orally peak concentration 2 hour, duration of action 6 hours. There may Brand names: Clopidogrel: Caplor, Clopivas, Zeter, Plavix, Orawis, Orawi, Cloplet,
Ph
Ph
Ph
be delayed therapeutic action and may lake 2 to 3 months, metabolized
inliver, excreted in Clodrel 75mg, 150mg tablets.
bile.
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TICLOPIDINE: It is a potent inhibitor of platelet aggregation induced by adenosine

Brand Names: Dipyridamole Tab Deplatol, Dynacord, Persantin, Thrombonil
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diphosphate and due to collagen arachidonic acid, thrombin, adrenaline and platelet
Cardiwel 75mg, 100mg tablets.
activation factors.
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Irecautions for patient:

Mechanism of action: Ticlopidine inhibit first and second phase of adenosine
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1. P'atient should quit smoking to prevent vasoconstriction.
diphosphate and platelet aggregation effect is induced. The active metabolite of ticlopidine
2. Not to take any other medicines, unless prescribed. prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the
3. To rise slowly from bed, orthostatic hypotension may occur. ADP-mediated activation of the glycoprotein GPib/1la complex. It is proposed that the
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4. Patient should take regular doses, not to skip dose nor to discontinue treatment at his inhibition involves a defect in the mobilization from the storage sites of the platelet granules
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own. to the outer membrane. No direct interference occurs with the GPib/iia receptor. As the
Overdose Treatment: 1LV. Phenylephrine. slycoprotein GPib/1la complex is the major receptor for fibrinogen, its impaired activation
prevents fibrinogen binding to platelets and inhibits platelet aggregation. By blocking the
CLOrIDOGREL: It inhibits platelet aggregation. It is newer congener of ticlopidine.
its amplification of platelet activation by released ADP, platelet aggregation induced by
action last for 7 days.
agonists other than ADP is also inhibited by the active metabolite of ticlopidine.
Mechanism of actio: It prevents binding of adenosine diphosphate (ADP) to
its platelet Indications: Transient ischaemic attack (TIA), coronary artery by pass grafts (CABG),
receptor, impairing the ADP-mediated activation of the glycoprotein GPib/iia complex. It
Secondary prevention of myocardial infarction.
is proposed that the inhibition involves a defect in the mobilization from the storage
sites of Dosage: Adult: Orally 250 mg twice day with meals.
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the platelet granules to the outer membrane. The drug specifically and irreversibly inhibits
the p2y12 subtype of ADP receptor, which is important in aggregation of platelets and Contraindications: Hypersensitivity, liver dysfunctions, duodenal ulcers.
Use with
precautions in lactation, pregnancy elderly, paediatrics. In pregnancy may cause
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cross-linking by the protein fibrin. There is no direct interference occurs with the uterine
GPib/iia bleeding, drug is excreted in breast milk may effect the baby.
receptor. as the glycoprotein GPiib/iia complex is the major receptor for fibrinogen,
its
impaired activation prevents fibrinogen binding to platelets and inhibits, platelet Side effects: Vomiting, nausea, diarrhoea, skin rash,
vertigo, cholestatic jaundice, increased
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aggregation. by blocking the amplification of platelet activation by released ADP, platelet cholesterol.
aggregation induced by agonists other than adp is also inhibited by the active metabolite Pharmacokinetics : Metabolised in liver, excreted
Ph
Ph
Ph
of inurine, feces. Peak plasma concentration
clopidogrel. Fig 1to 3 hour.
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Indications: Atherosclerosis, recent myocardial infarction. Drug interactions: With ticlopidine in presence
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of aspirin i.e. administration of aspirin, anti
Dosage: Adult orally 75mg daily. coagulants there is increased tendency of bleeding.
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Increased effect of theophylline.

Contraindications: Hypersensitivity, peptic ulcers, intracranial haemorrhage, decrease plasma level of digoxin.
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surgery,
hepatic impariment. Brand names: Ticlopidine: Tablet Ticlop,
Tikleen, Tyklid, Tikla, Ticlobest, Ticlopid 250mg
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tablet.
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121
Drugs Affecting on Hematopoietic Systems
PU AText Book of Pharmacology-1
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"plasminogen activators and
drug. Because of these actions, thrombolytic drugs are also called
CILOSTAZOL:It Inhibits Platelet aggregation and is used as anti-platelet
are cyclic AMP (CAMP) "fibrinolytic drugs."
Mechanism of action: Cilostazol and several of its metabolites
Streptokinase (SK), and Urokinase
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phosphodiesterase II inhibitors (PDE II inhibitors), inhibiting phosphodiesterase activity There are three major classes of fibrinolytic drugs:
(UK). tissue plasminogen activator (tPA), Alteplase, While drugs in these three classes all
and suppressing cAMP degradation with a résultant increase in cAMP in platelets and
Ph
Ph
Ph
differ in their detailed mechanisms
blood vessels, leading to inhibition of platelet aggregation and vasodilation. have the ability to effectively dissolve blood clots, they
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Indications:Intermittent Claudication. in ways that alter their selectivity for fibrin clots.
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Dosage: Adult orally initially 50mg twice daily, gradually increase dose to 100 mg twice Tissue factor
Contact activation
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daily half hour before meals. (intrinsic) pathway (extrinsic) pathway

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Contraindications:Hypersensitivity, congestive heart failure. Danagod ourfaco
Trauma
TFPI
Side effects: Vomiting, nausea, headache, dizziness, palpitation, tachycardia, diarrhoea,
rhinitis, flatulence. XII Xila
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Vlla VIN
Pharmacokinetics: Metabolized by liver, excreted in urine, feces. te Tissuo factor Trauma

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X IXa Vila
:
Brand names: Cilostazole Capsule, Tablet Pletoz, Stiloz, Pencil, Cletus 50mg, 100mg Antithrombin
tablet.
Prothrombin (11), Thrombin (lta) Common
Advantages of Antiplatelet drugs. paihwa
1Used in coronary artery disease, unstable angina and prevention of primary and Fibrinogan () Fbrin (la)
secondary myocardial infarction. Activo Prolein C xta XII
2The antiplatelet drugs are used in venous thromboembolism, and peripheral vascular Protain S Cross-linked
fibrin cot
disease to prevent intermittent caudication and reduce incidence of Protoin C Thrombomodulin
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thromboembolism. Also used in cerebrovascular disease, coronary angioplasty,
stents, bypass implants. Fig. 29. Mechanísm of action Fibrinolytics drugs
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The serious adverse effects of antiplatelet drugs are bleeding thrombocytopenia, jaundice
gastro intestinal upset. ne fibrinolytic drugs are described in details:
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Streptokinase (i) Urokinase (i) alteplase
2.6 FIBRINOLYTICS CTHROMBOLYTICS))
STREPTOKINASE :It is a sterile, purified preparation of a bacterial protein elaborated by
Ph
Ph
Ph
The fibrinolytic are the drugs used to decompose thrombi or clot to recanalize
group c (beta) -hemolytic streptocoei. It was discovered in 1933 by tillett and garner which
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obstructed blood vessels mainly coronary artery. These drugs decompose the clot by was derived from bacterial organisms non pathogenic for man which is capable of
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activating the natural fibrinolytic system. dissolving blood clot in vitro
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Thrombolytic drugs disolve blood clots by activating plasminogen, which forms a cleaved
Techanism of action : Streptokinase activates conversion of plasminogen to plasmin
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product called plasmin. Plasmin is a proteolytic enzyme that is capable of breaking cross (fibrinolysin), fibrinolysin (plasmin) breaks down clots (fibrin). Plasmin acts directly on
links between fibrin molecules, which provide the structural integrity of blood clots.
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fibrin breaking it down to form thrombosis. Plasminogen is an inactive molecule that

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122 PV A Text Book of Phamacology-ll Drugs Affecting on Hematopoietic Systems
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becomes activated to plasmin when the Arg/Val bond is cleaved. Plasmin breaks down Indications : Acute myocardial infaretion, pulmonary embolism, acute myocardial
nbrin clots created by the blood clotting cascade. Streptokinase formsa highly specific 1:1 infarction, venous thrombosis.
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enzymatic complex with plasminogen which converts inactive plasminogen molecules into
Dosage: Acute myocardial infaretion: Treatment should be started with in six hours of
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active plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma
onset of symptoms. Intracoronary 6000 IU per minute dissolved in 5% dextrose or normal
proteins. This in turn leads to the degradation of blood clots. Fig. 2.9
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saline. Total dose 10,000 1U per kg body weight. IV 250,000 FU/ 500,000 IU vial dissolve in
ations: Pulmonary embolism, acute myocardial infarction, deep venous thrombosis, 10 ml or 20ml Dextrose 5% or narmal saline administer over 5 to 10 minutes or slow V
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thrombosis of arteries. infusion in 30 minutes.
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Dosage : Acute myocardial infarction: Adult : IV. 750,000

to 1,500,000 IU diluted to a Pulmonary embolism: First day 50,00 IU in 10ml Dextrose 5% or normal soline, IV over
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volume of 45 mi to be given slow IV in one hour. 10 minutes, followed by 300,000 IU. In 200ml 5% dextrose or normal saline in 8 to 12 hours,
Coronary artery thrombi then 50,000 lu daily for 6 to 13 days regularly.
Adult: Intracoronary 20,000 IU stat followed Contraindications
by 2000 to 4000 TU per minute for one hour. Hypersensitivity, severe hypertension, pregnancy, recent trauma,
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Deep vein thrombosis, Pulmonary embolism urinary tract bleeding, liver disease, kidney disease, cerebral embolism, ulcerative colitis,
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Adult : 1.5 million I.U in 6 hours. for pulmonary embolism 100,000 IU per hour for 24 hours chrome obstructure pulmonary disease (COPD).
to 72 hours. For arterial thrombosis 100,000 TU unit per hour for 24-72 hours. Side effecs : Vomiting, nausea, headache, fever, shortness of breath, bronchospasm,
Sontraindications Hypersensitiily EOPD (chronic obstructive pulmonary disease), cyanosis, hypertension, periorbital edema, surface bleeding, low back pain, skin rash,
active bleeding, hepatic urticaria phelebitis at IV infusion site, itching, flushing, decreased hematocrit, anaphylaxis
disease, renal disease, recent major surgery, diabetes mellitus,
ulcerativecolitis severe hypertension, menstrual bleeding, pregnancy. (rare)
Pharmacokinetics: IV: onset action immediate : excred in urine.
ide effects : _Headache, fever, nausea, hypotension, pulmonary oedema, periorbital
oedema, skin rash, urticaria, bleeding, itching, flushing, low back pain, bronchospasm, Drug interactions: The risk of bleeding with anticoagulants, aspirin is increased.
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shortngss of brcath, peritoneal bleeding, phelebitis afIV. infusion site. Brand Names: Urokinase : Injection Uropase, Dabunase, Medinase, Urolyte unikinase
Amacokineties: IV. onset immediate action, duration of action 11 to 12 hours, plasma 250000, 500000, 750000 TU per ml.
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half life 15 to 20 minute, excreted in bile, urine.
Drug interaction : Increased bleeding with Aspirin, indomethacin ALTEPLASE
anticoagulants. : It is tissue plasmogen activator.
It is obtained or synthesized from human
Brand Names: Streptokinase : Injection Eskinase, Prokinase, tissue culture, ie., cultured melanoma cells by DNA technolo8y. It is used
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Kabinikase, STpase, to avoid bleeding
Streptase, Zykinase, 250000, 500000, 750000 1U per ml. caused by streptokinase and urokinase.
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UROKINASE: It is a thrombolytic enzyme. It is obtained Mechanim of action: It produce fibrin conversion of plasminogen to plasmin,
from human urine. It is now able to bind
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prepared from cultured human kidney cels. Urokinase acts on the endogenous fibrinolytic to fibrin, converts plasminogen in thrombus to plasmin.
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system.lit cleaves the arg-val bond in plasminogen to produce active plasmin. It binds to fibrin rich clots via the fibronectin finger-like
plasmin domain and the Kringle 2 domain.
degrades fibrin clots as well as fibrinogen and other plasma proteins.
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The protease domain then cleaves the Arg/Val bond

in plasminogen to form plasmin.
Mechanism of action : Urokinase promote thrombolysis
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)by directly converting Plasmin in turn degrades the fibrin matrix of
the thrombus, thereby exerting its
plasminogen to plasmin, break down clots. Fig, 29 thrombolytic action. Fig. 29.
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Drugs Affecting on Hematopoletic Systems 125
Indícationslysis-of occlusive coronary artery thrombi associated with acute myocardial
(vii) It should be pharmacodynamically, inert having stability and not take part in
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infaretion. ischaemic conditions requiring thrombolysis.
chemical action.
Dosage : Adult: V 100 mg over three hours, administer in hospital only.
(vii) The osmotic pressure, viscosity, pH value of the solution must be identical to the
Contraindications: Ulcerative colitis : Gastro intestinal bleeding, hypertension with cerebro
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vascular haemorrhage, recent trauma, pregnancy, lactation, children.
plasma.
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$ide effects: Skin rash, urticaria, sinus, bradycardia, surface bleeding, PLASMAEXPENDERS
retroperitoneal
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bleeding, intracranial bleeding.
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Brand name: Activase 50 mg. 50ml, Activase RT-PA Inj 29 m. Powder,
for solusíon, iv,
Cathflo 2 mg. Cathflo activase 2.2mg/ml.
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Plasma Expanders Blood and Blood products

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1. Human Albumin
27 PEASMA EXPANDERS 2. Dextran
The plasma expanders are the drugs usually a high molecular weight
dextran which is 3.Hydroxy ethyl starch (1HES
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administered intravenously to increase the decreased plasma volume.
4.Polyvinyl pyrrolidone (PVPp
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The normal plasma volume in males is 39 ml per kg of
body weight, in females 40 ml
per kg body weight. 5. Physiological saline
When the plasma volume of the body is decreased due 6. Gum saline
to dehydration, starvation,
haemorrhagic condition or in some disease plasma
expander are administered
intravenously to maintain volume of plasma and exert colloidal PLASMA EXPANDERS
osmotic pressure. The
plasma expanders are used to cure hypovolemia due to loss of HUMAN ALBUMIN: Human albumin is obtained from pooled human plasma. It may be
blood, blood plasma.
Properties of Plasma Expanders: prepared by precipitation with organic solvents such as alcohol under controlled conditions
of ph, temperature and ionic strength. Antibiotics or bactericide are not added at any stage
Plasma expander should be non toxic and pyrogen fre.
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during preparation of human albumin. The suitable treatment (method) or freez drying is
(i) Plasma expander should not interfere with blood
grouping and cross matching of used to remove residual solvent. The resultant protein is dissolved in waler and sodium
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blood.
caprylate is added to stabilize it to heat at ph 7.0.
iii) It should be cheap, easily sterilizable and stable.
The solution is heated at maintained temperature 59.5C to 60.5C for ten hours to
iv) prevent
Plasma expander should exert colloidal osmotic pressure as is exerted by
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blood transmission of Hepatitis B. Jhe sterilised solution by filteration is filled aseptically
into
plasma. containers which are then sealed to exclude microorganisms. The sealed
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containers are
(v) Plasma expander must be retained in blood circulation, tissues and should incubated for two weeks at 30 to 320C and are checked for the microbial
not act contamination.
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as a diuretic. It should not leak in tissued or rapidly disposed. Human albumin can be used without regard to the patient blood
group and it does not
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It should not be rapidly metabolised, should not readily diffuse into tissue and interfere with coagulation. It is free from the risk of transmitting
serum hepatitis, it is
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should not be rapidly excreted in urine. because the preparations are heat treated. 100 ml of twenty
percent human albumin
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solution, osmatically equal to about 400 ml of fresh frozen plasma or 800
ml of whole blood
The repeated administration of infusion of human albumin has no
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risk of sensitization. The

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26
A Text Book of Phamacology-l Drugs Atfecting on Hematopolotic Systems
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febrile reaction to human albumin
rarely occurs. The human albuin preparation is solution in normal saline. It interfere with cross matching of blood and blood grouping
expensive, and is used as blood derivative.
The solution of PVP is isotonic with plasma.
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eanism of action : Human aibumin exerts
oncotic presure (osmotic pressure) which PVP is used as safe effective replacement fluid for treatment of various shock. In
expands volume of blood circulation
and it
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maintains cardiac output and plasma volume. immediate requirement of blood, it provide support for the blood circulation. It is non
ications : Hypoproteinaemia,
burns, prevention of cerebral oedema, cardio-pulmonary allergic, nontoxic, noninfectious. It should be stressed that this preparation is for emergency
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by pass procedures, Hypovolaemic shock, plasma exchangge tfeatment in situations when whole blood or plasma is not available.
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Dosage: Hypovalaemic shock:
Adult 100 to 200 ml intravenous infusion, child 1 to 2 ml
per kg body weight .V. PHYSIOLOGICAL SALINE (0.9% Sodium Chloride): Physiologic saline has the same
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osmotic pressure as that of human blood. It is useful in emergency as it is isotonic with

Bums: Adult 200 to 400 ml 1st day, intravenous infusion
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first day followed by 100 to 200 blood. It is capable to maintain the raised blood pressure for longer period. It should be free
ml. Children 2 to 4 mi per kg body weight.
trom pyrogens. If the solution contains suspended particle it should not be used, discard the
ontraindications: Hypersensitivity, volume over load, severe anaemia, circulatory failure, solution. Sodium chloride 0.9% solution is also known as Normal Saline. It is most
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renal disease. important salt for maintaing osmotic tension of the blood and tissue.
Side effects : Vomiting, increased salivation, head
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ache, fever, chills, flushing. skin rash, Normal tissue fluids contains about 140 millimoles of sodium ions, and 100 millimoles of
urticaria. pulmnary oedema. chloride ions per litre. Sodium chloride is often given parenterally for the treatment of
Iharmacokinetics: Metabolized as protein energy source. shock and circulatory collapse in association with dextrose IV.
in Addison's disease the patient loses large quantity of sodium chloride in the urine due to
GUM SALINE: It is the preparation having 6 percent the deficiency of adreno cortical harmones, and for such harmones cortisone may be
acacia in normal saline. it has same
osmotic pressure and viscosity as that of blood. it helps to restore administered as replacement therapy or treatment, the additional salt (sodium chloride) is
blood pressure and
viscosity as that of blood. it helps to restore blood pressure for longer necessary to maintain the electrolyte balance of the body. During replacement therapy with
period than normal
saline. the side effects are (i) danger of gum decrease exchange of cortisone, it must be observed and to ensure that due to abnormal retention of sodium,
gases on the surface of
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red blood cells. (i) derangement of live may be caused. oedema may develop. Sodium chloride ina dosage of 10 to 12 grams a day is administered,
by aiding in excretion it is of value in the treatment of bromides and iodide poisoning.
rOLYVINYL PYRROLIDINE (P.V.P.): Polyvinyl pyrrolidone (PVP) is a
high molecular
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weight synthetic polymer. It is prepared by combining acetylene, formalidehyde The dietary intake of sodium chloride is restricted in case of hypertension and oedema
and
ammonia. In the formula * stands for number of vinylpyrrolidone molecules which patients.
are
united If no fluid is taken by mouth, 3.5 litre of normal saline iv is required daily in temperate
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climates.
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Sodium chloride injection is used to cure dehydration. If large quantity is administered may
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produce oedema. Owing to accumulation of sodium chloride in the tissues. Sodium

CH-CH2
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x chloride injecton may be administered intraperitoneally to infants.
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Poynypmolidon PVP)
DEXRANS: t is used as a plasma volume expander. it is used 67% in strength available as
to form a molecule of polymer P.v.P. Some polymers have molecular
weight range from
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dextran 40 injection and dextran 70. dextrans are produced by the fermentation of sucrase
20000 to 80000. PVP solutions are stable, non toxic and non
antigenic, and is used as 3.5%
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Drugs Affecting on Hematopoietic Systems 129
FU A Text Book of Pharmacology-l
by micro organism of strain leuconostoc mesenteroides, followed by hydrolysis and Contraindications Hypersensitivity, renal failure, excessive dehydration, pregnancy,
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fractionation to give dextran with different range of average molecular weight. the dextran active haemorrhage.
injections are viscious solution almost colourless. the dextrans are metabolised as Side effects : Skin rash, urticaria, chills, fever, angioedema, wheezing, dyspnea,
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polysaccharides or excreted and are not retained in the body. bronchospasm, pulmonary edema, vomiting nausea, increase AST, ALT. Osmotic
DEXTRAN-70: It is a sterile solution 6% of dextran-70 (molecular weight 70,000) in nephrosis, hypotension hyponatremia, cardiac arrest, Anaphylaxis (rare).
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dextrose injection 5 percent or in sodium chloride injection. Pharmacokinetics: I.V. Dextran expands blood volume to 2 X amount of dextran infused,
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Mechanism of action: Dextran 70 expands plasma volume by drawing fluid from the excreted in urine, feces.
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interstitial spaces to intravascular space, acts as plasma expander.
Brand Names: Dextran: Plasmex, Rallidex, Microspan 40, 500ml bottle.
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Indications: Used as effective temporary plasma substitute, prevention of post operative HYDROXY ETHYL STARCH (aHES): HES is a complex mixture of ethoxylated amylopectin
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thrombosis, by intravenous injection, it inhibits the intravascular aggregation of red blood
of various molecular sizes. The colloidal propcrties of 6% HES are almost same as of human
cells, called as sludging of blood, hypovolemic shock.
plasma. Haemodynamic status is improved after 24 hours. Plasma volume is increased in
Dosage: V infusion 500 ml to 1000 ml not to exceed 20 to 40 ml per minute, not to exceed excess the volume infused. It is excreted in urine. Smaller molecules are excreted rapidly by
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10ml per kg body weight in one day (24 hours). kidney, large molecules are broken slowly'to small molecules and are eliminating slowly.
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Contraindications: Hypersensitivity, renal failure, excessive dehydration, with precautions The plasma half life is 17 days
in pregnancy HES has side effects like uritcaria, skin rash, bronchospasm, vomiting, fever, chills,
Side effects: Increase bleeding time/clotting time, skin rash, uritcaria, chills, fever, itching, flu. It is available as 100 ml. 500 ml injection.
angioedema, wheezing dyspnea, pulmonary edema, osmotic nephrosis, hypernatremia, Therppetic Uses of Plasma Exapnders
vomiting, nausea, jaundice, anaphylaxis, Hypotension. Th
Pharmacokinetics: Dextran increase or expand blood volume 1 to 2 X amount of dextran
These are used to increase oxygen carrying capacity of blood in anaemia.
2. The plasma expanders are used to treat burns, to correct hypoproteinemia (as in
infused. excreted in urine, feces expands plasma volume nearly in 24 hours, excreted
marasmus).
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slowly.
3. They are used to restore blood volume, in shock after severe hemorrhage. The shock
DEXTRAN-40: Dextran-40 acts more rapidly than dextran 70. it acts similar to human
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is the main cause for the administration of fluid therapy.
plasma. it expands plasma volume by drawing fluid from interstitial space to intravascular
BLOOD PRoDUCTS
space, act as a plasma expander.
WHOLE BLOOD:Whole blood is used to combat shock, to restore plasma volume.
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Indications :Expands plasma volume, thrombosis, prophylaxis of embolism.
Shock is a state of acute circulatory failure accompanied by defective perfusion of tissues.
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Mechanism of action : Dextran 40 is a plasma expander similar to human albumin. It
Whole blood is obtained from human donors can be preserved with coagulant:
expands plasma volume by drawing fuid from inderstitial space to intravascular space. It is
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useful in shock. (usually citrate). It is stored at constant temperature of 2°C to 6°C. The preserved blooc
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should be used within 21 days. The advantages of blood transfusion is complete restoration
Dosage: Shock: Adult': Intravenous infusion 500 ml in 30 minutes dose in 24 hours not to
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of physiological deficiency with provision of oxygen transport.

exced 20ml per kg body weight. Therapy to be given not more than 5 days.
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Disadvantages:
Thrombosis / Embolism: V infusion 500 ml to 1000 ml first day then 500 ml daily for
3 i) There is difficulty in procurement of whole blood from human donors.
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days, then 500 ml after 2 to 3 days for 2 weeks if needed.

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130
P A Toxt Book of Phamacology-l Drugs Atfecting on Hematopoletlc Systems
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i)There is need of cross matching of blood
of donor with the blood of recipient 11. Any person with history of asthmatie attack, history of allergy history of epilepsy,
(patient) and need for blood grouping.
convulsions should be rejected for whole blood donation
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(i) There is danger of
reactions like sensitization, hemolytic and pyrogenic. 12. Any person who shows an evidence of being alcoholic or a person with drug
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iv) Human blood needs through
examination against HIV, T.B, malaria, hepatitis.B., like dependence is to be rejected for blood donation. He may not be reliable in his replies..
diseases that can be transmitted to the recipient, if the blood
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is transfused without 13. A person who had undergone major surgery within last six months and a person
pathological examination.
having dental extraction within one week is not to be accepted for blood donation.
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There are certain conditions of blood donations which
are to be followed strictly for 14. A person having fever, body temperature above 99.6f is a cause of rejection. A
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safe blood transfusion to the recipient. Precaution

and conditions as under. person with haemoglobin lower than 12 gm percentage should not be accepted for
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blood donation.
CONDITIONS FOR BLoOD DONATION 15. A person with underweight, weight less than 55 kg is a cause of rejection. There is no
1. Screening of potential blood
donor at blood bank. maximum weight limit if the person is in good health and free from any kind of
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2 Age of the donor minimum 18 years while maximum age is infection.
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59 years. Unmarried,
minors while donating blood to present statement of permission signed by 16. Blood containers, donor sets shall be sterile and pyrogen free. Anticoagulant solution
guardian
/ responsible person. should be sterile and pyrogen free.
3. Females during pregnamy, menstruation are not used as 17. Any person who has received blood or blood plasma during last six months is not
blood donors.
4. After blood donation operators of heavy equipments and job
requiring, climbing of acceptable for blood donation.
ladders/ scaffolds should take rest completely and should not return to work atleast 18. A person who has innoculated and vaccinated of killed virus, bacteria like small pox
12 hours after blood donation. Flight crew and millitary, force personnel should not vaccine yellow fever, Rabies vaccine typhoid, diphtheria, tetanus vaccination for the
return to work for one week atleast. last one to two week is not acceptable for blood donation for one year.
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5. Any person with history of tuberculosis is rejected for blood donation. 19. A person with bleeding abnormalities should be rejected for blood donation.
6. Any person with history of STD, syphilis / Hv, whose serological tests turns out 20. A person with active skin lesion of the mucous membrane or skin should not be
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positive for these diseases is not eligible for blood donation. accepted for blood donation.
7. A person with the history of viral hepatitis, jaundice in the last 1 to 2 years should be 21. The interval between donations should be minimum 12 weeks (3 months), the
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rejected for blood donation. maximum number of donations should not exceed five in any year.
8. A person with the history of clinical attacks of malaria during last 6 months to 1 year 22. The blood donor should be on fasting atleast 3 hours before donation or might have
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and had taken antimalarial therapy should not be acepted for whole blood donation. taken non fatty meal about 3 hours earlier before donation. Complete fasting to be
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9. Any individual with severe hypertension, give history of coronary artery disease, avoided. After blood donation one may take fruit juce, milk, tea, coffee toast. One
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congestive heart failure should be rejected for blood donation. should not take butter.
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10. Any one suffering from diabetes and is on insulin therapy is to be rejected for blood HUMAN PLASMA: Plasma can be used as a substitute for blood. Normal human plasma is
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donation for his own safety and protection. obtained by poling citrated blood of different people is separated by centrifugation.
Human plasma may be dispensed as liquid, frozen or dried plasma. Normal human plasma
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is used in the treatment of shock, hypoproteinemia. When plasma is lost in severe burns. It
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isälso used as a temporary substitute for whole blood for treatment of severe hemorrhage. Q4. Which type of anaemia was not cured with iron was described by Thomas Addison in 1849
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Freshly collected ctrated human plasma is a faint yellow or amber colour liquid. Ans. In 1849 Thomas Addison described a case of anaemia not cured with iron. This type of
Advantages: Human plasma can be stored and transported. anaemia was called pernicious anaemia, which was cured with by adding liver in diet which is
rich source of vitamin B12-
Disadvantages :It has a high cost (ii) There are dangers of virus transmitted jaundice.
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Uses Traumatic and surgical shock, burns, in the treatment of Q.5. How does deficiency of folic acid occurs ?
hypoproteinemia,
G) The deficiency of folic acid occurs due to increased demand of folic acid by body in
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malnutrition. Ans.
pregnancy, lactation, growth period, and hemolytic anaemia.
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REVIEWQUESTIONS Cii) Dueto inadequate dietary intake of folic acid.
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ii) In chronic alcoholism, because intake of folic acid is poor, release of folvite from liver cell
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SHORT ANSWER QUESTIONS and recirculation is interfered/disturbed.

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Q.1 What are haematinics? Deficiency of folic acid occurs with prolong therapy with drugs treatment, drugs like
Civ)
Ans. Haematinics are substances required in the formation of blood. These drugs phenobarbitone sodium, phenytoin, primidone and oral contraceptives.
are used for
the treatment of anaemia. These drugs increase the number of Q6. What are commonly used forms of iron in iron deficiency anaemia ?
red blood cells and the amount of
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haemoglobin is raised to normal level and above when they are Ans. The common forms of iron used for treatment of iron deficiency anaemia are Ferrous
below normal.
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02 What are the causes of anaemia to occur ? sulphate (i) Ferrous gluconate (ið Ferrous fumerate. It is estimated that ferrous sulphate
Ans. Anaemia occurs contains 20 percent elemental iron, ferrous gluconate contains 12 percent and ferrous fumarate
When the balance between production and reduction of red blood cells contains 33 percent of element iron, so these forms are given in different doses.
is disturbed may be
due to blood loss. Q.7. What are toxic effects of iron ?
i) Impaired red blood cells due to the deficiency of essential factors Ans. When iron is ingested in excess amount it causes gastric haemorrhage, circulatory collapse
like iron, folic acid and
vitamin B12 and finally death occurs. Fatal poisoning occurs in children, 1 gram of iron or more taken by
mistake by a child be considered fatal dose. The treatment of iron poisoning be started/ given
ii) Bone marrow depression, erythropoietin deficiency.
immediately.
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Gv) Increased destruction of Red blood cells (as in haemolytic
anaemia). Q.8. What is immediate treatment of overdose of iron in adult patient ?
Q.3. What is the disease Anaemia ?
Ans. In case of adult with iron poisoning, give eggs and milk untill lavage can be done. Induce
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Ans. Anaemia is a disorder ocured in human body characterized by a decreased
haemoglobin vomiting
in the blood, to levels below the normal range (normal value of hemoglobin 14 16
to gm %). This Q9. What are plasma expanders?
disorder or condition may occur due to decrease in red blood cells production or increased
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red Ans. The plasma expanders are drugs that are administered intravenously to increase (raise) the
blood cells destruction or blood loss. The symptoms appears due to the reduced
oxygen decreased plasma volume. The plasma volume of the body is decreased due to dehydration,
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carrying capacity of the blood. The symptoms of anaemia are characterised by weakness, pallor,
starvation, haemorrhagic conditions. Human albumin, Dextran, Polyviny! pyrrolidone (PVP)
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tachycardia, fatigability, dyspnoea on exertion. It may occur in any condition in which

there is etc. are used as plasma expanders to make up deficiency of the decreased plasma volume.
haemorrhage iron loss". This disease/disorder can be treated with haematinics and by taking
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balanced diet, whereas severe anaemia by blood transfusion. Q.10. What are the difficulties being faced during use of whole human blood transfusion ?
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Ans. () The major dificulty is faced in procurement of whole blood from human donors.
There may also be menstrual disturbance, oedema, rapid thin pulse, palpitation or heart
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failure. Gi)There is need of cross matching. The blood of donor with the blood of recipient also need
blood grouping and blood group matching.
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functions. The important drugs which are used
as antiplatelet are: Aspirin, Dipyridamole,
ii) There is danger of sensitization, hemolytic, pyrogenic reactions that may occur.
Clopidogrel, Ticlopidine and Cilostazol.
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iv)Human blood require through investigation (examination) against HIV infection,
Tuberculosis, Malaria, Hepatitis A, Hepatitis B like disease. There is risk of transmission of
LONG ANSWER QUESTIONS
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diseases if blood is transfused without pathological examination.
Refer 2.2.1
() There is need of screening of a potential blood donor which is also a time consuming factor. Q1. Describe the role of iron in blood formation
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cyanocobalamine (Vitamin B12) Refer. 2.2.1

o11.Explain the advantages and disadvantages of human plasma expander ? 02. Explain the pharmacology of
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Refer 2.2.1
Ans. Advantages : Human plasma can be stored and transported. Q3. Write the toxic effects of Toxicity of iron
pharmacolo8y of erythopoietin Refer 2.2.1.
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Disadvantages : 6) Human plasma is very costly. Q4. Discuss the erythopoietin, write the
effects, indication, contraindication and use of folic acid
Q5. Explain the mechanism of action, side
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There is danger of vinus transmitted jaundice.
(i)
Refer 2.2.1
Q.12.Vhat are coagulants ?
pharmacology of fibrinogen. Refer 2.3.
Q.6. Describe the role of Vitamin K in Coagulation write the
Ans. Coagulants are the drugs which promotes clotting. These drugs are used in haemorrhagic
the pharmacology of heparin Refer 2.4.
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states when there is bleeding occuring from wounds/injuries. Q7. Explain anticoagulants, classify them, write
Q8. Describe the fibrinolytics classify them write the
pharmacology of Streptokinase (SK). Refer 2.6
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Q.13.What is the main use of Protamine Sulphate 7
Q9. Describe the mechanism of action, adverse effect, indication, dose and brand name of
Ans. Protamine sulphate is used as antidote for heparin in overdose of hepain.
Q.14.What are Anticoagulants ?
danaparoid Refer 2.4.
Refer 2.5
Q.10. Define antiplatele drugs, write the pharmacology of dipyridamole
Ans. Anti coagulant are the drugs which prohibit the process of clotting.
Q11. the Pharmacology of warfarin sodium Refer 2.4
Q.15. Define shock Explain
Refer 2.5
Ans. It is defined as a state of cellular and tissue hypoxia due to reduced oxygen Q12. Describe the mechanism of action, side effect and cilostazol
delivery and/or increased oxygen consumption or inadequate oxygen utilization. This most Q.13. Write a note on plasma expender Refer 2.7
commonly occurs when there is circulatory failure manifest as hypotension (ie, reduced tissue
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perfusion). "Undifferentiated shock" refers to the situation where shock is recognized, but the
cause is unclear. While patients often have a combination of more than one form of shock MULTIPLE CHOICE QUESTIONS
(multifactorial shock), four classes of shock are recognized. Q1.Heparin is :
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Q.16. Describe the dietary Sources of Iron () Polysaccharide
Ans. The source of iron are wheat germ, yeast, dry fruits, dry beans, egg yolk, liver, oyster, root () Lipoprotein
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vegetables. Medium sources of iron are meat, chicken, fish, spinach, apple. Milk and milk ) Monosaccharide
products are poor sources of iron.
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() Ceramide.
Q.17. What is folic acid?
Q2Which of the following drugs does not have antiplatelet action ?
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Ans. It occurs as yellow crystals insoluble in water, its sodium salt is soluble in water.
(a) Paracetamol
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Chemically folic acid is Pteroyl glutamic acid. Mitchell in 1941 isolated folic acid from spinach
(b) Aspirin
and called it folic acid means from leaf. It is also called as vitamin B9.
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Q.18. What is Antiplatelet? () Dipiridamolde

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Ans. Antiplatelet are drugs which interfere with platelet function and are used as prophylaxis of (d) buprofen.
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thromboembolic disorders. The different drugs act differently to interfere with platelet
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PU A Text Book of Pharmacology-! Drugs Affecting on Hematopoletle Systems
36
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Q3Plátelet aggregationis inhibited by Q.9. The name of anti coagulant heparin is named as:
ta) Clofibrate (a) It was obtained from liver.
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C) Aspirin (6) t is strongest organic acid present in the body.
Dipyridamol (c) Do not prevent clotting.
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) All of the above (d) True as a and b.
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of the above. Q.10. In the function of heart, systolic arterial blood pressure is the
pressure in the arteries at thhe
None
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Q4.Constipation is caused by all except time of cardial systole shows
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(a) Morphine o) Maximum blood pressure

(6) Minimum blood pressure
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6) Codeine
(c)Verapamil () Moderate blood pressure

(a) magnesium sulphate. ) Differential blood pressure.
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Q.5.Digoxin toxicity can be treated by Q.11. Which of the following does not contribute to thrombosis?
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)Phenytoin (a) Blood flow abnormalities
(6) Potassium supplements (b) Contact surface abnormalities
(e) C. Complement abnormalities
(cDiuretics
(d) D. None of the above
()All of the above.
Q.6. Drug of choice in acute myocardial infaretion is:
) Morphine
A N'S WERS
C6)IV. Heparin
1.A 2. A 3.D 4.D 5. A&B 6.D
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Nitroglycerine 7.A 8.B 9. A 10. A 11.C
) Streptokinase.
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07. Antidote for heparin is :
a) Protamine
() Dipiridamole
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Aspirin
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C) Desferrioxamie.
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Q8. Plasma expander with oxygen carrying capacity is :

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a) Haemaccel
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Dextran-40o
) Dextran-70
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) FRuorocarbons.
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Pharmacology of Drugs Acting on Urinary System
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3 PHARMACOLOGYOF DRUGS ACTING There are three steps/ process involved in the formation of urine,
a
Selective Reabsorption : Reabsorption in the nephron may be either passive
or active
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ON URINARY SYSTEM considerably in
process, and the specific permeability of each part of the nephron varies
mechanisms of reabsorption
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terms of the amount and type of substance reabsorbed. The
into the peri-tubular capillaries include:
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ANTRODUCING THE CHAPTER Passive diffusion-passing through plasma membranes of the kidney epithelial cells by
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concentration gradients.
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Diuretics Active transport-membrane-bound ATPase pumps (such as NA*/K* ATPase pumps) with
epithelial
carrier proteins that carry substances across the plasma membranes of the kidney
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Anti-diuretia
cells by consuming ATP.
EY WORD
Co-transport-this process is particularly important for the reabsorption of water. Water can
Diuretices Diuretics are the drugs which increase the rate and volume of urine formation follow other molecules that are actively transported, particularly glucose and sodium ions
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These drugs mainly act on nephron and increase the excretion of excess fluid. in the nephron.
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Anti diuretics: These are the drugs which decrease urine output
Tubular Secretion: The mechanisms by which secretion occurs are similar to those of
reabsorption. However, these processes occur in the opposite direction.
ZDURETTCS The tubular secretion of H+ and NH4+ from the blood into the tubular fuid is involved in
Diuretics are the drugs which increase the rate and volume of urine formation. These blood pH regulation. The movement of these ions also helps to conserve sodium
drugs mainly act on nephron and increase excretion of excess fluid. bicarbonate (NaHCO;). The typical pH of urine is about 6.0, while it is ideally 7.35 to 745
INTRODUCTION: Glomerular Filtration: It is the first step in urine formation and for blood.
constitutes the basic physiologic function of the kidneys. It describes the process of blood pH regulation is primarily a respiratory system process, due to the exchange of carbon
ltration in the kidney, in which Ouid, ions, glucose, and waste products are removed from dioxide (a component of carbonic acid in blood), however tubular secretion assists in pH
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the glomerular capillaries. Many of these materials are reabsorbed by the body as the fuid homeostasis as well.
travels through the various parts of the nephron, but those that are not reabsorbed leave the The substances that are secreted into the lubular fluid for removal from the body include:
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body in the form of urine. Potassium ions (K+), Hydrogen ions (H+), Ammonium ions (NH4+), Creatinine, Urea,
Some hormones and Some drugs (e-g, penicillin).
Water as a diuretic : When water is given in excess quantity to a patientit acts as a diuretic.
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DCT
In this case, the anti diuretic harmone (ADH) remain inhibited and nephron becomes
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permeable to water. In water, diuresis water is excreted in excess of solute. In edema there
is retention of sodium in tissue and water retention is secondary in this disease. Water does
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K
not act as good a diuretic. The water as a diuretic is useful in urinary tract iníections.
Det
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AA Leep
Saka The functions of the kidney are know (1) Excretion of waste, urea, uric acid and creatinine.
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Urine
(2 Regulation of acid base and water salt balance in our body. The details of drugs and use
Kerelon
of high ceiling diuretics are as under.
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Fig 3.1 Site of action of diuretic drugs
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Pharmacology of Drugs Acting on Urinary System 141
PVA Text Book of Pharmacology-
DIURETICS DIURETICs OF HIGH EFFICACY (Inhibitors of Na+-K+-2CI Cotransport)
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of electrolytes
Diuretics are drug which increase the urine output FUROSEMIDE: Furosemide is a loop diuretic which reduces the absorption
henle. It increase excretion of
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with the help of proximal and distal renal tubules and loop of
increased. The
sodium potassium and chloride ion as a result of this water excretion is also
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CLASSIFICATION OF DrURETICS by mouth. There is

acid base balance is not changed. It is rapidly absorbed when given
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intense diuresis which last for four to six hours. It is given by
mouth in the dose of 40 mg
for cure of
once to three times a day. it is also administered orally to hypertensive patients
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mild to moderate hypertension. In cerebral oedema it is

administered intravenously. Its
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High Eficacy Diuretics Medium Eficacy Diuretics
Weak or Adjunctive molecular fomula is C12 H1 CI N2 Os Ss.
(nhibitors of Nat-K dInhibitors of Nat
Diurètics
2c Cotransport) C sympor)
cOOH
c
c
NH.CH
Sulphamoyl Derivatives
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Furosemide NH2-$O2
Bumetanide
Torasemide
Structural formula furosemide
Mechanism of action : The drug furosemide inhibits the reabsorption of sodium and
chloride ions at proximal and distal tubules, and in the loop of Henle.
Benzothiadiazines Thiazide like (related
(thiazides) heterocyclics)
Tubular Tubular Peritubular
Hydrochlorothiazide Chlorthalidone
Xipamide, lumen cell capillary side
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Benzthiazide
Hydrofumethiazide Indapamide 3Na-
Copamide Na
ATPase
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-2K
Furosemide CI
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Ph
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Na
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Ca) Carbonic anhydrase (c) Osmotic diuretics

(b) Potassium sparing Mg
inhibitors diuretics Mannitol
Isosorbide Ca
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Acetazolamide Aldosterone antagonist:
Glycerol
Spironolactone Fig. 3.2: Drug act on Na+-K+-2CI Cotransport)
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Cii) Tnhibitors of renal epithefial

Na+ channel: It a loop diuretic, inhibits water reabsorption in the nephron by blocking the sodium-
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Iriamterene, Amiloride
potassium-chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle
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This is achieved through competitive inhibition at the chloride binding site on the
cotransporter, thus preventing the transport of sodium from the humen of the loop of Henle
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into the basolateral interstitium. Consequently, the lumen becomes more hypertonic while
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TR
142, FU A Text Book of Pharmacology-l Phamacology of Drugs Acting on Urinary System.
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the interstitium becomes less hypertonic, which in turn diminishes the foOH
osmotic gradient for
water reabsorption throughout the nephron. Because the thick ascending limb is
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responsible for 25% of sodium reabsorption in the nephron.
NH,SO NH(CH),CH,
dfcations:
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Hypertension. pulmonary ocdema, oedema in congestive
heart failure,
cercbral oedema, toxaemia of pregnancy, renal disease, nephrotic
syndrome.
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(CHNO,5) Bumetanide
Dosage : Adult 20 mg to 80 mg single dose, if the results are not satisfactory, then 20 to 40 Indications : Edema in congestive heart failure, nephrotic syndrome, pulmonary oedema,
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mg after 6 hours, maximum upto 600 mg can be administered. hypertension, anasarca.
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Children: 2 mg per kg body weight, then 1.2 mg per kg body (infant to 12 year age) Dosage: Adult: By mouth 0.5 mg to 2 mg. 1/M/Inravenous injection 0.5 mg to 1 mg per
Wait 6
hours after the previus dose maximum upto 4Omg per day. day, may second, third dose at 3 hours intervals not to exceed 10 mg per day.
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ontraindictions Hypersensitivity, anuria, hypovoluemia, lactation, pregnancy, Children:Orally: Intramuscular/Intravenous 0.02 mg 0.1 mg per kg body weight - 12
hypokalemia, malnutrition, diarrhoea, renal failure. hourly. It is available as 0.5mg 1mg, 2mg tablets and injection 0.25 mg per ml.
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Side effects: Chest pain, ECG changes, loss of hearing, blurred vision, Head ache, Contraindications: Hypesensitivity, anuria, hepatic coma, dehydration, pregnancy,
weakness, vertigo, paresthesias, hypokalemia, metabolic alkalosis, hypocalcaemia, lactation.
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hypomagnesemia, hyperglycaemia, anemia, rash, pruritis urticaria, sweating, stevens Side effect : Polyurea, Head ache, hypokalemia, fatigue, weakness, nausea, vomiting, dry
johnson syndrome. mouth, Jaundice, Loss of hearing, ear pain (ottalgia), blurred vision, rash, urticaria,
Tharmacokinetics: Peak plasma concentration attained in 1 hour with oral dose of 80 mg sweating, stevens Johnson syndrome, sweating hyperglycemia, chest pain, hypotension,
Plasma half life 30 minutes, in patient with liver disease, renal failure plasma half life may ECG changes, dehydration.
be 20 hours, exareted in urine, breast milk, crosses placenta. Pharmacokinetics: Peak plasma concentration attained 30 minutes. duration of action 4
Drug Interactions : Decrease the effect of furosemide with indomethacin, metolazone hours. I.V administration onset action 5 minutes, duration 2 to 3 hours. IM onset action 20
There is increased ototoxicity with aminoglcosides, vancomycin. to 30 minutes duration of 4 hours. Excreted by kidneys, excreted in breast milk, crosses
Brand names: It is available as tablet Lasix, 40 mg Inj Lasix 10 mg per 2 ml ampoule placenta.
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Furosimide Frusimide): Tablet and injection Lasix, Frusemix, Tebemid, Lasiride, Drug interaction : Decrease diuretic effect by indomethacin, probencid drugs. Ototoxicity
Injection Frusix. increased with drugs vancomycin, aminoglycosides, cisplatin. bumetanide decrease the
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effect of antidiabetics.
BUMETANIDE: It is an odourless white crystalline powder with slightly bitter taste. It is Brand names: Bumetanide: Tablet Bumet Img
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rapidly absorbed after oral administration. It is a diuretic drug. It has more rapid onset
action. Its diuresis action begins within 30 minutes and maximum effect is produced with in TORASEMIDE: It is a loop diuretic. It acts on the loop of Henle proximal distal tubule by
Ph
Ph
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one hour. When intravenous Injection is administered, diuretic action occurs within few inhibiting absorption of chloride, sodium and water. It is available as tablets 5 mg, 10, 20
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minutes. The usual daily dose is 1 mg to 2 mg in single or divided doses. Its molecular mg and torasemde 10mg per ml vial of 2mi, Sml.
formula is C17 H20 N2055. It acts on ascending loop of Henle by inhibiting reabsorption of Mechanism of action: The drug Torasemide acts on loop of Henle, proximal and distal
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chloride, sodium. tubule by stopping absorption of sodium, chloride ions and water. It is useful in treating
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Mechanism of action: Bumetanide drug acts on ascending loop of Henle by inhibiting hypertension, oedema in CHF and liver disease.
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reabsorption of sodium and chloride ions. It is used in treatment of liver disease, edema in Indications: Hypertension, edema in congestive heart failure, renal and hepatic disease.
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CHE, Hypertension and Nephrotic syndrome. Dosage: In CHF (Congestive heart failure.
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144 Pharmacology of Drugs Acting on Urinary System
U A Text Book of Pharmacology-l 145
Adult: Orally or Intravenous 10 to 20 mg per day may increase upto 200 mg per day. 5) Hypercalcemia : In hypercalcemia the loop diuretics with normal saline are used to
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Hypertension: Adult: Orally 5 mg daily may be increased to 10mg per day. prevent volume depletion. Lasix (Furosemide) is a choice medicine. In case of the life
threatening hyponatremia loop diuretics are very helpful in treatment.
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Hepatic cirhosis: Adult: Orally /LV 5 to 10 mg per day, the dose may be increased to
200mg per day.
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Table showing Thiazides and related diuretics action time

Contraindications Hypersensitivity, anuria, hypovolemia, infants, Pregnancy,
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dehydration, lactation, electrolyte depletion, renal disease. S.No. Name of Drug Duration of Daily dose Carbonic anhydrase
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Side effects: Loss of hearing, ottalgia, blurred vision, tinnitus, head ache, insomnia, action (Hours) inhibitor
dizziness, postural hypotension, hypokalemia, alkalosis, hypocalcaemia, alkalosis, nausea,
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Hydrochlorothiazide 5 to 15 hours 12.5 to 100mg
rectal bleeding, rash, cramps, cough may be increased Chlorthalidone hours 50 to 100mng
Pharmacokineties: Rapidly absorbed when administered orally peak plasma concentration Hydroflumethiazide 12 to 18 hours 25 to 100m8
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30 minutes, duration 6 hour, plasma half life -4 hours, excreted in Urine, breast milk. Indapamide 5 to 8 hours 2.5 to 5mg
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Drug interactions: The toxicity is increased with muscle relaxants, digitalis, increased 5. Xipamide 5 to 8 hours 20 to 40mg
ototoxicity with aminoglycosides, vancomycin. The antihypertensive effect of torasemide is
decreased with drugs indomethacin, metolazone. Disadvantages of Diuretics
Brand names: Torasemide: Tablet, Injection. Toride, Torsinex, Tide, Dytor, Torsid, The disadvantages of use of diuretics are:
Torsemi 10mg, 20mg tablets. Hyperkalemia : In prolong use hyperkalemia occurs due to which patient have
muscular weakness, paralysis, diarrhoea, abdomen distension, cardiac arrest and

USES OF HIGH CEILING DIURETICS ventricular fibrillation, tall T wide QRS complex. Give the patient calcium
The following are the uses of high ceiling diuretics, which favours our health. gluconate, stop potassium sparing diuretics.
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)Hypertension : The high ceiling diuretics are given to a patient in the presence of renal
i) Metabolic acidosis: The metabolic acidosis occurs because H is retained with
insuficiency, CHF, in hypertension and the resistance cases. The reduction of blood potassium.
pressure depends on the reduction of blood plasma volume and cardiac output.
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ii) Hyperurecemia: It is due to the volume reduction in blood plasma, all the patients
2) Oedema: The diuretics are used in all oedema cases. The high ceiling diuretics are
using diuretics have this problem, because urates level in blood is increased.
used in CHF for rapid and quick decrease of oedema fuid. It is for the nephrotic and
iv) Hyperglycemia: This problem is raised due to decrease in glucose tolerence, the
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other forms of resistant oedema. The high ceiling diuretics are the choice medicine. In
level of glucose is increased in blood.
premenstrual oedema excess of estrogen cause an increase of fluid in extravascular
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space cause oedema and the diuretics are helpful to cure this condition. v)Gastrointestinal upset: The nausea, vomiting diarrea, pain abdomen occurs to the
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patient.
Pulmonary oedema : In pulmonary oedema the intravenous administration
of
3)
Frusimide or its congener drug gives immediate relief. This is due to decrease in blood vi) Photosensitivity occurs.
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volume and its vasodilator action which cause saluretic action. In cerebral oedema vii) CNS disturbance : There is headache, weakness, paresthesis, impotence are the
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osmotic diuretics are used in combination with frusemide to improve efficacy. complaints with using loop diuretics. Hepatic coma may occur.
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4) Anaemia : In anaemia cases during blood transfusion to prevent vascular overload the vii) Megnesium depletion: It is the condition which develops on prolong use of loop
diuretics, which increase risk of ventricular arrhythmias.
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diuretics are given.

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146
P A Text Book of Pharmacology-ll
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thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the
i Diuretics should not be used in the toxaemia of pregnancy due to which miscarriage
and foetal death occurs. The diuretics are contraindicated in pregnancy patients.
It is a
sodium-chloride symporter in the distal convoluted tubule, which is responsible for 5% of
total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium
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x)Hearing loss: The hearing loss rarely occurs with diuretics.
Allergie reactions : Skin rashes urticaria occurs in patients while using diuretics. and chloride from the humen into the epithelial cell lining the distal convoluted tubule. The
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Ph
energy for this is provided by a sodium gradient established by sodium-potassium ATPases
on the basolateral membrane. Once sodium has entered the cell, it is transported
out into
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MEDIUM EFFICACY DIAURETCIs BENZOTHIADIAZINES

the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the
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Inhibitors of Na+-C symport) osmolarity of the interstitium, thereby establishing an osmotic gradient for water
HYDROCHLOROTHIAZIDE: lt is available as a white crystalline odourless powgler with reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively
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a bitter taste. It acts as a thiazide diuretic. It is slightly soluble in water. It acts on distal reduges the osmotic gradient and water reabsorption throughout the nephron
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tubules and cortical thick ascending limb of the loop of Henle by increasing excretion of ndications : Hypertension, edema, congestive heart failure, diuresis, edemain
sodium chloride, potassium and water. Its molecular formula is C7 Hs CI Ng O452 corticosteroid therapy.
Dosage Oedema: Adult: 25 mg to 100 mg per day Children: age 6 month and above
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NH2$O2 orally 2.2 mg per kg body weight in divided doses.
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NH
Hypertension: Adult 25 mg to 50 mg daily.
Contraindications Hypersensitivity, anuria, hypomagnesmia, renal decompen-sation,
Cl pregnancy, lactation, hypokalemia, gout.
(Structural formula of Hydrochlorothiazide Stde effects Drowsiness, depression, headache, weakness fatigue, polyurea, uremia,
Mechanis nausea, vomiting, hepatitis, cramps, panéreatitis, blured vision_rash, urticaria, alopecia,
of action : Hydrochlorthiazide acts on distal tubule, Cortical thick ascending
loop of Henle by increasing the excretion of sodium, chloride, potassium and water. increased serum creatirnine, blood urea nitrogen increased, leukopenia, anemia, irreguar
pulse, hypotension palpitation.
Distal Pharmacokineties: On set action 2 hour, Peak plasma concentrations-4 hours. Plasma half
Interstitium
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Lumen convoluted
urine tubule blood life 6 to 15 hours excreted by kidneys, crosses placenta, enters breast milk.
QDrug interactions : Decreases effect of antidiabetics anticoagulants, decreases absorptionof
PTH
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Na colestipol, cholestyramine. It increases efect of loop diuretics.
Na* Brand names: Hydrochlorothiazide : Tablets Aquazide, Xenia, Hydride, Esidrex 12.5mg
CI 25mg and 50mg tablets. Drugs Benzihiazide and clopamide have similar duiretic action as
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K*
chlorothiazide or Hydrochlorthiazide.
Ph
Ph
Ph
Na
Ca2
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BENZTHIAZIDE: It promotes water loss from the body (diuretics). They inhibit Na+/Cl.
reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of
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potassium and an increase in serum uric acid.
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Fig. 3.2 Drug act on (Inkibitors of Na+-Cl symport) Mechanism of action: It inhibits active chloride reabsorption at the early distal tubule via
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the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and
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A Text Book of Phammacology-ll Pharmacology of Drugs Acting on Urinary System 149
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water. Thiazides like benzthiazide also inhibit sodium ion transport across the renal tubular Pharmacokinetics : On set action 1 to 2 hours, diuresis is maintained 6 to 12 hours. Peak
excreted
epithelium through binding to the thiazide sensitive sodium-chloride transporter. This plasma concentration 4 hours, plasma half life 15 hours, metabolised by kidneys,
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results in an increase in potassium excretion via the sodium-potassium exchange in urine, enters breast milk, crosses placenta.
drugs,
mechanism. The antihypertensive mechanism of benzthiazide is less well understood Drug Interactions: Increased efect of loop diuretics, decreases effect of antidiabetic
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although it may be mediated through its action on carbonic anhydrases in the smooth anticoagulants.
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muscle or through its action on the large-conductance calcium-activated potassium (KCa) thiazide
hannel, also found in the smooth muscle. CLOPAMIDE : It is an oral diuretic agent with antihypertensive activity. Like
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diuretics, it has an aromatic sulfonamide base but with no double-ring
structure.
Indications: It is indicated for the treatment of high blood pressure and management of
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edema. THIAZIDE LIKE (RELATED HETEROCYCLICcs)

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Uses: It is used to treat hypertension and edema. It is used as diuretics. CHLORTHALIDONE: Chlorthalidone acts as diuretic. It acts on distal tubule and thick
ascending limb of loop of Henle. There is increased excretion of sodium,
potassium,
HYDRO FLUMETHIAZIDE: It is an odourless, tasteless, white glistening crystals or chloride, magnesium bicarbonate and water. It is available as 15mg, 50mg, 100 mg tablets.
c
c
crystalline powder. It is slightly soluble in water. Pt is a thiazide diuretic. It decreases the
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reabsorption of electrolytes by the proximal part of the distal tubules and increases
exaretion of sodium, potassium and chloride ions and water. It does not change the body's NH
acid base balance. It is rapidly absorbed when administered by mouth. Its molecular -oH
formula is CgHgF3N304S2
NH2SO2 O=
SONH
NH
Structure of Chlorthalldone
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CF3 Mechanism of action : The drug Chlorthalidone acts on distal tubule and thick ascending
Structural formula of Hydroflumethiazide limb of the loop of Henle by increasing excretion of sodium, potassium, chloride,
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Mechanism of action : Hydrofumethiazide is a thiazide diuretic. t decreases the bicarbonates and magnesium. It is used in Hypertension, Oedema, CHF and diuresis.
reabsorption of electrolytes, by proximal part of tubules, loop of Henle. It increase excretion Indications: Hypertension, edema, congestive cardiac failure, nephrotic syndrom.
of sodium, chloride, potassium and water from the body. It does not change acid base Dosage: Adult: Orally 25mg to 200 mg per day. Then 100 mg daily.
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balance of human body. Child:by mouth 2 mg per kg body weight.
Indications:Hypertension,oedema
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Ph
Contraindications : Hypersensitivity, hypokalemia, pregnancy, lactation, diabetes mellitus,
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Dosage: Hypertension Adult: 25 mg to 50 mg, once or twice daily. elderly, hyperlipidemia, anuria.
Oedema: Adult : 25 mg to 100 mg. once or twice daily. Side effects: Headache, fatigue, weakness, polyuria, uremia, impotence, nausea, vomiting.
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Contraindications:Hypersensitivity, pregnancy, lactation, hypokalemia, anuria. cramps, gastro intestinal iritation, rash, urticaria, hepatitis, blurred vision, hyperglycaemia,
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Side effects: Weakness, head ache, fatigue, polyuria, nausea vomiting, uremia, increased blood urea nitrogen, serum creatinine, irregular pulse, postural hypotensian,
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palpitation, hypokalemia, volume depletion.
pancreatitis, blurred vision, anemia, rash, urticaria, blurred vision, hypotension, palpilation.
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150 Phamacology of Drugs Acting on Urinary System
PU A Toxt Book of Pharmacology-l
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to 5 mg if needed, to be
hannacokinetics: On set action 2 hour, peak concentration 6 hour, plasma half life 36 Dosage: Adult: For Edema : 2.5 mg daily, dose may be increased
hours, excreted by kidneys, crosses placenta, enters breast milk. taken early morning as oral dose.
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8 weeks duration.
Drug interactions: Chlorthalidone decreases effect of antidiabetics, anticoagulants, For Hypertension: Adult: 1.25 mg to 5 mg per day for
antigout drugs : Hypersensitivity, anuria, hepatic coma, pregnancy lactation,
Ph
Ph
Ph
Contraindications
Brand names: Chlorthialidone: Tablet Hythalton, Clothalton, 15mg, 100mg dehydration, hypokalemia, renal disease.
ha
Side effects Hyperglycaemia, hypokalemia, polyuria, nocturia, impotence,

anorexia,
hypomagnesemia, headache, fatigue, weakness, depression, nausea, vomiting,
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XiPAMIDE: t acts as diuretic. It acts on the distal tubule and inhibits sodium reabsorption, hypotension, palpitation,
cramps, dry mouth, abdominal pain, constipation, rash, postural
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chloride, and sodium are retained in the tubule. Due to its action there is a deçrease in
insulin release resulting increase of blood sugar level. It is available as 20 mg tablets. It is blurred vision, sinusitis
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36
Phamacokinetics: Administered by mouth, onset action hour, duration of action
1
quickly absorbed when administered orally.
Indications : Oedema of pregnancy, oedema due to renal disease, hepatic disease, cardiac hours, excreted in urine, plasma half life 18 hours.
anticoagulants, decrease
disease. Drug interactions: It decreases effect of antidiabetics drugs,
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cholestyramine. The effect of indapamide is decreased by drugs indomethacin,
Dosage: Adult: 20 to 60 mg daily single early morning dose. absorption
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and Non steroid antiinflammatory drugs.
Contraindications : Electrolyte deficiency, dehydration, renal disease, hypersensitivity, 1.5mg, 2.5mg
Brand names: Indapamide: Tablet Perifer, Lorvas, Diurix, Indicontin, Divret,
Hypokalemia.
tablets
Side effects: Weakness, hearing loss, fatigue muscle cramps, Gastro intestinal disturbances,
dry mouth, hyperglycemia, head ache, blurred vision. WEAK DIURETICS (CARBONIC ANHYDRASE INHIBITORS)
Drug interactions: It decrease effect of antidiabetics, anticoagulants. ACETAZOLAMIDE: It is a diuretic drug. It is a fine white crystalline powder have no
renal trubules. It
Brand names: Xipamide : Tablet Xipamid 20mg odour and is tasteless. It inhibits carbonic anhydrase activity in proximal
decreases reabsorption of water, sodium, chloride, potassium, bicarbonate. It reduces intra
a metabolic acidosis.
ocular pressure and is used in the treatment of glaucoma. produces
It
INDAPAMIDE : It acts as diuretic. It acts on proximal section of distal renal tubule and
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250 mg tablets,
loop of Hende by inhibiting reabsorption of sodium.
It block calcium channel and Its molecular formula is C4HgN4O3S2. It is available as acetazolamide
vasodilation is caused. It is available as 1.25mg, 1.5 mg tablets. capsule slow release, 500 mg, Inj. acelazolamide 500 mg.
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and thick
Mechanism of action : Indapamide acts on porximal part of distal renal tubule
reabsorption of sodium, chloride ions. It acts by sO2.NH 2
ascending loop of Henle by inhibiting CH3.CO.NH-
channel used in oedema, hypertension.
direct vasodilation caused by blocking of calcium
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rectifier potassium current (IKs) without altering
It blocks the slow component of delayed
Ph
Ph
Ph
It diuresis
inward rectifier current. Specifically it blocks or Ifacetazolamide is regularly administered it has a limited value of diuretic.
the rapid component (IKr) or the acetazolamide drowsiness numbness
cause
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KCNE1. Indapamide is also thought to action is ceased by the sixth day. Large doses of
KCNQ1 and
antagonizes the action the proteins
prostaglandin PGE2 and tingling of face, arms and legs.
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stimulate the synthesis of the vasodilatory hypotensive proximal
treatment of Hypertension, diuresis, edema in Mechanism of action: Acetazolamide drug inhibits carbonic anhydrase action in
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Indications: Indapamide is useful in the chloride, bicarbonate,

renal tubules, it decreases the reabsorption of sodium, potassium,
congestive cardiac failure.
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Text Book of Pharmacology
2 PA
This leads to alkaline urine and an increase in the excretion of bicarbonate, sodium, Pharmacokinetics: Onset action-1 hour, peak plasma concentration 4 hours, duration 6 to
crosses placenta, enters
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12 hours, plasma half life 5 hours to 6 hours, excreted by kidneys,
potassium, and water. also decrease carbonic anhydrase in the central nervous system
increasing seizure thresh hold. breast milk.
Ph
Ph
Ph
Drug interactions : Increased toxicity with salicylates. Increase action of amphetamines,
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Lumen quinidine.
Acetazolamide Blood
Diamox, lopar SR,
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Brand names: Acetazolamide: Tablets, Capsule. Actazid, Avva SR,
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Actamide 250mg tablets

H2O+CO co CO,
Prevent the of Overdose :Lavage taken orally, administer dextrose-normal saline.
if
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Carboni Treatment
enhrdreNco, reabsorptioa
POTASSIUM sPArING DIURETICS (Aldosterone antagonist)
RCO3,Na odourless
SPIRONOLACTONE : It is a potassium sparing diuretic. It is a buff coloured
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HcO mouth. It increascs
powder. It is very slightly soluble in water. It is usually administered by
retention of sodium and excretion of potassium by acting on distal part of
the distal tubules.
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Na
Epithellal cell
is decreased. It is an
of renal tubule The excretion of sodium is increased and excretion of potassium
effective when
inhibitor of natural corticosteroid harmone aldosteron. Spironolactone is
patients on low salt diet. If aldosteron output is low it is ineffective. It
given by mouth to a
Fig. 34 Role of carbonic anhydrase sodium retention by epithelial cell of renal tuble is effective in the treatment of hypertension, edema due to CCF,
female hirsutism, nephrotic
O4S.
syndrome. It is available as 25mg, 100mg tablets. Its molecular formula is C24 H32
Inthe eyeaintra ocular pressure is also decreased. Useful in drug induced oedema. Mechanism of action : The drug spironolactone is a potassium sparing diuretic. It competes
Ipteations: Open angle glaucoma, edema in CHE, epilepsy (petit mal, grand mal), drug of sodium,
with aldosterone at receptors site in the distal tubule resulting in increase
induced oedema, mountain sickness.
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chloride ions and water.
Dosage: Adult: Mountain sickness, orally 250 mg 12 hourly.
LInterstitial
Lumen
Renal stones Adult: 250, mg at bed time space
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Spironolactone
Closed angle glaucoma : Adult: orally 250 mg 12 hourly, to be used as short term aldosteron
antag9u MR
treatment. ALD ALDo-ALDO
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Open angle glaucoma : Adult by mouth (orally) 250 mg to gm daily in divided doses.
1
Nucluus
body
Ph
Ph
Ph
Edema in CHF : Adult IM or IV 250 mg daily early morning. Child: 5 mg per kg mNA
ha
weight at 8 AM once daily.

Seizures: Adult: Orally 375 mg to 1000 mg per day.
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Nat
Chil 8 tó 30 mg per kg body weight orally in equal three doses daily.
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Mitochondria
Contraindications: Hypersensitivity, Liver disease, renal disease, pregnancy, acidosis,
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sodium potassium depletion. Lactation, diabetes, gout.
calculi, head
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Side effect: Acidosis, hypokalemia, drowsiness, rashes, fever, dysuria, renal

ache, confusion, fatigue, nausea, weight loss, taste alteration, urticaria,
anemia, leukopenia,
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Fig. 3.5 Drug act on the late distal tuble and collecting duct
hyperglycemia. myopia, tinnitus, constipation, stevens johnsons syndrome.
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154 FU A Text Book of Phermacology-
It is a specifñc antagonist of aldosterone, acting primarly through competitive binding of Mechanism of action: Triamterene acts on distal tubule, it inhibits reabsorption of sodium
y
recptors at the aldosterone-dependent sodium-potassium_exchange site in the distal and chloride ions, it increases retention of potassium. It is useful in oedema, hypertension,
convoluted renal tubule. Spironolactone cãuses increased amounts of sodium and water to and is used with the other diuretics.
Ph
Ph
Ph
be excreted, while potassium is retained. Spironolactone acts both as a diuretic and as an Indications: Edema, hypertension, CCE, nephrotic syndrome.
ha
antihypertensive drug by this mechanism. It may be given alone or with other diuretic
Dosage: Adult orally 10 mg once or twice daily after meals. Maintenance doses may be
agents which act more proximally in the renal tubule. Aldosterone interacts with a administered on alternate days.
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ytoplasmic mineralocorticoid receptor to enhance the expression of the Na+, K+-ATPase
Contraindications: Hyperkalemia, renal failure, diabetes, pregnancy, lactation, gout,
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and the Na+ channel involved in a Na+ K+ transport in the distal tubule. It binds to this
hepatic dysfunction.
mineralcorticoid receptor, blocking the actions of aldosterone on gene expression.
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Aldosterone is a hormone; its primary funetion is to retain sodium and excrete potassium in Side Effects: Headache, dry mouth, nausea, cramps, rash, weakness, blood dyscrasias.
the kidneys Pharmacodynamics: Orally onset action 2 hours, peak plasma concentration 4 hours,
aications: Hypertension, edema of CHF (congestive heart failure) Hypokalemia, excreted in urine.
c
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Dasage : Adult : 25mg to 200 mg daily in single or divided doses orally Drug interactions: Increased effect of antihypertensive drugs NSAIDs reduce diuretic
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effect of hydrochlorthiazide.
hild: to 2 mg per kg body weight, in equal two doses.
1
Brand names: Triamterene: Tablet Ditide, Frusemene 50mg

oniraindications: Hypersensitivity, anuria, hypokalemia, pregnancy, dehydration,
lactation, renal disease. AMILORIDE : (Amiloride hydrochloride): Amiloride hydrochloride is a mild diuretic. It
acts on distal part of the distal tubule. It increase excretion of sodium, chloride and decrease
Side etfecisProlong use in young patients may cause hirsutism. The other side effects are:
:
the excretion of potassium. Its an odourless, yellow crystalline powder soluble in water. Itis
metabolic acidosis, hyperkalemia, hyponatremia, impotence, gynecomastia, irregular
administered orally and its effect/action begins after 2 hour and duration of action is 24
menses, hirsutism, deepening voice, ammenorrhea, headache, confusion, drowsiness,
hours. It is available as tablet containing amiloride hydrochloride 5 mg with
ataxia, rash, urticaria, cramps, nausea, vomiting, anorexia, gastritis.
hydrochlorthiazide 50mg. Usual dose for, adult is amiloride 5mg to 10 milligrams, orally
armacokinetics: On set action 24 hours, peak concentration 48 to 72 hours, metabolized
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dose may be increased to 20 milligrams daily if needed. Its molecular formula is CgH9 Cl2
in liver, excreted in urine, crosses placenta.
NyO:2420
interactions Decreaselithium. effect of anticoagulants, increased effect of antihypertensives
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(antihypertensives) digitalis, Structural Formula :
Spironolactone: Tablet Aldactide, Aldactone 25mg, 100mg

frand names: cO.NH.C.NH
Cl
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ireatment of overdose of spironolactone. Lavage if taken orally, administer IV fluids,
monitor hydration. H2N
NH NH2 HCI: 2H20
Ph
Ph
Ph
"NH2
1NIIRITORS OF RENAL EPITHELIAL NA+ CHANEL:
ha
(Amiloride Hydrochloride)
IRIAMTERENE It is an odourless, yellow crystalline powder with a bitter taste. It is Mechaniom of action : The dnug Amiloride acts primarily on the proximal distal tubule by
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soluble in water. When administered orally, tablets are better absorbed than capsules. It is increase of sodium, chloride ions and water.
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effective in the treatment of oedema, hypertension, hepatic cirrhosis, nephrotic syndrome.

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Triamterene is available as capsules containing 50mg of triamterene. In combination with
benzthiazide, frusemide preparations are available
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PU A Toxt Book of Pharmacology- Pharmacology of Drugs Acting on Urinary System 157
Drug interactions : Increased efect of antihypertensive drugs, the diuretic effect is reduced
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LATE DISTAL TUBULE/COLLECTING DUCT
with NSAID'S.
Collecting duct wall Interstittum
Ph
Ph
Ph
Lumen
Brand names: Amiloride : Tablet Biduret, Amilochlor, Biduret-L
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oSMOTIC DIURETICS
MANNITOL : Mannitol acts as osmotic diuretic. It is an odourless, white crystalline
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Na Natchannel
Na" Na
powder with sweet taste. It is soluble in water. its molecular formula is CsH14°6
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AMILORIDE BLOCKS NaK Reduces Na*/K*pumping

pump OH QH
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K Kchannel
K* HOH2C-C c-C-CH2OH
K
OH OH H
c
c
Reduces K ls (Structural formula of mannitol.)
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KSPARING DIURETIC AMILORIDE Mannitol is administered by intravenous route. it is available as, 5%, 10%, 20% solution
mannitol infusion. Mannitol act by increasing osmolarity of glomerular filterate due to
Fig. 3.6 A representative amiloride bind to sensitive sodium channels
which the osmotic pressure of fluids in renal tubules increases. There is a decrease in
t inhibits sodium reabsorption in the distal onvaluted tabules and collecting duets in the reabsorption of electrolytes and water, which results increase in urinary output, sodium
kidneys by binding to the amiloride-sensitive sodium channels. This promotes the loss of chloride exCTetion.
sodium and water from the body, but without depleting potassium. Amiloride exerts its Mechanism of action Mannitol acts by increasing osmolarity of the glomerular filterate
potassium sparing effect through the inhibition of sodium reabsorption at the distal which increase osmotic pressure of fluid in the renal tubules. It decrease reabsorption of
convoluted tubule, cortical collecting tubule and collecting duct; this decreases the net the sodium, electrolytes, and increase the urinary excretion, sodium and chloride ions
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negative potential of the tubular lumen and reduces both potassium and hydrogen excretion.
secretion and their subsequent excretion. Amiloride is not an aldosterone antagonist and its
Indications: Edema, systemic diuresis in cerebral oedema, chemical poisoning, renal
effects are seen even in the absence of aldosterone It cause increase in retention of
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failure, decrease intraocular pressure.
potassium.
Dosage: Adult: Oliguria (prevention) Intravenous 50gm to 100 gm, 5% to 25% mannitol
Dosage: Adult 5 mg to 10mg orally, daily.
solution daily in 3 to 6 hour duration.
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Indications: Oedema, mild to moderate hypertension, congestive cardiac failure, nephrotic
Oliguria treatment : 300 to 400 mg per kg body weight up to 100 gm 15% to 20% solution, in
syndrome.
Ph
Ph
Ph
2 to 6 hour duration.
Contraindications : Hypersensitivity, renal failure, hyperkalemia, pregnancy, lactation,
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Child:250mg to 2gm per kg body weight 209% sohution in 2 to 6hour duration.

diabetes, hepatic dysfunction.
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of Renal failure : Adult: Intravenous route 50gm to 200gm in 24 hours 10% to 20% solution.
Side effects: Abdominal distension, anorexia, nausea, vomiting, constipation, dryness
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cramps, postural hypotension, rashes, confusion, pruritis, visual Intra ocular pressure : Adult : 2gm per kg weight 10%, 20% solution run over 1 to 2 hours.
mouth, weakness, muscle
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disturbances. Child:1 gm per kg weight 10%, 20% solution run in 1 to 2 hours
Pharmacokinetics: When oral dose of 20mg administered peak plasma concentration is Contraindications : Hypersensitivity, intracranial, bleeding, dehydration, renal failure,
ac
attaíned with in 2 to 3 hours. Serum half life 6 hours. excreted unchanged in urine. pregnancy, lactation, congestive heart failure.
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158 A Tert Book of Pha mecology- Pharmacoloay of Drugs Acting on Urnary System
159
Side efiecta Hradache, marked diursis, thiret, dry meuth, nausen, vomiting.
hypotension B82ANTT DIDRETICS
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dry motth hest pain, chilla, feves, electrolyte imbalance, Jos of hearing, blurred vision,
tasal rutestíon. Anti dioreties are the drugs which decrease urine qutput, The following
Ph
Ph
Ph
drugs have specific
anti-dnureti effect. The drug are classified
Jhamarnkinrtin: On aet action
ha
3) minutes,
ura. plasma half life-2 hurs. excreted in urine.
diuresls occur ; hour duration of nction 4 to6
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Cassification of anti-diuretics
Drug interactions Increase etfet of EDTA (ethyl enedeamine tetra acetic acid).
Decrease
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eftet of lithium
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irand names: Mannitol Under same
brand name of Mannitol 20% by diffefent Mig Drug act on Anti-diaretie
orhpanies Thiazide diuretics Other drug
hormone (ADH, Vaserressin)
Amuloride Indomethktn
Treatment ef over dose: The infusion should be discontinued. Correct Vasopressin Carbamazpine
fluid and electrolyte Desmopressin
c
c
imbalance. Lypressin
Chlorpropamide
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Terlipressin
sOsoRBIDE AND GLYCEROL: These are orally active osmotic diuretics. These drugs
may be used to reduce intraccrular or intra cranial tension. Intravenous glycerol can cause
haemolysis. Iose 0.5 to 1.5 gm per kg as oral liquid/solution.
:
ANTIDIURETIC HARMONE (ADDp

The anti diuretic harmone is released by the posterior lobe of piutary along
Table 1 showing diuretic drugs and their action on the excretion of electrolytes. with oxvtocin.
it has a vasopressor effect so it is called as vasopressin. The
degree of dehydration and
irculating blood volume insluence the scretion of anti diuretic harmone. Alcohol and
S.No.Name of Diuretic Exeretion of Urinary Electrolytes Efficacy of drug
chlorpromazine depress release of ADtH.
drug Na K* HCO3
CI Antidiuretic harmone acts by increasing reasbsorption of water in the distal tubules and in
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the loop of Henle, due to which the amount of water in the urine is decreased. It does
Acetazolamide Mild not
effet the ercretion of electrolytes. Antidiuretic harmone is used in the treatment of
rid patients
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Ammlornde Low suftering from Diabetes insipidus.
Furasimide (lasix) High eficacy Pharmacological action of Antidiuretic harmone
Mannitol 20 High Kidneys: Due to the effect of anti diuretic harmone the distal tubules and collecting duct of
y
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nephron berones permeable to water which leads to reduction of total volume of urine.
Spironolactone low The absence of antidiuretic harmone cause the disease diabetes insipidus.
Ph
Ph
Ph
Thiazide Intermediate Cardiovascular System: ln large doses ADH raise blood pressure due to direct stimulation
ha
of vascular smooth muscles. due to direct depressant effect of Antidiuretic harmone, on

7 Triamterene Low
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myocardium, blood pressure falls due to narrowing of coronary blood vessels.
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Smooth Muscles: Antidiuretic harmones in large doses stimulates smooth muscles of

Means more action gastro intestinal tract cause increase in peristalsis. ADH should not be administered orally
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Means negative or less action as it is destroyed by trypsin. It is administered by parenteral route
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VA Text Book of Phamacology-l
5. There is reduction in cardiac output and increased risk of
arrhythmia which is
The antidiuretic drugs are as under
reverseble, the cardio toxic effect, by nitroglycerin tablets.
y
CIDThiazides
There is reduction of secretions, as in the central diabetes insipidus. The urine
6.
in
The thiazide diuretics have an antidiuretic effect in diabetes insipidus. They (Thiazides) act
Ph
Ph
Ph
diabetes insipidus is tasteless where as the taste of urine in diabetes mellitus is
by decreasing the rate of glomerular filteration by producing negative sodium balance. The on urine of a
The example is to see ants and other insects are found collected
ha
voume of urine is decreased due to this action. Hydrochlorthiazide 25mg to 50mg is Sweet.
diabetes mellitus person where he urinates on ground. The condition Polyurea,
commonly used.
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Polydipsia, Hypoosmolarity of urine and hyperosmolarity of plasma is observed.
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VASOPRESSIN (8-L-Lysine Vasopressin)

DESMOPRESSIN: It is a synthetic antidiuretic harmone. It promotes reabsorption of water
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It is a synthetic polypeptide harmone which have antidiuretic action. It have no effect on
by the action on renal tubular epithelium, cause smooth muscles contraction. It has
electrolyte reabsorption. It causes contraction of blood vessels, and cause blood clotting
vasopressor effect similar to vasopressin. It is available as intra nasal pippets 0.01 mg per
stimulation. It is administered subcutaneous, intramuscular or intravenously. It is available
ml, injection 4 Hg per ml, tablets 0.1 mg., 02 mg
c
c
as Injection vasopressin 8-L-Lysine 20 IU per ml ampoules.
Mechanism of action: Desmopressin drug promotes and increases reabsorption of water
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sdtcations : Pitutary diabetes insipidus, oesophageal bleeding
and electrolytes by its action on renal tubules epithelium. It causes constriction of smooth
Dosage: 1M. IV. or subeutaneously 0.5ml (10units). 20 units dissolved in 5% dextrose
muscles. It increases platelet aggregation by the increase of the plasma factor VIl levels,
solution 100 to 200 ml, and the solution is infused in 15 to 30 minutes.
and results in the vasopressor effect.
ontraindications: Chronic nephritis, vascular disease, hypersensitivity.
Indications: Hemophilia, non nephrogenic diabetes insipidus, symptoms of polyuria,
Side effects: Nausea, pallor, abdomen cramps, myocardial ischaemia, untimely desire to polydipsia caused by pituitary dysfunction, nocturnal enuresis.
defecation (defacate), headache, drowsiness, vulval pain, increased blood pressure,
Dosage:
sweating, urticaria.
Diabetes insipidus: Adult: Intra nasal 0.1 to 0.4 mg daily in divided doses one to four
Vasopressin is a harmone released by posterior pituitary and it is very powerful natural
sprays with pump. IV/ SC 0.2 to 04 mg daily in divided doses. Child:6 month to 12 year
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antidiuretic drug) hormone. The anti diuretic hormone (ADH) is synthesized in supraoptic
intra nasal 3mg daily in divided doses.
nucleus and paraventricular nucleus of the hypothalamus. The principal stimuli for Anti
Diuretic Hormone (ADH) is as under. Primary noctural enuresis :
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Child above 6 year age intranasal 20 pg (0.2 mg) at bed
Hyper-osmolality of blood Osmoreceptors stimulation Antidiuretic secretion. time.
Reabsorption of water from renal tubules to Normal osmolality.
Hemophillia, / Von willebrands disease.
v Adult and Child: 0.3 g per kg body weight,

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The main action of ADH (Anti Diuretie Hormone) (through receptor) is platelet intravenously in sodium chloride infusion to
be administered over 15 to 30 minutes.
aggregation, vasoconstriction, gastro intestinal tract smooth muscles stimulation and
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Contraindications: Hypersensitivity, nephrogenic
neurotransmitter at the central nervous system. It also helps in the blood coagulation. diabetes insipidus, pregnancy, lactation,
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hypertension.
The adverse effects of the ADH are:
Side effects: Nasal irritation,
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1. Allergy, the iritation in nose, oedema, ulceration, rhinitis and nasal congestion. head ache, drowsiness, flushing, vulval
Cramps, increased blood pressure. pain, nausea,
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2 Facial pallor due to vasoconstriction.

Pharmacokinetics : Onset action
1 hour, plasma peak concentration 2 hours,
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3. Increased chances of gangrene. duration 8 to
20 hour,
4. There is precipitation of Angina due to reduced coronary blood circulation. DrugInteraction: Increase effect: carbamazepine
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clofibrate, chlorpropamide.
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Text Book of Pharmacology-ll
Pharmacology of Drugs Acting on Urfnary System
Brand names: Desmopressin : Tablet Minirin 0.1mg. Minirin
163
injection, D-void, Minirin Mechanism of action : [t antagonizes COX by binding to the
Nasal spray Sml pack 1meg/one mi. upper portion of the active
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site, preventing its substrate, arachidonic acid, from
entering the active site. Indomethacin,
unlike other NSAIDs, also inhibits phospholipase A2, the enzyme responsible
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TERLIPRESSIN: Terlipressin is an analogue of vasopressin for releasing
used as a vasoactive drug in arachidonic acid from phospholipids. It is more selective for COX-1 than COX-2,
the management of hypotension. It has been found to be effective which
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when norepinephrine accounts for its increased adverse gastric effects relative to other NSAIDs.
not
does heip. COx-1 is
required for maintaining the protective gastric mucosal layer.
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Mechanism of action: It an analogue of vasopressin, acts on three different Indications : Acute gouty arthritis, rheumatoid arthritis, not controlled by
receptors, aspirin,
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vasopressin receptor Vla (which initiates vasoconstriction, liver gluconeogenesis, ankylosing spondylitis. Bartte's syndrome.
platelet
aggregation and release of factor VIl), vasopressin receptor Vlb (which fnediates
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Dosage: Adult 25 mg to 50 mg bid or tid not to exceed 200 mg per day.
corticotrophin secretion from the pituitary) and vasopressin receptor V2
which controls free Contraindications : Hypersensitivity, asthma, renal disease, hepatic disease, ulcers
water reabsorption in the renal medullar. The binding of terlipressin to disease,
the V2 receptor pregnancy, lactation.
activates adenylate cyclase which causes the relcase of aquaporin 2 channels into the
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cells
lining the renal medullar duct. This allows water to be reabsorbed down Pharmacokinetics: Orally onset action 1 hour. Peak plasma concentration hour,
an osmotic 3 half life 1
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gradient so the urine is more concentrated. to 1% hour. It is metabolized in liver excreted in urine, crosses placenta,
excreted in breast
milk.
Indication: It is indicated commonly used to stop bleeding of varices in the food
pipe
(ocsophagus). Drug interactions: Increased action of phenytoin, sulphunamides.
Decreased action of
triamterene. It should not be administered with antacids.
Uses: It is a medicine similar to a naturally occurring hormone present in the body, known
as antidiuretic hormone (ADH) or vasopressin. It causes narrowing of blood vessels Side effects: Nephro toxicity, hematuria, oliguria vomiting
nausea, anorexia, diarhoea,
(vasoconstriction), thereby limiting blood flow to a particular area of the body. flatulence, cramps, dry mouth, peptic ulcers, ulceration, perforation,
drowsiness, dizziness,
fatigue, insomnia, anxiety, depression, tachycardia, hypertension,
rash (skin), pruritis,
sweating. hearing loss, blurred vision, tinnitus, blood dyscrasias.
OTHER DRUCS
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Brand names: Indomethacin : Microcid, Recticin, Indocap,
INDOMETHACIN: It has been found to decrease polyuria in diabetes inspidus. It can be Indoflam, Insure capsule 25mg
50mg. 75mg
given in combination with hydrochlorthiazide or amiloride in nephrogenic diabetes
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insipidus. Indomethacin is a prostaglandin G/H synthase (also known as cyclooxygenase
CARBAMAZEPINE : It is an antiepileptic drug. It reduces
or COX) inhibitor that acts on both prostaglandin G/H synthase 1 and 2 (COX-1 and -2). the urinary volume in diabetes
insipidus of pituitary origin. Its higher doses are not required.
It is a strong non steroidal anti inflammatory drug. It promptly act as antipyretic. It relieves Its side effects are marked.
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The adverse (side effect) are more harmful
inflammation of tissue injury related pain. It is an odourless, tasteless, yellow brown than its uses, due to this reason it is of little
value in the treatment of diabetes insipidus.
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crystalline powder. It is slightly soluble in water. its chemical formula is C19Hi6CINO4
Mechanism of action: It inhibits sustained repetitive firing
by blocking use-dependent
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is rapidly absorbed when taken by mouth. It was introduced in 1963. sodium channels. Pain relief is believed to be associated with blockade
of synaptic
transmission in the trigeminal nucleus and seizure control with reduction
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of post-tetanic
potentiation of synaptic transmission in the spinal cord. It also possesses anticholinergic,
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central antidiuretic, antiarrhythmic, muscle relaxant,

antidepressant (possibly through
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CH0 LcHCOOH blockade of norepinephrine release), sedative, and neuromuscular-blocking
properties.
(Struclurad formula Indomehacin)
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PUA Text Book of Phamacology-l Pharmacology of Drugs Acting on Urinary System 165
164
Indications: It is used for the treatment of epilepsy and pain associated with true trigeminal 3. Weak diuretics: It include drugs (i) Acetazolamide (ii) spironolactone (ii) Triameterne iv)
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neuralgia. Amiloride.
4. Osmotic diuretics : It include drugs () mannitol Gi) Isosorbide lii) Glycerol.
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Uses: It is an anticonvulsant structurally similar to tricyclic antidepressants. It is used to
treat partial seizures, tonic-clonic seizures, pain of neurologic origin such as trigeminal Q.5. How does water act as a diuretic?
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Ans. When water is taken in excess quantity it acts ad diuretic. The anti diuretic harmone
neuralgia, and psychiatric disorders including manic-depressive illness and aggression due (ADH)
to remain inhibited and nephron becomes permeable to water. In water diuresis water is excreted
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dementia.
Brand name: Apo Carbamazepine Tab 200rmg.oral. Carbamazepine 200 Tab 200mg. oral. from body in excess of solute. In edema there is retention of sodium in tissue, and water
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Carbamazepine CR 400mg. oral. retention is secondary in this disease. Water does not act as good diuretic. The water as diuretic
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is useful in urinary tract infections.
CHLORPROPAMIDE: It is a long-acting oral hypoglycaemic drug. It reduced urine Q6. What are the precautions to be used while administering diuretics?
volume in diabetes insipidus of pituitary origin. It is effective in diabetes insipidus of renal Ans. The diuretics cause postural hypotension. The blood pressure of the patient falls, which should
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origin. It is not active when antidiuretic harmone is totaly absent. A thiazide may be added be monitored in siting, standing and lying position. If blood pressure is observed low, patient
be advised to rise slow from sitting lying position. Patient be advised to take oral
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in increase response of the drug. It is useful in the treatment of D.. (diabetes insipidus)
dose 125 mg to 500 mg daily. liquids/fluids to maintain blood pressure and electrolytes balance.
Q7. What should be the time for administration of diuretics ?
The above drugs act as antidiuretics.
Ans. The diuretics should be administered early morning at 8 am. The diuretics cause diuresis. The
patient has to pass urine for number of times. In case diuretic drug is given to patient at bed
REVIEWQUESTIONSS time, the sleep of the individual will be disturbed since he has to go to urinal for passing of
urine. To prevent nocturia the diuretics should be given to patient in the morning
Q.8. What are antidiuretics ?
VERY SHORT ANSWER QUESTIONS Ans. Antidiuretics are the drugs which decrease urine output.
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Q1. What are diureties? Q9. Name the drugs which acts as antidiuretics
Ans. The drugs which increase the rate and volume of urine are called diuretics. Ans. i) Antidiuretic harmone (ii) Thiazides (ii) Vasopressin (iv) Desmopressin, (vi) Amiloride {vi)
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Indomethacin (vii) Carbamazepine (vii) Chlorpropamide.
02 How diuretie drugs impart action in our body?
Q.10. If dose of anlidiuretic drug is missed, then what steps are to be taken by the patient ?
Ans. The diuretic drugs have action mainly on nephrons which increase excretion of excess fluids.
The diuretic drugs cause a net loss of sodium ions and water from the human body. Ans. If by mistake one dose is lapsed/missed, take dose when remembered that may be
up to 2
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hours before next dose. Two doses i.e. one missed dose plus one next dose should not be taken,
Q3. What is the use of diuretic drugs?
it will make a double dose which is harmful. Take only
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one dose. The steps be taken not to
Ans. The diuretic drugs are used in the treatment of hypertension, oedema, drugs poisoning to miss/skip dose next time. To take.double dose or over dose may prove harmful as it may cause
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increase excretion. toxicity.

94. Explain the classification of diuretics.
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Q.11. What are urinary antiseptics ?
Ans. Diuretics are classified in following groups: Ans. The drugs when administered, attain antibacterial
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concentration in urine and have no action or

1. Loop diuretics, diuretics of high efficacy. It include drugs () Furosimide (i) Bumetanide other body systems are called urinary antiseptics.
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(ii) torasemide Q.12. Name the urinary antiseptie drugs.
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2. Medium efficacy diuretics: It include drugs: 6) Hydrochlor thiazide (i) Benzthiazide (ii) Ans. () Nitrofurantoin, (ii) Methenamide (ii) Nalidixic
acid (iv) Phenazopyridine are common
Clopamide iv) Hydroflumethiazide, (v) Indapamide, (vi) Xipamide, (vii) Chlorthiazide.
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used as urinary antiseptics.
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166
PV
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A Text Book of Pharmacology- Pharmacology of Drugs Acting on Urinary System
Q.33. What is stevens johnson 167
syndrome ?
Ans. It is a serious, some times fatal 9.21. What is Brucellosis?
inlammatory disease which effects children and young
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It is characterised by onset adults. Ans. Brucellosis is a disease caused by one of the species gram
of fever, ulcers on lips, eyes, nasal passage, negative coccobacillus brucella. This
due to which pneumonia. Joint mouth and genetalia, disease is found occuring in rural areas among, slaghterhouse
pains may occur. The syndrome may be an workers, farmers, meat packers.
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allergic reaction to certain drugs. This syndrome It is primarily a disease of animals like
may also develop in herpes virus infection sheeps goats, pigs, other animals. This disease 1s
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and during pregnancy due to complications. aquired by men humans) by ingesting contaminated milk or milk products.
It is also acquired
Q.14. What is the treatment of stevens Johnson by persons (humans) through a break in the skin like
cut injuries/wounds. The sign and
syndrome ?
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Ans. Treatment includes drugs symptoms of this disease are chills, fever, malaise, sweating, weakness,
antibiotics to cure pneumonia, and glucocorticoids, headache, anorexia,
analgesic, mouth weight loss. The spleen is enlarged, the individual. Suffer from joint pain,
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wash, sedatives. The patient be advised myalgia. The fever

to take complete bed rest. comes in waves fever rises in the evening and subsides
Q.15. What is plasma peak concentration? during day time. Brucellosis is also
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known as malta fever, rock fever, cyprus fever. Though it is rarely
fatal disease yet pneumonia,
Ans. It the maximum amount of a drug, as the highest concentration of drug measured meningitis, encephalitis can develop due to severe infections complications
immediately I due to the
after the drug has been administered. The time takern to disease.
attain highest concentration in the.
blood of the drug administered is calculated. Q.22. What is the treatment of Brucellosis?
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Q.16. What is plasma half life ? Ans. Brucellosis can be cured by tetracyclines, and with
streptomycin. The patient should be
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Ans. It is the length of time reauired to reduce a drug level advised complete bed rest with treatment. Nalidixic acid is also useful in the
to one half of its initial value. It refers to treatment of
time necessary for a drug to reduce plasma value to one half of its initial value. It Brucellosis.
is also called
radio active half life. Q.23. What is Anuria?
Plasma half life (serum half life) is the term applied to the disappearance of total amount Ans. Anuria is the inability to urinate. The urine output is less
of than 100 ml to 250 ml. per day. It may
drug from the body. be due to kidney dysfunction or kidney failure. A patient can live upto 2 weeks suffering
from
Q.17. What is peak level? anuria, A rapid decrease in urine out leads ultimately to anuria and uremia. Death may occur
with in 24 hours of the total loss of urinary function. Anuria is also called anuresis.
Ans. It is the time taken by a drug administered to attain highest concentration
in the blood of
patient for action, after attining highest concentration, the concentration declines, and the LONG ANSWER QUESTIONS
pharmacological action of the drugs goes on decreasing
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Q.1. Describe the uses of high ceiling diuretics Refer 3.1
Q.18. What is biologic half life ?
Q.2. Explain the pharmacology of Furosemide Refer 3.1
Ans. It is also known as metabolic half life, efective half life. It is the time required by the body by
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Q.3. Discuss the medium efficacy diauretcis benzothiadiazines, write the pharmacologY
regular physiologic processes to eliminate half of an administered dose of drug. of
hydrochlorothiazide Refer 3.1.
Q.19. Which drug is used in the treatment of mountain sickness ?
Q4. Explain the mechanism of action, side effects, indication, contraindication and use of hydro
Ans. Tablet acetazolamide is used in the treatment of mountain sickness. It is administered orally
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flumethiazide: Refer 3.1
250 mg 12 hourly. Individual should take complete rest during treatment. Q.5. Describe the weak diuretics (carbonic anhydrase inhibitors) explain the pharmacology of
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Q.20. What is hirsutism ? acelazolamide R<fer 3.1
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Ans. Hirsutism means excessive growth of hair on the body, may be due to hormonal dysfunction Q6. Explain diuretics, classity them, write the pharmacology of chlorthalidone. Rgtr 31
or drugs side effect (as in spironolactone) when treatment of specific disease is completed the 07. Describe the anti-diuretic, cassify them write the pharmacology of Vasopresin. Refer 3.2
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excessive growth of hair is stopped. The excess hair can be removed by shaving, plucking,
Q.8. Describe the mechanism of action, adverse effect, indication, dose and brand name of
rubbing with pumice or chemical depilation. Facial hair may be removed by bleaching
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spironolactone Refer 3.1.

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Q9. Explain the Pharmacology of amiloride :Refer 3.2
010. Describe the mechanism of action, side effect of xipamide Refer 3.1
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268 PV A Text Book of Pharmacology-l Pharmacology of Drugs Acting on Urinary System
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I. MULTIPLE CHOICE QUESTIONS The diurectic drugs be adminislered ealy morning for the reason
1. Diuretics are the drugs while acting on nephrons. (a) To avoid vomiting
(a) increase rate and volume of urine (b) To prevent fever
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b) decrease urine volume
To avoid nocturia
neither decrease nor increase urine volume
(c)
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(d) To avoid weakness
(d) none of the above. Diuretic when administered there may be a side effect ?
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2. Which of the following drug is diuretic of high efficacy?. a) Posturnal hypotension
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(a) Mannitol b) Increased blood pressure
(b) Amiloride
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(c) Decrease urine output

Xipamide
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(d) None of the above
(d) Frusemide (Lasi) If the diuretics are administered to a diabetic patient what should be the precautions/action
The diuretic action of frusimide (Furosemide) goes on increasing with increasing dose. How taken7
much urine quantity is produced in a day by Lasix (frusemide):
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a) To check blood sugar, urine sugar of the patient
(a) 1 litre b) Advice the patient to stop smoking
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b) 5 litre )No need to monitor blood glucose
10 litres (d) None of the above.
(d) 20 litres 10. Mannitol is administered to the patient by
Which of the following is weak diuretic? (a) Oral route
(a) Spironolactone (b) Intravenous infusion
b) Copamide (c) By nasal inhalations
Bumetanide (d) By none of above routes.
(d) Torasemide
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The Antidiuretic Harmone (ADH) has vasopresor effect due to which it is called as
Name the medium efficacy diuretic (a) Electrolyte
(a) Acetazolamide
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b) Trypsin
)Hydrochlorthiazide (c) Vasopressin
( Bumetanide (d) None of these.

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(d) Isosorbide 12. Which of the following drugs is used as urinary antiseptic?
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6 Water in excess quantity acts as a diuretic or otherwise (a) Nitrofurantoin
(a) No b) Indomethacin
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c6) Yes c) Desmopressin

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() Neutral (d) Chlorpropamide
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(a) Cause edema 13. Which of the following drugs is used as acidifier?
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a) Dilute hydrochloric acid
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(b) Sodium bicarbonate

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170 PU A Text Book of Pharmacology!
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c) Magnesium sulphate
20. fa drug administered causes drowsiness, patient be given
(d) Potassium permenganate what advice ?
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(a) To operate machinery
fa dose of drug to be taken at 3AM is missed, the patient b) To drink alcohol
should take drug
(a) As soon as he remembered
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(c) Not to drive and to avoid work with machinery
b) He should take two doses at 8 PM
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(d) To discontinue therapy.

He should wait for 8am next day 21. Anuria is meant for
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(d) He should stop taking treatment (a) Polyuria
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15. Hirsutism is a discase having which of the following characteristics/

symptoms? (b) Oliguria
(a) Alopecia
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()Enuresis (Bed wetting)
b) Excessive growth of hair on body (d) Inability to urinate
c) Grey colour of hair 22 When frusemide is administered there is a change in ?
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(d) None of these (a) Acid base balance is changed
16. Brucellosis is primarily a disease occurs in
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b) Edema is increase
(a) Monkeys () No change in acid base balance
Rats a) No change in blood pressure.
() Goats, sheeps, pigs 23. First symptom of digoxin overdose is-
(d) Children a) Fainting spells
7. Name the drug of choice for the treatment of Brucellosis ? b) CIT disturbance
(a) Chloroquine c) Ectopic on ECG
(b) Tetracycline, streptomyin d) U wave changes on ECG
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(c)Alprazolam 24. Digoxin act on heart by-
(d) Anti diuretic harmone a) Decreasing preload
18. Anti diuretics are the drugs which have following action ? b) Decreasing heart rate
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a) Increase urine output ) Increasing force of contraction
b) Decrease urine output d) Decreasing after load

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(c) Stops urine formation 25. Master's test is used to evaluate clinically
(d) cause drowsiness a) Anti epileptic drugs
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19. Phenazopyridine drug impars which colouration to urine ? b) Antidiabetic drugs
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a) Colden yellow Anti anginal drugs

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(b) Red, orange colouration d) Anti hypertesive drugs
26. The drug of choice of treatment of diabetes insipidus is
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(c) No colour
(d) Green colouration a) Chlorpropamide
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b) Diazoxide
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Desmopressin
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d) Thiazide diuretics
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172 PUA Text Book of Pharmacology-
4
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27. The drugs are useful in diabetes insipidus except AUTOCOIDS AND RELATED DRUGS
a) Chlorpropamide
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CHAPTER
b) Lithium eaaaycea
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Desmopressin
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Hydrochlorthiazide
,
Constipation is caused by all except-
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28.
FINTRODUCINGITHECHAPTER
a) Morphine
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b) Verapamil Introduction to autacoids
Magnesium hydroxide Classification of autocoids
d) Codeine
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c
Histamine and their antagonists
29. Which of the following diuretics decrease the renal lithium clearance. 5-HT and their antagonists
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a)Hydrochlorthiazide Prostaglandins
b) Acetarolamide Thromboxanes
Furosemide Leukotrienes
d Spironolactone Angiotensin
30 The potassium sparing diuretics includes. Bradykinin
a) Spironolactone Substance P
b) Amiloride Non-steroidal anti-inflammatory agents
Triamterene
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Anti-gout drugs
d) All the above Antirheumatic drugs
e) None of the above
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KEY WORDS
A N S WE RS Rnalgesics : The drugs that relieve or suppress the pain sensation by their action without causing
loss of unconsciousness, makes the individual unaware of pain.
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1. a) 2 ) 3. c)4. (a) 5. (b)6. (b) 7. c) 8. (a)
9 a) Antipyretics : The antipyretics are the drugs which reduce (bring down) elevaled body
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10. 11. 12 (a) 13. (a) 14. (a) 15. (b) 16. ) 17. 6) 18. ) temperature does not cause hypothermia.
24. () 25. (c) 26. () 27. (b) Anti inflammatory drugs: Anti inflammatory are the drugs which produces symptomatic relief
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19. (b) 20. (c) 21. (d) 22 (c) 23. (b)

from inflammation (swelling) along with relief from
pain.
28. c) 29. (a) 30. (d)
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Serotonin:It was isolated from the blood serum as a substance causing powerful smooth muscle
contraction. Only later was it demonstrated to be tryptamine with a hydroxyl group at the 5-
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position.
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Prostaglandins :It is an enzyme in the serum called angiotensin-converting enzyme
(ACE then
converts angiotensin I into an octapeptide
(consisting of eight amino acids) called angiotensin I.
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Angiotensin II acts via receptors in the adrenal glands to stimulate the secretion ofaldosterone,
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173)

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Autocoids and Related Drugs
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174 PU A Taxt Book of Pharmacology-
eukotrienes: The straight chain lipoxygenase products of arachidonic acid are produced by a Few autacoids are also found in nervous tissues. These are: Histamine, Serotonin
(
more limited number of tissues (LTB4 mainly by neutrophils; LTC4 and LTD4-the cysteinyl
y
hydroxytryptamine), Prostaglandin.
LTsainly by macrophages), but probably they are pathophysiologically as important as PGs.
Bradykinin Difference between autacoids and hormones: (1) Autacoids are produced by virtually all
: Itis a peptide produced by the body to help control
blood pressure and
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cells but hormones are produced by specific cels. Eg, insulin can only be produced by B
a
inftammation It is simply called peptide. Plasma kinins are polypeptides split off from a
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plasma globulin Kinnogen by the action of Kallikreins. cells of islets of Langerhans of pancreas.
Substance P:ltis an undecapeptide.la peptide composed of a chain of 11 amino acid residucs). It Autacoids mainly act locally, ie, act near their site of synthesis but hormones are
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is the member of the tachykininneuropcptide family. It is aneuropeptide acting as ,
transported through the blood and act at distant target tisues.
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a neurotransmitter and as, a neuromodulator-

The aulacoids play an important role in Inflammation, allergie reactions, anaphylactic
Nonstervidal anti-inflammatory agents: These are medications that relieve or redpce pain.
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Nonsteroidal anti-inflammatory drugs (NSAIDs) also come under the wider definition of non- not
reactions( so much), neurotransmission, gastric acid secretion and neuroendocrine
regulation. However, in the central nervous system, they are responsible for Wakefulness,
opioid analgesics.
Anti-gout drugs : It is manifest as sudden onset of severe inflammation and pain in decreased appetite, regulation of drinking, regulation of temperature, Secretion of ADH,
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metatarsophalengial joint of the Teater toe due to precipitation of urate crystals in the joint control of blood pressure and perception of pain.
space. The joint becomes red, swollen and painful
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42:4TSTAMINE
istamine is a substance that plays a major role in many allergie reactions, dilating blood
INTRODUCTIONTOAUTACOIDS vessels and making the vessel walls abnormally permeable. Histamine is part of the body's
Auto means self and Akos means remedy, So autacoids basically can be defined as the natural allergic response to substances such as pollens
ehemical substances produced within the body to help in the remedy of local injuries. It is a biologically active substance found in a great variety of living organisms. It is
Autacoids can be released by various stimuli and when released they bring about
many distributed widely, albeit unevenly, throughout the animal kingdom and is present in
many plants and bacteria and in insect venom.
itching, bronchospasm, etc
physiological changes such as reddening of the skin pain,
flistamine Liberators: It has been clinically observed that physical and chemical substance
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The Classification of autacoids release histamine which produce by the body. The histamine cause the headache, Nausea,
Vomiting. Warmth, Hypotension, Tachycardia, Bronchospasm, Oedema, Skin rashes,
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etc.
Ttchings skin, Hyperacidity
3) Eicosanoid
physical Substances : The physical substances cause the body's cell and tissue damage and
1) Decarboxylated amino acids 2)Polypeptide a) Leukotrienes release the histamine such as Physical injury, trauma, sun rays, due to cold, thermal and
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Angiotensin radiation energy injury, all cause release of histamine. Injury due to snow, ice ie. in cold
(a) Histamine (a) b) Thromboxanes
Plasmakinin Prostaglandins climate also considered for release of histamine.
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b) Serotonin b)
Chemical Substances: The alkaloid drugs antibiotics, amides liberate histamine. The other
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()Vasopressin
drugs or chemical substances like Morphine, Dextran, Tubocurarin, Toxins, Vemons,
d) Vasoactive intestinal Polypeptide
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Chymotrypsin drugs also cause libration of histamine for our safety.
Ae) Substance P
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Synthesis, metabolism and degradation of histamine : Histamine is a biogenic amine that

D Slow reacting substance of anaphylaxis stimulates multiple histamine receptor types. In mammals, histamine is found within
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granules of basophils and mast cells (90% of body stores) and within tuberomammillary
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176 PU A Toxt Book of Phamacology-llL Autocoids and Related Drugs 177
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neurons
of the CNS. When released, histamine induces complex physialogical and Histamine receptor and their path
pathological effects, including allergie reactions, gastric acid secretion, multiple-CNS
regulated effects, smooth muscle contraction and profound vasodilation that can lead to
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cardiovascular collapse. Receptor Action Path Site of Agonist
The physiological levels of L-histidine are converted to histamine by specific L-histidine

Receptor
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decarboxylase (HD), which differs fronm the nonspecific DOPA decarboxylase. H1 Cause constriction.
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contraction, IP CNS, Bronchi, | 2 Methyl
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HISITIDINE wakefulness | DAG Intestine Histamine
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suppresses appetite Ca+2

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HISTAMINE
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denosymethionn Gastric cells, 4 Methyl
Acts on gastric acid secretions.
Heart, Brain Histamine
DAO HNMT-*-- CAMP
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Sdenosyhomoeysteine-
Dimaprit
IMIDAZOLLE N-METHYLIMIDAZOLE DAO)
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ACETALDEHYDE *METHYLHISTAMINE
ACETALDEHYDE
MAO-BV Release of
CAMP Tesynaptic Methyl Histamine
Histamine,
Aldheyde Aldheyde
dehydrogenase dehydrogenase
IMIDAZOLE ACETATE N-METHYLIMIDAZOLE ACETATE
H4
Inflammation and allergic CAMPEosinophils, Clobenropit
Fig. 41 Synthesis and degradation of histamine response Neutrophils
Histamine is methylated at the imidazole nitrogen furthest from the ethylamine side chain
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termed tele-N or N9 by the enzyme histamine-N-methyltransferase.(HMTD through a ping- HYSTAMINE
pong mechanism using Sadenosyl-L-methionine as cofactor. The tele-methylhistamine (t- It is a depressor amine derived by enzymatic
MH produced is a substrate for monoamine oxidase-B_ (MAO-B) and semicarbazide- decarboxylation of histidine. It is a powerful
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sensitive amine oxidases (ESAOs), such as diamine oxidase (DAO) and benzylamine a
stimulant of gastric secretion, constrictor of bronchial
smooth muscle, a vasodilator, and
also a centrally acting neurotransmitter.
oxidase (Bz.SSAO) The aldehyde intermediate is further oxidized by aldehyde
o Méchanism of action : It acts directly
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dehydrogenase (ALDDHIL tele-methylimidazoleacetic acid (t-MIAA). In the oxidative on the blood vessels to dilate arteries and capillaries;
pathway,histamine is oxidized by the SSAOs, particularly DAO and Bz.SSAO, but is a poor this action is mediated by both H 1
and H 2-receptors. It has a direct stimulant
action on
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imidazolacetaldehyde is rapidly converted by ALD
substrate for the MAOs. The resultant smooth muscle, producing contraction if H 1-receptors
are activated, or mostly relaxation if
H2-receptors is activated.
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DH to imidazole-+-acetic acid (IAA). IAA induces numerous effects in the CNS where it
has been shown to act as both a GABAA receptor agonist and a GABAc receptor partial Pharmacology action of histamine
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agonist. It has a broad spectrum of
actions involving many organs
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understand the roles of histamine, and organ systems. To

it is useful to consider the physiologic
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histamine in each tissue. effects of
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178 PU A Text Book of Pharmacoloay-
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Smooth muscle : Histamine causes some muscle fibers to contract and others to relax. In the terminals. This effect is responsible for the pain and itch experienced after an insect bite, for
human respiratory system, it causes bronchoconstriction (the effect varies in other species). example.
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However, the sensitivity of bronchial smooth muscle to histamine varies among The combined actions of histamine on vascular smooth muscle, vascular endothelial cells,
individuals; those with asthma may be up to 1,000 times more sensitive to histamine- and peripheral nerve terminals are responsible for the wheal-and-flare response noted after
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mediated bronchoconstriction than nonasthmatic individuals. Other smooth muscles-such histamine release in the skin. Endothelial cell contraction causes the edematous wheal
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- as those in the bowel, bladder, iris, and uterus also contract on exposure to histamine, but response, while the red, painful fare results from vasodilation and sensory nerve
these effects are not thought to play a large role physiologically or clinically. stimulation. It also causes a similar process to occur in the nasal mucosa. Endothelial cell
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contraction, increased vascular permeability, glandular hypersecretion, and stimulation of
Cardiac cffect: Histamine consist of minor increases in the force and rate of cardiac
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contraction. It enhances Ca2* influx into cardiac myocytes, leading to increased ifotropy. irritant receptors contribute to mucosal edema and rhinorrhea, as well as the itching and
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Theincrease in heart rate is caused by an increase in the rate of phase 4 depolarization in sneezing ypical of allergic rhinitis.
sinoatrial nodal cells. es: It has no therapeutic use. It is also has been used to test the acid secreting capacity of
Vascular smooth muscle : Histamine dilates postcapillary venules
and terminal arterioles. thepheochromocytoma,
stomach, bronchial hyper-reactivity in asthmaties. It is used for diagnosis
however, these pharmacological tests are risky and obsolete now.
of
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however, constrict on exposure to histamine. The vasodilatory effect on the
Veins,
postcapillary venule bed is the most prominent effect of histamine
on the Brand name: Ceplene sol. o.5mg/5ml, Histamine Phosphate Injection USP, Img/ml,
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infection or injury, histamine-induced venule dilation engorges the Histatrol sol 0.275.,
vasculature. During
access of immune cells that initiate repair BETAHISTINE It is an orally active, it has H1 selective histamine analogue, which is used
local microvasculature with blood, enhancing the
explains the erythema observed in to control ertigo in patients of Meniéré's disease. It is possibly acts by causing
processes to the damaged area. This engorgement
It also causes contraction of vascular endothelial cells. Histamine-induced vasodilatation in the internal . It is contraindicated in asthmatics and ulcer patients.
inflamed tissues.
from one another, allowing the
endothelial cell contraction causes these cells to separate Vertin 8 mg tab, 1/2 to 1
tab. QID.
fluid from postcapillary venules and thereby causing edema.
release of plasma proteins and
local responses at sites of injury. SHISTHMINEANTAGONISIYANIUEISTAMINICS
Thus, histamine is a key mediator of
gastrin-induced
histamine in the gastric mucosa is to potentiate Antihistamines are the drugs which antagonize the histamine that is liberated in the body.
GIT: The primary role of
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molecules that stimulate acid secretion in the stomach, the
acid secretion. It is one of three stomach These drugs are used for symptomatic treatment of allergic disorders. The antihistamines
The activation of histamine receptors in the
others being gastrin and acetylcholine. results in increased secretion of have been divided into H1 and H2 blockers, depending on their response to histamine they
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Ca2*in parietal cells and
Jeads to an increase in intracellular prevent. It includes drugs.
hydrochloric acid by the gastric mucosa. .Drugs producing low sedation chlorpheniramine
:
CNS. Histaminergic neurons

as a neurotransmitter in the
CNS Histamine functions Drugs producing moderate sedation: Trimeton
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nucleus of the hypothalamus and project diffusely 2.
originate in the tuberomammillary functions of histamine in the CNS are 3.Drugs producing high sedation: Diphenhydramine, Promethazine,
meclizine, cinnarizine
Although the
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throughout the brain and spinal cord.
of sleep-wake cycles Mechanism of action of antihistamines: Antihistamines do
not neutralise histamines
believed to be important in the maintenance
not well understood, It is
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learning), and feeding to the allergic

processes (attention, memory, and chemiclly.They do not prevent release of histamine when exposed
(circadian rhythms), cognitive histamines for receptors in the tissue.
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substance. They act by competing with
behaviors (appetite suppression).
to histamine. The sensations actions
sensory nerve terminals also respond Jhe antihistamines have following pharmacological
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Others Peripheral depolarizing action of histamine on afferent nerve conventional antihistamines block all the action of the histamines on
skin, mucous
direct
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of itch and pain result
from a
The membranes and muscles. They do not antagonize histamine
induced gastric secretion
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80 P A Text Book of Pharmacology-ll
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The antihistamines produce sedation when administered. So driving, to work with Classification of antihistamine based on clinical aspect and doses
machinery be avoided. Skilled work is not advisable after taking antihistaminic Napedf Drug Clinical Dose, Route
(antihistaminic) drugs.
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Tntense sedation:
The antihistamines exhibit anticholinergic effect and produce dryness of mouth, and 25-50mg by mouth,
Promethazine Hydrochloride
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Ph
drying of nasal secretions. Inj I.M. 1mg per kg of body weight
Diphenhydramine Hcl 25mg to 50mg orally
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/The antihistamines posess a local anaesthetic effect. Preparations of antihistamines

Dimenhydridate
meant for Ilocal application have their own local anaesthetic effect. 25mg to 50mg orally
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5.7 Antihistamines have a quinidine like effect on heart and are useful in controlling Hydroxyzine 25mg to 50mg orally and Instra-
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fibrillation of heart. muscularly

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6. The antihistamines suppress motion sickness, caused by vestibular dist-urbances and Moderate sedation
/prevent vomiting caused due to labyrinthine disturbances. Cinnarizine 25mg to 50mg orally
Thegpeutic Uses of Antihistamines Cyproheptadine 4mg orally
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Used for symptomatic treatment of allergic disorders, urticaria, Rhinitis. Meclizine Hydrochloride 25mg to 50mg orally
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bSUsed for preventing allergic reactions in blood transfusion. Buclizine 25mg to 50Omg orally
Sen the treatment of vomiting due to motion sickness, common cold with nasal discharge. Mild sedation:
Histamine is a substance isolated from Ergot, later on scientists came to know that
it is
Cyclizine 50mg orally
present in number of our body tissues. Histamine chemically is a imidazole derivative Clemastine
formed by decarboxylation of amino acid histidine in presence of histidine decarboxylase. 1mg to 2mg by mouth
Dimethindine Img orally
The high concentration of histamine compound is found in lungs,
intestinal mucosa and Dexchlorpheneramine
skin, heart and brain. The main places of storage are (iCels of epidermis, (ii) Mast 2mg orally
cells as
Basophils, i) CNS neurons, (iv) Mucosal layer of gastro intestinal tract Chlorpheniramine
and (v) Rapidly 2mg to 4mg orally,IM0.1mg per kg
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growing tissue cells. Second Generation Antihistamine:
Toxicity ok antihistamiiés Cetirizine Hel 10mg orally
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Anorexia, epigastric pain kevocetirizine
5mg to 10mg orally
(Gi) Dryness
of mouth, nose and eyes Fexofenadine
120 to 180mg orally
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CinCause drowsiness, sedation Ebastine
10mg orally
io) Hypotension, palpitation Rupatidine
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Ph
10mg orally
(D)Blood dyscarasias : agranulocytosis, leucopenia, haemolytic Azelastine
anaemia
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4mg oral, intranasally

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PROMETHAZINE HYDROCHLoRIDE:
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It is an odourless, white crystalline
bitter taste. It is soluble in water.
Promethazine hydrochloride
powder with
ac
is a strong and long acting

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182 PU A Text Book of Pharmacology-l Autocolds and Rolated Drugs
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antagonistic drug of H-1 receptor effect of histamine. The effect of promethazine lasts for 20 DIPHEN HYDRAMINE HYDROCHLORIDE: Its Molecular Formula: C17H22NOCL It is
hours so attention must be paid while administration of the drug. It is available as
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promethazine hydrochloride and promethazine theoclate preparations. It is available as 10 an odourless, white crystalline powder with a bitter taste. It is soluble in water. It is readily
mg. 12.5 mg 25 mg. 50 mg Promethazine hydrochloride tablets, injection 25 mg per 2m absorbed after being administered orally. It causes drowsiness, person should not drive and
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ampoule, named tablet phenargan, Inj Phenargan. operate machinery. It is available as 25 mg, 50 mg capsules/Kapseals. Benadryl syrupP
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containing 12.5 mg per 5 ml is available.

Chemical Fomula: C17 H21 N2 Ci sS
Mechanism of action : It acts on blood vessels, respiratory system and astrointestinal tract
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by competing with Histamine for H1 receptor site. It decreases allergic response by
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*%.CHNCH blocking histamine. It acts as antihistaminic drug

CH3
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HCI Indications : Allergic rhinitis, motion sickness, night time sedation, anti Parkinsonism.
Contraindications Hypersensitivity, acute asthmatic attack, lower respiratory tract
infections.
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Side cffects: Drowsiness, anxiety, confusion, wheezing, chest tightness, dry mouth,
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(PROMETHAZINE HYDROCHLORIDE) nausea, anorexia, dry nose, dry mouth, dilated pupils.
Mechanism of action : Promethazine hydrochloride acts on blood vessels, gastrointestinal Pharmacokinetics : Peak plasma concentration attained in 2 hours, half life 7 to 10 hrs
tract, respiration tract system by competing with histamine at Hj receptor site It decreases excreted in urine metabolised by hydrolysis in liver, crosses placenta, excreted in breast
allergic response by blocking histamine Itjs used in the treatment of motion sickness. milk.
Indications : It is effective in allergy, motion sickness, rhinitis, sedation, pre-operative and Drug interactions : Increased CNS depression with alcohol, barbiturates, narcotics,
postoperative sedation. antidepressants, decrease effect of oral anticoagulants, heparin
Contraindications: Hypersensitivity, asthma attack, respiratory tract disease, pregnancy, Dosage: Adult 25-50 mg, 25 mg 6 hourly, orally, not to exceed 400 mg per day.
cardiac disease, hyperthyroidism. Children:5 to 10 ml syrup 8 hourly.
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Side effects: Drowsiness, hypotension, tachycardia, chest tightness, hemolytic anaemia, Brand names: Diphenhydramine: Capsule and Syrup Benadryl, Synermin Ext, Jfen Hcl,
rash, urticaria, nasal stiffness, dry nose, dry mouth. Trexy cough syrup, Sedohist, Kofom
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Pharnacokinetics : Peak plasma concentration in 1 to 2 hours half life 7 to 10 hours. Treatment of over dose: Ipecac syrup orally, diazepam, vasopressors.
Drug interactions: Decrease the effect of oral anticoagulants, heparin, increased CNS
depression with alcohol, narcotics, barbiturates. DIMENHYDRIDATE : It is also known as Dramamine or Gravol, is an over-the-counter
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Dosage : Oraly 1M/1V 10 to 25 mg, for nausea and vomiting as single dose or in divided drug.
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Ph
Ph
doses. Mechanism of action The mechanism by which some antihistamines exert their
For motion sickness by mouth 25 mg half an hour before departure. antiemetic, anti-motion sickness, and anti-vertigo effects is not precisely known but may be
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related to their central anticholinergic actions. They diminish vestibular stimulation and
For allergy 12.5 mg 6 hourly or 25 mg at bed time.
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depress labyrinthine function. An action on the medullary chemoreceptive trigger zone
For sedation 1M or by mouth 25 mg to 50 mg at bed time.
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may also be involved in the antiemetic effect. It is a competitive antagonist at the histamine
Brand names: Promethazine : Tablet, Injection, Syrup Phenargan, Avomine MD, Emin,
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Phenakid, Promet, Velpro
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Treatment of overdose: Administer syrup Ipecac, diazepam, vasopressor's.

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Autocoids and Related Drugs 185
A Text Book of Pharmacology-!
184 P
Vertigon, Stedicin, Diziron
anti-emetic effect is probably due Brand names: Cimarizine: Tablet Vertiron, Stugeron, Stugenol,
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Hl receptor, which is widely distributed in the brain. Its 25mg, 75mg tablets.
to Hl antagonism in the vestibular system in the brain.
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Ph
Pharmacokineties: It is well absorbed after oral administration. Is proteins
binding are 98
blocker used as
system). Its half life 14 hours CYPROHEPTADINE: It is a serotonin antagonist and a histamine HI
to 99%. It is metabolized in liver hepatic (cytochrome P-450
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post-gastrectomy dumping
antipruritic, appetite stimulant, antiallergic, and for the
and excreted though urine.
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sickness. syndrome.
Uses: It is used to prevent nausea, vomiting, and dizziness caused by motion HA-receptor sites.
Mechanism of action: It competes with free histamine for binding at
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Brand name : Dimenhydrinate Inj 10,mg. Dimenhydrinate Inj 50,mg USP. leading to a reduction of the
This antagonizes the effects of histamine on HA-receptors,
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It also competes with
negative symptoms brought on by histamine HA-receptor binding.
locations.
HYDROXYZINE :Itis a histamine H1 receptor antagonist serotonin at receptor sites in smooth muscle in the intestines and other
Mechanism of action:It competes with histamine for binding at Hi-receptor sites on the account for its
Antagonism of serotonin on the appetite center of the hypothalamus may
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The
effector cell surface, resulting in suppression of histaminic edema, flare, and pruritus. ability to stimulate appetite.
CNS. Secondary to
sedative properties of hydroxyzine occur at the subcortical level of the vasomotor rhinitis,
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Uses: It is used for treatment of perennial and seasonal allergic rhinitis,
its central anticholinergic actions, hydroxyzine may be effective as an antiemetic. allergic conjunctivitis due to inhalant allergens and foods, mild uncomplicated allergic skin
Pharmacokineties: It is rapidly absorbed from the gastrointestinal tract. Their protein manifestations of urticaria and angioedema, amelioration of allergic reactions to blood or
binding is 93 %. It is metabolized in liver. The half life is 20-25% hours. It is excreted
in
plasma, cold urticaria, dermatographism, and as therapy for anaphylactic reactions
urine. adjunctive to epinephrine
Uses: It is used in the treatment of chronic urticaria, dermatitis, and histamine-mediated Brand name Cyproheptadine Hydrochloride tab.
:
pruritus. Unlike its major metabolite cetirizine, it does

caus drowsiness. It is also effective
as an antiemetic, for relief of anxiety and tension, and as a sedative. :
MECLIZINE HYDROCHLoRIDE It is known as meclozine hydrochloride. It is a white
Brand name: Apo Hydroxyzine Cap 10-50 mg. Atarax tab, Atarax Cap 10, 25mg. crystalline powder, odourless and tasteless. It is soluble in water. It is a long acting
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antihistaminic drug, causes less sedation and less anticholinergic. Its action is long about 24
CINNARIZINE: It is an antihistamine drug having anticholinergic sedative and hours duration. It is very effective in the treatment of vomiting due to pregnancy. It also
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for motion
vasodilator properties. It is effective as antivertigo drug and as protective drug protects against sea sickness, the effect of single dose lasts for 24 hours.
before
sickness. The antimotion sickness drugs are effective if taken 30 minutes to hour
1
Chemical formula: C25 H29 N2 Cla (Meclizine hydrochloride)

becomes very difficult to
starting of journey. Once motion sickness has been developed, it
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It is available as meclizine hydrochloride tablets containing 12.5 mg meclizine +50 mg
control. In that case, either higher dose is required or parenteral (Injection) administration
sickness. nicotinic acid, meclizine hydrochloride 25 mg plus pyridoxine hydrochloride 50 mg tablels,
of the drug may be required to control motion
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Ph
Ph
brain meclizine hydrochloride 25 mg plus caffeine 20 mg tablets.
Indications : Vertigo, motion sickness, improves blood circulation to Labyrinth and
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Mechanism of action : Meclizine acts centrally by blocking chemoreceptor trigger zone

stem, tinnitus, loss of memory, meniere's syndrome.
which further acts on vomiting centre and the vomiting is stopped. It acts as antihistaminc,
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Contraindications: Hypersensitivity, pregnancy, lactation, infants, children. antiemetic drug.
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Side effects : Sedation, rash, drowsiness, gastro intestinal upset. Dose :25 mg to 50 mg daily in divided doses.
with
Drug Interactions: With alcohol increase CNS depression. action is increased
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Indications: Nausea, vomiting, sea sickness, motion sickness, vertigo, meniere's syndrome.
domperidome
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Contraindications: Hypersensitivity, liver discase, epilepsy.

Dosage: Adults:25 to 75 mg 8 hourly, orally.
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PV Autocoids and Rolated Drugs
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186 A Text Book of Pharmacology-! 37
Side effects: CNS depression, dry mouth, gastro intestinal upset. Children:3 mg per kg body weight in equal 3 divided doses.
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Drug intetactions: Increased CNS depression with alcohol, barbiturates,opioid analgesics. Motion Sickness : Adult: 50 mg orally then after 6 hours not to exceed 200 mg per day.
Brand names: Meclizine : Tab Pregnidoxin, Pregnitab MCz, PNV, Diligan.
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Ph
Children: 25 mgby mouth, 6 hourly.
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Drug interactions : Increase effect with alcohol, tranquillizers narcotics.

BUCLIZINE : It is an antihistamine of the piperazine derivative. It acts to block the CLEMASTINE : It is an ethanolamine-derivative, first generation histamine Hl antagonist
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histamine receptors in the vomiting centre and thus reduce activity along these pathways used in hay fever, rhinitis, allergic skin conditions, and pruritus. It is a selective histamine
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Furthermore since buclizine possesses anti-cholinergie properties as wel, the muscarinic H1 antagonist and binds to the histamine Hl receptor. This blocks the action of endogenous
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receptors are similarly blocked. It is used as an antivertigo/antiemetic agent. It is used in histamine, which subsequently leads to temporary relief of the negative symptoms brought
the prevention and treatment of nausea, vomiting, and diziness associated with motion on by histamine. Clemastine Fumarate tab.
sickness. Additionally, it has been used in the management of vertigo in diseases affecting DIMETHINDINE: It (Fenistil) is an antihistamine/anticholinergic used orally and locally
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the vestibular apparatus. as an antipruritic. It is a selective histamine H1 antagonist and binds to the histamine H1
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receptor. This blocks the action of endogenous histamine, which subsequently leads to
MILD SEDATION: temporary Telief of the negative symptoms brought on by histamine. It is used reatment of
CYCLIZINE : It is a white colourless crystalline powder with a bitter taste. It is soluble in allergic reactions: urticaria, allergies of the upper respiratory tract such as hey fever and
perennial rhinitis, food and drug allergies; pruritus of various origins, except pruritus due
water. It is used in motion sickness, prevention of postoperative vomiting. It acts centrally
to cholestasis; insect bites
by blocking chemoreceptor trigger zone, which further acts on vomiting center. It is
available as 50 mg tablet and injection molecular formula: C1sH23N2C DEXCHLORPHENERAMINE : It is an antihistamine drug with anticholinergic (drying)
and sedative actions. It disrupts histamine signalling by competing with histamine for cel
Mechanism of action: Cyclizine is an antiemetic and antihistamine drug. t action is
receptor sites on effector cels.
centrally by blocking the chemoreceptor trigger zone which further acts on the vomiting
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CHLORPHENIRAMINE : It is a histamine H1 antagonist used in allergic reactions, hay
centre and stops vomiting.
fever, rhinitis, urticaria, and asthma. It has also been used in veterinary applications. One of
CH (CeHs
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the most widely used of the classical antihistaminics, it generally causes less drowsiness
and sedation than promethazine. It binds to the histamine Hl receptor. Its block the action
: HCI
of endogenous histamine, which subsequently leads to temporary relief of the negative
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symptoms brought on by histamine. Histamine, acting on H-receptors, produces pruritis,
CH3 vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction.
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Ph
Ph
Structural formula of cyclizine hydrochloride. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine is a
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Indications : Motion sickness, prevention of post-operative vomiting histamine Hl antagonist (or more correctly, an inverse histamine agonist) of the alkylamine
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class
Contraindications: Hypersensitivity, pregnancy,lactation, shock
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Side effects: Drowsiness, fatigue, headache, insomnia, nausca, anorexia, dry mouth, ÉOND GENERATION ANTIHISTAMINE
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CETIRIZINE HCL: It is a potent second-generation histamine H1 antagonist., the active
tinnitus.
metabolite of the piperazine Hirreceptor antagonist hydroxyzine.
Pharmacokinetics: Peak plasma concentrations 4-6 hours. Half life less than 1 day
ac
excreted in urine.
Mechanism of action : It competes with histamine for binding at Hr-receptor sites on the
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effector cell surface, resulting in suppression of histaminíc edema, flare, and pruritus. The
Dosage and Route : Vomiting: Adult: IM 50 mg half hour before termination of surgery.
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Telegram - Study Pharmacy PU A Text Book of Pharmacology- Autocolds and Related Drugs 189
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as an antagonist
can be attributed to reduced penetration of cetirizine into the competes with histamine for the Hl-receptor sites on effector cells and acts
low incidence of sedation the allergic response.
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inhibiting the release of histamine and other mediators involved in
the lipophilic carboxyl group on the ethylamine side chain. by
CNS as a result of less
It is a relatively selective histamine H1 antagonist, which inhibits
the release of histamine
pollen-induced
sas Tt is used in the treatment of allergic rhinitis, chronia urticaria, and and other mediators from cells (e.g. mast cells) involved in the allergic
response. It has some
cause drowsiness or
many traditional antihistamines, it does not
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asthma. Unlike affinity to H2 receptors.
anticholinergic side effects.
Ph
Ph
Ph
Tablet, Rhinaris Relief, tab, Zyrtec tab.
Brand names: Cetirizine tab, Reactine 20mg OTHER HISTAMINE ANTAGONIST (ANTI HISTAMINES)
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for the
LEVOCETIRIZINE: It is a third-generation non-sedative antihistamine indicated
Antihistamines are the drugs which antagonise the action of histamines that is liberated in
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seasonal and perennial allergic rhiniis and
relief of symptoms associated with This group
R-enantíomer of the body. These drugs are used for the symptomatic relief of allergic disorders.
uncomplicated skin mani festations of chronic idiopathic urticaria. It is the
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decreases activity at includes drugs () Chlorpheniramine, (i) Diphenhydramine ii) Promethazine.

the cetirizine racemate. Levocetirizine is an inverse agonist that
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Second generation antihistamines: Loratadine, Fexofenadine, Desloraladine are not
histamine H1 receptors. The active enantiomer of the cetirizine, it is anti-histamine; its
effective as drugs for the treatment of cough, bronchitis associated with allergic disorders.
principal effects are mediated via selective inhibition of H1 receptors. It is rapidly and
extensively absorbed following oral administration. The volume of distribution
is CHLORPHENIRAMINE MALEATE : It is an odourless, white, crystalline powder with
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taste.
approximately 0.4 L/kg. The proteins binding is 91 to 92%. It is poorly metabolized and biter It is soluble in water. It acts on blood vessels, Gastro Intestinal system,
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mostly excreted via the urine. respiratory system by competing with histamine for H1 receptor site. It decreases allergic
FEXOFENADINE: It competes with free histamine for binding at H1-receptors in the GI reaction/response by blocking histamine. The anti histamine drugs have similar action. The
tract, large blood vessels, and bronchial smooth muscle. Its block action of endogenous side effects of chlorpheniramine and other drugs are (i) dryness of mouth, throat and nose,
(eg.
histamine, which subsequently leads to temporary relief of the negative symptoms abdominal pain with vomiting, cause drowsiness, dizziness. So the persons taking
anticholinergic,
nasal congestion, watery eyes) brought on by histamine. It exhibits no treatment antihistamine drugs should avoid driving and to work with moving machinery.
antidopaminergic, alpha1-adrenergic or beta-adrenergic-receptor blocking effects. It is used Is chemical formula or molecular formula is C2oH23CI N2O4
in the treatment of hayfever and similar allergy symptoms.
It
EBASTINE:It is under investigation for the treatment of Irritable Bowel Syndrome (IBS).
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has been investigated for the treatment of Urticaria. FH.COOH
CH.coOH
RUPATIDINE: It is a dual histamine H1 receptor and platelet activating factor receptor
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-CH (CH>> NICHa
as
antagonist that is used for symptomatic relief in seasonal and perennial rhinitis as well
chronic spontaneous urticaria. It is used as anti allergenic and acts to reduce allergic
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symptoms like urticaria, rhinorrhea, sneezing and itching Structural formula of chlorpheniramine maleate. C2oH23CIN204.
Brand name : Rupall tab.
Ph
Ph
Ph
Mechanism of action: The Chlorpheniramine drugs decrease allergic reaction response
by
AZELASTINE: It is a phthalazine derivative, it is an antihistamine and mast cell stabilizer blocking Histamine. It acts on blood vessels, Respiratory tract,
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Gastro intestinal tract by

It
available as a nasal spray for hay fever and as eye drops for allergic conjunctivitis. competing with histamine H1 receptor site. It is useful in allergies
symptoms.
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Dosage: Adult: By mouth (orally) 2 mg to 4 mg 6 to 8 hourly
not to exceeed 36 mg per day.
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Intra muscular intravenous 5 mg to 50 mg maximum

per day in severe allergies.
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Children:6 years to 12 years age 2 mg orally every 6 to 8 hourly
not to exceed 12 mg per
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day. Children age 2 year to 5 years by mouth 1mg 6

hourly not to exceed 4 mg per day.
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190 PA Text Book of Pharmacolo9y-1 Autocolds and Related Drugs
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Indications:Allergy symptoms, rhinitis, cough (allergic). Side Efects : Dizziness, poor coordination, anxiety, euphoria, paraesthesia, neuriti,
Contraindications: Hypersensitivity to Hj receptor antagonists, Asthma, lower respiratory constipation, dry mouth, nausea, vomiting, anorexia, chest tightness, thrombocytopenia,
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dysuria, blurred vision, nasal stiffness, dry nose.
disease, hypertension, seizure disorders, pregnancy, lactation, cardiac disease.
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rharmacokinetics : Peak plasma concentration attained in 1 to 2 hours, plasma half life 4
Side Effects: The following side effects have becn observed drowsiness, fatigue, anxiety,
hours (by intravenous injection), metabolised in liver excreted by kidneys.
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cuphoria, confusion, neuritis, chest tightness, thrombocytopenia, dry mouth, nausea,

anorexia, dilated pupils, nasal stiffness. Drug Interactions: Promethazine's action is increased as CNS depression in presence of
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drugs barbiturates, narcotics, hypnotics, alcohol.
Pharmacokinetics : Peak plasma concentration with oral dose appears in 1 to 2 hours,
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Plasma half life 12 to 15 hours, excreted in the urine. Brand names : Promethazine: Avomine MD, Phenergan, Phenercof, Promasum, Velpro,
Phena kid tablets 25mg. Syrup 5mg per Sml
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Drug Interactions: Increased CNS depression with barbiturates hypnotics, antidepressants,
alcohol. Treatment of Over dose : The treatment for overdose of promethazine is to administer inj
diazepam, syrup ipecac or lavage, short acting barbiturates.
Brand names: Chlorpheniramine malcate : Tablets, Injection, Avil, Phencip, Avil RC, Avil
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Retard tablets, 25mg, 50mg SEROTONIN (S-HT AND THEIR ANTAGONISTS
4
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Treatment of Over dose : Treatment of over dose is the administration of Diazepam, Ipecac 5erotonin was isolated from the blood serum as a substance causing powerful smooth
syrup muscle contraction. Only later was it demonstrated to be tryptamine with a hydroxyl group
at the 5-position. Only 1-2% of the serotonin in the body is in the brain, insofar as serotonin
PROMETHAZINE - HYDROCHLORIDE: It is an odourless, white, crystalline powder is widely distributed in platelets mast cells, etc. But there is no equilibration between body
effect of histamine.
soluble in water. It is a strong and long acting antagonist of Hj receptor serotonin and brain serotonin- he serotonin in the brain is independently synthesized
administered by mouth, its action ie., the action of from tryptophan transported across the blood-brain barrier.
It is very active drug when
promethazine lasts for 20 hours. Its molecular formula is C7 H21 CI N2S. SYNTHESIS, STORAGE, RELEASE AND TERMINATION OF SEROTONIN
Mechanism of action:It acts on blood vessels, respiratory
system, gastrointestinal tract by Synthesis: Serotonin (5-hydroxytryptamine) synthesis is a 2-step process, he first step o
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receptor site. It decreases allergic reaction by blocking which requires the enzyme tryptophan hydroxylase with oxvgen, iron and THB as co-
competing with histamine Hj
factors. Neither the enzyme nor the co-factors are rate-limiting for either step of these
histamine. The drug is used in motion sickness, allergies.
reactions-virtually all brain tryptophan is converted to serotopin. It is also synthesized in
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sickness, sedation, nausea, preoperative and
Indications: Allergic reactions, motion the pineal gland as a precursor for the subsequent enzymatic formation of the pineal
postoperative sedation. hormone melatonin (N-acetyl-5-methoxytryptamine).
disease, cardiac disease, seizure
Contraindications: Hypersensitivity, asthma attack, renal
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8orage and release: It is principally found stored in three main cell types-i) serotonergic
bladder, neck obstruction.
disorder, pregnancy, hypertension, hyperthyroidism, neuronsin the CNS and in the intestinal myenteric plexus, ii) enterochromaffin cells in the
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Ph
Ph
20 mg to 50 mg maximum per day as a single dose or mucosa of the gastrointestinal tract, arnd ii) in blood platelets.Serotonergic 'neurons and
Dosage: Adult: Promethazine orally
deep intra muscular, dose not to exceed 50 mg per
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in divided doses. It may be administered enterochromafin_cells can synthesize serotonin from its precursor amino acid L
tryptophan, whereas plateles rely upon uptake of serotonin for their stores. Ljikewise,
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day.
daily orally to 5year age 10 mg to 15 mg daily orally, 6 to
1 12years serotonergic neurons also have the capacity for amine uptake via serotonin transporters.
Children upto year age, 5mg to 10mg
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daily oraly in thre equal divided dosages

age 15mg to 25mg
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promethazine may be administered orally, as dosage
To children in equal three doses,
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mentioned above.
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PU A Toxt Book of Pharmacology-! Autocolds and Related Drugs
I9.
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Metabolism & Termination: Metabolism of serotonin is carried out primarily by the outer
mitochondrial membrane enzyme monoamine oxidase (MAO), which occurs as two 5-HT PhospholipaseC IP DAG CNS: cerebellum Endothelium dependant vaso
activation hypothalamus relaxation via NO production
molecular subtypes called MAO-A and MA0-B. _Both subtypes have a widespread (PKO
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PNS: Vascular and stomach fundus contraction
pccurrence in the brain and in peripheral tissues, although they do show some differences,
endothelium,
including species-related variations, with respect to the extent of their presence in certain
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Stomach
and cell types.
ISSues PhospholipaseC
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5-HTc IP3DAG CNS: choroid plexus, Modulation of transferin

SEROTONIN RECEPTOR: The classification scheme proposes 7 subfamilies of 5-HT activation (PKC) hippocampus, production and modulation of
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receptors. The main receptors and their subtypes, eg, 5-HTI (5-HTIA, 5-HTIB, 5-HTID, 5 hypothala-mus CSF volume
HTTE and 5-HTIF), 5-HT2 (5-HT2A, 5-HIT2B
and
5-HT2C), 5-HT3, 5-HT4, 5-ITS (5-HT54,
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-HIs Ligand gated ion lons CNS: area postrema

1.Suimulate vomiting by acting
5-HT5B), 5-HT6 and 5-HT7 have been identified. receptor channel PNS: Abdominal on CTZ and by vagal neuro
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visceral afferent excitation
Recepptor Regulate Path Second Location 2Physiological Action 2. Stimulate nociceptive (pain
Neuron
Subype Messenger mediating) nerve ending led to
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IcAMP pain
5-HTIA Inhibitadenylate CNS: Raphe nuclei, Seretonergic auto receptor
yclase and activate Hippocampus 5-HT4 Activation cAMP CNS: Hippocampus Neuronal exitation
2. Neuronal inhibition of
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receptor operated PNS: Cholinergic adenylate cyelase PNS: GIT Increase Gl motility
K+ channel. Inhibit
aFacilitate Ach and nor
heteroreceptor in adrenaline release 5-HTsA Unknown CNS: olfactory bulb, Unknown
voltage gated Ca2+
myenteric plexus ACholinergic nerve terminal in Hebenula
channel
myenteric plexus 5-HTsu Unknown CNS: oXactory bulb, Unknown
5. Hyperphagia (led to obesity) |Hebenula
SHTi Inhibit adenylate cAMP CNS: Cranial blood Seretonergic auto receptor 5-HT Activation TCAMP CNS: caudate putamen, Modulation of CNS Ach release
yclase vessel 2. GABAergic and Cholinergic adenylate cyclase hippocampus
PNS: Vascular smooth heteroreceplor PNS: Superior cervical
muscle ganglia
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3. Vasoconstriction of
intracranial blood vessel smooth 5-HT Activation cAMP CNS: hypothalamus
muscle adenylate cyclase PNS: gastrointestinal
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5-HTiD and vascular smooth
Inhibit adenylate cAMP CNS: cortex striatum Unknown Smooth muscle relaxation
yclase PNS: m-RNA in muscle
vascular tissue
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Inhibit adenylate JCamp CNS: Spinal cord Tigemina! (V) neuro inhibition
5HT RECEPTOR AGONISTS
Ph
Ph
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Syclase CPKA hippocampus in guinea pig and rat
5-HTiF BUSPIRONE: It is an anxiolytic agent and a serotonin
PNS: Uterus, mesentery, receptor agonit belonging to the
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vascular smooth muscle azaspirodecanedione class of compounds. Its structure

is unrelated to those of the
IP DAG benzodiazepines, but it has an efficacy comparable to
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Neuro excitation
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HTAD PhospholipaseC CNS: cerebral cortex diazepam.
receptor activation PNS: GIL, vascular and Broncho constriction
PK) Mechanism of action: It binds to 5-HT type 1A serotonin receptors
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bronchial Platelet aggregation on presynaptic neurons

smooth muscle, platelets Smooth muscle contractión
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(S
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194 TA Tert Book of Phamacology- Autocolds and Related Drugs
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195
in the dorsal raphe and on postsyraptic neurons in the hippocampus, thus inhibiting the Mechanism of action : t is a potent and selective 5-HT receptor antagonist. 5
firing rate of 5-HT-containing neurons in the dorsal raphe. It also binds at dopamine type 2 HTreceptors are nonselective cation channels that are extensively distributed on enteric
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(DA2) reeptors, blocking presynaptic dopaminc receptors. neurons in the human gastrointestinal tract, as weli as other peripheral and central
Ph
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P'harmacakineties: It is rapidly absorbed. Its bioavailability is low and variable locations. Activation of these channels and the resulting neuronal depolarization affect the
(aproximately 5%) due to extensive first pass metabolism. It is approxvimately 70% bound regulation of visceral pain, colonic transit and gastrointestinal secretions, processes that
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to allumin, 30% bound to alpha 1-acid slycoprotein). It is metabolizod in liver and excreted relate to the pathophysiology of irritable bowel syndrome aBS). 5-HT receptor antagonists
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in the urine. such as alosetron inhibit activation of non-selective cation channels which results in the
modulation of serotonin-sensitive GI motor and sensory processes.
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Side effects: Dizziness, nausea, headache, nervousness, lightheadedness, drowsiness,

feeling tired and blurred vision Pharmacokinetics: Its absorption is about 50 to 60 %. Its volume of distribution 65 to 90 L
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The plasma proteins binding is 82 %. It is metabolized in liver and excreted in urine.
Uses: It is used for the management of anxiety disorders or the short-term relief of the
symptoms of anxiety. and also as an augmention of SSRI-treatment against depression. Uses: It is used for the treatment of symptoms of severe diarrhea-predomínant iritable
bowel syndrome (1BS) in women with chronic symptoms
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rand name Buspar Tab 10mg. Buspirone HCL tab. 5, 10, 30 mg.
:
Brand name Alosetron Hydrochlorid 0.5,1mg., Lotronex tab 1 mg.
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PSAPIRONE: KETANSERIN: This compound beiongs to the class of organic compounds known as
of Cocaine-related disorders alkylphenylketones. These are aromatic compounds containing a ketone substituted by one
GErIRONE: t has been used in trials studying the treatment alkyl group, and a phenyl group. It has been investigated for the treatment of Septic Shock
sUMATRIrTAN: t is a serotonin agonist that acts
selectively at 5HT1 receptors. It is used
Severe Sepsis, and Diabetic foot ulcer. This drug is not recommended.
in the treatment of uigraine disorders. ZIPRASIDONE: It is a psychotropic agent belonging to the chemical class of benzisoxazole
receptors function as autoreceptors, which
Mechanism of action: The 5-HTn and 5-HTv derivatives and is indicated for the treatment of schizophrenia.
in the synthesis and releaseof
inhibit the liring of serotonin neurons and a reduction Mechanism of action: It is antipsychotic activity is lkely due to a combination of its
receptors, adenylate cyclase activity is inhibited
erotonin upon activation. It binds to these antagonistic function at D2 receptors in the mesolimbic pathways and at 5HT2A receptors
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regulatory G proteins, increases the intracellular calcium, and affects other intracellular
via in the frontal cortex. Alleviation of positive symptoms is due to antagonism at D2 receptors
vasoconstriction and inhibition of sensory nociceptive (trigeminal)
events. This results in while relief of negative symptoms are due to 5HT2A antagonism.
release.
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nerve firing and vasoactive neuropeptide
Side effects: Dizziness, drowsiness, unusual tiredness; nausea, upset stomach; diarrhea,
Side effect: Mild
headache (not a migraine), pain or chest tightness, pressure or heavy constipationy feling restless; tremors; rash; or. runny nose, new or worsening cough.
feeling hot or cold, dizziness, spinning
feeling in any part of your body, weakness,
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Pharmacokinetics: The absorption is 60 %. The volume of distribution is 1.5 LKg. The
sensation and drowsiness. plasma proteins binding is 99 %. It is approximately 20% of the dose is excreted in the urine,
2.7
15% absorbed. The volume of distribution is
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Pharmacokinetics: It is approximately excreted in urine.
with approximately 66% being eliminated in the feces
21%.It is metabolized in liver. It is
L/kg The plasma proteins binding
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Brand name: Geodon cap. 20,60, 80mg.

50,1001mg, Alsuma Inj. 0.6mg/0.5ml. Imitrex.
Brand name: Act Sumatriptan 25,
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ANTAGONISTS: METHYSERGIDE It is an ergot derivative that is a congener of lysergic acid
S-HT RECErTOR
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the action of serotonin. These are the diethylamide. It antagonizes the effects of serotonin in blood vessels and gastrointestinal
Serotonin antagonists are the agents which inhibit
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smooth muscle, but has few of the properties of other ergot alkaloids. It is used
tollowing drugs. diarrhoea-
5-HT3 antaganist used only for the management of severe
ac
ALOSETRON: It is a
irritable bowel syndrome (IBS)
predominant
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Autocolds and Related Drugs
V A Toxt EBook of Phemacology- 197
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prophylactically in migraine and other vascular headaches and to antagonize serotonin in Pharmacokinetics: The absorption is slow. The volume of distribution is 8.3 2.5 L/kg.
the carcinoid syndrome. The protein binding is 62 %. It is metabolized in liver and excreted in urine.
Mechanism of action: It is serotonin antagonists acts on central nervous syslem (CNS), Side effects : Headache, constipation, diarrhea,dizziness, or and tired feeling
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which dirertly stimulates the smooth muscle leading to vasoconstriction. Some alpha- Uses: lt is used for the prevention of acute and delayed nausea and vomiting associated
adrenergic blocking activity has been reported.
Ph
Ph
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with initial and repeat courses of moderately emetogenic cancer chemotherapy. It is as well
slde effects : Nausea. vomiting, heartburn., abdominal pain, diarhea., constipation, as prevention of acute nausea and vomiting associated with highly emetogenic cancer
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drowsiness and dizziness. chemotherapy. It is also used for the prevention of postoperative nausea and vomiting for
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Usee: It is used for the treatment of vasecular headache. up to 24 hours post operation.
Brand name : Aloxi inj. 0.25 mg.
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mg
Brand name :Sansert 2
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CYPROHEPTADINE : It is a serotonin
antagonist and a histamine H1 blocker used as
LOZAPINE: It is a tricyclic dibenzodiazepine, classified as an atypical antipsychotic antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy
dumpin8
Bgent.I binds everal types of central nervous system receptors, and displays a unique syndrome.
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pharmacological profile.
Mechanism of action : It competes with free histamine
for bindingg at HA-receptor sites.
Mechaniem of action : It is a selective monoaminergic antagonist with high affinity for the
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This antagonizes the effects of histamine on
HA-receptors, leading to a reduction of the
serotonin Type2 (5HT:), dopamine Type 2 (D2), 1 and 2 adrenergig.and H1 hitaminergic negative symptoms brought on by histamine HA-receptor
binding. Cyproheptadine also
egptors. Its antipsychotic action is likely mediated through a combination of antogistie competes with serotonin at receptor sites in
smooth muscle in the intestines and other
effects at D2 receptors in the mesolimbic pathway and 5-HT2A receptors in the frontal locations. Antagonism of serotonin on the
appetite center of the hypothalamus may account
cortgx 2 antagonism relieves positive symptoms while 5-1T2A antagonism alleviates for Cyproheptadine's ability to
stimulate appetite.
negative symptoms.
Pharmacokinetics: It is well absorbed
after oral administration The volume of
side effects: Weight gain, tremor, dizziness, spinning sensation, headache, drowsiness; 96 to 99. It is metabolized in distribution
liver and excreted in urine and feces.
nausea, constipation, dry mouth, or increased salivation, blurred vision; or, fast heart rate,
Uses: It is used for treatment
increased sweating. of perennial and seasonal allergic
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allergic conjunctivitis due to inhalant rhinitis, vasomotor rhinitis,
Pharmacokineties: It is rapid and completely absorbed. the serum proteins binding is 97%. allergens and foods, mild uncomplicated
manifestations of urticaria and allergic skin
It is metabolized liver and approximately 50% of the angioedema, amelioration of allergic
administered dose is excreted in the plasma, cold urticaria, dermatographism, reactions blood or
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urine and 30% in the feoes. and as therapy for anaphylactic
adjunctive to epinephrine. reactions
Uses: It is used in the treatment-resistant schizophrenia.
RISPERIDONE: It inhibits
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Brand names: Clozapine tab. 25,100 mg. Clozaril tab. 100mg. dopaminergic D2 receptors
in the brain. It is also said to and serotonergic 5-HT2A receptors
block histamine receptors.
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Ph
Ph
Mechanism of action: It
PALONOSETRON: It is a 5-HT3 antagonist used in the prevention inhibit the D2 dopaminergic
receptors in the brain. Schizophrenia receptors and 5-HT2A serotonergic
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and treatment of
chemotherapy-induced nausea and vomiting is thought to be
D2 and serotonergic caused by an excess of dopaminergic
5-HT2A activity, resulting
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Mechanism of action : The inhibition of 5-HT3 receptors in turn pathways and mesocortical in overactivity of central
inhibits the visceral pathways,
respectively. mesolimbic
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afferent stimulation of the vomiting center, likely indirectly

at the level of the area
postrema, as well as through direct inhibition of serotonin activity within
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the area postrema
and the chemoreceptor trigger zone.
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L98 A Toxt Book of Pharmacology-l
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Pharmacokinetics: It is well absorbed. The volume
of distribution is 1 to 2 L/kg. The HT3 receptors in turn, inhibits the visceral afferent stimulation
plasma proteins binding is 88%. It is extensively metabolized in of the vomiting center, likely
the liver and excreted in indirectly at the level of the area postrema, as
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urine well as through direct inhibition of serotonin
activity within the area postrema and the chemoreceptor
Uses: It is widely used in the treatment trigger zone.
of schizophrenia and mood disorders, including
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Ph
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Side effects : Diarrhea,constipation, stomach
bipolar disorder and depression with pyschosis pain or upset, loss of appetite, weakness, fever
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and dizziness,
Brand name: Act Risperidone tab. 4 mg. Perseris 120 mg/a.8 ml. sc.
Q-risperidone tab. Pharmacokinetics t is rapid and
0.5 to 2 mg completely absorbed. The plasma proteins binding is 65
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9%. It is metabolized
in liver and excreted in urine and 38% in the feces.
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Uses: It is prevention of nausea

DOLASETRON: It is a highly specific and selective serotonin 5-HT3 and vomiting associated with initial and repeats courses of
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receptor antagonist. emetogenic cancer therapy incuding high dose cisplatin),
This drug is not shown to have activity at other known serotonin receptors, and has low postoperation,
Brand name: Granisetron HCI Tablets 1mg. Granisetron
affinity for dopamine receptors. Hydrochloride Injection, Kytril
inj 1mg/4ml.
Mechanism of action:It is a selective serotonin 5-HTs receptor antagonist. The
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antiemetic
activity of the drug is brought about through the inhibition of 5-HTs receptors present both SPROSTAGIANDINS:THROMBOXANES AND LEUKOTRIENES
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centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-
The term eicosanoid is used to represent a large family
HT receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely of endogenous compounds
containing oxygenated unsaturated 20-carbon fatty acids and includes
indirectly at the level of the area postrema, as well as through direct inhibition of serotonin the prostaglandins
(PGs), thromboxanes (TXs), and leukotrienes (LTs). The
activity within the area postrema and the chemoreceptor trigger zone. name PG was derived from the
gland from which these compounds were first isolated,
Side effects and the LTs derive their name from
Headache, dizziness, drowsiness, feeling tired, tremors, twitching or white blood cells and the inclusion of "trienes" or three conjugated
double bonds. The PGs,
uncontrollable muscle movements, agitation, anxiety, restless feeling, depressed mood, dry TXs, and LTs are synthesized. Most
pathways originate with the parent
mouth, upset stomach, diarrhea, constipation, weight gain, or cold symptoms such as stuffy compound arachidonic acid, a major component of membrane phospholipids.
Catalysis
nose, sneezing and sore throat. by cytochrome P450 monooxygenases produces epoxides,
whereas the action of
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Pharmacokinetics : It is well absorbed orally. The volume of distribution is 5.8 L/kg. The the cyclooxygenases (COXs) produces PGs and TXs,
and that of the 5-lipoxygenases (5
plasma proteins binding is 69 to 77%. It is metabolized in liver. It is eliminated by multiple LO) produces LTs.
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routes, including renal excretion.
Parent fatty aclds
Uses: It is used for the prevention of nausea and vomiting associated with emetogenic
Arachldonicacld
cancer chemotherapy, including initial and repeat courses of chemotherapy. Also used for Eicosapentaenolc acld
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Dihomorlinolenic acid
the prevention of postoperative nausea and vomiting.
Brand names : Anzemet tab. 50 mg. Anzemet inj. 100 mg
Ph
Ph
Ph
Cytochrome P-450
5-Llpoxygenases
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monooxy9enases cyclooxygenases
gKANISETRON: It is a serotonin receptor (SHT-3 selective) antagonist that has been used
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Prostacyclin ThrombOxane
as an antiemetic and antinauseant for cancer chemotheraPy TXA)
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Epoxldes (PG) Leukotrienes

Prostaglandins
Mechanism of action: It is a potent, selective antagonist of 5-HT receptors. The antiemetic (PGE, PG) (LTB, LTC, LTD)
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activity of the drug is brought about through the inhibition of 5-HT3 receptors present both Fig. 43 Synthesis.of prostaglandins, prostacyelin, Thromboxane and leukotrienes
centrally (medullary chemoreceptor zone) and peripherally (GI tract. This inhibition of S-
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200 PUA Text Book of Pharmacology-
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COXs are Pharmacology action and role of Prostaglandins, thromboxanes and prostacyclin
COXs convert arachidonic acid into the PG endoperoxides PGG, and PGH2.
inhibited by NSAIDS (see 4.10), leading toinhibition of PG and TX formation. Two distinct Prostaglandins are fatty acids containing 20 carbon atoms cyclopentane ring. they contain
a source
COXs have been described and have been designated as COX-1 and COx-2. COX-1
is one or more double bonds. the number of the double bond is indicated by richest
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present iris, fluid, brain, thymus kidneys and
constitutively expressed, whereas COX-2 is inducible and expressed in response to of prostaglandins, also in lungs, menstrual
to
pancreas. the prostaglandin are synthesized from polyunsaturated acids belonging
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iniflammatory mediators such as cytokines and lipopolysaccharides. Corticosteroids
are destroyed
suppress the induction of COX-2 suggesting that control of PG synthesis is involved in the linoleic or alpha linolenic series. they are active in low concentrations, and
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antiinflammatory actions of these compounds. In addition, selective cOx-2 inhibitors such quicklythey have short duration of action.
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as celecoxib are useful in treating chronic inflammation, because they may cause less gastric Pharmaolegical actions
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disturbance than NSAIDS by allowing formation of cytoprotective PGEthrough COX-1. Cardiovascular system : PGE2 and PGA2 produce vasodilatation and cause tall in
blood pressure. PGF produces vasoconstriction.

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The lipoxygenase pathway of arachidonic acid metabolism produces a variety of acyclic
ipid peroxádes hydroperoxyeicosatetraenoic acids or HPETES). The HPETEs can yield the gterus Most prostaglandins stimulate human myometrium. PGE, PGF stimulate the
:
oxdrane (epoxide) LTA4 which may be hydrolyzed to LTB4 or conjugated with glutathione tone and amplitude of uterine contractions.
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to yield LTC4. Modifñaction of the glutathione conjugate amino acids by hydrolysis yields 3. Gastro intestinal trait : Prostaglandins are present in human gastric mucosa and PGE
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the other leukotrienes LTD4, LTE4 and LTFA. and PGA inhibit gastric and secretions.
4. Reproductive System: Prostaglandins produce luteolysis and decrease in progesterm
:
PROSTAGLANDINS It is a group of compounds derived from unsaturated 20-carbon secretions. They prevent implantationof fertilized ovum. Used for induction of labour
fatty acids, primarily arachidonic acid, viathe cyclooxygenase pathway. They are extremely and for therapeutic abortion:
potent mediators of a diverse group of physiological processes. It act on his receptors and
show the effect. Slatelets TXA2,which can be produced locally by platelets, is a potent inducer of
aggregation and release reaction. The endoperoxides PGG2 and PGH2_ are also
Table 1.3 Type of receptors and their path proaggregatory. On the other hand PGI2 (generated by vascular endothelium) is a
PG Receptor Endogenous Ligand Signaling Pathway potent inhibitor of platelet aggregation. PGD2 has antiaggregatory action, but much less
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EP1 PGE2 Increased Ca++ via PLC stimulation potent than PGI2. PGE2 has inconsistent effects.
6 Bronchial muscle PGF2a, PGD2 and TXA2 are potent bronchoconstrictors (more potent
EP2 PGE2 Increased cAMP via AC stimulation
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than histamine) while PGE2 is a powerful bronchodilator. PGI2 produces mild
EP3 PGE2 Decreased cAMP via AC inhibition dilatation Asthmatics are more sensitive to constríctor as well as dilator effects of PGs.
PGE2 Increased cAMP via AC stimulation PGE2 and PGI2 also inhibit histamine release and are effective by aerosol-but produce
EP4
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Increased Ca++ via PLC stimulation irritation of the respiratory tract and have a brief action.
PGF2
7GIT ()
Ph
Ph
Ph
In isolated preparations, the longitudinal muscle of gut is contracted by PGE2
PGD2 Increased Ca++ via PLC stimulation
and PGF2a while the circular muscle is either contracted (usually by PGF2a) or relaxed
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3 PGI2 Increased Ca++ via PLC stimulation (usuallyby PGE2). Propulsive activity is enhanced in man, especially by PGE2 colic
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TxA2 Increased Cat+ via PLC stimulation and watery diarrhea are important side effects. PGE2 acts directly on the intestinal
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mucosa and increases water, electrolyte and mucus secretion. PGI2 does not produce
diárrhoea and infact opposes PGE2 and toxin induced fluid movement.
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Kidney PGE2 and PGI2 increase water, Na+ and K+ excretion and have a diuretic
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effect. PGE2 has been shown to have a furosemide-like inhibitory effect on C

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Autocolds and Related Drugs 203
PVA Text Book of Phammacology-l
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202
reabsorption as well. They cause renal vasodilatation and inhibit tubular reabsorption. lloprost Peripheral vascular disease
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PGE2 antagonizes ADH action, and this adds to the diurctic effect.
In
contrast, TXA2
causes renal vasoconstriction. PGI2, PGE2 and PGD2 evoke release of renin.
Epoprostenol Pulmonary Hypertension
Ph
Ph
Ph
Treproslinil Pulmonary Hypertension
9. ANS Depending on the PG, species and tissue, both inhibition as well as augmentation
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Misoprostol Ulcers:
of NA release from adrenergic nerve endings has been observed.
Enoprostil Ulcers
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Role PGs may modulate sympathetic neurotransmission in the periphery.
10. Peripheral nerves pGs (especially E2 and 12) sensitize afferent nerve endings to pain
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Omoprostil Ulcer
inducing chemical and mechanical stimuli (Fig 13.2). They iritate mucous meimbranes Buerger's Disease
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Limaprost
nd produce long lasting dull pain on intradermal injection.
Latanoprost
Glaucoma
y Eye: PGF2a induces ocular inflammation and lowers
iot by enhancing uveoscleral Unoprostone isopropyl Glaucoma
outflow. Non irritating congeners like latanoprost are now first line drugs in wide angle
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glaucoma. Traroprost Glaucoma
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RoleLocally produced PGs appear to facilitate aqueous humor drainage, since COX-2 Bimatoprost Glaucoma
pression in the ciliary body has been found to be deficient in wide angle glaucoma Arthrotec Arthritis
patients.
12. Metabolism PGES are antilipolytic, exert an insulin like effect on carbohydrate
metabolism and mobilize Ca2+ from bone: may mediate hypercalcaemia due to bony
CARBOPROST TROMETAMOL : It is a synthetic prostaglandin. It is a nonsteroidal
metastasis. abortifacient agent that is effective in both the first and second trimesters of pregnancy.
Mechanism of action: It binds the prostaglandin E2 receptor, causing myometrial
contractions, casuing the induction of labour or the expulsion of the placenta. It occurs
SIDE EFFECTS : The side effects are common in the use of PGs, but their intensity varies
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naturally in the body and act at several sites in the body including the womb (uterus). They
with the PG, the dose and the route. These are: naugea, vomiting, watery diarrhoea, uterine
act on the muscles of the womb, causing them to contract.
cramps, unduly forceful uterine contractions, vaginal bleeding, Tlushing, shivering, Tever
Uses: It is used for aborting pregnancy between the 13th and 20th weeks of gestation as
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malaise, fall in BP, tachycardia and chest pain.
Prostaglandin drug Products Used Worldwide calculated from the first day of the last normal menstrual period and in the following
conditions related to second trimester abortion:
General Therapeutic Indication
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Prostaglandin Drug 1. It is mainly used to failure of expulsion of the fetus during the course of treatment
Carboprost trometamol Abortifacient by another method:
Ph
Ph
Ph
Abortifacient 2. Premature rupture of membranes in intrauterine methods with loss of drug and
Gemeprost
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insufficient or absent uterine activity;

Sulprostone Abortifacient
3. Requirement of a repeat intrauterine instllation of drug for expulsion of the fetus;
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Dinoprostone (PGE2) Child Birth 4. Inadvertent or spontaneous rupture of membranes in the presence of a previable
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Alprostadil (PGE1) - many products Male sexual dysfunction and Peripheral fetus and absence of adequate activity for expulsion. Also for the treatment of
postpartum hemorrhage due to uterine atony which has not responded to
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Basclar disense
conventional methods of management.
|Peripheral vescular disense
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Beroprost
Brand name : Hemabate solution 250 meg
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Text Book of Pharmacology-|l
204 PA Autocolds and Related Drugs 205
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GEMEPROST: It is a prostaglandin El (PGE1) analog and antiprogestogen used for circulation) and also counteracts any increase in cytosolic calcium levels which would result
preoperative dilation of the cervix before the surgical abortion. It is available as vaginal from thromboxane A2 (TXA2) binding leading to platelet activation and subsequent
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suppositories and also used in combination with the antiprogestin and mifepristone for coagulation). PGI2 also binds to endothelial prostacyclin receptors and in the same manner
termination of 1st- and 2nd-trimester pregnancy. raise cAMP 1levels in the ytosol. This cAMP then goes on to activate protein kinase A
Ph
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Mechanism of action: It is a prostaglandin analog, it binds to prostaglandin E2 and E3 (PKA). PKA then continues the cascade by phosphorylating and inhibiting myosin light-
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receptors as an agonist to cause myometrial contractions and progressive cervical dilation chain kinase which leads to smooth muscle relaxation and vasodilation.
Uses: It is used for the long-term intravenous treatment of primary pulmonary
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via tissue sensitization to oxytocin. It softens and dilates of the cervix prior to transcervical
intrauterine operative procedures. It is a prostaglandin El analog that potently stimulates hypertension and pulmonary hypertension associated with the scleroderma spectrum of
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uterine contractions and causes cervical ripening and relaxation. disease in NYHA Class IlIl and Class IV patients who do not respond adequately to
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conventional therapy.
Uses: It is used for the softening and dilatation of the cervix uteri prior to transcervical,
intrauterine operative procedures in the first trimester of pregnancy or facilitating Brand name: Caripul powder for solution 0.5 mg iv, Epoprostenol powder for solution 1.5
therapeutic termination of pregnancy in patients in the second trimester of gestation. mgiv, Flolan inj. 0.5 mg. iv. Veletri inj. Iv.
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ILOPROST: It is a synthetic analogue of prostacyclin PGl2. It dilates systemic and
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pulmonary arterial vascular beds. It is used to treat pulmonary arterial hypertension. TREPROSTINIL: It is a synthetic analogue of prostacyclin. It is used to treat pulmonary
hypertension.
Mechanism of action : It binds with equal affinity to human prostacyclin (Prostanoid IP)
and prostaglandin EP1 receptors. It constricts the ilium and fundus circular smooth muscle MISOPROSTOL: It is a synthetic analog of natural prostaglandin E1. It produces a dose-
as strongly as prostaglandin E2 (PGE2) itself. It inhibits the ADP, thrombin, and collagen- related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to
induced aggregation of human platelets. In whole animals, iloprost acts as a vasodilator, injury. It is an effective anti-ulcer agent and also has oxytocic properties.
hypotensive, antidiuretic, and prolongs bleeding time. Mechanism of action : It seems to inhibit gastric acid secretion by a direct action on the
Brand name : Ventavis solution 20 pg/ml. parietal cells through binding to the prostaglandin receptor. The activity of this receptor is
mediated by G proteins which normally activate adenylate cyclase. The indirect inhibitüon
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EPOPROSTENOL: It is a prostaglandin that is a powerful vasodilator and inhibits platelet of adenylate cyclase by it may be dependent on guanosine-5"-triphosphate (GTP).
aggregation. It is biosynthesized enzymatically from prostaglandin endoperoxides in It has also been shown to increase the amplitude and frequency
of uterine contractions
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human vascular tissue. The sodium salt has been also used to treat primary pulmonary during pregnancy via selective binding to the EP-2/EP-3 prostanoid receptors.
hypertension. Uses: It is used for the treatment of ulceration (duodenal, gastric and NSAID induced)
and
Mechanismn of action: It is ultimately inhibition of platelet aggregation. Prostacyclin (PGI2) prophylaxis for NSAID induced ulceration.
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is released by healthy endothelial cells and performs its function through a paracrine Brand Name: Cytotec tab. 100-200 pg. Cytotec 100 Mcg.
signaling cascade that involves G protein-coupled receptors on nearby platelets and
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Ph
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endothelial cells. The platelet Gs protein-coupled receptor (prostacyclin receptor) is LIMAPROST:It is an oral prostaglandin El analog. Prostaglandins
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act on a variety of cells

activated when it binds to PGI2. This activation, in turn, signals adenylyl cyclase to produce such as vascular smooth muscle cells causing constriction
or dilation, on platelets causing
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cAMP. CAMP goes on to inhibit any undue platelet activation Gin order to promote aggregation or disaggregation and on spinal neurons
causing pain. It acts as an agonist at
prostraglandin E2 receptors. It likely stimulates the adenylate
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cyclase coupled E2 subtype of

these receptors to produce smooth muscle relaxation.
It is used for the improvement of
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various ischemic symptoms such as ulcer, pain and feeling
of coldness associated with
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206
207
thromboangiitis obliterans as well as improvement of subjective symptoms (pain and eyeball. Bimatoprost may also lower the rate of aqueous formation in the
numbness of lower less) and gait ability associated with acquired lumbar spinal canal
eye. Bothi these
effects decrease the pressure within the eye.
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stenosis.
Brand names: Latisse sol.0.3 mg/1mL, Lumigan soi 0.1 mg/1mL, Lumigan
sol. PF o.003%
Ph
Ph
Ph
LATANOPROST: It is ophthalmic solution is a topical medication used for 4.5.1 THROMBOXANES
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controlling the
progression of glaucoma or ocular hypertension, by reducing intraocular pressure. It is THROMBOXANE : A substance made by platelets that causes blood clotting and
a
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prostaglandin analogue that works by increasing the outflow of aqueous fluid constriction of blood vessels. It also encourages platelet
from the aggregation. There are two
eyes.
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thromboxanes. Thromboxane A2 (TXA2) is active but is very

It is a prostaglandin Fza analogue. Specifically, Latanoprost is unstable and has a half-life of
a prostanoid seleétive FP only 30 seconds before it undergoes hydrolysis
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to form thromboxane B2CTXB2) which is
receptor agonist that is believed to reduce the intraocular pressure (1OP) inactive. The thromboxanes are derived from
by increasing the arachidonic acid and are related to
outflow of aqueous humor. It is used as a opthalmic solution is a prostaglandins. Aspirin acts by inhibiting the COX enzyme
topical medication used
for controlling the progression of glaucoma or ocular hypertension, from synthesizing precursors of
by reducing intraocular thromboxane in platelets thereby reducing platelet
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pressure. aggregation.
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Brand name : Act Latanopro 50meg. Bl Latanoprost 4.5.2 LEUKOTRIENES
50 mcg. Latanoprost 50
Monoprost 50 meg. Sandoz Latanoprost 50 mcg. Xalatan mcg.,
50 meg. The straight chain lipoxygenase products
of arachidonic acid are produced
limited number of tissues (LTB4 by a more
mainly by neutrophils; LTC4 and
LTD4-the cysteinyl
UNOPROSTONE ISOPROPYL: t
is a prostaglandin
0.15% is a synthetic docosanoid. It is mainly
analogue. Ophthalmic Solution
LTs-mainly by macrophages), but probably
PGs.
they are pathophysiologically as important as
used for the treatment of glucoma. .
TRAVOPROST: It is ophthalmic solution is a topical Pharmacology action leukotrienes

medication used for controlling
progression of glaucoma or ocular hypertension, the CVS and blood: LTC4 and LTD4
by reducing intraocular pressure. injected iv. evoke a brief
rise in BP followed by a more
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synthetic prostaglandin F2alpha analogue. It is It is a prolonged fall. The fall in BP
free acid is a selective FP is not due to vasodilatation
receptor agonist and is believed to reduce intraocular prostanoid been seen on blood vessels. because no relaxant action
pressure by increasing the drainage It is probably a result of has
aqueous humor, which is done primarily of in cardiac output coronary constriction induced
and reduction in circulating decrease
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through increased uveoscleral
lesser extent, trabecular outflow facility. It outflow and to a permeability. These LTs volume due to increased capillary
is used for the reduction of
elevated intraocular
markedly increase capillary
pressure in patients with open-angle glaucoma histamine in causing local permeability and are more
or ocular hypertension. edema formation. LTB4 potent than
monocytes; this property is highly chemotactic
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Brand name: Izba sol. 30 pg/ml. Sandoz is shared by HETE but for neutrophils and
Travoprost sol. 0.004 %. through capillaries and not by other LTs. Migration
Travatan 40 ug/ml. of neutrophils
their clumping at sites of
Ph
Ph
Ph
by LTB4. inflammation in tissues is
BIMATOPROST: It is ophthalmic solution also promoted
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is a topical medication Role LTs are

progression of glaucoma or ocular used for controlling the important mediators of
hypertension, by reducing inflammation. They are
intraocular pressure. It is a locally at the site of produced (along with PGs)
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prostaglandin analogue that works by injury. While LTC4
increasing the outflow of and D4 cause exudation
eyes. It binds to the prostanoid FP aqueous fluid from the inflammatory cells which of plasma, LTB4 attracts
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receptor. It is a synthetic reinforce the reaction. the

natural prostaglandins, and works by compound related to one of release of histamine from 5-HPETE and 5-HETE
increasing the drainage the mast cells. may facilitate local
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of aqueous humour
out of the
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FU A Text Book of Pharmacology- Autocoids and Related Drugs 209
208
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Smooth muscle LTC4 and D4 contract most smooth muscles. They are potent TP Has greatest affinity for TXA2; PGH2 also acts on it. It utilizes IP3/DAG as second
bronchoconstrictors and induce spastic contraction of gi.t. at low concentrations.They also messengers which mediate platelet aggregation and smooth musele contraction.
y
increase mucus secretion in the airways.
Role The cysteinyl LTs (CA and D4) are the most important mediators of human allergic
Ph
Ph
Ph
LEUKOTRIENE RECEPTORS
asthma. They are released along with PGs and other autacoids during AG: AB reaction in
Separate receptors for LTB4 (BLT) and for the eysteinyl LTs (LTC4, LTD4) have been
ha
the lungs. In comparison to other mediators, they are more potent and are metabolized defined. Two subtypes, cys LTI and eystT2 of the cysteirnyl LT receptor have been cloned.
slowly in the lungs, exert a long lasting action. LTs may also be responsible for abdominal
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All LT receptors funetion through the ir3/DAG transducer mechanism. The cysLT1
colics during systemic anaphylaxis.
receptor antagonists, viz. Montelukast, Zafirlukast, etc are now valuable drugs for bronchial
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Afferent nerves Like PGE2 and 12, the LTB4 also sensitizes afferents carrying pain asthma inserted 3 hours before attempting dilatation can minimise trauma to the cervix by
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impulses- contributes to pain and tenderness of inflammation. reducing resistance to dilatation. Medical termination of pregnancy of upto 7 weeks has
PROSTANOID RECEPTORs been achieved with high success rate by administering mefepristone (antiprogestin) 600 mg
PGs, TX and prostacyclin act on their own specific receptors located on cell membrane. Five orally 2 days before a single oral dose of misoprostol 400 pg. Uterine contractions are
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major types of prostanoid receptors have been designated, each after the natural PG for provoked and the conceptus is expelled within the next few hours. Ectopic pregnancy
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which it has the greatest affinity. This has been supported by receptor cloning. All should be ruled out beforehand and complete expulsion should be confíirmed afterwards.
prostanoid receptors Uterine cramps, vaginal bleeding, nausea, vomiting and diarrhca are the possible
are G-protein coupled receptors which utilize the IP3/ DAG or cAMP transducer complications. Methotrexate administered along with misoprostol is also highly successful
mechanisms. Some selective antagonists of prostanoid receptors have been produced. in inducing abortion in the first few weeks of pregnancy. PGs have a place in midterm
abortion, missed abortion and molar gestation, though delayed and erratic action and
The prostanoid receptors are:
incomplete abortion are a problem. The initial enthusiasm has given way to more
DP Has greatest affinity for PGD2, but PGE2 also acts on it; activation increases cAMIP
considered use. PGs convert the oxytocin resistant midterm uterus to oxytocin responsive
which inhibits platelet aggregation.
one: a single extraamniotic injection (PGE2) followed by iv. infusion of oxylocin or
EP Has greatest affinity for PGE2; enprostil is a selective agonist. It has been subdivided into intraamniotic (PGF2a) with hypertonic solution produces 2nd trimester abortion in a high
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EP1 which causes smooth muscle contraction through IP3/DAG pathway and EP2 which percentage without undue side effects. Pretreatment with mifepristone improves the
mediates smooth muscle relaxation by increasing cAMP. Cloning studies have identified efficacy of PGE as abortifacient.
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two more subtypes EP3 and EP4. PGE2 enhances Cr and water secretion in intestinal 1. Inductionlaugmentation of labour PGs do not offer any
mucosa also by increasing cAMP. However, in some tissues (adipocytes) PGE2 inhibits advantage over oxytocin for
induction of labour at term. They are less reliable and show wider individual
cAMP formation-responsible for its antilipolytic action. EPI receptors are activated by variation
in action. PGE2 and PGF2 (rarely) have been used in
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PGF2 also. place of oxytocin in toxaemic
and renal failure patients, because they do not cause fluid
retention. PGE2 may also be
Ph
Ph
Ph
FP Has greatest affinity for PGF2a: flhuprostenol is a selective agonist. The most prominent used to augment labour, if it is slow, in primipara. Intravaginal
route is preferred now:
effect of activation of this receptor is smooth muscle contraction mediated through side effects are milder; extra/intra amniotic route is infrequently
ha
used.
Ir3/DAG formation. 2. Cervical priming Applied intravaginally
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or in the cervical canal, low doses of PGE2
IP Has greatest affinity for PGI2; PGE also acts on it and cicaprost is a selective agonist. It which do not affect uterine motility make the cervix soft
and compliant. This procedure
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functions by activating adenylyl cyclase in platelets (inhibiting aggregation) and smooth has yielded good results in cases with unfavourable
cervix. If needed labour may be
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muscles (relaxation). induced 12 hours later with oxytocin: chances of failure
are reduced.
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210 PU AText Book of Pharmacology-l 211
3. Postpartum hacmorrhage (PPH) Carboprost (15-methy! PGF2a) injected im. is an
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alternative for control of PPH due to uterine atony, especially in patients unresponsive Angiotensinogen
to ergometrine and oxytocin. Renin
Ph
Ph
Ph
Peptic ulcer Stable analogue of PGEI (misoprostol) is occasionally used for healing -PA Angiotensin
4. ACE
Chymase
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peptic ulcer, especially in patients who need continued NSAID therapy or who continue
Cathepsin G
Cathepsin G
ACE inhibitors
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to smoke. Angiotensinll
Glaucoma Topical PGF2a analogues like latanoprost and isopropyl unoprostone are one of
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5.
AT receptor LATT receptor - ARBs
the first choice drugs in wide angle glaucoma
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6. To maintain patency of ductus arteriosus in neonates with congenital heart
defccts, till Vasodilation Vasoconstriction
inhibition of cell growth Sympathetic Activation
is undertaken. PGE1 (Alprostadil) is used; apnoea occurs in few cases.
surgery Apoptosis Cell growth
Sodium and fluid retention
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PROSTIN VR 0.5 mg in 1 ml amp; dilute and infuse i.v.
To avoid platelet damage PGI2 (Epoprostenol) can be used to prevent platelet aggregation
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7. Fig. 4.4 A systematic representation of Angiotensin
bypass. It also improves
and damage during haemodialysis or cardiopulmonary
hypertension have
harvest of platelets for transfusion. Few cases of primary pulmonary ANGIOTENSIN-II: It is under investigation for the treatment of sepsis, septic shock,
maintained on epoprostenol infusion.
been successfully diabetes mellitus, and acute renal failure. It has been investigated for the treatment, basic
science, and diagnostic of Hypertension, Renin Angiotensin System, and ldiopathic
26ANGIOTENSIN Membranous Nephropathy.
from specialized cells that encircle the arterioles
Renin is an enzyme secreted into the blood Mechanism of action : The direct action of angiotensin I on surrounding vessel walls is
of the kidneys (the renal capillary networks that are the facilitated by binding to the Gprotein-.coupled angiotensin II receptor type 1 AT-1) on
at the entrance to the glomeruli
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units of the kidney). The renin-secreting cells, which compose the juxtaglomerular vascular smooth muscle cells, which stimulates Ca2+/calmodulin-dependent
filtration
flow and blood pressure. The primary stimulus
apparatus, are sensitive to changes in blood phosphorylation of myosin and causes smooth muscle contraction that results in
flow to the kidneys, which may be caused
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decreased blood vasoconstriction. The RAAS is ultimately regulated by a negative fecdback effect of
for increased renin secretion is vomiting, or
of sodium and water (as a result of diarrhea, persistent angiotensin Il on renin production by the juxtaglomerular cells of the renal aferent
by loss of
or by narrowing of a renal arteryRenin catalyzes the conversion arteriole. Unresuscitated septic shock associated with marked hypovolemia, extracellular
excessive perspiration) (consisting of 10 amino acids)
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angiotensinogen into a decapeptide fluid volume depletion, decreased cardiac output, low arterial blood pressure and
a plasma protein called
decreased systemic vascular resistance causes an increase in renin secretion by the
Ph
Ph
Ph
called angiotensin I.
enzyme (ACE) then juxtaglomerular cells, resulting in elevated angiotensin II plasma levels and an increased
It is an enzyme in the
serum called angiotensin-converting
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(consisting of eight amino acids) secretion of aldosterone from the adrenal cortex. Angiotensin II binding to AT-1 receptors
converts angiotensin linto an octapeptide glands to stimulate the causes dose-dependent vasoconstriction of both afferent and efferent glomerular arterioles.
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ll acts via receptors in the adrenal
called angiotensin II. Angiotensin kidneys, and The most pronounced effect of angiotensin II results on efferent arterioles,
resulting in
stimulates salt and water reabsorption by the
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secretion of aldosterone, which increase in blood pressure. reduced renal blood flow and increased glomerular filtration pressure
arteries (arterioles), which causes an
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the constriction of small reuptake with septic or
blood vessels through its inhibitory actions on the Uses:It is a vasoconstrictor indicated for increasing blood pressure in adults
Angiotensin II further onstricts
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the hormone norepinephrine. other distributive shock

into nerve terminals of
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Brand name: Giapreza Inj. 2.5 mg/1mL.
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PUA Text Book of Phamacology-l
212 FATHOPHYSIOLOGICAL ROLES OF BRADYKININ
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4:2BRADYRININ
of 1060 g/mol, It is a 1Mediation of inflammation :Kinins produce all the signs of inflammation-redness,
formula is Co Hr Nis Ou with a molecular weight
Ph
Ph
Ph
Amolecular pressure and inílammation. Some exudation, pain and leukocyte mobilization. Tissue injury can
cause local kinin
peptide produced by the body to help control blood processes.
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degraded, so that it can production which then sets in motion the above defensive and reparative
blood pressure medications act by ensuring that bradykinin isn't IL-1, TNF-a and
pressure. It is simply calleda peptide. lPlasma Activation of Bl receptors on macrophages induces production of
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blood vessels, thus reducing blood
dilate of plasma kinins HMW
from a plasma globulin Kinnogen by the action
of other inflammatory mediators. Generation and degradation
-kinins are polypeptides split off
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High molecular weight; LMW-Low molecular weight.

Kallikreins. The two important plasma kinins,
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Mediation of pain : By directly stimulating nerve endings and by increasing PG
Kallidin (decapeptide) (2) Bradykinin (nonapeptide) 3 production kinins appear to serve as mediators of pain. Th B2 antagonists block acute
alpha-2 globuilin. A
"Bradykinin probably starts out as a plasma protein, specifically of
Torms a high molecular weight kininogen
pain produced by bradykinin, but induced B1 receptors appear to mediate pain
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proteolytic deavage of the plasma protein
Then the enzyme kallikrein chronic inflammation.
HMWK, which is a plasma protein that helps blood coagulate.
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3. Functional hyperemia lin glands during secretion) and regulation of microcirculation
can convert the HMWK into Bradykinin".
especially in kidney may be occurring through local kinin production.
SUrtace
Factor XII, Prekallikrein, HK 4. Production of kinins is integrated with clotting, fibrinolysin and complement systems.
TiSsueKallikrein
tmK Kallikreins may have roles in these systems which are independent of kinin production.
LK- Lys-Bradykinin Plasma Kallikrein 5. Kinins appear to play no significant role in regulation of normal BP. However, they may
serve to oppose overactive RAS and exert antiproliferative influence on vascular
U smooth muscle in hypertensive states.
Bradykinin HK 12 mK 6. Kinins cause closure of ductus arteriosus, dilatation of foetal pulmonary artery and
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Kininase
CKininase TACE))
constriction of umbilical vessels-they may be involved in adjusting from foetal to
neonatal circulation.
Argo pro pro gly phe ser pro+ phe arg
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Des arg-bradykinin
7. Kininsplay a major role in the development of angioedema. They also appear to be
(Kininase TACCE) | ACE)
ATS Pro pro gy phe ser pro involved in shock, rhinitis, asthma, ACE inhibitor induced cough, carcinoid,
Arg pro pro gy phe ser pro phe
postgastrectomy dumping syndrome, fluid secretion in diarrhoea, acute pancreatitis
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Fig. 45. Synthesis and metabolism of bradykinin and certain immunological reactions. Because of evanescent and unpleasant actions,
Ph
Ph
Ph
kallikrein; kinins have no clinical use.
Hageman Factor (or Factor XI) is activated it cleaves prekallikrein to produce
BRADYKININ RECEPTOR :Bradykinin acts on a receptor (B2 receptor) located on the
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XII so that the intrinsic way is

then HMWK is to be complexed with kallikrein and Factor
proteolytic cleavage blood vessel or blood cells to cause the swelling. Evidence has accumulated that a second
performed. Kallikrein also allows the Bradykinin to be producted by
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enzyme for the inactivation of Bradykinin due to bradykinin receptor (Bl receptor) may also be involved; however, little is known about the
of HMWK The ACE is the most important
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decreases its blood bradykinin B1 receptor in angioedema. The figure below shows how these two receptors
the turn-over plot. In fact, once produced bradykinin rapidly
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by ACE. The two function.
concentration while a big rise of 1-5 bradykinin peptide performed
bradykinin fairly basic. Since arginine has the highest pKa out of
arginine residues makes
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Autocolds and Relatod Drugs
PU A Text Book of Pharmaco/ogy
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214
are constitutively
kinin actions in noninflamed tissues are mediated by B2 receptors which
82 Receptor present on:
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) Visceral smooth muscle-contraction of intestine, uterus, airway.
L Tissue
HK
Vascular endothelium-NO release, vasodilatation, increased permeability.
Ph
Ph
Ph
Ci) .
Plasma BK Kallikreln Sensory nerves-acute pain. The B2 receptor is a G-protein coupled receptor which
Kallikrein -Kininase ! (i)
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des-Argl Lys-BK utilizes the phospholipaseC-IP3/DAG-intracellular Ca2+ mobilization

des-Argl BK
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transducer mechanism.
Giv) Certain responses to kinins, e.g. bronchoconstriction and renal vasodilatation
are
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NF-xBIL-1 B1 Receptor attenuated by pretreatment with PG synthesis inhibitors (aspirin).

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(v) Aspirin injected ip. before bradykinin through the same cannula blocks
its algesic
of
Fig. 4.6 Bradykinin act on receptors action. These responses are mediated by phospholipase A activation-release
arachidonic acid and generation of PGs.
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(vi) The B1 receptor is located on the smooth muscle of large arteries and veins-
Pharmacological actions of Kallidin and Bradykinin are similar actions. mediates contraction of these vessels, but is expressed minimally in normal tissues.
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histamine.The dilatation is
CVs: Kinins are more potent vasodilators than AChand Inflammation induces synthesis of B1 receptors, so that they might play a major role
PGI2 generation, and involves mainly the arterioles B1 receptors, while
mediated through endothelial NO and at inflamed sites. Bradykinin has higher affinity for B2 than for
endothelium are constricted through
Larger arteries, most veins and vessels with damaged Kallidin is equipotent on both. The desArg metabolites of bradykinin and kallidin
they can release histamine and other
direct action on the smooth muscle. In addition, are the natural selective agonists of Bl receptor.
throbbing headache and fall in
mediators from mast cells. Injected iv.kinins cause flushing Uses: Bradykinin has been investigated for the basic science and treatment of Hypertension
to separation of endothelial cells
BP. They markedly increase capillary permeability due
injected in a tissue. Intradermal injection and Diabetes Type 2.
exudation and inflammation occurs if they are
(similar to histamine). Kinins have no direct action on heart;
produces wheal and flare 4.7.1 BRADYKININ ANTAGONISTS
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BP.
reflex stimulation occurs due to fall in After characterization of Bl and B2 kinin eceptors, several peptide and nonpeptidekinin
is slow (bradys-slow, kinein-to
Smooth Muscle: Kinin induced contraction of intestine antagonists have been produced. The synthetic peptide HOE 140 is a selective B2 antagonist
in guineapigs and in asthmatic patients.
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move). They cause marked bronchoconstriction resistant to kinin degrading enzymes and having longer th, while Icatibant, and some
some may be relaxed also.
Action on other smooth muscles is not prominent, others are orally active nonpeptide B2 antagonists that have helped in defining the
Neurones: Kinins strongly stimulate nerve endings that transmit pain and produce a pathophysiological roles of kinins and have undergone limited trials as analgesic,
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base/injected intraperitoneally or in the brachial antiinflammatory drugs and in pancreatitis, head injury, etc
burning sensation. APplied to blister
produces intense, transient pain and has been used in analgesic testing.
Ph
Ph
Ph
artery, bradykinin
Kinins release CAs from adrenal medulla.
Injected directly in brain they produce a variety 4/8 SUBSTANGEP
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sympathetic discharge. They increase permeability of the

of effects including enhanced Substance P was first isolat from horse brain and gut extracts in the 1930's as a mystery
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bloodbrain barrier. substance with strong blood pressure-lowering and smooth muscle contractile properties
facilitate salt and water excretion by
Kidney: Kinins increase renal blood flow as well as
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Substance P(SP) is an undecapeptide (a peptide composed of a chain of 11amino

is reduced by kinin B2 receptor
acid residues). It is the member of the tachykininneuropeptide familyfis a neuropeptide,
effect of furosemide
action on tubules. The diuretic
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participation of locally generated kinins in this response. the terminals of
antagonists, indicating
receptors (B1, B2) has been established. Most
acting as neurotransmitter and as a neuromodulator. It released from
a
ac
Kininreceptors Existance of two types of kinin specific sensory nerves. It is found in the brain, spinal cord and gut which is
associated with
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PU A Text Book of Pharmacology-l Autocolds and Related Drugs
inflammatory processes and pain. It has blood pressure-lowering and smooth muscle
in the central nervous system, but also binds neurons
to of the peripheral nervous system as
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contractile properties Because it was in powdered form, it was named substance P ("P" for
well as to leukocytes, endothelial cells and
powder). It is widely dispersed throughout the body. It keratinocytes.
is synthesized in cell bodies of
Ph
Ph
Ph
vagal sensory ganglia and transported bidirectionally toward the CNS and thoracic and
ingur sacin
abdominal viscera.
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Pioton
Bradykinin Vasodiletion
Substance P precursor (NKNA)
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CGRP
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CRLR
Sensory
neurohe P, AN
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NeurokininAJ Substance P (necövated) ending
Peptidylglycine emidating
monooxygenase
(PAM-
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Substance P (octivated
Piasm oxtravaeation
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Angiotensinconverting Vasogenig
EYme (dACE)
*0a
Fig4.8. Role of substance P in pain mechanism and effect
other tissue
on
Substance P receptor
NK1 receptor) (NK1R) J Degradation Activation of Substance P
Its levels are increased in stressful or anxiety-provoking
Fie. 4.7 svnthesis of substance P situations. It is stressful stimuli like heat and pain trigger
the release of substance P from
sensory nerve endings. The amount of its release
is proportional to the intensity and
Substance P Function: Due to its broad distribution frequency of stimulation. Once released,
in the body, substance P influences a substance P may have direct actions as a
diverse range of functions. It also amplifies or excites most cellular processes neurotransmitter or other functions on non-nerve cell targets.
The Substance
P is involved in: Pain perception, Emotional behavior, Stress, Nausea Role of Substance P
and vomiting,
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Inflammation,Smooth muscle contractijon, Saliva production, Blood cell formation, Wound Blood vessels t is a
powerful vasodilator (widens blood vessels) of
healing and Allergy large blood vesselsin
animals and humans. It dilate the blood vessels
by binding to nk1 receptors on the vessel
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RECEPTOR :The neurokinin 1 receptor (NK-1R) is the main wall and causing the release of nitric oxide.
receptor for the tachykinin Unlike other neurotransmitters, vasodilation
family of peptides. GPCRs mediate their signaling through heterotrimeric G proteins caused by substance p declines during
continuous injection.
transmitting signals from a variety of surface cell receptors to enzymes and ion channels. Pain management :It helps transmit pain signals from different parts of the
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This complex is composed by three distinct subunits: the Gasubunit that binds to spinal cord and brain (where the pain body to the
is perceived) specifically, sensory nerve fibers (i.e.,
GDP/GTP and the Gß and Gy subunits that form the Gßy complex (which present strong
Ph
Ph
Ph
primary afferent nerve fibers) detect pain and
bindings between them). After binding SP to the specific NK-1 receptor, a change occurs in release substance p, which in urn binds to
nk-1 receptors in the spinal cord.
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Nerve cells in the spinal cord then relay

the Gasubunit, allowing it to exchange GTP for GDP and permitting the dissociation of the information to the brain. It also increases the pain
sensitivity to pain indirectly by its inflammatory
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Gpy dimer. These subunits (Ga and Gpy) begin their own signaling cascade separately and effects (swelling, immune cell recruitment,
vasodilation).
positively or negatively regulate the activity of enzyme efectors and ion channels that are Inflammation :It is secreted
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cell type- or GPCR-specific. Substance P is a neuropeptide that acts as a mediator of pain

by many inflammatory immune cells
eosinophils, lymphocytes, and dendritic i.e., macrophages,
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cells) and initiates the production of inflammatory
transmission in the central nervous system and during neurogenic inflammation in the cytokines. In turn, most cytokines bind to substance
periphery. Substance Pbinds preferentially to the neurokinin 1 (NK i) receptor on neurons p and nk-1 receptors. It causes brain
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inflammation, a local inflammatory response

to some types of infection or injury.
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FU AText 80ok of Pharmacologyl
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218
Leaming and Memory: It has excitatory effects in the hippocampus or the memory center
A9 NONSTEROIDAL ANT:INELAMMATORY AGENTS (NSAID)
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of the brain. t promotes long-term potentiation, which is associated with learming and the Nonsteroidal anti-inflammatory drugs are medications that relieve or reduce pain.
formation of memories Nonsteroidal anti-inflammatory drugs (NSAIDs) also come under the wider definition of
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Role in NauUsea: Substance P and its receptor are present in high levels in the area non-opioid analgesics. This means they are a separate type of painkiller from opioid drugs
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postrema (the vomiting center in the medulla) along with other neurotransmitters (such as morphine) that are typically used for more severe types of pain. However NSAID
eg.choline, histamine, dopamine). Drugs that block nkl receptors can help treat nausea are usually taken for less severe types of pain that result from various problems involving
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associated with chemotherapy. aches and pains.
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Itching sensation : Substance P (injected in the skin) causes an itch sensation in human Analgesics: "Analgesics" are the drugs which relieve or suppress the pain sensation by
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skin by stimulating histamine release from mast cells. their action on central nervous system without causing loss of consciousness"
Enhances wound healing : It is acclerated wound healing in the eyes (Gin rabbits) and The analgesics decrease pain or make the individual unaware of existing pain.
spinal cord (in rats) by promoting a local inflammatory response essential for healing
It is very difficult to define pain. Humans has ransacked the entire world to obtain drug
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Role in other disorders: Substance P and eczema, psoriasis, pruritus, stress, anxiety, and with the help of those (drugs) man that might get relief from pain. Pain is recognised as
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depression, obesity, promote cancer growth, arthritis, bowel syndrome (ibs) have elevated warning signal of danger in a person or inidividual that may be due to some disease or
substance p and mast cell levels, worsens sickle cell disease symptoms, measles alzheimer's infection. The intractable pain can cause damage to organs heart and kidneys.
and type 1 diabetes. Pain can not be measured, it is only felt by an individual. It can be explained
s used for Substance P: These drug are Nk-1 Receptor Blockers: These drugs work by unpleasant sensation resulted from some disease or infection. Clinically
as an
pain can be divided
preventing the binding of substance P to its main receptor, Nk-1. in three categories : ) Acute pain (i) Chronic pain (ii) Psychogenic
pain. The acute pain
has quick onset action. It is a temperorary pain. Chronic pain has
gradual onset action. It is
persistant and dull. Psychogenic pain is not concerned with physiological
or anatomical
procedures. It concerns with psychological condition. The analgesic
administered to an
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individual should be ideal and safe.
Narcotics: Homones That Lower Substance P
The intensity of pain is not proportional to the
Morphine Somatostatin large size of wound and severity of tissue
damage. In the year 1946, during World War lInd,
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Cinhibits substance p recently wounded 215 injured men were
Serotonin (5-ht) questioned. There wounds were severe, tissue damage
was of large area. All were almost
Release from nerve endings). Estrogen rational having equal injuries. Among injured
persons only 24% patients reported "bad
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pain". The other wounded patients expressed only
moderate, mild pain, or no pain.
These Drugs such as Muscarinic acetylcholine receptor activators: Anetholetrithione, Analgesic drugs should be an ideal drug, sáfe
Ph
Ph
Ph
in nature. An ideal analgesic should have
pilocarpine, and cevimeline elevate substance P levels in human saliva following properties.
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Stress: Physical and emotional stressors stimulate the release of substance P from sensory 1) The analgesic dru should be a cheap, chemically
stable and tasteful.
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nerves. 2) Analgesic drug should effectively relieve severe pain of different organs.
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3) Analgesics should produce

rapid action when administered by mouth (orally) or
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parenternally (by injections) with long duration of
action.
4) Analgesics should not cause
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addiction or tolerance habbit making, narcosis.

5) It should not depress
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respiratory system and should have maximum safety
to
individual.
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powder having biter taste. It is soluble in waler. Its molecular formula is CgHsNO2: In
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Membrane ipkd
ProsphokgeseA- cordcosterold small doses paracetamol is rapidly and completely absorbed, whereas absorption of higher
Protein
synthess
doses varies. t is also known as acetaminophen, It does not stimulate respiration and do not
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Arechidonic ackd alter acid base balance.
NH.CO.CHa
Ph
Ph
Ph
Lipamypenase] Drcloonypenae (COX-1, CO2)]
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leuton-e MSAID
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Hydroperoaddes Endoperoxddes
HPETEs) (FGG, PGn)
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OH
Leukotriene Prostacyclin hromboxANe
(Structural formula Paracetamol)
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LTB, LTC, LTO) Prostaglandins AA)
Zafirtukest (PGE, PGP
Mechanism of actig The drug Paracetamol or Acetaminophen block pain impulses
Recepior
peripherally which occur in response to inhibit prostglandin synthesis. The antipyretic
Fig. 4.9 Mechanism of NSAID action is due to inhibition of prostglandins in the hypothalamic heat regulating center. It is
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useful in pyrexia, body pains
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Classification of NSATL
Ipaidations: Fever, mild to moderate pain, headache, tooth ache.
ontraindications: Hypersensitivity, alcohol, saccharin
nausea, hepatotoxicity, rash urticaria, angioedema, drowsiness,
Shde effects: Vomiting,
Anti-inflammatory Selective anaphylaxis, cyanosis, anemia, jaundice, convulsions, coma, death purpura.
actio
Paraamingphenol deriative:
Prderential
Cox-2 COX-2
Salicylates: Aspirin.
Propionic acid derivatives:
Paracetamol inhibitors inhibitors buprofen, Naproxen,Ketoproren smocokinetics: Onset action 10 to 30 minutes, peak concentration 12 hou duration of
Acetaminophen). Nimesulide, Celecoxub
action 3 to 4 hours. Plasma half life 4 to 5 hours crósses placenta, excreted
in
Pyrazolone derivatives Etoricoxib

breast mil
Meloicam/ Anthranilic acid derivative
Metamizol (Dipyrone) Nabumetone Parecoxib Mephenamic acid. excretedin urine.
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ropphenaron Aryl-acetic acid derivatives:
BenzozAZOCÍne derivative: Diclofenac, Aceclofenac ig interactions: Paracetamol with alcohol, there are increased chances of hepato
Nefopam. Oricam derivafives:
Piroxicam, Tenoxicam.
toxicity. The effect of chloramphenicol is increases. Severe hypothermia with
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Pyrrolo-pyrole derivative: Ketorolac. phenothiazines.
Indole derivative: Indomethacin.
Pyrazolone derivatives: Dosage: Adult and child aged 10 years and above 325 mg to 650 mg 4 hourly not to exceed
Phenylbutazone,Oxyphenbutazone
4gms per day child under 1 year, the dose is 120 mg, child 1 to 5 year age 250 mg is the
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usual dos
Ph
Ph
Ph
Brand names: Paracetamol: Tablet Crocin, Babymol, Dolo, Metacin, Pacimol, Paracip,
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DERIVATI Pyregesic, Starmol, Ultragin 500mg.

VEARAAMINOPHENOL
PHENACETIN: It is an odourless white crystalline powder with slight bitter taste. It is
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ARACETAMOL (ACETAMINoPHEN). It belongs to group para amino phenol
slightly soluble in water. Phenacetin is metabolized to paracetamol and has similar
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antiinflammatory and
derivatives. It has an analgesic and antipyretic action. It do not have analgesic and antipyretic action. It is used to relieve headache, toothache, neuralgic pain
impairment of concentration.
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uricosuric effects. It_produces mild drowsiness and and rheumatic pains. The usual dose is 300 to 600 mg as a single dose.
drug. It is an odourless white crystalline
Paracetamol is used as an analgesic and antipyretic
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Its molecular formula is C1oH13NO2

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222 FU A Tert Book of Phamacology-l Autocolds and Related Drugs
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ml. 1 year to 4 year 02 ml. 5 to 7 years 04 mil, 8 to 11 years 05 mi. 12 to 15 years 08 mi. 16
NHCOCH
years and above adult dose.
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Brand names:Analgin : Tablet Novalgin, Baralgan M, Ini Ultragin, Novalgin RC.
Ph
Ph
Ph
PROPIPHENAZONE:It is a pyrazolone derivative with anti-infammatory, analgesic and
antipyretic activity. The coupling of propyphenazone with other widely used adidic
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(Structural fomda Phenacein)

NSAIDs such as ketoprofen, ibuprofen, and diclofenac produced mutual prodrugs with
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Phenacetin is given in combination with caffeine, aspirin. The use of phenacetin for long
synergistic analgesic effects. It was introduced for the treatment of different typés of pain
period should be avoided.
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and fever and theumatic disorders. Propyphenazone structurally relates to

Indications :Fever, pain. aminophenazone it has been associated with severe blood dyscrasias.
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Side effects : Prolong use may cause hemolytic anaemia, methaemoglobinaemia, analgesic
neuropathy.
BENZOXAZocINE DERrVATIVE:
Contraindications :Hypersensitivity.
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NEFOPAM:This compound belongs to the class of organic compounds known as
P'harmacokenetics :Onset action 15 to 30 minutes, peak plasma concentration attained in 2 aralkylamines. These are alkylamines in which the alkyl group is substituted at one carbon
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hours. Plasma half life 2 hours, excreted in urine. atom by an aromatic hydrocarbyl group.
Drug interactions : Absorption of phenacetin is increased by metoclopramide. Absorption
is decreased by pethidine, alcohol, propanthline, hepatotoxicity is increased by PREFERENTIAL COX-2 INHIBITORS
paracetamol
NIMESILIDE It is a non steroidal anti inflammatory drug acts is antipyretic and
:
Dosage :500 mg to 1 gram, upto 4 gram per day in divided dose. analgesicanti inflammatory. It is absorbed rapidly and completely when given orally.
Indications :Osteoarthritis, low back pain, dental pain, ENT inflammation, rheumatoid
AMINOrYRINE Aminopyrine (amidopyrin) and antipyrine drugs were introduced in arthritis, dysmenorrhea, musculo skeletal disorders.
1884 as an analgesic and antipyretic. These drugs were associated with high incidence of Dosage :Adult: 100 mg twice daily.
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agranulocyosis, This drug is banned in India and many other countries because of its toxie Children:5 mg per kg body weight in divided doses wo to three times a dayi
effects.
Contraindications: Hypersensitivity, ulcer disease, hepatic disease, pregnancy, lactation,
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RAZOLONE DERIVATIVB: elderly.
Side effects:Vomiting, nausea, heart burm, epigastric pain, skin rash, pruitis, diziness,
METAMIZQL (Dipyrone): analgin, novalgin : It is a derivative of amidopyrin. It can be
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headache.
8iven orally, intramuscular injection or intravenous. It is an promptly acting analgesic and Brand names: Nimesulide: Tablet, Suspension, Nicip, Nise, Nimutab, Mesulid, Genlide,
Ph
Ph
Ph
antipyretic. It is not uricosuric drug. It has poor anti inflammatory action. Achrid, Ralgesic, Zega, Remulide 50mg 100mg tablets.
ha
Indications:Fever, pain. MELOXICAM :lt is a new non steroidal anti inflammatory drug, which greater inhibitory
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Contraindications :Hypersensitivity, infants below 3 months pregnancy, lactation. action against eyclooxygenase (COX:2) with greater anti inflammatory response.
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Side effects :Shock, red colour urine, agranulocytosis. Indications:Osteo arthritis, ankylosis spondylitis, rheumatoid arthirits.
2
Dosage:Oral dose 500 mg to 1.5 gm daily in 2 to 3 equally divided doses. Intramuscular
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Dosage :75 mg to 15 mg daily.
ml I.M. 2 to 3 times a day children: 30 to 60 mg per kg body weight daily in divided doses, Contraindications :Hypersensitivity.
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11 months 0.1
8 hourly. IV injection 3 to 4 times a day slow intravenous dose 3 months to
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Brand names Meloxicam: Tablet Melwin, Mexam, M Cam, Melogesic, Movac, Ecwin, PARECOXIB: It is a water-soluble and injectable prodrug of valdecoxib. It is a COX2
Muvera 7.5mg. 15mg. selective inhibitor in the same category as celecoxib (Celebrex) and rofecoxib (Vioxx). As it
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is inectable, it can be used perioperatively when patients are unable to take oral
arylalkanoic
NABUMETONE: It is a nonsteroidal anti-inflammatory drug (NSAID) of the medications
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acid family. Itis a potent inhibitor of prostaglandin synthesis, most ikely through binding SALICYLATESE
to the COX-2 and COX-1 roceptors. It is well absorbed from the gastrointestinal tract.It
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Pharmacologic actions of salicylates

undergoes rapid biotransformation to the principal active metabolite, 6-methoxy-2.
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naphthylacetic acid (6MNA). Antipyretic action: Salicylates lowers elevated body temperature. They do not lower the
normal temperature of body. They bring down elevated body temperature to normal body
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SELECTIVE COx-2 INHIBITORS temperature by following mechanism.

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It a selective cyclooxygenase-2 (COx-2) inhibitor, is classified as a (a) The salicylates produce sweating due to which the elevated body temper-ature is
CELECOXTB
nonsteroidal anti-inflammatory drug CNSAID). The inhibition of prostaglandin E2 synthesis lowered.
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which (a mediator of pain) results from the inhibition of CcOx-2, and helps to alleviate pain 6) The hypothalamic heat regulating centre is set for high temperature in fever. The
ymptoms salicylates reset hypothalamic centre to lower the elevated temperature to normal
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of cyclooxygenase-2 (COX- body temperature.
Mechanism of action : tis a selective noncompetitive inhibitor
2 enzyme. The mechanism of action of celecorib is the inhibition of prostaglandin synthesis
Rnti inflammatory and antirheumatic effect: Salicylates have powerful antirheumatic
through COx2 inhibition. cox-2 is expressed heavily in inflamed tissues where it is effect. This effet is produced by reducing inflammation and pain of joints.
induced by inflammatory mediators. COx2 also plays physiological roles in a limited Analgesic action: Salicylates do not relieve severe pain. They act by inhibiting pain
number of tissues, including those of the female reproductive tract, the kidney, and sensation in the thalamus, they do not change emotional reaction of pain. Salicylates are
possibly the vascular endothelium effective only in dull pain of low intensity.
Uses: It is used in the treatment of osteoarthritis, rheumatoid arthritis, acute
pain, painful
Action on respiratory system: The salicylates stimulate respiration by directly stimulating
menstruation and menstrual symptoms, and is also used to reduce numbers of colon and the respiratory system and indirectly through carbon dioxide reducing and increased
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rectum polyps in patients with familial adenomatous polyposis oxygen utilisation by skeletal muscles.
Brand name: Act Celecoxib cap. 100 mg. oral. Celebrex 100 mg Action on blood: The salicylates lowers erythrocytic sedimentation rate (ESR) which is
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It selectively inhibits isoform 2 of raised in rheumatic fever. The salicylates lowers prothrombin plasma level.
ETORICOXIB: It is a new COX-2 selective inhibitor.
cyclo-oxigenase enzyme (COX-2). This reduces the generation of prostaglandins (PGs) from Action on skin : Salicylates, methyl salicylate and salicylic acid have fungistatic; keratolytic
arachidonic acid. and antiseptic efect and are used locally for treatment of skin infections and diseases.
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2 of cyclo-oxigenase enzyme (COx-2). Urocosuric efect: Salicylates increases the excretion of uric. The salicylates action on uric
Mechanism of action :It selectively inhibits isoform
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This reduces prostaglandins (PGs) generation from arachidonic acid. acid depends upon the dose of salicylates. Salicylates in a dose of 3 gms per day blocks
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Pharmacokinetics: Its Bioavailability is 100%o following oral administration. Its proteins tubular secretion of uric acid and it raises blood uric acid level. In 5 gm or above daily
doses. It prevent reabsorption of uric acid and increases its excretion. In higher doses
binding is 92 %. Its half life is 22 hours.
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treatment of rheumatoid arthritis, osteoarthritis, ankylosing salicylates acts as uricosuric and in low doses cause retention of uric acid.
Uses: It is used for the
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back pain, acute pain and gout. Action on cardiovascular system: Normal doses of the salicylates has no effect on heart, in
spondyitis, chronic low
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higher doses cause paralysis of vasomotor centre.
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Immunological effects : Salicylates inhibits the antigen-antibody reaction, and prevent the It isan odourless colourless white crystalline powder with slight acid taste. It is soluble in
release of histamine. water. Aspirin is used in the treatment of acute and chronic rheumatoid arthritis. Aspirin
should not be given to children under year age except under medical supervision if under
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Action on Gastro intestinal tract: When administerd or taken by patient emply stomach
some circumstances it is must to be administered. Aspirin should not be administered in
salicycates can cause gastric uloeration and intestinal
blecding. Salicylates produce nausea
combination with anticoagulant drugs it may increase risk of hemorrhage. Aspirin increase
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and vomiting due to stimulation of CTz (Chemoreceptor Trisger Zone).
toxicity (toxic effects) of methotrexate, reduces uricosuric action of probenecid, with Aspirin
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Action of endecrine glands : Salicylates actvate release of adrenaline from adrenal

platelet activation is a key step in acute arterial thrombosis.
medulla, also stimulate release of adrenocortico trophic harmones (ACTH). The salicylate
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interferr with binding of thyrovine with plasma proteins, the free thyroxine depress the Mechanism of action : Aspirin decrease platelets aggregation, it blocks pain impulses in
central nervous system. The antipyretic action is resulted by vasodilation of peripheral
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eretion of TSH (Thyroid stimulating harmone).

wessels. It inhibits prostaglandin synthesis.
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Salicyclates produce hyperglyeemia and glyeosuria.
Indications: Aspirin (Acetyl salicylic acid) is useful in mild to moderate pain, fever,
Uses of salicylates: () Salicylates acts as an antipyretic in case of fever.
rheumatoidarthritis, osteoarthritis, thromboembolic disorders, prophylaxis of myocardial
(7 As an analgesics used to alleviate mild pain to moderate pain._
infecion.
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Salicylates are used as an anti rheumatic drug.
Transient ischaemic disease: 325 mg 6 hourly
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Used locally as fungistatic, keratolytic and antiseptic. Methyl salicylate and
Thromboembolic disorders: 325 to 650 mg two times a day/once daily.
salicylic acdd are used in ointment for local application to skin.
Adverse effects of salicylate
entraindications: Hypersensitivity to salicylates. G.L bleeding pregnancy, lactation,
Salicylates cause gastro intestinal disturbanoe like nausea, vomiting, ulcer-ation,
ulcers, asthma, liver disease.
peptic
harmacokinetics: Orally onset 15 to 30 minute, peak concentration 1 to 2 hour, during 4 to
performation and gastric haemorrhage.
6hour. Metabolized by liver, excreted by kidneys, crosses placenta, excreted in breast milk.
2. Cause bone marrow depression leading to aplastic anemia, agranulocytosis. Plasma half life to 2 to 4 hours.
Intolerance leads to rash, urticaria.
Drug interactions: Antacids, urinary alkalisers, steroids decrease the effect of Aspirin.
3. In large doses salicylism is developed characterised by lethargy, confusion, tinnitus,
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Toxic effect with sulfonamides, furosemide increased. There is decreased blood sugar level
hearing loss, headache. by salicylates.
4. As salicylates increase breakdown of fatty acids there is fatty infilteration of liver and
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Dosage: Fever/pain.
kidneys.
Adult: Orally 325 mg to 650 mg 4 hourly not to exceed 4 gm per day.
SPIRIN: tAcetyl salicylic acid) Children:50 to 100 mg per kg body weight in divided doses four hourly.
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Von Gerhardt synthesized Aspirin in the year 1853. In the medicine field it was
Arthritis: Adult: 26 to 5.2 gm per day in divided doses 4 to 6 hourly
introduced in 1899. In the 20th centrury Aspirin has constantly gained popularity and is
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used as a handy medicine for headache, bodyache, fever etc. Molecular fornmula of Aspirin Child: orally 90 to 130 mg per day in divided doses 4 hourly.
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is:Cy Hs O4 Brand names: Aspirin : Aspin, Ecosprin, ASA, Aspent, Lorpin 75, Cotaspirin, Ascad,
Zosprin 50mg. 75mg. 150mg, 325mg tablets.
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ÇoOH
soDIUM SALICYLATE: t is a oxdourless, colourless white crystalline powder with a salty
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-o cOCHs sweet taste. Its molecular formula is CtigNaOg. It is soluble in water. It has antipyretic and
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analgesic actions. When given by mouth it is absorbed through intestine. Sodium salicylate
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(Stucural formula Acotyl Salioylic acid (Apirin) USP is gastrie irritant, sodium carbonate is given with sodium salicylate to reduce its effect.
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Sodium salicylate cause dilation of skin vessels due to which perspiration and heat
15
he ointment containing methyl salicylate should be stored in air tight containers. The
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increased which result in fall in body temperature. containers should be kept tightly closed.
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CPROPIONIC ACID DERIVATIVES>
OH
BUPROFEN: (BRUFEN) : It is a synthetic drug. It was introduced in medicines in 1969. I
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is used as antipyretic analgesic and anti inflammatory. it is administered orally. Its
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(Structural fomula Sodium Salicylate)

molecular formula is C13H1802
nervous
Mechanism of action: Sodium salicylate blocks the pain impulses in central
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CH,CH.COOH
system which occur in response to inhibit prostglandin synthesis. The Antipyretic action of
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sodium salicylate result from inhibition of Hypothalamic heat regulating center. Useful in
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Gout, fever, body pains.
Indications:Used as an analgesic and antipyretic. CHCH.CH, CH,
Dosage:0.6 to 2 gm, as mild analgesic.

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Structure of Ibuprofen
Rheumatic fever : 2 gm sodium slaicylate every 3 hours by mouth, till fever or body Mechaniam of action : It inhibits prostaglandin synthesis by decreasing enzyme secretions
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temperature is lowered or subsided. In acute rheumatism it is administered orally 5 to 10 required for biosynthesis. It acts as antipyretic, analgesic and anti inflammatory.
gms daily in divided doses. Indications: Antipyretic, analgesic, rheumatoid arthritis, osteoarthritis, dysmenorrhoea,
Contraindications: Hypersensitivity, pregnancy, lactation, gastric ulcers, renal disease, acute gout, dental pain, tooth extration, post operation, post partum.
liver disease. Rontraindications: Hypersensitivity, asthma, active peptic ulcers, pregnancy, lactation,
Side effects : Headache, tinnitus, confusion, dyspnoea, excessive sweating, diminished renal disease, hepatic disease.
vision. Side effects: Vomiting, nausea, jaundice, dry mouth, cramps, purpura, rash, sweating
strong characteristic
METHYL SALCYLATE:ltis a colouriess or slight yellow liquid with blood dyscrasias, hematuria, oliguria, oliguria, azotemia, hearing loss, blurred vision,
aromatic odour. It is slightly soluble in water. When winter green oil or oil of winter green
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dizziness, drowsiness, tremors, confusion muscle cramps, hypertension, tachycardia,
is demanded or prescribed, methyl salicylate is supplied. It is not administered by mouth. peripheral edema.
Its chemical formula is CgHgO3. It is readily absorbed through skin. It is applied in
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Pharmacokinetics: Orally onset action 30 minutes, peak concentration1-2 hour plasma half
ointments liniments. life: 2 to 4 hours. excreted in urine, metabolized in liver.
ço.o.CH3 Drug interactions: Increase action of phenytoin, sulphunamides. The salicylates
decrease
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action of ibuprofen.
OH
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Dosage:Analgesic : Adults: By mouth 200 mg to 400 mg 4 to 6
hourly, not to exceed 3.2 gm
per day.
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(Structural formula of Methyl Salicylate)

Antipyretic: Adult 200 to 400 mg 6 hourly orally children: Age
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6 months and above 5 mg
Indications : Sciatica, rheumatic conditions, lumbago. Methyl salicylate ointment should
be
per kg body weight 6 hourly, maximum 40 mg per kg weight
per day in equal divided
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locally to the skin. It should not be applied to broken skin (wounds/injuries) near doses 6 hourly.
massaged
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eyes, mucous membrane. Anti inflammatory: Adult : Orally 300 to 800 mg 6 to
8 hourly, maximum 3.2 gm per day.
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Child: Orally 30 to 40 mg per kg body weight in equal divided dose 3 to 4

times a day.
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A Text Book of Pharmacology-! Autocolds and Related Drugs
230
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Brand names: lbuprofen: Tablet Cipgesic, Emflam, Cipgesic, Tbugesic, Intafen, Nurern, CH
Norswel, Tbupid lablets 200mg, 400mg. 600mg HC-COOH
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NAPROXEN: It is a non steroidal anti infammatory drug. It is more valuable in gout. It is
also useful in ankylosing spondilitis.
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Mechanism of action: Naproxen inhibits prostaglandin synthesis by decrease of an
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enzyme required for biosynthesis. It acts as an Analgesic, Antipyretic and Anti
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inflammatory drug
Indcations: Gouty arthritis, osteo arthritis, spondilitis primary dysmenorrhea. (Structure of Ketoprofen)
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Side effects : Nephrotoxicity, dysuria, hematuria, azotemia, oliguria, vomiting, nausea, Indications: Osteo arthritis, analgesic for mild to moderate pain, dysmenorrhea
anorexia, jaundice, cholestatic hepatitis, cramps, dry mouth, peptic ulcers, drowsiness, Contraindications: Hypersensitivity, asthma, renal disease, liver disease, ulcers disease
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insomnia, anxiety, depression, tachycardia, peripheral edema, palpitaiton, rash, pruritis, pregnancy, lactation, cardiac disorders, elders.
Sweating, blood dyscrasias, hearing loss, blurred vision.
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Side effects: Vomiting, nausea, anorexia, diarrhoea, jaundice, cramps, dry mouth, peptic
Pharmacokinetics: Onset action 20 to 30 minutes, peak plasma concentration 2 to 4 hour. ulcers, drowsiness, dizziness, fatigue, tremors, insomnia, anxiety, depression tachycardia,
Plasma half life 3 to 4 hour metabolized in liver, excreted in urine. hypertension, palpitation, peripheral edema, nephrotoxicity, hemahuria, azotemia, hearing
Drug interactions: May increase action of heparin, with lithium, increased lithium toxicity. loss, blurred vision, blood dycarasias.
Contraindications: Hypersensitivity, asthma, ulcer disease, renal disease, hepatic diseas Pharmacokinetics : Onset action 15 to 30 minutes, peak concentration 2 hours, plasma half
pregnancy, lactation, children below 2 year age, bleeding disorder, cardiac disease. life 3 to 3% hour metabolized in liver, excreted in urine, excreted in breast milk
Dosage : Adult: Orally 250 mg to 500 mg 12 hourly (bid) not to exceed 1 gm perday. Drug interactions : Increased action of probenecid, coumadin.
Child : Orally 10 mg per kg body weight in equal two divided doses. Dosage: Ketoprofen is administered
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Brand names Naproxen: Tablet Napryn, Naprosyn, Artagen, Nalyxan, Xenar CR, 250mg. Analgesic: Adults: 25-50 mg orally 6 to 8 hourly
275mg tablets. Anti inflammatory : Adults: Orally, 50-100 mg three times a day, not to exceed
300 mg per
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day.
KETOPROFEN: 1t is a (NSAID) non steroidal anti inflammatory drug acts as anti pyretic, Brand names : Ketoprofen: Capsule, Tablets, Ostofen, Redufen, Vofane, Maxigesic
plus
analgesic and anti inflammatory. Its action is similar to ibuprofen. Molecular formula
is S0mg, 100mg, 200mg tablets.
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Ciol14O3
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FLURBIPROFEN: 1t is a (NSAIDs) non steroidal anti inflammatory
drug. It is more
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effective drug than ibuprofen. It is also used as an ocular anti inflammatory.

Dosage: Adults orally 50 mg twice to four times a day maximum dose 300 mg per day.
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Brand names: Flurbiprofen: Tablet Froben, Arflur, Flurofen 50mg, 100mg, 200mg
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Eye drops: Flur, Flurbin, Cadiflur eye

drops containing 0.03% furi-biprofen sodium. 1-2
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drops to be instilled in each eye 6 hourly.
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A Text Book of Pharmacology- Autocolds and Related Drugs
232 P 233
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ANTHKANILIC ACID DERIVATIV DEUg nteractions : Diclofenac decreases antihypertensive action of diuretics, Beta blockers,
MEPHENAMIC ACID : It is a derivative of anthranilic acid. It has weak anti increased toxicity : phenotoin, digoxin, sulphunamides, digoxin.
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inlammatory efect of mephanamic acid exert peripheral as well as central analgesic action. Dosage:Orally 50 mg three times a day.
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It is used as an antipyretic analgesic and anti inflammatory drug Analgesic and dysmenorrhea
Indications : Joints pain, myalgia, soft tissue pain, antipyretic, dysmenorthea,
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Adults 50 mg Diclofenac potassium threetimes a day. Maximum 150 mg per day, oraly (by
osteoarthrities, rheumatoid arthritis. mouth)
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Contraindications : Hypersensitivity, epilepsy, pregnancy, lactation. Osteoarthritis :Orally 100 to 150 mg daily ie. 50 mg three times a day.
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Side effects: Diarrhoea, epigastirc, skin rashes, hemolytic anaemia, dizzines, haemolytic :
Rheumatoid arthritis 50 mg orally 6 hourly maximum 200 mg daily.
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anaemia. Ankylosing spondylitis : 25 mg 6 hourly orally, 25 mg HS may be given 100 to 125 mg per
VPharmacokinetics: Orally absorption is slow, metabolized by liver, excreted in urine, day.
plasma half life 2 to 4 hours
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Post cataract surgery : Diclofenac sodium eye drops 0.1 % solution 4 times a day.
Drug interactions: Increased effect of oral anticoagulants. Brand names: Diclofenac Sodium: Tablet Voveran, Tromagesic, Relaxyl, Oxalgin D, Jonac,
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Dosage: 250 mg to 500 mg orally three times daily. Divon, Diclomol, Diclonac 50mg, 100mg.
Brand names : Mefenamic acid: Tablet, Suspension, Meftal, Mefdol, Ponstan, Pontax,
Meflup, 100mg, 250mg, 500mg tablets. DICLOFENAC POTASSIUM: It is a non steroidal anti inflammatory drug having
antipyretic, analgesic and anti inflammatory action. Its action, indications, side effects,
ARYL-ACETIC ACID DERIVATIVSD Contraindications are similar to diclofenac sodium. It is suited ideally to patients on sodium
DICLOFENAC: It is a (NSAID) non steroid anti inflammatory drug. It acts as an free diet, hypertensive patients, to treat painful inflammatory conditions to patients on
antipyretic, analgesic and anti inflammatory drug. It is well absorbed when administered diuretic therapy.
:
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orally. it is an inhibitor of prostaglandin synthesis. It has a powerful anti inflammatory Brand names Diclofenac potassium: Tablet Voltaflam, Volini, Ultra K, Dicpot, Dofenic,
action besides its analgesic and antipyretic action. Topac, 50mg. 100mg tablet.
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Indications : (Uses): Acute musculo skeletal disorders, sprains, bursitis, tendonitis, peri
arthritis (frozen shoulder), primary dysmenorrhoea, low back pain, osteoarthritis, ACECLOFENAC: It is a non steroidal anti inflammatory drug. It is a phenyl acetic acid
heumatoid arthritis, tenosynovitis, post operative painful conditions, dental surgery pains, derivative having effective analgesic and anti inflammatory action. It is effective in variety
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in gynecological painful anti infammatory conditions. of painful conditions. It activates glycosamino glycans (GAG) synthesis.
Contraindications: Hypersensitivity to NSAID's, asthma. Gastro intestinal disorders, Indications (Uses): Relieve pain and inflammation in ankylosing spondylitis, rheumatoid
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cardiac disorders. arthritis, osteo arthritis.
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Side effects : Blood dyscrasias, epistaxis, eharing loss, blurred vision, nephrotoxicity, Contraindications : Hypersensitivity, gastro intestinal hemorrhage, pregnancy
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dysuria, hematuria, uremia, purpura, rash, sweating, erythema, alopecia, vomiting nausea, Side effects: Vomiting, nausea, heartburn, dyspepsid, diarhoea,
abdominal pain,
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anorexda, jaundice, cramps, dry mouth, peptic uleers, gastro intestinal bleeding, dizziness, flatulence convulsions.
drowsiness, confusion, insomnia, anxiety, depression weakness (muscles), fatigue, tremors,
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Drug interactions: Increase action of digoxin, lithium
photosensitivity, hypertension, CHF, palpitation, tachycardia. increase action of oral
anticoagulants.
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Pharmacokineties: Onset action orally 15 to 30 minutes peak concentration 2 to 3 hours,

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plasma half life 1-2 hours, metabolize in liver, excreted in urine.
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PU A Text Book of Phamacology-i
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234
cylooxygenase-2 (COX
administered 100 Mechanism of action: It inhibit both cylooxygenase-1 (COX-1) and
Dosage : 100 mg orally twice daily. In liver disease dose in reduced and inhibition of prostaglandin synthesis leading to decreased formation
2) which leads to the
thromboxanes from arachidonic acid. Analgesia is
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mg O.D. by mouth.
of precursors of prostaglandins and impulse generation
Brand names: Aceclofenac: Tablet Arfur 100, Acota, Acenac, Aceroc,
Acebloc, Aclopic,
probably produced via a peripheral action in which blockade of pain
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of the synthesis or.
Dolokind, Micronac 100mg, 200mg tablet. results from decreased prostaglandin activity. However, inhibition
receptors to mechanical or chemical
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actions of other substances that sensitize pain

DERIVATIVES: stimulation may also contribute to the analgesic effect.
ARICAM
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Pharmacokinetics: It is rapidly and completely absorbed after oral administration. The
TIROXICAM : It is a long acting non steroidal anti inflammatory drug. It is effective to 8 years old]. The plasma proteins is
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volume of distribution is 0.26 : 0.08 L/kg [children 4

antipyretic, analgesic drug with anti inflammatory properties.
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99%.
Indications: Acute musculo skeletal disorders, osteo arthritis, rheumatoid arthritis, gout. is metabolized. The major metabolites are a
The primarily hepatic is Less than 50% of dose
a
is
Contraindications Hypersensitivity, pregnancy, asthma lactation, hypertension, liver glucuronide conjugate. The principal route of elimination of ketorolac and its metabolites
renal. Approximately 6% of a dose is excreted in the feces.
disease kidney disease, children below age 6 years. Heart disease, ulcers.
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is used to
Uses: It an antiinflammatory agent with analgesic and antipyretic properties,
Side effects: Vomiting, nausea, anorexia, jaundice, dry mouth, cramps, diarrhoea,
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headache, peripheral oedema, treat osteoarthritis and control acute pain. It is a peripherally acting analgesic.
dorwsiness, dizziness, fatigue, insomnia, depression,
Brand names: Acula solution 50 mg/1mL
palpitation, tachycardia, rash, purpura, sweating, nephrotoxicity, hematuria, hearing
loss,
blurred vision, blood dysrasias

NDOLE DERIVATIVE
Pharmacokinetics: Peak concentration-2 hour, metabolize in liver excrteted in urine.
ÎNDOMETHACIN: It is a strong non steroidal anti inflammatory drug. It promply act as
Drug interactions: Increase action of sulphunamides, phenytoin, warfarin.
Roxicam, antipyretic. It relieves inflammation of tissue injury related pain. It is an odourless, tasteless,
Brand names Piroxicam: Tablet, Capsule, Injection, Suganril, Pirox, Movon, yellow brown crystalline powder. It is slightly soluble in water. its chemical fornula is
Dolonex, Dolokam, Dolocip DT 10mg, 20mg, 40mg C19H16CINO4. It is rapidly absorbed when taken by mouth. Indomethacin was introduced
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n 1963.
TENOXICAM: It is a non steroidal anti inflammatory drug congener of piroxicam. It is
having same action and properties similar to peroxicam.
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MELOXICAM: It is a new non steroidal anti inflammatory drug, which greater inhibitory
action against cyclooxygenase (COX-2) with greater anti
inflammatory response. CH0 -cH2COOH
(Structural formula Indomethacin)
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Indications: Osteo arthritis, ankylosis spondylitis, rheumatoid arthirits.
Indications : Acute gouty arthritis, rheumatoid arthritis, not controlled by aspirin,
Dosage: 7.5 mg to 15 mg daily.
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Ph
Ph
ankylosing spondylitis. Bartte's syndrome.
Contraindications: Hypersensitivity. Contraindications: Hypersensitivity, asthma, renal disease, hepatic disease, ulcers disease,
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Brand names: Meloxicam: Tablet Melwin, Mexam, M Cam, Melogesic, Movac, Ecwin, pregnancy, lactation.
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Muvera 7.5mg, 15mg Pharmacokinetics: Orally onset action 1 hour. Peak plasma concentration3 hour, half life 1
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to 1% hour. Metabolized in liver excreted in urine, crosses placenta, excreted in breast milk.
&TRROLO-PYRROLE DERIVATIVE: Drug interactions: Increased action of phenytoin, sulphunamides. Decreased action of
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KETOROLAC: t is a pyrrolizine carboxylic acid derivative structurally related to triamterene. It should not be administered with antacids.
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indomethacin. It is an NSAID and is used principally for its analgesic activity.

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PVA Text Book of Pharmacology-ll
DRUGS
Side effects: Nephro toxicity, hematuria, oliguria vomiting
nausea, anorexia, diarrhoea, 4-10 GOUT AND ANTIKGOUT
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Gout is a disorder of purine metabolism which there is deposition of urate
drowsiness, dizziness, crystalsin and
flatulence, cramps, dry mouth, peptic ulcers, ulceration, perforation,
rash (skin), pruritis, and swelling in joints. Ihe
fatigue, insomnia, andeity, depression, tachycardia, hypertension, around the joints. It is characterised by recurrent attacks of pain
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men than in women. It is a
sweating, hearing loss, blurred vision, tinnitus, blood dyscrasias. bIg toe 1s more áffected. This disorder ocur more commonly in
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Dosage: Adult 25 mg to 50 mg bid or tid not to exceed 200 mg per day. hereditary disease that was known to ancient Greeks and Romans. The word Gout is
by
derived from Latin word "Gutta" means drop, a drop in the joints. Gout accompanied
is
Indomethacin : Microcid, Recticin, Indocap, Indoflam, Insure capsule 25mg
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Brand names: acid, a
hyperuricaemia. This disease owes its origin to an increased próduction of uric
50mg, 75mg
decreased rate of uric acid destruction or a failure or decreased excretion of uric acid.
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The problem of therapy in gout is :
PYRAZOLONE DERIVATIVEŠS
(9 To suppress the acute attack of gout.
PHENYLBUTAZONE: It is an white crystalline powder, odourless and has bitter taste. It
is
formula is (i) Prevention and mobilization of urate deposits in the joints tissues.
slightly soluble in water. It is variably absorbed when given orally. Its molecular
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C19H20N202. It is available as 100 mg, 200 mg tablets. It was introduced in 1949. ii) Prophylactic treatment which includes preventing of acute attack of gout and to
prevent chronic joints disability.
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Structure of Phenylbutazone
Acute joint manifest as sudden onset of severe inflammation and pain in
Phenylbutazone: C19H20N202. Mol. wt. = 308.4
metatarsophalengial joint of greater toe due to precipitation of urate crystals in the joint
space. The joint becomes red, swollen and painful. This condition of joint pain is called
Gout and it requires quick or immediate treatment to reduce swelling and alleviate severe
pain.
Various drugs used in the treatment of Gout are called antigout drug as under:
CH,CH,CH,CH
Indications: Analgesic, anti inflammatory.

Clo rodts
effect. It blocks
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Side effects: Phenylbutazone is uricosuric action, and has sodium retention
iodine uptake by thyroid and number of other intracellular enzyme processes, due to which
A) For acute gout: B) For chronic Gout, Hyperuricaemia
oedema is developed : Rashes, gastric upset, mouth ulceration, hemetemesis and malena,
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nephrotoxicity, bone marrow depression. i) NSAID's
Dosage: Adults, by mouth 300 mg daily in divided doses with meals. i) Colchicine
Children:5 to 10 mg per kg body weight daily 6 hourly.
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ii) Corticosteroids
Uricosuric drugs Synthetic drugs
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oxYPHENBUTAZONE: It is a metabolite of phenylbutazone. Its action, pharmacokinetic,
toxic effects are similar to phenylbutazone.
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is high. Oedema due to

)Probenecid Allopurinol
The gastric toxicity of phenylbutazone and oxyphenbutazone
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nervous sysem are ii) Sulfinpyrazone
sodium (Nat) and water retention is frequent side effects to central
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serious in nature, hypersensitivity reaction, hypothyroidism bone marrow depression is

noticed so these drugs are banned in India and many other countries.
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(A) Acute Gout Acute gout manifest as sudden onset of severe inflammation &
pain ina
small joint. The metatarsophalangeal joint greater toe is common. It is due to precipitation
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of urate crystals in the tissue of joint space. The joint (joints) becomes red, tenderness,
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242
P A Text Book of Pharmacology-!
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More modern DMARDs have included potent, small molecule immunosuppressive agents harmacokinetics : On set action 4 to7 days. Poak plasma concentration 1 to 2 weeks
such as leflunomide, cyclosporine, tacrolimus and mycophenolate. duration of action 3 weeks, crosses placènta, excreted in urine.
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More recently, monoclonal antibodies and biologics have been developed that act on the :
Drugs interactions Sulfanomides, phenylbutazone, tetracyclines, aspirin, alco-hol,
phenytoin, radiations, probencid, nerease toxicily. Folie actd decreases effect of
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primary cytokines and inflammatory pathways that are active and play a major role in methotrexate.
rheumatoid arthritis. These important agents include the tumor necrosis factor antagonists,
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Brand names: Methotrexate : Tablet, Injection, Vibzi, Zexate, Merex, Mexate, Neotrexate,
- anticytokines (such as anakinra) and other major immunosuppressive agents (rituximab, Plastomet 25mg, 50mg.
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abatacept, and tocilizumab).
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AZATHIOPRINE : t is an immunosuppressant drug and is purine analogue. It has more

effect as immunosuppressant than antitumar action. The important function of the drug
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iasification of Discase modifying antirheumatic drugs (DMARDS) azathioprine is prevention of renal and other graft rejection. The patient developing
cyclosporine drug toxicity azathioprine is given to them. It is also effective in the treatment
of rheumatoid arthritis and some auto immune diseases. It acts to produce
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immunosuppression by inhibiting purine synthesisi in the cells.
Mechanism of action: Azathioprine produces immunosuppression by inhibiting purine
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Immunosuppressants Sulfasalazine Chloroquine Leflunomide Gold sod.
synthesis in body cells. It is used in Renal transplant to prevent graft rejection, bone
Methotrexat Hydroxychloroquine Aurothiomalate, marrow transplant.
Azathioprine Auranofin Indications: Used in kidney transplant to prevent graft rejection, rheumatoid arthritis
D-Penicillamine
Cyclosporine Idiopathic thrombocytopenic purpura. bone marrow transplant.
Contraindications Hypersensitivity, pregnancy, lactation.
:
Side effects: Vomiting, nausea, stomatitis, hepatotoxicity, jaundice, leucopenia, anaemia,

METHOTREXATE (MTX) It is a yellow to orange crystalline powder, slightly soluble in pancytopenia, rash, muscle wasling,
water. It is read-ily absorbed when given by mouth and rapidly excreted through kidneys.
methotrexate is a cytotoxic antimetabolite. methotrexate inhibits an enzyme which reduces Pharmacokinetics : Metabolises in liver, excreted in urine, crosses placenta.
folic acid synthesis in cells, in this way cell division is stopped. it induced Drug interactions: Do not admix with other drugs.
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immunosuppression. Dosage: Transplantalion (prevention of rejection)
Mechanism of action: Methotrexate (MTX) inhibits (stops) an enzyme which reduces folic Adult and child: Orally and 1.V. 3 to 5 mg per kg body weight daily, maintenance dose
2
of
acid which is required for Nucleic acid formation in all body cells, specifically phase
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mg per kg body weight daily.
cell cycle. 1t is useful in head and neck carcinoma, lymphosarcoma. Rheumatoid arthritis: Adults: orally1 mg per kg body weight dailly after two month
carcinoma breast, lung,
Indications: Acute lymphoblastic leukaemia, leukaemic meningitis, increase dose by 0.5 mg per kg body weight per day.
head, neck carcinoma lymphosarcoma, rheumatoid arthritis, mycosis fungoides.
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Drand names: Azathioprine : Tablet Imuran, Zymurine, Azimune, Imuzat, Azoran 50mg
body surface area twice
Dosage: L-ymphoblastic leukaemia 20 to 40 mg per square meter CYCLOSPORINE: Cyclosporine is an immunosuppressant drug. it suppress humoral
:
weekly. Chorio
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weekly, 1M/1V. maintenance dose 15 to 30 mg per square meter twice immunity and cell mediated reactions. it also inhibits lympholine production and release. it
carcinoma : 15 to 30 mg daily for 5 days. is acyclic polypeptide containing eleven amino acids.
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leucopenia,
Contraindications: Hypersensitivity, serious anemia thrombocytopenia, severe Mechanism of action: The drug cyclosporine produces immunosuppression by inkibiting
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pregnancy, Lactation. lymphocytes (T). It is uscd for organs transplant to prevent rejection.
anorexia, stomatitis hematoemesis, ulcers, urinary
Side effects: Vomiting, nausea, Indications: Used in organs transplant to prevent rejection orally used to prevent graft
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leucopenia, thrombocytopenia,
Telention, menstrual irregularity, spermatogenesis, anemia, rejection after kidney liver, heart, pancreas, lungs transplant. Intravenous infusion is
acne, alopecia, ecchymosis,
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uritcaria, rash, gastro intestinal hemorrhage, folliculitis, administered in bone marrow transplant.
dizziness, headache, convulsions, fatigue, chills, fever.
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Autocolds and Rolated Drugs
PU A Text Book of Phamacology-l 245
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intravenous infusion : Starting dose one day before surgery for transplantation 3 to 5 mg Uses : () Ulcerative coitis, i) Crohn's disease a chronic inflammatory bowel disease of
per kg body weight daily. To continue two weeks after transplant. Then oral maintenance unknown origin, which affects ileum and the colon) chrohn disease is characterized by
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dose of 12.5 mg per kg body weight daily in two divided doses for 6 months to 1 year attacks ot diarrhoea, severe abdomen pain, nausea, fever and weakness (ii) Rheumatoid
arthritis.
Contraindications: Hypersensitivity, lactation.
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Precautions : Use carefully in Renal disease, hepatic disease, hypertension, pregnancy.
CHLOROQUINE : It is an odourless, white, crystalline, powder with bitter taste.
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paediatrics, is
soluble in water. It is used in the treatment of malaria and amoebiasis. Chloroquine kills
Side effects: Vomiting nausea, hepatotoxicity, pancreatitis, rash, acne, hirustism,
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malaria schizonts at all stages of malaria. It causes less toxic effects and is used in the
headache, tremors, heamturia renal failure.
Suppressive treatment of malaria. It is available as 250 mg, 500 mg tablets and 40 mg per ml
Pharmacokinetics: Peak concentration 4 hour, plasma half life 1 to 2 hour, 25 hour, crosses
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injections.
placenta, excreted in breast milk, metabolized in liver, excreted in feces.
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Mechanism of action: It is a synthetic drug. It inhibits parasite replications, transcription
Drug interactions: Increased action of cyclosporine with amphotericin-B, ketoconazole, of DNA to RNA by forming complex substance with DN of bacteria. It acts as antimalarial
cimetidine. Phentoin, rifampin decrease action of cyclosporine. drug.
Dosage: By mouth (orally) first dose is given 4 to 12 hours before transplantation 10 to
:
Indications Malaria, Extra Intestinal Amoebiasis, Giardiasis, Rheumatoid Arthritis,
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15mg per kg body weight. This dose is ontinuously used daily for 2 weeks. Then Amoebiasis (Entamoeba histolytica)
maintenance dose if 2.5 mg per kg body weight daily is continued.
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Contraindications: Hypersensitivity, alcoholism, hepatic disease, pregnancy, lactation,
Brand Names: Cyclosporine: Graftin soft gel, Immunosporin, Zymmune, Panimum Bioral retinal field changes, eczema, psoriasis, children.
25mg, 50mg 100mg capsules.
Slde effects: Nausea, vomiting, Headache, itchings, retinal damage, rash, loss of
SULEASALAZINE :Its Molecular formula: C18 H14 N4OsS. It is an odourless yellow hearing,
greying of hair, mental disturbances, cinchonism.
powder. It is insoluble in water. When administered orally, it is partially absorbed, Pharmacokinetics : Peak serum concentration 1-6 hour, half life 3 to 5 days, metabolised
remaining is metabolised by gut flora and converts it into sulphapyridine which is in
liver, excreted in urine, breast milk, feces, crosses placenta.
absorbed, and 5 amino salicylic acid, which is absorbed to small extent.
Dose: For malaria: 1gm stat followed by 500 mg after six hours 1st
Sulphasalazine is a sulfunamide derived from sulphapyridine and amino salicylic acid. It is day then 500 mg daily
for next two days.
effectively used in the treatment of ulceratine collitis, alone or in combination with
Suppressive treatment 500 mg chloroquine on the same day of week
corticosteroids or surgery. It is available as 500 mg tablets (Tablet Salazopyrin). for the period May to
September-October of the year.
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Mechanism af action The drug Sulfasalazine acts to deliver Sulfapyridine and 5
For extra intestinal amoebiasis Adult: 200-250
Aminosalicylic acid to colon. It acts as antiinflammatory drug. mg 1M 6 hourly for 10 to 12 days. Children
10 mg per kg body weight,
1/M or orally.
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Contra Indications : Hypersensitivity to sulfunamides, pregnancy, lactation, Bronchial Brand names: Chloroquine : Tab Lariago, Cadiquin, Maliago,
asthma, urinary obstruction, children below 2 years. Nivaquine, Resochin tablets.
Side Effects:Nausea, vomiting, abdominal pain, hepatitis, headache, insomnia, depression,
LEFLUNOMIDE: It is a pyrimidine synthesis
fatigue, anxiety, leucopenia, hemolytic anaemia, rash, dermatitis, urticaria, increased blood inhibitor belonging to the DMARD (disease-
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urea nitrogen, creatinine, allergic, myocarditis. modifying antirheumatic drug) class of drugs,
which are chemically and pharmacologically
very heterogeneous.
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Pharmacokinetics : Partially absorbed, Peak plasma concentration 1 to 6 hours, excreted in
urine, serum half life 6 hours.
Mechanism of action : The mechanism of
action of leflunomide has not been fully
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determined, but appears to primarily involve

Drug Interactions : Increased anticoagulant effects of orally administered coagulants, regulation of autoimmune lymphocyte
has been suggested that leflunomide exerts its
immunomodulating effects by preventing
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increased hypoglycaemic response with oral hypoglycemics. Decrease absorption of the expansion of activated autoimmune lymphocytes
digoxin, food and drug decrease iron and folic acid absorption. via interferences with cell cycle
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progression. In-vitro data indicates that leflunomide

Dosage : Adult dose one to two grams per day in equal divided doses 6 hourly by mouth interferes
by inhibiting dihydroorotate dehydrogenase (a mitochondrial with cell cycle progression
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for 2 to 3 weeks. pyrimidine ribonucleotide uridine enzyme involved in de novo
monophosphate (rUMP)synthesis) and
Children: Dose 40 to 60 mg per kilogram body weight daily in equal divided doses orally antiproliferative activity. It is also a
tyrosine kinase inhibitor. Tyrosine has
ac
(by mouth) kinases activate

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PU A Text Book of harmacology-1 Autocolds and Related Drugs
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signalling pathways leading to DNA repair, apoptosis and cell proliferation. Inhibition of D-PENICILLAMINE : t is a pharmaceutical of the chelator class. The pharmaceutical form
tyrosine kinases can help to treating cancer by preventing repair of tumor cells. is D-penicillamine, as Lpenicillamine is toxic (it inhibits the action of pyridoxine). It is an a-
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Uses: It is used for the management of the signs and symptoms of active rheumatoid amino acid metabolite of penicillin, although it has no antibiotic properties.
arthritis (RA) to improve physical function and to slow the progression of structural Mechanism of action: The mechanism of action of penicillamine in rheumatoid arthritis is
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damage associated with the disease. It has also been used for the prevention of acute and unknown although it appears to suppress disease activity. Unlike cytotoxic
chronic rejection in recipients of solid organ transplants.
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immunosuppressants, penicillamine markedly lowers IgM rheumatoid factor but produces

Brand name: Arava 10 mg tab. no significant depression in absolute levels of serum immunoglobulins. Also unlike
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cytotoxic immunosuppressants which act on both, penicillamine in vitro depresses T-cell
activity but not B-cell activity.
It is a gold compound that is used for its
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GOLD SODIUM THIOMALATE:

Pharmacokinetics The absorption is rapidly but incompletely, The plasma proteins
immunosuppressive anti-rheumatic effects. Gold Sodium Thiomalate is supplied as a
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binding is >80%. It is metabolized in liver, and excretion is mainly renal, mainly as
solution for intramuscular injection containing 50 mg of Gold Sodium Thiomalate per mL disulfides.
It is most effective in active progressive rheumatoid arthritis and of little or no value in the
presence of extensive deformities or in the treatment of other forms of arthritis. Indication: Take penicillamine on an empty stomach, at least 1 hour before or 2 hours after
a meal. Do not drink milk within I hour before or 1 hour after you take penicillamine.
Mechanism of action: The precise mechanism of action is unknown. It is known that
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sodium aurothiomalate inhibits the synthesis of prostaglandins. The predominant action Side effect: decreased sense of taste, skin rash or peeling, watery blisters, skin changes such
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appears to be a suppressive effect on the synovitis of active rheumatoid disease. It may as wrinkling or pimples, stomach pain, nausea, vomiting, diarrhea, loss of appetite,
decrease prostaglandin synthesis or may alter cellular mechanisms by inhibiting sulfhydryl numbness or tingly feeling ringing in your ears and a wound that will not heal.
systems. Uses: It is used in the treatment of Wilson's disease. It is also used to reduce cystine
Pharmacokinetics: It is rapidly absorbed following IM injection, with peak serum excretion in cystinuria and to treat patients with severe, active rheumatoid arthritis
concentrations occurring in 3-6 hours. The apparent volume of distribution is 0.26 +/-0.051 unresponsive to conventional therapy. It is used as a form of immunosuppression to treat
kg-. It is About 85-90% of the drug is protein bound. Its urinary excretion, with a mean of rheumatoid arthritis.
35% of the dose found in the urine in ten days. Fecal elimination accounts for an additional Brand names: Cuprimine cap.250 mg. Depen Tab 250mg
9.4% of the IV dose excreted in ten days.
Uses: It is used as anti-inflammatory agent for the treatment of arthritis. Disease-modifying
antirheumatic drug. DMARD. REVIEWQUESTIONS
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Injection BP Sol. 10
Brand names: Myochrysine Sol. 10-50 mg, Sodium Aurothiomalate
50 mg
SHORT ANSWER QUESTIONS
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Q.1. What are analgesics?
AURANOFIN It is a organogold compound classified by the World Health Organization
:
Ans. Analgesies are the drugs which relieve or suppress the pain sensation by their
as an antirheumatic agent. action on
It may act as an central nervous system without causing loss of consciousness.
Mechanism of action: The mechanism of action is not well understood. to a decreased
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lead Analgesics decrease pain. They makes the individual unaware of existing pain.
inhibitor of kappab kinase and thioredoxin reductase which would Q.2. What should be the properties of analgesics?
respectively. In patients with
immune response and decreased free radical production,
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arthritis, gold salts can
inflammatory arthritis, such as adult and juvenile rheumatoid
Ans. Analgesics should be safe in nature and be an ideal drug with following
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of bone qualities/properties.
decrease the inflammation of the joint lining. This effect can prevent destruction
1. Analgesic drug should be cheap, chemically stable and be tasteful.
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and cartilage.
second-line drugs 2. Analgesic drug should effectively relieve severe pain of different organs.
Uses: It is used in treating inflammatory arthritis. Gold salts are called
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because they are often considered when the arthritis

progresses in spite of antiinflammatory 3. Analgesic drug should produce rapid action when administered orally or parenterally with
long during of action.
drugs (NSAIDs and corticosteroids).
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4. Analgesic should not cause, addiction, tolerence, habit, making, narcosis.
Brand names: Ridaura 3 mg.
5. It should not depress respiratory system and should have maximum safety to the individual.
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Book of Pharmacology- Autocolds and Related Drugs 249
PU A Text
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Q.13. What is Serotonin7
04. What are Antipyretics? Ans. It was isolated from the blood serum as a substance causing powerful smooth muscle
elevated body temperature. group at ihe
Ans. Antipyretics are the drugs which reduce contraction. Only later was it demonstrated to be tryptamine with a hydroxyl
1s widely
Q.5. What are anti inflammatory drugs? poSiion. Only 1-29% of the serotonin in the body is in the brain, insofar as serotonin
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(swelling)
Ans. These are the drugs which produces
symptomatic relief from inflammation distributed in platelets, mast cells, etc.
Q.14. Explain the side effects of Prostaglandins
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along with relief from pain.
the PG, the
Q.6. Define histamine. Ans. The side effects are common in the use of PGs, but their intensity varies with
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major role in many allergic reactions, dilating dose and the route. These are: nausea, vomiting, watery diarThoea, uterine
cramps, unduly
Ans. Histamine is a substance that plays a
the vessel walls abnormally permeable. Histamine is part of the body's torceul uterine contractions, vaginal bleeding, flushing, shivering, fever, malaise, fall in Br',
vessels and making
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natural alergic response to substances such as pollens. tachycardia and chest pain.
Q.15 What is the uses NSAID
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Q.7. Explain the uses of histamine stomach,

test acid secreting capacity df Ans. It is used for the treatment of ulceration (duodenal, gastric and NSAID induced) and
Ans. It has no therapeutic use. It is also has been used to
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It is used for diagnosis of
pheochromocytoma,
bronchial hyper-reactivity in asthmatics. prophylaxis for NSAID induced ulceration.
obsolete now.
however, these pharmacological tests are risky and Q.16. Define the thromboxane
Q.8. What is Antihistamines drugs? Ans. It is a substance made by platelets that causes blood clotting and constriction of blood
the histamine that is liberated in the body.
Ans. Antihistamines are the drugs which antagonize vessels. It also encourages plateiet aggregation. There are two thromboxanes. hromboxane
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allergic disorders. The antihistamines have A2 (TXA2) is active but is very unstable and has a half-life of only 30 seconds before it
These drugs are used for symptomatic treatment of
on their response to histamine they prevent.
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been divided into Hj and H2 blockers, depending undergoes hydrolysis to form thromboxane B2(TXB2) which is inactive. The thromboxanes are
derived from arachidonic acid and are related to prostaglandins.
0.9. Explain the toxicity of antihistaminies Q.17. What is leukotrienes?
(0 Anorexia, epigastric pain
Ans. The straight chain lipoxygenase products of arachidonic acid are produced by a more
(i) Dryness of mouth, nose and eyes limited number of tissues (LTM mainly by neutrophils; LTC4 and LTD4-the cysteinyl LTs
(ii) Cause drowsiness, sedation mainly by macrophages), but probably they are pathophysiologically as important as PGS.
(iv) Hypotension, palpitation Q.18. What is angiotensin
() Blood dyscarasias :agranulocytosis,
leucopenia, haemolytic anaemia Ans. It is an enzyme in the serum called angiotensin-converting enzyme (ACE) then
Q.10. Describe the Mechanism of action of hydroxyzine converts angiotensin I into an octapeptide (consisting of eight amino acids) called angiotensin II.
competes with histamine for binding at H Angiotensin II acts via receptors in the adrenal glands to stimulate the secretion of aldosterone,
Ans. It is a histamine H1 receptor antagonist. It
suppression of histaminic edema, flare,
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which stimulates salt and water reabsorption by the kidneys, and the constriction of
receptor sites on the effector cell surface, resulting inoccur at
hydroxyzine the subcortical level of the CNS. small arteries (arterioles), which causes an increase in blood pressure. Angiotensin further
and pruritus. The sedative properties of may be effective as an antiemetic. constricts blood vessels through its inhibitory actions on the reuptake into nerve terminals of
Secondary to its central anticholinergic actions, hydroxyzíne
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the hormone norepinephrine.
Q.11. Write a short note on cetirizine
Q.19. What is bradykinin?
Ans. It is a potent second-generation
histamine Hl antagonist., the active metabolite of the
It competes with histamine for binding at Hr Ans. It is a peptide produced by the body to help control blood pressure and inflammation. Some
piperazine Hirreceptor antagonist hydroxyzine.
in suppression of histaminic edema, flare, blood pressure medications act by ensuring that bradykinin isn't degraded, so that it can dilate
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receptor sites on the effector cell surface, resulting
can be attributed to reduced penetration of blood vessels, thus reducing blood pressure. It is simply called a peptide. Plasma kinins are
and pruritus. The low incidence of sedation
lipophilic carboxyl group on the ethylamine side polypeptides split off from a plasma globulin Kinnogen by the action of Kallikreins.
cetirizine into the CNS as a result of the less
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chronic urticaria, and pollen-induced Q.20. Define the Substance P (SP)
chain. It is used in the treatment of allergic rhinitis,
not cause drowsiness or anticholinergic
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asthma. Unlike many traditional antihistamines, it does Ans. It is an undecapeptide (a peptide composed of a chain of 11 amino acid residues). It is the
side effects. member of the tachykininneuropeptide family. It is a neuropeptide, acting as a neurotransmitter
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Q.12 Explain the Side Effects of diphenhydramine and as a neuromodulator.
anxiety, confusion, neuritis, chest
82. Describe the Nonste roidal anti-inflammatory drugs
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Ans. It has following side effects: drowsiness, fatigue,

dilated pupils, tinitus, nasal stiffness, dry nose
tightness, dry mouth, nausea, anorexia, dysurea, Ans. These are medications that relieve or reduce pain. Nonsteroidal anti-inflammatory drugs
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and throat. (NSAIDs) also come under the wider definition of non-opioid analgesics. This means
they are a
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250 A Tort Book of Phemecology-i Autocolds and Related Drugs
251
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eparate tyT* of painkiller from oioid drugs (ouch as morphine) that are typically used for
merr vere tyys ol pain.
022 What is antigout drug? Q4 Which of the following statements about serotonin is correct
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Ans. It is manifest as sudden onset of nevere inflammation and pain a)5-HTi receptors are found on nerve endings and are stimulatory.
in metatarsophalengial
foint ot geater toe due to prrdpitation of urate crystals in the joint space. The joint becomes
red, b) 5T2 receptors are found on smooth muscle and are stimulatory.
wvlen and painhul. This condition of joint pain is called. Various drugs used fn the treatment
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of Gout are called anti-gout drugs. These drug to reduce swelling and alleviate 5HT3 receptors are found on smooth muscle and are inhibitory.
evere pain. d) Cyproheptadine is a highly selective antagonist of 5-IT2 receptors.
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LONGANSWER QUESTIONS Q.5. Which of the following statements conceming bradykinin is not true
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a)It is generated by the action of the enayme kininase.
Dexribe dasily and function of autacoids Refer 4.1 b) The substrate for its generation is kininogen, a plasma globulin.
VWEyprlain the synthesis, metabolism and degradation of histamine
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Refer 42
c)It is inactivated by the loss of its C-terminal arginine
0.3 Discuss Antihistamines are the drugs, write the pharmacology of cetirizine Rcfer4. 3.
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d) It is a potent vasodilator.
04 Explain the mechanism of action, side effects, indicaion, contraindication and use of
Diphenhydramine Refer i.3. Q.6. Which of the following eicoasanoids is released from platelets and promotes their
EEregation?
O.5. Describe the eicosanoid autacoids explain the pharmacology of prostaglandins Refer 4.5.
a) PGI TXA2
c
c
Oe Eplain leukotrienes, and its reoeptor write the pharmacology action of leukotrienes, Refer 1.5.2
LTB4 d LTC4
07 Describe the angiotensin, write the pharmacology of angiotensin-11 Refer 4.6.
y
y
98 Describe the mechanism of action adverse effec, indication, dose and brand name of
07. Single dose NSAIDs drug is-
a) Aspirin b) Diclofenac
Paracetamol (acetaminophen). Rder 4 9
0° Explain the 1'hthophysiological role of bradykinin Kder 4.7 Piroxicam d) Naproxen
Q.8 What is recommended as the first-line pharmacologic urate-lowering therapy approach in
10.Describe the mechanism of action, side effect and uses Aspirin of Refer 4.9 8out?
11.Describe the mechanism of action, adverse effect, indication, dose and brand name of Colchicine A. Colchicine
Reder 4.10.
B. Xanthine oxidase inhibitor therapy with
allopurinol or febuxostat
Decrbe the anti-gout, write the pharmacology of allopurinol: Rder 4.10
C.Corticosteroids
MULTIPLE CHOICE QUESTIONS D. NSAIDs
Q.9. What is the minimum target for lowering the serum urate level sufficiently to
durably
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Q1. Which of the following stalenments aboul histamine is correct? improve signs and symptoms of gout?
a) Histamine is stored in peripheral nerve endings. A. 4 mg/dL B.5mg/dL
b) Histamine is released from mast cells following an allergic challenge. C.6 mg/dL
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D.7 mg/dL
Histamine is a vasoconstrictor. Q.10. What is the recommended starting dosage of allopurinol?
d) Histamine is an essential amino acid. A.S 100 mg/d B. 200-300 mg/d
0.2 Which of the following activities ocurs following the stimulation of H2 receptos C. 400-600 mg/d
y
y
D. 800 mg/d
a) Vasodilation. Q.11. Which of the following is NOT a first-line option for treatment of acute gout?
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b) Uterine contraction. A. NSAIDs B.Corticosteroids
Bronchial smooth muscle contraction. C.Oral colchicines D. Aspirin
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d) Enhanced secretion of hydrpchloric acid in the stomach. Q.12. Which of these medications were recommended as acceptable first-line options for gout
prophylaxis?
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03 Which of the following stalements about histamine is not correct?
a) it is a bronchodilator. A. Prednisone B.Low-dose colchicine and low-dose NSAIDs
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b) Large scale release of it may cause a fall in blood pressure. C. Prednisolone D. Intravenous colchicines
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c)Large scale release of it may cause a fall in blood volume.
d) Histamine release contributes to the symptoms of anaphylaxis.
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PU A Text Book of Pharmacology-ll Autocolds and Related Drugs 253
a familial metabolic disease characterized by recurrent episodes of acute arthritis Q.21. Inflammation is:
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Q.13. Gout is
due to deposits of monosodium urate in joints and cartilage. a)A localized protective reaction of a tissue to irritation, injury, or infection, characterized by
This consideration is: pain, redness, swelling and sometimes loss of function
b) False b) A deficiency of the normal immune response.
True
y
Q.14.. Probenecid and sulfinpyrazone are uricosuric drugs employed to decrease the body pool of A reaction resulting from an immune reaction produced by an individual's white blood
urate in patients with tophaceous gout or in those with increasingly frequent gouty attacks. cells or antibodies acting on the body's own tissues or extracellular proteins.
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This consideration is: d) All of the above
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a) True b) False Q.22. An acute, transient phase, of inflammation is characterized by:

Q15. Which of the following drugs is an uricosuric agent: a) Local vasodilatation and increased capillary permeability (phase of damage)
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a) Allopurinol b) Sulfinpyrazone b) Infiltration of leucocytes and phagocytic cells (phase of exudation)
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)Colchicine d) Indomethacin Tissue degeneration and fibrosis occurrence (phase of proliferation)

Q.16. Uricosuric drugs are the following, EXCEPT d) All of the above
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a) Probenecid b) Sulfinpyrazone 0.23. A delayed, subacute phase, of inflammation is characterized by:
) Colchicine d) Aspirin (at high dosages) a) Local vasodilatation and increased capillary permeability (phase of damage)
Q17. Which of the following drugs used in the treatment of gout acts by preventing the b) Infiltration of leucocytes and phagocytic cells (phase of exudation)
c
c
migration of granulocytes: c) Tissue degeneration and fibrosis occurrence (phase of proliferation)
y
y
a) Allopurinol b) Sulfinpyrazone d) All of the above
Colchicine d) Indomethacin
024. A chronic, proliferative phase, of inflammation is characterized by:
Q.18. Which of the following drugs used in the treatment of gout has as its primary effect the a) Local vasodilatation and increased capillary permeability (phase of damage
reduction of uric acid synthesis b) Infiltration of leucocytes and phagocytic cells (phase of exudation)
a) Allopurinol b) Sulfinpyrazone
Tissue degeneration and fibrosis occurrence (phase of proliferation)
Colchicine d) Indomethacin d) All of the above
Q.19. Immediate allersy reaction (type I allergic reaction) is: Q.25. The following substances are considered to be referred to as elcosanoids:
a) An allergic or immune response that begins within a period lasting from a few minutes to
Prostaglandins
a) b) Leukotrienes
about an hour after exposure to an antigen to which the individual has been sensitized
)Thromboxanes d) All of the above
b) An allergic reaction that becomes apparent only hours after contact
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Q.26. Correct statements about cortisol (hydrocortisone) include all of the
)An allergic reaction that results from the formation of antigen-antibody complexes between following, EXCEPT:
a) Cortisol is synthesized from cholesterol
a foreign antigen and IgM or IgG immunoglobulins. It occurs during blood transfusion
b) ACTH governs cortisol secretion
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reactions and in hemolytic disease of the newborm)
d) An allergic reaction that is due to the presence of elevated levels of antigen-antibody Most cortisol is inactivated in the liver
complexes that cause tissue damage d) The half-life of cortisol in the circulations is
normally about 60-90 hours.
0.20. Delayed allergy.reaction (type IV allergic reaction) iss
y
y
Q.27. Physiologie doses of glucocorticoid can result in:
a) An allergic or immune response that begins within a period lasting from a few minutes to a) Increased liver glycogen stores, gluconeogenesis
and lipolysis
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about an hour after exposure to an antigen to which the individual has been sensitized b) Maintenance of cardiovascular function (by
potentiation of norepinephrine) and skele!
b) An allergic reaction that becomes apparent only hours after contact muscle function
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e)An allergic reaction that results from the formation of antigen-antibody complexes Increased hemoglobin synthesis, resulting in elevated of red blood
cell count
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between a foreign antigen and lgM or IgG immunoglobulins. (at occurs during blood d) All of the above
transfusion reactions and in hemolytic disease of the newborn)
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Q.28. Anti-inflammatory effect of glucocorticoids is caused

d) An allergic reaction that is due to the presence of elevated levels of antigen-antibody by
a) Reducing the prostaglandin and leukotriene
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complexes that cause tissue damage which results from inhibition of phospholip
A2
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b) Reducing macrophages migration

into the site of inflammation
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Decreasing capillary permeability Q.35. Selective COX-2 inhibitors are safer than nonselective COx-1 inhibitors but without loss of
d) All of thee above efficacy. This consideration is:
True b) False
y
Q.29. Which of the following statements concerning the anti-inflammatory effect of
glucocorticoids is TRUE? Q.36. The constitutive COX-2 isoform tends to be homeostatic in function, while cOx-1 is
a) Anti-inflammatory effect of glucocorticoids results from inhibition of cyclooxygenase induced during inflammation and tends to facilitate the inflammatory response. The
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consideration is:
b) Anti-inflammatory effect of glucocorticoids results from inhibition of phospholipase A2
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and reducings prostaglandin and leukotriene synthesis a) True b) False

Induction of cyclooxygenase II expression which results in reducing amount of an enzyme Q37. Which of the following property combinations is peculiar to the majorily of NSAIDS?
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available to produce prostoglandins a) Antihistaminic, antipyretic, analgesic
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d) All of the above b) Immunodepressive, anti-inflammatory, analgesic

Q.30. Immunosupressive effect of glucocorficoids is caused by: Antipyretic, analgesic, anti-inflammatory
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a) Reducing concentration of lymphocytes (T and B cells) and inhibiting function of tissue d) Anti-inflammatory, immunodepressive, antihistaminie
macrophages and other antigen-presenting cells Q.38. Which of the following NSAIDs is a propionic acid derivative?
b) Suppression of cyclooxygenase 1I expression which results in reducing amount of an a) Tbuprofen b) Indomethacin
c
c
enzyme available to produce prostoglandins ) Metamizole (Analgin) d) Diclofenac
O Ativation of phospholipase A2 and reducing prostaglandin and leukotriene synthesis.
939. Which of the following NSAIDs is an indol derivative?
y
y
d) All of the above a) lbuprofen b) Indomethacin
Q.31. Which of the following statements concerming the anti-inflammatory effect of NSAIDs are Meclofenamic acid d) Diclofenac
TRUE?
Q40. Which of the following NSAIDs is a pyrazolone derivative?
a) Anti-inflammatory effect of NSAIDs results from inhibition of cyclooxygenase a) Tbuprofen b) Indomethacin
b) Anti-inflammatory effect of NSAIDs results from inhibition of phospholipase A2 and )Metamizole (Analgin) d) Diclofenac
reducing prostaglandin and leukotriene synthesis
Q.41 Which of the following NSAIDs is a fenamate derivative?
c)Anti-inflammatory effect of NSAIDs results from induction of cyclooxygenase II expression
a) Phenylbutazone b) Indomethacin
which results in reducing the amount of an enzyme available to produce prostoglandins
c) Meclofenamic acid d) Diclofenac
d)All of the above
Q42. Which of the following NSAIDs is an oxicam derivative?
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Q.32. Indication of glucocorticoids is:
a) Piroxicam b) Indomethacin
a) Chronic (Addison's disease) and acute adrenocortical insufficiency
b) Organ transplants (prevention and treatment of rejection immunosuppression)
-
)Meclofenamic acid d) Diclofenac
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Q.43. Which of the following NSAIDs is a selective COX-2 inhibitor?
Infiammatory conditions of bones and joints (arthritis, bursitis, tenosynovitis).
a) Piroxicam b) Indomethacin
d) All of the above
c)Celecoxib d) Diclofenac
Q.33. Indications of glucocorticoids are following, EXCEPT
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Q.44. Which of the following NSAIDs is a nonselective COX inhibitor
a) Gastrointestinal diseases (inflammatory bowel disease)
a) Piroxicam b) Rofecoxib
b) Postmenopausal hormonal therapy
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)Celecoxib d) All of the above
cInflammatory conditions of bones and joints (athritis, bursitis, tenosynovitis)
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Q.45. The following statements concerning aspirin are true, EXCEPT:

d) Skin diseases (atopic dermatitis, dermatoses, localized neurodermatitis)
a) In contrast to most other NSAIDs, aspirin ireversibly inhibits COX
Serious side effects of glucocorticoids include the following. EXCEPT:
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Q.34.
b) Aspirin interferes with the chemical mediators of the kallikrein system
a) Acute peptic ulcers
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Aspirin inhibits phospholipase A2

b) latrogenic Cushing's syndrome (ounding, puffiness, fat deposition and plethora alter the
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d) Aspirin inhibits tromboxane A2 formation
appearance of the face - moon faces)
c)Salicylism (vomiting, tinnitus, decreased hearing, and vertigo)
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d) Hypomania or acute psychosis

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256 PUAText Book of Pharmacology-1 Autocolds and Related Drugs
Q46. Indication for aspirin administration are the following, EXCEPT:

A N SWE RS
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a) Inflammatory conditions
b) Decreasing the incidence of transient ischemic attack, unstable angina, coronary artery 1.B 2.D 3.A 4.B 5.A 6.B
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thrombosis with myocardial infarction, and thrombosis after coronary artery bypass grafting 7.C 8.B 9.C 10.A 11.D 12.B
Relieving severe visceral pain, eg. myocardial infarction, cancer pain condition, renal or
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biliary colic
19. A 20. B 21.4A 22. A 3. B 24.
d) Reducing elevated body temperature
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28.D 9. 30. A
9.47. Side effects of aspirin include following:
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1. .A 2. D 33. B 34. C 35. A 36. B

a) Gastric upset (intolerance)
7. C 38.4A 39. B 40. C 41. C 42.A
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b) Salicylism (vomiting, tinnitus, decreased hearing, and vertigo)
43.C 44. A 45.C 46.C 47.D 48.A
Gastric ulcers and upper gastrointestinal bleeding
49.D 50.A 51.B 52.B 53.C 54A
d)All of the above
Q48. Serious side effects of metamizole (analgin) include the follovwing:
c
c
a) Agranulocytosis, aplastic anemia
y
y
b) Salicylism (vomiting, tinnitus, decreased hearing and vertigo) ***
latrogenic Cushing's syndrome (rounding, puffiness, fat deposition and plethora alter the
appearance of the face -moon faces)
d)All of the above
Q49. Side effects of indometacin incdude the following:
a) Abdominal pain, diarrhea, gastrointestinal hemorrhage and pancreatitis
b) Dizziness, confusion and depression
c) Trombocytopenia
d) All of the above
Q.50. Ketoprofen
is a propionic acid derivative that inhibits both cyclooxygenase
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(nonselectively) and lipoxygenase. This statement is:
a) True False
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Q51. Ketorolac is an NSAID that is promoted for systemic use as an anti-inflammatory, not as an
analgesic drug. This statement is:
a) True b) False
Q.52 Which of the following drugs is a 5-lipoxygenase (5-LOG) inhibitor?
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y
a) buprofen b) Zileuton (Zyflo)
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Metamizole (Analgin) d) Diclofenac
Q53. Which of the following drugs is a leucotreine Di receptor (LTD4) blocker?
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a)buprofen b) Zileuton (Zyflo)

(Accolate)
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Zafirleukast d) Diclofenac
Q54. Which of the following drugs is a thromboxane A2 receptor (TXA2) antagonist?
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a) Sulotroban b) Zileuton (Zyflo)

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PUA Text Book of Phamacology-l
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Pharmacology of Drugs Acting on Endocrine System
3. With the growth of larynx there is thickening of vocal cord voice becomes low nausea, weight gain, constipation, nasal angestion, hematuria, vaginitis,
Side effects: Vomiting,
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pitched, voice is changed. decreased libido, breast size deceases, testicular atrophy, aaps,
spasm, hypetension, headache
4. Androgen cause change in skin, hair, axdillary hair, pubic hair and beard hair. oily skn, alopedia, hirsiutism
paresthesia, sweating anicty, insormnia, carpal tunnel syndrome, skin nsh
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disease
5.. There is growth of prostate, seminal vesicles and induction of spermatogenesis. Severe renal disease, severe cardiac disease, hepatic
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Cohtra indications :
6. There is growth on body tissue, penile and scrotal growth. hypersensitivity, pregnancy, lactation, diabetes mellitus
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milk, crosses placental
The production of testosteron is controlled by the pitutary release of leutinizing hormone. Pharmacokinetics: Metabolized in liver, excreted in urine, breast
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Adverse efects: barrier.

increase effect of oral antidiabetics
Drug interactions:Decreases effect of insulin, it
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1. There is retention of sodium ion and edema formation.
2. Deepening of voice, hirsutism, baldness, acne, enlargement of clitoris and oxyphenbutazone.
masculinization in females Uses: Testosterone increase weight by building body tissue, increases potassium,
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3. With large doses there is suppression of spermatogenesis and degeneration of
phosphorus, chloride level and increase bone development.
Brand Names: Testosterone: Injection, capsules, Aquaviron,
Nuvir, Sustanon-250, Cermos,
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seminiferous tubules.
Androfol testocaps, Andrinol 40mg capsules, Injection 20mg per one ml Ampoule.
4. There is early dosure of epiphysis and blocking of its growth.
Preparations Tablets: Methyl testosterone tablet 25 to 50mg daily
to males, 5 to 200mg
5.14.1 TESTOSTERONE daily for females.
Testosterone is secreted by the interstitial cells of the testes under the influence of ANABOLIC STEROIDS
leutinising harmones from pitutary. Testosterone is responsible for all the changes which Testosterone has an anabolic effect, it has an androgenic effect. The anabolic steroids
occurs in a body at puberity. It is needed for normal spermatogenesis and maturation of has been synthesized to produce more anabolic effects.
spermatozoa.
Mechanism of action: It can bind to the androgen receptor, or can be reduced to sa Anabolic steroids can be classified as:
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dihydrotestosterone (DHT) by the cytoplasmic enzyme 5a-reductase. DHT binds to the
same androgen receptor even more strongly than T, so tht its androgeñic potency is about
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2.5 times that of T. The T-receptor or DHT-receptor complex undergoes a structural change
that allows it to move into the cell nucleus and bind directly to specific nucleotide
sequences of the chromosomal DNA. The areas of binding are called hormone response Derivatives of testosterone Derivative of methyl
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elements HRES), and influence transcriptional activity of certain genes, producing the () Nandrolene decanoate testosterone
Cii) Ci) Oxymethalone
androgen effects Nandralone decanoate
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Cti) Oxandralone
Jndications Endocrine impotence, testicular failure, loss of libido, delayed puberity,
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ii) Oxymesteróne
osteoporosis, carcinoma of breast, In females: Genital carcinoma, breast carcinoma,
endometriosis, menopausal syndrome, weight loss in AlDS patients, oligospermia.
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Dosage:Oligospermia Adult IM 100 to 200 mg every 2 to 4 weeks. Breast cancer: 50 to Actions of Anabolic Steroids
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100 mg IM weekly for 4 to 6 months. 1. Anticatabolie effect: The catabolic effect of glucocorticoids are counteracted and a
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positive nitrogen balance in produced.
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318.
PV A Toxt Book of Pharmacology-!l Pharmacology of Drugs Acting on Endocrine System 319
2. Protein anabolism :The anabolic steroids promote protein anabolism. This increases Estradiol is the most important estrogen produced by the ovaries. Other estrogens (estrone,
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muscle mass and body weight. estriol) may be weaker, but in principle have the same effect. Estrogens are steroids that are
responsible for the growth and functions of the female reproductive tract and the secondary
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3. Progestational action decrease in bone reabsorption which prevents osleoporosis.
Side effect of anabolic steroids sexual characteristics. Their effects are based on a bond to estrogen receptors and the
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subsequent synthesis of specific proteins.

1.Cause edemia due to sodium and water retention on prolong continuous use
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2. Cause liver damage and cholestatic jaundice. 5,143PROGESTERONE
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3. Cause virilization of foetus when given during pregnancy to pregnant It is odourless, colourless white crystalline powder. It is insoluble in water. It is rapidly
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ladies/women. absorbed from all routes of administration. Its molecular formula is C21H3002
Uses
1. Used in the treatment of carcinoma breast in females
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2. In chronic illness accelerates tissue growth.
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3. Produce growth in hypogonadal patients children.
Antt Androgens: The drugs which antagonise the action of androgens. Cyproterone
Structure of Progesterone
accetate acts as an anti androgens. It is used to decrease excessive sexual drive.
Progesterone is the major progestin in humans. A micronized form is used orally for HRT,
5,14.2 ESTROGENS and progesterone-containing vaginal creams are also available. Synthetic progestins (eg.
medroxyprogesterone) have improved oral bioavailability. The 19-nortestosterone
Estrogen, or oestrogen: It is the primary female sex hormone. It is responsible for the
compounds differ primarily in their degree of androgenic effects. Older drugs (eg
development and regulation of the female reproductive system and secondary sex L
norgestrel and norethindrone) are more androgenic than the newer progestins
characteristics. (eg
norgestimate, desogestre!).
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There are three major endogenous estrogens in females that have estrogenic hormonal
Mechanism of action: Progesterone inhibits secretions of pituitary gonadotropins which
activity: estrone, estradiol, and estriol. The estrane steroid estradiol is the most polent and Krevents follicular maturation, ovulation.
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prevalent of these.
Effects: Progesterone induces secretary changes in the endometrium and is required for the
Their presence in both vertebrates and insects suggests that estrogenic sex hormones have maintenance of pregnancy. The other progestins also stabilize the endometrium but do
an ancient evolutionary history. The three major naturally occurring forms of estrogen in
not
support pregnancy. Progestins do not significantly affect plasma proteins, but they do affect
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females are estrone (E1), estradiol(E2), and estriol (E3). Another type of estrogen carbohydrate metabolism and stimulate the deposition of fat. High doses suppress
called estetrol (E4) is produced only during pregnancy. Quantitatively, estrogens circulate
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gonadotropin secretion and often cause anovulation in women.
at lower levels than androgens in both men and women.
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Indications: Contraceptive, abnormal uterine bleeding, amenorrhea, pre menstrual

While estrogen levels are significantly lower in males compared to females, estrogens syndrome.
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males./41
nevertheless also have important physiological roles in
Once inside Dosage: Pre menstrual syndrome : (Natural micronised progesterone) 200mg to 400mg. 1
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Like all steroid hormones, estrogens readily diffuse across the cell membrane. to 2 times a day from 12th to 14th day of the cycle untill onset of menstruation. Maintenance
(ERs) which in turn modulate the
the cell, they bind to and activate estrogen receptors
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of pregnancy in case of habitual abortion or Threatended abortion 200 to 400mg in divided
activate rapid-
expression of many genes.51 Additionally, estrogens bind to and doses.
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GPER (GPR30).101
signaling membrane estrogen receptors (mERs),J7l such as
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A Text Book of Pharmacology-1 Pharmacology of Drugs Acting on Endocrine Systemn
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d) By preventing maturation of ovum.
Contraindications Breast cancer, pregnancy, hypersensitivity, genital bleeding.
e)The drugs change the cervical mucus which inhibits sperms penetration in the ovum.
undiagnosed vaginal bleeding.
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Side-effects : Headache, diziness, depression, vomiting, nausea, acne, anorexia, weight 9 The drugs interfere with the implantation of fertilized ovum.
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gain, hypotension, breast changes, edema, testicular atrophy, impotence, urticaria,
ORAL CONTRACEPTIVES: When ovulation is prevented, pregnancy is prevented by
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hirsutism, hyperglycemia, melasma.

Pharmacokinetics: IM, vaginal route, rectal route duration of action 24 hours, IV plasma inhibiting ovulation in females, there is rare chance of pregnancy. ovulation can be
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half life 90 minutes, metabolized in liver, excreted in urine. prevented by the administration of progesterone or estrogen or both. the oral contraceptive
pills contains progesterone or estrogen or both. during pregnancy period there is a high
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Brand names: Progesterone : Capsules, Tablet, Injection, Algest, Dubagest, Escot tab,
level of ovarian hormones. these hormones prevent ovulation formation.
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Capsules,
Harigest, Firm up, Ferti capsules, Corgest 100, Endogest 100mg, 200mg tablet,
Injection 50mg 100mg per one ml.
TYPES OF PREPARATIONS
The oral contraceptive preparations are
5.14.4 ORAL CONTRACEPTIVES
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G)Progestines along
Alarming population growth has increased the need of antifertility drugs. In developing
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(Gi) Combination of estrogen and progestins.
countries the mortality rate has been decreased and birth rate has been increased due
to
(ii) Estrogen alone followed by estrogen + progestin combination.
urbanization.
Method of administration :
In 1955 Rock and Pincus successfully prepared progestin pills for contraception, separating
to the pill of 1) Combination method: The estrogen and progestin is administered from 5th day to 25th
fertility control from coitus. Later on small quantity of estrogen was added
pills for contraception have day of menstrual cycle
progestion which increased the efficacy. Now a days combined
These 2) Sequential method : Estrogen alon is administered alone and is given from 5th day to
become popular. Million women worldwide are using hormonal contraceptives.
complete return of 20th day, from 21st day to 25th day estrogen+ progestin combination is administered.
contraceptive drugs suppress fertility at will for a desired period with
fertility on discontinuation of oral contraceptive drugs. Machanism of action: In the combination method FSH rise and LH peak concentration is
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ContraceptivesContraceptice are drugs which prevent conceptiom. These drugs control fertility suppressed due to which follicular growth is decreased. This prevents ovulation. In
sequential method the estrogen given suppress FSH secretions on the contrary stimulates
so are also called as antifertility drugs.
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LH secretion. This unusual rise of LH suppresses early follicle
Physiology of reproduction: Ovulation is the key process in human reproductive system 1 stimulating hormones rise
28 days cycle. During this menstrual cycle due to which growth of follicle is reduced and ovulation formation
cycle. It usually occurs on 14th (+-2days) day of is prevented.
F S H (Follicle Stimulating Pharmacological actions:
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the graffian follicles become mature under the influence of
Hormones) released from anterior pitutory. The ovulation occurs when there is ruputure of Ovaries: The combined drugs and sequential drugs depresses
function of ovaries. The
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Hormone (LH) released by anterior pitutary. The follicular development is decreased. In ovulating
the follicle is stimulated by Leuteinizing women morphological changes are not
the sperm. This fertilised ovum is
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ovum enters the fallopian tube and gets fertilised by observed.

and is implanted by 21
converted into blastocyst. This blastocyst reaches the uterine cavity Endometrial change:
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The endometrial change varies
35th day. with the preparation used as
to 23rd day of the cycle which is completed on contraceptive.
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Feztility control by drug The drugs control fertility by following mechanism. 1)With combination of drugs estrogens
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and progestins.. There is stromal deciduation
aBy inhibiting ovulation in females. towards end of the menstrual cycle.
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By inhibiting spermatogenesis in males.

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322
2 There is no change with sequential drugs. Progestational effect on glandular tissue is is achieved above 90%. The side effects in some cases are anorexia, abdominal disomforts,
seen during the last 5 days of cycle.
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loose motions, uterine cramps, prolonged bleeding and failed abortion.
3) There may be increase in transcortin (cortisol binding protein). 2) Post coital contraceptive: Mifepristone 600mg given within 72 hours of intercourse
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4) These contraceptive dugs may cause hyperglycemia, glycosuria, hypertension. interferes with implantation. It is a highly effective method of emergency conception. The
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menstrual cycle may be disturbed.

5) There may be increase in Thyroxine binding globulin.
3) Induction of labour: Mifepristone can be used in cases of intra uterine foetal death and
Sidoeffects: Due to estrogen contents there may be vomiting, nausea, anorexia. There may
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to deliver abnormal foetuses.
be weight gain, fuid retention, breast engorgement, hypertension, carcinogenicity, There
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may be mid cycle spotting, break Ihrough bleeding.

4)Contraceptive: 2 to 5mg per day orally given for 30 days inhibits ovulation and delays
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menstruation.
ORAL CONTRACEPTIVE PREPARATIONS 5) Once amonth contraceptive pill: Orally 200mg of mifepristone taken as a single dose,
second day after the mid menstrual cycle.
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PROGESTIN ESTROGEN NAME
Pills Brand names: Mifepristone : Tablet Mifty, MT Pil, Undo, Rempreg, Mefiwis, Mefipil,
OCombined
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MALA-D (21 tablets +7 Mifegest, 200mg tablets.
1) Norgestrel 0.3mg Ethinyl estradiol 304g
tablets ferrous sulphate
60mg) INJECTABLE CONTRACEPTIVES
05mg Ethinyl estradiol 504g Tab OVRALG Injectable contraceptive drugs have been developed to obviate need for taking daily oral
2) Norgestrel
Desogestrel 0.15mg Ethinyl estradiol 20H8 Tab FEMILON contraceptive pills. Injection is given IM as oily solution that are highly effective. DEPOT
3)
Levonargestrel Ethinyl estradiol 504g Tab OVRAL PROVERA 150mg per Iml vial for deep IM use as injection during first five days of
4) 0.25mg
menstrual cycle, repeat after 3 months duration.
Phased Pills
50-75 Ethinyl estradiol 30Hg Tab TRIQULAR (6+5+10 Depot medroxy Progesterone Acetate (DMPA) 150mg (Depot Provera) 150ng at 3 month
1) Levonorgestrel
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tablets intervals.
Post Coital Pills i) Nor ethindrone (Nor ethisterone) enanthate (NEE) 200mg in Iml vial at 2 months
Ethinyl estradiol 504g'DUOLUTON-L
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1) Levonorgestrel 0.25mg intervals. Injection NORISTERAT 200mg in 1ml vial deep intra muscularly injection during
Tablets 2+2 tablets first five days of menstrual cycle. Repeat injection every two, monthly for regular
Pills contraception. NEE is short acting.
Mini
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Ethinyl estradiol 504gTab MICRONOR Side effects: Excessive bleeding or am enorrhoea, weight gain, headache, vaginal dryness,
1Norethindrone t 0.3mg
decreased libido. Return of fertility may take 6 to 30 months, after discontinuation,
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permanent sterility in some women occurs. DMPA is not suitable for young adolescent girls
ANTI PROGESTIN MIFE PRISTONE
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steroidal with having ani progestational, antigluco corticoid and anti and lactating women.
It is a synthetic 19 non
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It has following use
androgenic properties Mifepristone is active orally.
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to 7 weeks 600 mg mifepristone
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pregnancy of up MALE CONTRACEPTIVES

1) Termination of pregnancy: The success rate
abortion in cases 70 to 85% to improve The only way is to suppress male fertility by drugs is to inhibit spermatogenesis. It takes
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oral dose cause complete
single With this complete abortion
oral dose 400mg misoprostol. more than 2 months (about 65 days) in spermatogenesis. There are chances of loss of libido
administer after 48 hours a single
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- U.A Toxt Book of Pharmacology-. Pharmacology of Drugs Acting on Endocrine System
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and impotence that is unacceptable to all men and to majority of spouses. So no satisfactory Tlerine stimulants are the drugs which increase uterine motility, uterine contractions and help
solution is acceptable so far because of serious side effects in male contraceptives. expulsion of its contents.
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Thedrugs used are
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HORMONAL CONTRACEPTIVES
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Hormonal contraceptives contain either a combination of an estrogen and a progestin or a

progestin alone. Hormonal contraceptives are available in a variety of preparations,
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including oral pills, long-acting injections, transdermal patches, vaginal rings, and
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Ergot alkaloids: Prostaglandins

intrauterine devices (TUDs). Three types of oral contraceptives for women are available in Posteriorpitutary hormone
i Oxytocin )Ergometrine
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the United States: combination estrogen-progestin tablets that are taken in constant dosage
Ci)Desamino oxytocin (Ergonovine)
throughout the menstrual cycle (monophasic preparations); combination preparations Ci) Methyl ergometrine
biphasic and triphasic) in which the progestin or estrogen dosage, or both, changes during
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the month (to more closely mimic hormonal changes in a menstrual cycle); and progestin- Miscellaneous drugs
only preparations. Quinine
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i) Ethacridine
The postcoital contraceptives (also known as "emergency contraception" prevent
pregnancy if administered within 72 h after unprotected intercourse. Oral preparations
containing a progestin (L-norgestrel) alone, estrogen alone, or the combination of an
estrogen and a progestin are effective. The progestin-only preparation causes fewer side oxrroCIN: It is a polypeptide contains 9 amino acids. it is secreted by posterior pituitary
effects than the estrogen-containing preparations. along with adh. oxytocin is used to control post partum haemorrhage. it is less effective
when administered orally. it is suitable for labour. the body and the fundus contracts while
MEhanism of Action: The combination hormonal contraceptives have several actions,
the cervix dilates, this helps in the easy expulsion of the foetus.
mcluding inhibition of ovrulation (the primary action) and effects on the cervical mucus
In small doses oxytocin increase the tone and amplitude of contractions. Excessive doses
glands, uterine tubes and endometrium that decrease the likelihood of fertilization and
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give rise to violent contractions with danger of uterine ruputure or foetal asphyxiation and
implantation. Progestin-only agents do not always inhibit ovulation and instead act
water retention. Oxytocin is used for the induction of labqur, to overcome uterine inertia.
through the other mechanisms listed. The mechanisms of action of postcoital contraceptives
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are not well understood. When administered before the LH surge, they inhibit ovulation. Pharmacological action of Oxytocin
They also affect cervical mucus, tubal function, and the endometrial lining. Uterus : In humans a small dose of oxytocin given increase the tone
and amplitute of
contraction. Large doses produce tonic contractions, there may be uterine rupuure, water
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5.15 DRUGS ACTING ONTHEUTERU retention and foetal asphyxiation. Oxytocin cause fundus to contract
while to cervix dilates,
this helps in easy
expulsion of the foetus. Oxytocin is used for
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Ph
OTERINE STIMULANTS: The drugs acting on uterus effects endometrium or induction of labour.
Mammary glands: It stimulates the myoepithelium and help increasing
myometrium. the drugs that effects endometrium are estrogen, progestins and their
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in expulsion of
milk-from mammary glands. It is ineffective when given
antagonists. orally. The absorption is rapid on
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intramuscularinjection. The oxytocinase present in blood
plasma, pacenta of pregnant
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women and uterine tissue inactivates oxytocin.

Kidneys : Oxytocin in large dose cause decreased urine output.
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Pulmonary oedema occurs
if large quantity of intravenous fluids and
oxytocin are administered together. The
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conventional doses of oxytocin do not cause

any adverse effect.
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P A Toxt Book of Phamacology- Pharmacology of Drugs Acting on Endocrine System
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326
sat (CVS): The normal doses (conventional

doses) used in induction of labour cause no
effect on blood pressure. Large doses cause vasodilatation causing fall in blood pressure,
DESAMINO OXYTOCIN: It has been prepared as buccal formulation. Its action is similar
y
to injected oxytocin. It is available as Tablet Buctocin 50 IU Desaminooxytocin. In induction
tachycardia.
lushing, and reflex of labour one 50 1U buccal tablet repeated every 30 minutes maximum 10 tablets per day.
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ees: It is used in the induction of labour (i) used to control post partum haemorrhage (Gii) For breast engorgefíent 25 to 50 IU just before breast feeding
to promote milk cjection it is given as intra nasal spray few minutes before suckling.
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ERGOMETRINE: It contains several substance (drugs) like alkaloids, histamine,

xytocin does not increase milk production. it is used to stimulate milk release (iv) it is used acetylcholine, steroids, tyramine acids etc. Ergot is compact mycelium of a fungus claviceps
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to
induce abortion during 2nd to 3rd trimester. purpurea. Ergot is cultivated in ussia, germany, hungary, switzerland, yugoslavia in
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orérse effects : Oxytocin cause premature birth and foetal death if large doses given natural way ergot is prepared (produced), the rye plant is cultivated and is subsequently
labour. (i) It causes water retention and cause water intoxication when administered with infected by fungus. Ergometrine is an amine alkaloid of ergot ergometrine is also known as
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LV. infusions injudiciously. ergonovine. It acts as oxytocic and produces stimulation of uterine muscles.
MEchanism of action : Oxytocin acts directly on myofibrils, produce uterine contractions, Mechanism of action It stimulates uterine contractions and vascular smooth muscle and
:
decreases bleeding
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stimlate milk ejection by breast.
Indications : Stimulant uterine muscles, post abortion haemorrhage.
adications: Induction of labour, post partum haemorrhage abortion, breast engorgement,
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uterineincrtia, cesarean section. Contraindications: Hypersensitivity, spontaneous abortion, pelvic inflammatory disease.
Use with precautions in anaemia, asthma, Hepatic disease convulsive disorders
Dosage: Post partum haemorthage
Side effects : Headache, nausea, vomiting, dizziness, cramping, tinnitus, sweating.
Adult: 1.V. 10 IU drip infusion slowly.
Pharmacokinetics: LV onset action immediate, IM injection 2 to 5 minutes, duration of
Adult: IM 10 IU after delivery of placenta.
action 45 minutes, metabolized in liver, excreted in urine.
Induction of labour: IV drip infusion of 5% Dextrose solution containing IU oxytocin per
1
Drug interactions : Hypertension with sympathomimetic drugs.

100 ml then 5IU slowly IV slowly until contraction occur, then decrease dose.
Dosage : Oxytocic : Adult 1M 02 mg. IV 02 mg to be given over 1 to 2 minutes, not to
Incomplete abortion : Adult V 10 IU infusion in 500 ml Dextrose 5% solution or
0.9%
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exceed 5 doses.
sodium chloride, slow Iv (20 to 40 U/ml)
Contraindications: Hypersensitivity, foetal distress,
serum toxcinia. Use with precaution in :
Brand Names: Ergornetrine Tablet, Injection, Methargin, Atorgine, Hergin, Methocin,
Vargine, Zotargin, Ergotab tablets of 0.125mg, Injection 0.2mg per ml.
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patient with uterine surgery uterine sepsis.
nausea, Treatment over dose : To discontinue drug therapy give vasodilators, Heparin sodium.
e effects : Hypotension, increased pulse rate, jaundice anorexia, vomiting,
constipation, skin rash, asphyia, hypoxia.
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action 30 minutes, plasma half PROSTAGLANDINS: Prostaglandins are fatty acids containing 20 carbon atoms
Pharmacokinetics: I.V. on set action 1 minute, duration of
cyclopentane ring. they contain one or more double bonds. the number of the double bond
Ph
Ph
Ph
Jife 12 to 17 minutes.
Use with prostaglandins increase is indicated by a richest source of prostaglandins, also present in iris, lungs, menstrual fuid,
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Drug interactions: Useful combination with ergotamine. brain, thymus kidneys and pancreas. the prostaglandin are synthesized from
and cervical laccerations.
of uterine rupture
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risk polyunsaturated acids belonging to linoleic or alpha linolenic series. They are active in low
Emtocin, Evatocin, Oxytar, Partocin,
Brand Names: Oxytocin : Injection Pitocin, concentrations, and are destroyed quickly they have short duration of action. Refer
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Syntocinon, Meritocin 5 IU per one ml. prostaglandin chapter-4

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before breast feeding.
Promotion of lactation : 1 tablet five minutes
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Telegram - Study Pharmacy Pharmacology of Drugs Acting on Endocrine System
333
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PV A Toxt Book of Pharmacology-
which drug
Adiabetic patient treated with oral
hypoglycemic drug develop hyponatremia,
Explain the Anti thyroid drugs write the pharmacology carbimazole Refer 5.4.1
Q.5.
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Q.3.
responsible for the effect.
is
Q4. Write the mechanism of action, side efect, Pharmacology action and uses of radio active iodine b) Chlorpropamide
a) Glimepiride
Refer 5.4.1 d) Glyburide
Q.5. Define hormones regulating plasma calcium level write a note on Calcium Refer 5.5
)Tolazamide
y
most potent androgen ?
Describe the pharmacology of Parathyroid Hormone (PTHH Refer 5.6 Q6. Which of the following drugs is
Q6. b) Androstendione
a) Testosterone
Discuss the mechanism of action, side effect, uses of calcitonin salmon Refer 5.7
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Q7. d) Dihydroepiandrosterone
)Dihydrotestosterone
Q8. Discuss the regulation of hormones vitamin D. Refer 5.8
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Q.7. Drug of choice in diabetes inspidus is?

Q9. Bplain the difference between Type-I and TypeI and Diabetes melitus and Diabeles b) Dizoxide
insipidus Refer 5.9.1 a) Desmopression
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c)Chlorproparmide d) Thiazide diuretics
Q.10. Classify Oral hypoglycaemic drugs, explain the pharmacology of Tolbutamide Refer 5.10
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Q1. Explain Oral hypoglycaemic drugs, cdassify them, describe the Pharmacology of metformin Q.8. Humulin is?
b) Thyroxine
a) Human insulin
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Refer 5.10
d) Human gonadotrophic hormone
Q12. Discuss corticosteroids, write the mechanism of prednisolone Refer 5.13 Newer penicillin
Q.13. Describe androgens and its function Refer 5.14 0.9. Which of the following is orally effective?
b) FSH
Q.14.Define write a note on oral contraceptive Refer 5.14.3 a) TSH
c
c
d) Insulin
Q15. Write the pharmacology of Bromocriptine Refer 5.3 )Thyroxine
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except
Q19. Describe the Pharmacology of Oxytocin Refer 5.15 Q.10. The following are likely adverse effect of oral contraceptives
b) Galactorrhea
0.20. Explain the mechanism of action side effect and use of calcitonin salmon Refer 5.16 a) Weight gain
) Thromboembolism d) Carbohydrate intolerance
Q.11. Estrogen is contra indicated in ?

MULTIPLE CHOICE QUESTIONS a) PID b) Liver disease
01. All are true regarding oral hypoglycemic drugs except c) Menorrhagia d) Carcinoma prostate
a) Metformin causes lactic acidosis Q.12. Which of the following antidiabetic has shortests duration of action
b) Useful in obese diabetics. a) Gliclazide b) Repaglimide
Effective only after complete pancreatectomy. c) Gipizide d) Glibenclamide

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d) Cause release of insulin from beta cels. Q.13. Blood glucose is lowered in diabetics by?
0.2 All are true about Metformin except ? a) Codeine b) Insulin
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a) Increase peripheral utilisation of glucose. Adrenaline d) Betamethasone
b) Act by increase of insulin secretions. Q.14. Main advantages of human insulin is?
Cause no hypoglycemia in non diabetic patient.
c) a) Greater efficiency
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d) With alcohol increase risk of acidosis. b) Less side effects
Q3. Antidiabetic drug can be used safely in renal impairment ? c) Can be given to patients allergic to animal insulin
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a) Glimeperide b) Rosiglitamide d) Quickly excreted
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c)Repaglinide d) All the above Q.15. Which drug is not a progesterone?

e) None of above a) Megestrol Mestranol
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b)
Q.4. The drug of choice for thyrotoxicosis treatment during pregnancy is 7
Norgesterol dD Dyhdrogesterone
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a) Propyl thiouracil b) Carbimazole Q.16. Hormones are:

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c)lodine therapy d) Metimazole a). Products of endocrine gland secretion b) Mediators of inflammatory process
c) By-products of tissue metabolism d) Product of exocrine gland secretion
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334 PV A Text Book of Pharmacology-l- Pharmacology of Drugs Acting on Endocrine System 335
Q.17. Select an endocrine drug which is an amino acid derivative: d) All of the above mechanisms
a) Insulin
y
b) Hydrocortisone Q27. The common side effect of thyroid hormones is following
c) Caldtonin d) Thyroxine a) Increases in basal metabolic rate b) Angina pectoris
Q.13. Select an endocrine drug which is a peptide derivative
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c) Tremors d) Exopthalmos
a) Oxitocin b) Prednisolone
Q.28. Currently used antithyroid drugs include the following, EXCEPT
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c)Nandrolone d) Progesterone a) Propylthiouracil (PTU b) Diatrizoate sodium (Hypaque)

Q19. Select an endocrine drug which is a steroidal derivative:
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Methimazole (Tapazole) d) Potassium perchlorate
a) Gonadorelin b) Insulin Q.29. In an area where goitre is endemic, which of the following drugs is used?
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c) Levothyroxine d) Hydrocortisone a) lodide 1 part in 100000 b) Propylthiouracil 200 mg daily

Q20. Which of the following hormones is produced by the hypothalamic gland?
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c) Methimazole 40 mg daily d) Any of the above can be used.
a) Growth hormone-releasing hormone (GHRH) Q.35. Iodide preparations can be used in following situations, EXCEPT:
b) Follicle-stimulating hormone (FSH) a) In thyroid disorders b) In granulomatous lesions eg. Syphilis
Aldosterone
c)
c)Asan antiseptic d) IN IODISM
c
c
d)Estradiol Q.36. Sulphonylureas act by:
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021. Which of the following hormones is produced by the anterior lobe of the pituitary? a) Reducing the absorption of carbohydrate from the gut
a) Thyrotropin-releasing hormone (TRIH b) Increasing the uptake of ghucose in peripheral tissues
b Corticotropin-releasing hormone (CRI1D c)Reducing the hepatic gluconeogenesis
c) Growth hormone (somatotropin, GH) d) Stimulating the beta islet cls of pancreas to produce insulin
d) Growth hormone-releasing hormone (GHRHD Q37. Currently used second-generation sulfonylureas include the following, EXCEPT
Q.22. The posterior pitutary does NOT secret: a) Glyburide (Glibenclamide) b) Glipizide (Glydiazinamide)
b) Oxytocin c) Glimepiride (Amaril)
a) Vasopressin d Tolbutamide (Orinase)
c) Growth hormone d) All of the above Q38. Currently used oral hypoglycemic thiazolidinediones include the following, EXCEPT
Q.23. Indications of vasopressin are following: a) Pioglitazone (Actos) b Rosiglitazone (Avandia)
b) Hypertension c) Troglitazone (Rezulin) d) All of the above
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a) Diabetes mellitus
c) Pituitary diabetes insipidus d) Incompleted abortion Q.39. Thiazolidinediones act by:
Q24. Vasopressin possesses the following: a)Diminishing insulin resistance by increasing glucose uptake and metabolism in muscle and
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adipose tissues
a) Antidiuretic property
b) Vasodilatation property b Reducing the absorption of carbohydrate from the gut
c)Stimulating the beta islet cells of pancreas to produce insulin
c) Release of a thyroid hormone into the plasma
d) All of the above
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d) Diuretic property
Q.40. Currenty used alpha-glucosidase inhibitors include the following, EXCEPT:
Q25. Oxytocin produces the following effects:
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a) Pioglitazone (Actos) b) Acarbose Precose)
a) It causes contraction of the uterus
c) Miglitol (Glyset) d) All of the above
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b) It assists the progress of spermatozoa into the uterine cavity

Q41. Tamoxifen is:
)It brings about milk ejection from the lactatingg mammary gland
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a) Antiprogestin b) Antiandrogen
d) All of the above c) Antiestrogen d) Androgen
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Q.26. Vasopressin causes a pressor effect by:

terminals Q42. Progesterone is secreted by:
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a) Releasing noradrenaline from the nerve a) Ovarian folicles b) Corpus luteum
system
b) Releasing and activating renin-angiotensin
Granulosa and theca cells d) All of the above
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blood vessels
A direct action on smooth muscles of the
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PU A Text Book of Pharmacology BIOASSAY
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Q43. The major natural
progestin is:
5
CHAPTER
y
b) Estron
a) EstradiolN
d) Estriol
Progesterone
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glucocorticoids is an intermediate-acting drug?
Q44. Which of the following
b) Triamcinolone
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à) Cortisone
Butamethasone
d) All of the above INTRODUCING THE CHAPTER
biologicak system like
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is a long-acting drug? by use of a suitable n 1
D4s. Which of the following glucocorticoids designed to analyse any

compound
b) Dexamethasone Bioassay: It is an assay
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Prednisolon etc. s
d) All of the above animals, tissues, microbes a positive effect is measured
on each animal
Triamcinolone threshold dose producing (one receiving standard and
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chemical structure?
glucocorticoids have one fluoride atom in its Quantal assay: It is the average results of two groups of animals and
Q46. Which of the following
b) Fluocinolone the comparison between the
a) Prednisolon other the test) is done
d) All of the above the grade point assay procedure is
Triamcinolone based on the method iused during
have two fluoride atoms in its chemical
structure? Graded Response Assay: It is sample.
c
c
Q47. Which of the following glucocorticoids delermination of the type of activity and Potency of the
b) Dexamethasone
for
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a)Prednisolon
d) Triamcinolone KEY WORDS
Fuocinolone
glucocorticoids has no fluoride atoms in its chemical structure? Bioassay of ACTH
Q48. Which of the following Principles of Bioassay
b) Dexamethasone
a)Prednisolon
Applications of bioassay Bioassay of Gonadotrophin
d) Triamcinolone
Fluocinolone
is caused by
Bioassay of D-tubocurarine
949. Anti-inflammatory effect of glucocorticoids Types of bioassay
which results from inhibition of phospholipase Bioassay of digitalis
a) Reducing the prostaglandin and leukotriene Bioassay of insulin
A2 Bioassay of oxytocin Bioassay of histamine
b) Reducing macrophages migration into the site of inflammation
Bioassay of vasopressin
Decreasing Capillary
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d) All of the above
FAN'SWERS 6.1 3OASSAY
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4. A 5. B 6. C Definition: It is defined as estimation or determination of concentration or potency of a
1.C 2.B 3.D
7. A 8. A 9. C 10.1B 11.1B 12. C physical, chemical or biological substance (agent) by means of measuring and comparing
the magnitude of the response of the test with that of a
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16. A 17. D 8 A
13. B 14. C 15. B
biological system under standard set of conditions.
standard over a suitable
20. A 21. C 22. c 23. C 24. A
19. D
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27. D 28. D 29. A 35.1D The response produced by the test compound
25. D 26. C is compared with that of standard sample the
way similar to other analytical methods
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36. D 37. D 38. C 39. A 40. A 41. C but here the biological system is involved in the
45. B 46. C 47. C determination.
12 B 43. C 44.
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PRINCIPLES OF BIOASSAY: The
18. A 49.D basic principle of bioassay is to compare
substance with the International the lest
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Standard preparation of the same

much test substance is required
to produce the same biological and to find out how
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standard. The standards are effect, as produced by the
internationally accepted
recommended by the Expert
Committee of the Biological
samples of drugs maintained ana
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Standardization of W.HO. They

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Bloassay
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38 339
represent the fixed units of activity (definite weight of preparation) for drugs. In India, (IT). The bioassays cover that measure toxicity, including those for chemical toxicity and
standard drugs are maintained in Government institutions like Central Drug Research hepatoxicity-a particularly significant consideration in the development of safe and
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Institute, Lucknow, Central Drug Laboratory, Calcutta, etc.
The problem of biological variation must be minimized as far as possible. For that one .
tolerable medications
Highlights clinically relevant methods, ideas, and techniques to support any
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should keep uniform experimental conditions and assure the reproducibility of the pharmaceutical researcher
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responses. suggests the guidelines and systems enhance communication between

pharmacologists, chemists, and biologists
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(VD. Provides an informative analysis of pharmaceutical bioassay technologies and lab
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applications
To
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measure the pharmacological activity of new or chemically unidentified
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substances.
Response
FTo investigate the functions of endogenous mediators.
measure drug toxicity and undefined effects ED so
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and Lvso
(X). Drug discovery the ability of extracts of the posterior
lobe of the pituitary to produce
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the rise in+, and contractions of uterus. Eg. oxytocin
6:2.1YPESO BIOASSAY
It is basically two types of bioassays as per the technique used in the determination
Log Vol of the
Sample under test. There are three main types of bioassays (other than qualitative assays)
1. Direct Assays
M=potency ratio between S/U 2. Indirect Assays based upon quantitative responses
Fig.6.1 A graphical representation shows the most bioassays will give results with 5% 3. Indirect Assays based upon quantal responses (,all
or none")
confidence limits lying within +20% Direct Assay: Doses of the standard and test preparations are sufficient to
produce a
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specified response, and can be directly measured.
APPLICATIONS OF BIOASSAY: Bioassays are useful tools in modern biosciences. The Indirect Assay: In indirect bio-assays, the relationship between the dose
and response of
applications include the development of new drugs; measurement of biological activity
in each preparation is first ascertained. Then the dose corresponding to a
given response is
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of
undefined substances; investigation of endogenous mediator function; determination obtained from the relation for each preparation separately.
as
drug toxicity; and measurement of the concentration of known substances such An agonist may produce graded response or quantal response.
Graded response means that
pollutants or herbal products. the response is proportional to the dose and response may lie
between no response and the
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the
Demonstrating the specific ways in which various pharmaceutical bioassays interpret maximum response. By quantal, it is meant that the response is in the
form of "all or none",
screening of drug
activity of drug molecules, the book covers the evaluation and ie. either no response or maximum response. The drugs
producing quantal effect can be
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compounds in a wide spectrum of therapeutic categories. bioassay by end point method. The drugs producing graded responses
can be bioassay by
bioassays is vital to (1) Matching or bracketing method or (2) Graphical method.
9t provides the fundamental knowledge of pharmaceutical
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discovered, and
understanding how bioactive agents and new drugs are defined,
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developed, so too is this indispensable reference. 11.2.1 End Point or Quantal Assay
bioassays and their specific 11.2.2 Graded Response Assay
It offers a complete reference on pharmaceutical
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(I).
Alzheimer's, diabetes, epilepsy,
applications in the assessment of therapies for cancer, End Point Method: It is the threshold dose producing a positive effect is measured on each
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major therapeutic areas
inflammation, antimalarials, pharmacogenomics, and other animal and the comparison between the average results of two groups of animals (one
receiving standard and other the test) is done. e.g. bioassay of digitalis in cats. Here the cat
ac
is anaesthetized with chloralose and its blood pressure is recorded. The

drug is slowly
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PU A Tert Book of Pharmacology-! Bloassay
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dose which produces head drop of
therats and remove the seminal vesicles or the prostate glands from each animal. Remove the second day of expt. and vice versa. The mean the
standard preparation.
any extraneous fuid and tissue from the vesicles or glands and weigh them immediately. test sample is compared with the mean dose of
Calculate the result of the assay by standard statistical methods using the weight of the
y
vesicles or prostate glands as the response. other method: is pithed and laid on its back on a
Frog's Rectus Abdominis muscle Preparation:A frog
abdomen is cut away and
cork covered board to which it is pinned. The skin covering the
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6.8 BIOASSAY OFD:TUBOCURARINE
the rectus abdominis muscle of one side is dissected from the pelvic
girdle to its insertion in
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Rabbit Head-drop Method: the cartilage of the pectoral girdle. The muscle is then pinned to the
cork by four pins to
Tndple: D-Tubocararine hydrochloride is injected into the marginal vein of a rabbit's ear keep its normal length while a thread is sewn through
each end. It is then mounted in the
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the rabbit's neck musdes are relaxed such that the animal cannot hold head up. The 6.5 12 gm.; KCI, 0,29
organ bath containing frog's Ringer solution which contains Nacl,
:
till is gm.; CaCI2, 0.24 gm.; NaHCO3, 0.4 gm.; glucose, 1.5 gm. and distilled water
total amount of test sample required to produce the endpoint is compared with the total 2000 ml
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amount of the standard sample required to produce similar endpoint. Oxygenation is carried out to keep the tissue alive. The muscle is stabilized for 30-45 min. in
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Selection of Rabbits: Rabbits weighing2 kg. are used. Animals should be free from disease, order to get critical quantitative response. The responses are recorded using isotonic frontal
obtained from a healthy colony and should be accustomed with the experimental writing lever with 1 G. tension.
procedure. Two similar contractions with the same concentration of acetylcholine are obtained. Three
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Eperimental Procedure: Each rabbit is placed in a holder with its head protruding outside. doses of the standard sample and one intermediate dose of the test sample are selected and
The head should be freely movable. Minimum 8 rabbits are used. They are divided into two the reduction in height of contraction induced by acetylcholine is noted down.
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groups each containing 4 rabhits. The first group receive a standard sample and the
will Acetylcholine contraction is recorded on slow moving dum for 90 sec. d-Tubocurarine is
second group is received the sample under test. D-Tubocurarine solution is injected at a allowed to act for 30 sec. The percentage reduction at each dose levels is calculated and log
constant speed by infusion apparatus through the marginal vein. dose response curve of the standard drug is plotted. A linear response is obtained. The
potency of test sample is calculated from the standard curve.
6.9 BTOASSAYOF DIGITAUIS

The bioassay of digitalis is mainly used two methods
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Guinea-Pig Method Pigeon Method
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(ii) End point method End potnt method
Fig 6: Rabbit head drop method for the bioassay of d-tubocurarine. PrinciplePotency of the test sample is compared with that of the standard preparation by
:iv.inj. of d-tubocurarine. (i): Head drop after injection. determining the action on the cardiac muscle. Any other equivalent method, which gives
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Injection should be given at a rate of 0.4 ml/min and should take about 10 min. Infusion is results similar to those obtained by this method, is also valid.
continued till the rabbit will not be in a position to hold its head erect or there will be no
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Standard Preparation and Units: The standard preparation is
response by focussing light on the eyes and the neck gets elongated and toneless. a mixture of dried and
powdered digitalis leaves (1 unit = 76 mg.)
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(i) Suitable dose of d-tubocurarine is 0.0129% w/v in saline. Rabbits recover immediately Preparation of Extracts:Exact amount of the powder is extracted
with dehydrated alcohol
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in a continuous extraction apparatus for six
from the effect of furarization. During the expt. there is a possibility or respiratory hours. The final extract should contain 10 ml.
ml. alcohol + 5 ml. water) per 10 g. of digitalis 6
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embarrassment which is treated by injecting neostigmine methyl sulphate (0.05 mg) powder. It should be stored in between 5 oC
and atropine sulphate immediately through the marginal ear vein. and-5 0C.
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(ii) Cross-over test is arried out to minimise biological error due to animal variation. Those
rabbits which received the standard sample on the first day will be given test sample on
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iA Tern Rook of Pharmecoiogy
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Biosy 355
UINE-m6 MITTD (UND POINT MITHODanndnrd nnd
dlutaf with nomal znlinr in sturh o way tlhat 1 g of dy/talh powder 1rt vtcts
sumple
u dihuted to BO mi A
are
Trachea is eannslahed for giving artificial nespiration. Histamnie produces a fall in BP by
uinea pir e anarathrtized with a auitable: nnarethtir. It f disarertrd ron the
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The rslar vvin j: trarrd uI by wwvinp perntion tuble. dilatig eripheraí blewed vessels. This principle is utilizet for its bioassay. The extent to
ndhring tinnue and ranulated whch tak due o the est sample is compared with the fall by the stardard preparation.
etoa ranmula A pin is inaerted n the hear1, Atrh that it pete ty menns cf
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inserted In the npen f the Guinenpig liewm Gunea pig is killed by a blov en he hext and bled to death. The
heet fn thi way. wr ran t the hean rata by up and
down merements of the pin. abdominal wall it dessected out s as to isoiate the ideum, the faecal matter. mesentery and
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The tmtntits i evmtinurd dirnh venous cannula untill the

ahunt t *ntrart mured tu pmalurr
hrar1 in nrreeted in ayetole The
thi efet in tnken an the ethal doe of the etra
Mod
vek are removed from the piece of ileum.
t
is ligated on both sides and
suserded in mammalian organ bath containing Tyrode solution maintained at 37.0C and
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Anmther s 1 animale of
the same **te ar ued for this eaperiment «nd the averege yAd cortintmously. Histamine contracts the ileum. This principle is utilized for its
ltha) «dae s determnnd It s not neremaary to determine
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ach tme ol the eapriment

the lethal doe of tiw
std. during bioasay Te event of contrartion produced by the test sample is compared with the
it it ahould he orcasionally chedd standard preparation of histamine. The bioassay of histamine can be performed by
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The ethal dew of the teat aanye ia determmined in a Matching Pioassay
similar way using minimum 6 guinea-
ga of tte same strain.
(2). Interpolaton bsoasaay
1he poteney o the test samle s mleulated in relation to
that of the tid. 0) Bracthettng Bioassay
divding the average ethal dome of the sanmpe to the test and expressed as preparation by
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units per gram. (4).Multiple pount Brassay
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Anaesthetized Dog Compare the extent of fall in BP of the test sample with that produced
PmGON MATHOIh this method mirumum
si pigeons are ued for testing ench satple.
They should be Ire Irom gross evidence ol disease or emaciation.
by the standard preparation.
The weipkt
heavst pigen should not exmad twicr the weight of the lightest pígeen
Food withheld
1à 28 houn betoe the experiment. Pigeons are
divided on the basis of thuir se>, w ght and
bned, nto two greus They are anaesthetized with
anaesthetk ether
e de of the winy, is disseNted and the alar vein is cannulated by mw.ns of a venous
Annia Dilutiona ae made with normal saline. Average lethal duse e cach sample
is
FREMEWQUESTONS
determinrd, results are tabulatrd and caleulated as per guinea pig, nethod. The lethal dose
er ky ot body weigh' t detrmined tor each pigeon. The juotenry of the test sample is VERY SHORT ANSWER QUESTIONS
determned br divitig, the mean lethal dose of standard by the mean lethal dose of the test
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sample Q.1. Define bioamay
m, stoppage of heart is associated with a characteristic vomiting response called Ans It defiuned as etimaticn or determinatton of
is
concentration or potency of a physical, chemical
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wesis. The milk trom the crop sac of pigeons is being ejected out. This may be taken as biological substance agent) by means of measuring
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and comparing the magnitucde of
reepone of the test with that of stanlard over a uitable biological the
the end point Pesponse of digíualis. systern under standard set of
conditions.
02.Classifty bioassay
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6.10 BIOASSAY OFHISTAMINE Ans. There are three main typs ot bioassays (other than
Pirasay of histamine can be perforned by Isolated, atropinized contractile ettect terminal .
Direct Assays
qualitative assays)
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ikem p of na pig and anaesthetized and Fall in blood pressure atropinized cat/dog. 2 Indirext Assays bused upon quantitative respunses
3 Indirect Assays based upon quantal respunses
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Pincipler.aency of the tert sample is compared with that of the standand preparation. al or none)
CTervera biologirai methods for its assay 03 Explain quintal Bioas>ay
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Ans It is neant that the response is in the torm of "all or none",
Rectus Abdominis Muscle of Frogsect the rectus muscle and aranpr the asscmbly as ie enther no response or maximum
rporse. The drugs producing quantal effect can be bioassayed by end point
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per assay o .ropine let log dose response curve and find out the p:teuy ni the sample method
of acetulecholne
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Cat's Blood Pressure cat is anaesthetized with suitable anaesthetic. The carotid artey is
ac
cann'att mxpdang B'. The femaral vein is cannulated for injecting tistamine
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356 A Text Book of Pharmacolo9y-1 BloassayY
Q4 Describe the graded bioassay biological assay of vasopressor

Q.15. Write the principle of
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with that of the
Ans. The graded dose response curve is obtained by plotting a Ans. It is estimated by comparing the
activity of the preparation being examined
graph with dose on the X-axis and under the conditions of a suitable method of
response on the Y-axis. It is usually sigmoid in shape however the log dose response curve tandard Preparation of arginine vasopressin
is
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almost a straight line and particularly useful in bio assay. assay.
Q.5. What is matching bioassay? D-tubocurarine bioassay
Q.16. Explain the principle of
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is injected into the marginal vein of a rabbit's ear till the

Ans. Matching bioassay is a method the constant dose of the test is bracketed by varying doses of Ans. The d-Tubocararine hydrochloride
standard the animal cannot hold its head up. The total amount
till the exact match is obtained between test dose and the standard dose. rabbit's neck muscles are relaxed such that
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thee
15 compared with the total amount of
Initially, two responses of the standard are taken. of test sample required to produce the endpoint
endpoint.
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Q.6. What is potency? standard sample required to produce similar

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Ans. Potency is the amount of drug required to produce a given percentage of its maximal effect,
irrespective of the size of maximal effect.A drug can have high potency but poor efficacy, meani
LONG ANSWER QUESTIONS
ng that response is seen at very low doses and remains small evenat high doses
Refer 6.1,6.2
Q7. What is efficary? Q1. Define bioassay and its type in detail
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exampleRefer 6.I
Ans. In pharmacoloEy, efficacy (Ema) is the maximum response achievable from an applied or dosed Q,2. Explain the principal of bioassay with
Q3. Describe the application of BioassayRefer
6.2
agent, for instance, a small molecule dnug. Intrinsic activity is a relative term for adrug's
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efñicacy relative to a drug with the highest observed efficacy. methodRefer 6.2
Q4. What is graded bioassay, explain any two
Q.8. Explain the use of bioassay exampleRefer 6.2
Q.5. Describe in detail the end point bioassay with
Ans. Provides an informative analysis of pharmaceutical bioassay technologies and lab Q.6. Discuss the methods of bioassay of insulih
Refer 6.3
applications oxytocinRrfer 64
Q7. Describe the method of biological assay of
(i). To measure the pharmacological activity of new or chemically unidentified substances.
Q8. Write a note on biological assay for vasopressorRefer b.5
Cii). To investigate the furnctions of endogenous mediators.
Q9. Explain the bioassay of D-TubocurarineRefer 6.8
iv). To measure drug toxicity and undefined effects ED s' and Lo
Q.10. Discuss the bioassay of digitalisRefer 6.9
(v). Drug discovery" the ability of extracts of posterior lobe of pituitary to produce rise in +, and
Q11. Write a note on bioassay of histamineRefer 6.10
contractions of uterus. Eg. oxytocin Q12. Describe the bioassay of ACTHRefer 6.6
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Q.9. Deseribe Interpolation assay
Q13. Explain the three point bioassay assay and Four- point (2+2) assay Refer 6.2
Ans. It is a log dose-response curve is plotted with the standard. The concentration of the test is then
Q14. Discuss the Matching point and Interpolation bioassay R<fer 6.2
read from the graph.
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Q.10. Explain graphical method MULTIPLE CHOICE QUESTIONS
Ans. It is based on the assumption of the dose-response relationship. Log-dose-response curve is
Q.1. Biological assays are
plotted and the dose of standard producing the same response as produced by the test sample is
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directly read from the graph a. Qualitative b. Quantitative
Q.12. What is Standard preparation and unit of insulin for bioassay? c. Both A and B d. None of the above
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Ans. It is pure, dry and crystalline insulin. One unit contains 0.04082 mg. This unit is specified by Q.2. Biological assay are carried out for
Ministry of Health, Government of India and is equivalent to international unit. b. Unknown compound
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a. Known compound
Q.13.What is radioimmuno assay? c. Both A and B d. None of the above
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Ans. It is the estimation of the concentration of the substance in a unit quantity of preparation using Q.3. Biological assays are
radiolabelled antigens. A number of drugs are estimated now days by radioimmunoassy
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a. More difficult to perforn b. Provide greater error

methods because these methods are highly specific and highly sensitive. c. Less reproducible d. All of the above
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Q.14. Explain the principle of oxytocin bioassay
Q.4 Test organisnms used for Bioassay should
Ans. The potency of oxytocin is determined by comparing its activity with that of the Standard a. Be bacteria
ac
Preparation of oxytocin under the conditions of a suitable method of assay. b. Not be a pathogen
c.Grow at all pH d. All of the above
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358 PA Text Book of Pharmacology-l1
()
Q.5.. is example of bioassay

INDEX
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a. Acid Base Titration Assay b. Metabolic Response Assay
cChromatoraphy Assay d. All of the above 351
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Q.6. An agonist is a substane that: (A) Bioassay of gonadotrophin
354
Bioassay of histamine
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a) lnteracts with the reoeptor without producing any effect

b)Interacts with the receptor and initiates changes in cell function. producing various effects Action potential 343
30 Bioassay of insulin
Aderno rorticotrophin hormones
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Increases concentration of another substance to produce efect 337
analgesics 17 Bioassay
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d) Iateracts with plasma proteins and doesn't produce any effect 348
25 Biological assay for vasopressor activity
Q7.If an agonist can produce maximal effects and has high efficacy it's called: Androgens 345
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a) T'artial agonist b) Antagonist 314 Biological assay of oxytocin
Androgens and anabolic steroids 174
Bradykinin
dAgonist-antagonist d) Full gonist
Angiotensin blockers 2 215
Qs If an agonist can produce submaximal effects and has moderate efficacy i's called 21 Rraiykinin antagonists
Angiotensin
c
c
a) Partial agonist b) Antagonist
19 Bradykinin 212
Angiotension converting inhibitors
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Agonist-antagonist d) Full agonist
(C)
Q9. An antagonist is a substance that Anti anginals
a)Binds to the receptors and initiates changes in cell function, producing maximal effect Anti arrhythmic
Cardiotonicss
b) Binds to the receptors and initiates changes in cel function, producing submaximal effect
Anti arrhythnie drugs 5 Cardiotonics
84
Interacts with plasma proteins and doesn't produce any effect Anti coagulants 10 Coagulants
d Binds to the receptors without directly altering their functions 13 Coagulants 102
Anti diuretics
Q.10. A competitive antagonist is a substance that:
Anti inflammatory drugs 17 Conduction
a) Interacts with receptors and produces submaximal effect
Anti thyroid drugs 27 Contraceptives 259
b) Binds to the same reoceptor site and progressively inhibits the agonist response
Antianginal Corticosteroids 309
Binds to the nonspecific sites of tissue
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d Binds to one receptor subtype as an agonist and to another as an antagonist Anti-coagulants (D)
Q.11. The substance bin ding to one receptor subtype as an agonist and to another as an antagonist Anti-gout drugs 174 Diabetes mellitus (dm) 290
is called:
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Antihypertension Diuretics 138
a) Competitive antagonist b) ITeversible antagonist
Agonist-antagonist d) Partial agonist Antihypertension 1 Drug used in the therapy of shoc 85
Antiplatelet drugs 11 Drugs acting on the uterus 324
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ANSWER'S Anti-platelet drugs & Drugs used in anaemia 93
.
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C 2 C 3. D 4. B 5. B B Antipyretics 17 (E)
Antirheumatic drugs 24 Electrophysiology of heart
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7. D s.A D 10. B 11. C

(B) Estrogens 318
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Basic concepts in endocrine pharmacology
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25 Fibrinolytie 84
Bioassay of adrenocorticotrophic hormone
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Fibrinolytics (thrombolytics) 120
34 (G)
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Bioassay of digitalis 5
351 Ghrh inhibitors 267
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Bioassay of d-tubocurarine
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y

IKAS AND COMPANY (MEDICAL PUBLISHER5)

cER CARE: Fer aty quenes. piease centact-0S4756-14148 B00RS

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structure of question paper. Diagrammatically mechanism of drug have been fully

will be highly appreciated.

contained In this book and cannot accept legal

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Chapter 6 Bioassay 337-358

1.3 Cardiotonics 8, Pharmacology of cardiac glycoside 9,

269, 54 Thyroid and antithyroid drugs 272, 5.5 Hormones regulating

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prevent terminate attacks of angina pectoris.

arrhythmias occur as a result of defective impulse conduçtion

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and by blood viscosity. The pharmacologic viewpoint,

constrict, resistance rises, causing blood flow to decline. To maintain adequate.low

Pressuregradient sitsesi-ias Muscular2i Bloodpressure. a as ib a:) ttieie

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contractile fibers, hence

gh open fest *rogh

channels, but with a much slower ime course

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13 CARDIOTONICS (USED IN GHE

Fig.1.5 Mechanism of sction

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The Na* 7 K exchange requires

change with potassium that leaves increased intracellular Na*. This

intracellular biochemical events that ultimately result in an

systolic blood pressure may rise whereas diastolic blood

liigiu u viinai) T1ulii sr.ibnt>ot tts isuor

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geriod. therapeutically. In digitalis therapy it becomes necessary

TOXIeEFFECTS OF CARDIAC GLYCOSIDES

7)Gastro intestinal tract toxicity: Digitalis produce vomiting nausea

vomiting is due to cardiac failure or toxicity of digitalis.

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Digoxin inhibits the TPatient, should take salt restricted,

shock, atrial flutter, atrial

i itdg*ionn saiiima trh

recommended or prescribed medicine in correct dosage.

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gas tro intestinal tract. The action of

due to renal, endocrine or vascular

STROPHANTHUS: The important gycoside of strophanthus

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the enzyme responsible for the conversion

which arise from

a Adrenergic Vasodilators Central Diuretics 1-PA Angiotensinl

Pharmacokinetics: It has an oral bioavailability of 25 percent 4 percent, which is unaffected

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with diabetes mellitus and microalbuminuria or overt nephropathy.

of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or

(duodenum/jejunum). It is rapidly and completely hydrolyzed to principle active

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4 hours, half life IV 4 minute orally 3 to 7 hours,

time before meals,