Pharmacology

PostRN BScN 1st year semster 1

UNIT-I INTRODUCTION TO BASIC

PRINCIPLES OF PHARMACOLOGY
By Asif Ali Lashari
RN, DP, BScN,
NURSING LECTURER
 Course Objectives:
On completion of this course, student will be able to:
1. Describe the factors in the environment, which
contribute to produce changes in Physiological
processes of the body.
2. Discuss the relationship of normal body function with
altered physiological mechanisms in disease process.
3. Integrate the knowledge of the basic principles of
pathophysiology and pharmaco dynamics and
phamaco kinetics in the disease process..
4. Discuss the application of the knowledge in learnt
principles of pathophysiology and pharmacology in
their clinical practice.
 UNIT OBJECTIVES
By the end of this unit students will be able to:
• Describe basic terminologies used in
pharmacology such as efficacy, potency,
therapeutic index, drug induced toxicity and
adverse effects.
• Describe the basic pharmacokinetic principles
such as absorption, distribution, metabolism and
elimination of drugs.
• Describe pharmaco-dynamics such as agonist,
antagonist and drug receptor interaction.
 Introduction
• Pharmacology is a branch of science that studies drug
effects with in a living organism. It deals with all the
drugs used in the society today, legal or ill-legal, street,
prescription or nonprescription.
• A nurse understands thoroughly any medication,
before giving to a client. Nurse must know the usual
dose, rout of administration, indication, significant side
effects and adverse reaction, major drug interaction,
contraindication and appropriate nursing assessment,
planning, implementation and evaluation techniques
necessary to safely administer the drug.
 Drug
• Any substance used in the diagnosis, cure and treatment or
prevention of a disease or condition is known as drug. A drug
pass through investigational stages before it is approved and
marketed.
• Drugs and biological compounds have been identified of
derived from four main resources.
• (1) plants: digitals, vincristine, colchicine.
• (2) animals and humans: epinephrine, insulin and ACTH.
• (3) minerals or mineral products such as iron, iodine, Epsom
salts synthetic or chemical substances in laboratory. The
drugs made of chemical substance are pure drugs such as
sodium bicarbonate and magnesium hydroxide.
 Types of names
• 1- Chemical name: description of drug composition
and molecular structure.
• 2- Generic /Non- propriety name: name assigned by
manufacturer. Generic name is simpler the chemical
name. It is the official name listed in official
compendium.
• 3- Trade / Propriety name: name of a product
registered by its owner as a trade mark and usable
by others without permission. The copy right
restricts the use of the name of a drug to only the
individual drug company.
 Properties of a drug
• 1. Drugs do not confer any new function on tissues or
organ in the body, they only modify existing functions
e.g to treat anemia, drug used can replace iron to
restore the adequate production of red blood cell.
Atropine reduces rate of salivation preoperatively.
• 2. Drugs exert multiple actions rather than a single
effect because of their potential to modify more than
one function.
• 3. Drug action results from physio-chemical interaction
between the drug and functionally important molecule
in the body. Some drugs act by combining with micro
molecule e.g antacids neutralize gastric acid.
 DRUG ACTION
• Most drugs enter systemic circulation after
administration and expose almost all tissues to
possible effects of the drug . Most drugs have an
affinity for certain organs or tissues and exert
their greatest action at the cellular level on the
specific areas called target sites. Two main
actions are :
• 1- Alteration in cellular environment:
• 2 - Alteration in cellular function
 Describe Basic Terminologies
Efficacy:
 Efficacy is the magnitude of response a drug causes when it
interacts with a receptor.
 Efficacy is dependent on the number of drug–receptor
complexes formed and the intrinsic activity of the drug (its
ability to activate the receptor and cause a cellular response).
 Maximal efficacy of a drug (Emax) assumes that all receptors are
occupied by the drug, and no increase in response is observed
if a higher concentration of drug is obtained.
 Efficacy is a more clinically useful characteristic than is drug
potency, since a drug with greater efficacy is more
therapeutically beneficial than is one that is more potent.
 shows the response to drugs of differing potency and efficacy .
 Describe Basic Terminologies
Potency:
• Potency is a measure of the amount of drug necessary to produce
an effect of a given magnitude. The concentration of drug
producing 50% of the maximum effect (EC50) is usually used to
determine potency.
 Describe Basic Terminologies
Therapeutic index:
• The therapeutic index (TI) of a drug is the ratio of the
dose that produces toxicity in half the population
(TD50) to the dose that produces a clinically desired
or effective response (ED50) in half the population:
TI = TD50 / ED50
• The TI is a measure of a drug’s safety, because a
larger value indicates a wide margin between doses
that are effective and doses that are toxic.
'Drug toxicity' can be defined as a diverse array
of adverse effects which are brought about
through drug use at either therapeutic or non-
therapeutic doses. From: Concepts and
Experimental Protocols of Modeling and
Informatics in Drug Design, 2021.
 Pharmacokinetics
• Pharmacokinetics examines the movement of a drug
over time through the body. Pharmacological as well
as toxicological actions of drugs are primarily related
to the plasma concentrations of drugs.
• Thus, it must recognized that the speed of onset of
drug action, the intensity of the drug's effect, and
the duration of drug action are controlled by four
fundamental pathways of drug movement and
modification in the body
 Conti…
• 1. drug absorption from the site of administration
(Absorption) permits entry of the therapeutic agent.
• 2. the drug may then reversibly leave the bloodstream and
distribute into the interstitial and intracellular fluids
(Distribution).
• 3. the drug may be metabolized by the liver, kidney, or other
tissues (Metabolism).
• 4. the drug and its metabolites are removed from the body in
urine, bile, or feces (Elimination). This ppt describes how
knowledge of these four processes (Absorption, Distribution,
Metabolism, and Elimination) influences the clinician's
decision of the route of administration for a specific drug, the
amount and frequency of each dose, and the dosing intervals.
 Drug Administration
The route of administration is determined primarily by the properties of
the drug (for example, water or lipid solubility, ionization, etc.) and by the
therapeutic objectives (for example, the desirability of a rapid onset of
action or the need for long-term administration or restriction to a local
site). There are two major routes of drug administration, enteral and
parenteral.
A. Enteral
1. Oral
2. Sublingual
B. Parenteral
3. Intravenous
4. Intramuscular
5. Subcutaneous
C. Inhalation, D. Intranasal, E. Intrathecal/intraventricular, F. Topical, G.
Transdermal, H. Rectal
 Absorption
• Absorption is the transfer of a drug from its site of
administration to the bloodstream. The rate and efficiency of
absorption depend on the route of administration. For IV
delivery, absorption is complete; that is, the total dose of drug
reaches the systemic circulation. Drug delivery by other routes
may result in only partial absorption and, thus, lower
bioavailability. For example, the oral route requires that a drug
dissolve in the GI fluid and then penetrate the epithelial cells of
the intestinal mucosa, yet disease states or the presence of food
may affect this process.
• Schematic representation of drugs crossing a cell membrane of
an epithelial cell of the gastrointestinal tract.
• ATP = adenosine triphosphate;
• ADP = adenosine diphosphate.
 Conti…
• Transport of a drug from the GI tract Depending
on their chemical properties, drugs may be
absorbed from the GI tract by either passive
diffusion or active transport.
• Passive diffusion: The driving force for passive
absorption of a drug is the concentration gradient
across a membrane separating two body
compartments; that is, the drug moves from a
region of high concentration to one of lower
concentration.
• Active transport: This mode of drug entry also
involves specific carrier proteins that span the
membrane. A few drugs that closely resemble
the structure of naturally occurring
metabolites are actively transported across
cell membranes using these specific carrier
proteins. Active transport is energy-dependent
and is driven by the hydrolysis of adenosine
triphosphate (ATP).
 Endocytosis and exocytosis
• This type of drug delivery transports drugs of
exceptionally large size across the cell membrane.
Endocytosis involves engulfment of a drug molecule by
the cell membrane and transport into the cell by
pinching off the drug-filled vesicle. Exocytosis is the
reverse of endocytosis and is used by cells to secrete
many substances by a similar vesicle formation process.
For example, vitamin B12 is transported across the gut
wall by endocytosis.
• Certain neurotransmitters (for example, norepinephrine)
are stored in membrane-bound vesicles in the nerve
terminal and are released by exocytosis.
 Effect of pH on drug absorption
• Most drugs are either weak acids or weak bases.
Acidic drugs (HA) release an H+ causing a charged
anion (A-) to form: 2 Weak bases (BH+) can also
release an H+. However, the protonated form of
basic drugs is usually charged, and loss of a
proton produces the uncharged base (B): Passage
of an uncharged drug through a membrane: A
drug passes through membranes more readily if it
is uncharged . Thus, for a weak acid, the
uncharged HA can permeate through
membranes, and A cannot.
 Conti…
• For a weak base, the uncharged form, B,
penetrates through the cell membrane, but BH+
does not. Therefore, the effective concentration of
the permeable form of each drug at its absorption
site is determined by the relative concentrations
of the charged and uncharged forms. The ratio
between the two forms is, in turn, determined by
the pH at the site of absorption and by the
strength of the weak acid or base, which is
represented by the pKa.
 Physical factors influencing absorption
Blood flow to the absorption site
• 1-Blood flow to the absorption site: Blood flow to the
intestine is much greater than the flow to the
stomach; thus, absorption from the intestine is
favored over that from the stomach. [Note: Shock
severely reduces blood flow to cutaneous tissues, thus
minimizing the absorption from SC administration.]
• 2-Total surface area available for absorption: Because
the intestine has a surface rich in microvilli, it has a
surface area about 1000-fold that of the stomach;
thus, absorption of the drug across the intestine is
more efficient.
 Conti…
• 3. Contact time at the absorption surface: If a drug
moves through the GI tract very quickly, as in severe
diarrhea, it is not well absorbed. Conversely, anything
that delays the transport of the drug from the stomach
to the intestine delays the rate of absorption of the drug.
• [Note: Parasympathetic input increases the rate of
gastric emptying, whereas sympathetic input (prompted,
for example, by exercise or stressful emotions), as well as
anticholinergic (for example, dicyclomine), prolongs
gastric emptying. Also, the presence of food in the
stomach both dilutes the drug and slows gastric
emptying. Therefore, a drug taken with a meal is
generally absorbed more slowly.]
 First-pass hepatic metabolism
• When a drug is absorbed across the GI tract, it
enters the portal circulation before entering the
systemic circulation. If the drug is rapidly
metabolized by the liver, the amount of
unchanged drug that gains access to the systemic
circulation is decreased. Many drugs, such as
propranolol or lidocaine, undergo significant
biotransformation during a single passage
through the liver.
 Solubility of the drug
• Very hydrophilic drugs are poorly absorbed because of their
inability to cross the lipid-rich cell membranes or the have
the ability to mix well, dissolve, or to be attracted to water..
• Paradoxically, drugs that are extremely hydrophobic are also
poorly absorbed, because they are totally insoluble in
aqueous body fluids and, therefore, cannot gain access to
the surface of cells.
• For a drug to be readily absorbed, it must be largely
hydrophobic, yet have some solubility in aqueous solutions.
• This is one reason why many drugs are weak acids or weak
bases. There are some drugs that are highly lipid-soluble,
and they are transported in the aqueous solutions of the
body on carrier proteins such as albumin.
• Chemical instability:
Some drugs, such as penicillin G, are
unstable in the pH of the gastric contents. Others, such
as insulin, are destroyed in the GI tract by degradative
enzymes.
• Nature of the drug formulation:
Drug absorption may be altered by factors
unrelated to the chemistry of the drug. For example,
particle size, salt form, crystal polymorphism, enteric
coatings and the presence of excipients (such as
binders and dispersing agents) can influence the ease
of dissolution and, therefore, alter the rate of
Absorption.
 Conti…
• Bioequivalence: Two related drugs are bioequivalent if
they show comparable bioavailability and similar times to
achieve peak blood concentrations. Two related drugs
with a significant difference in bioavailability are said to
be bio-inequivalent.
• Therapeutic equivalence: Two similar drugs are
therapeutically equivalent if they have comparable
efficacy and safety.
[Note: Clinical effectiveness often depends on both the
maximum serum drug concentrations and on the time
required (after administration) to reach peak
concentration. Therefore, two drugs that are bioequivalent
may not be therapeutically equivalent.]
 Distribution
• Distribution is the process by which a drug reversibly leaves
the bloodstream and enters the interstitium (extracellular
fluid) and/or the cells of the tissues.
• The delivery of a drug from the plasma to the interstitium
primarily depends on blood flow, capillary permeability, the
degree of binding of the drug to plasma and tissue proteins,
and the relative hydrophobicity of the drug.

• A-Blood flow: The rate of blood flow to the tissue capillaries

varies widely as a result of the unequal distribution of
cardiac output to the various organs. Blood flow to the
brain, liver, and kidney is greater than that to the skeletal
muscles; adipose tissue has a still lower rate of blood flow.
 Conti…
• This differential blood flow partly explains the short duration
of hypnosis(tending to produce sleep) produced by a bolus IV
injection of thiopental.
• The high blood flow, together with the superior lipid solubility
of thiopental, permit it to rapidly move into the central
nervous system (CNS) and produce anesthesia.
• Slower distribution to skeletal muscle and adipose tissue
lowers the plasma concentration sufficiently so that the
higher concentrations within the CNS decrease, and
consciousness is regained.
• B-Capillary permeability Capillary permeability is determined
by capillary structure and by the chemical nature of the drug
 Conti…
• To enter the brain, drugs must pass through the endothelial
cells of the capillaries of the CNS or be actively transported.
• For example, a specific transporter for the large neutral
amino acid transporter carries levodopa into the brain.
• By contrast, lipid-soluble drugs readily penetrate into the
CNS because they can dissolve in the membrane of the
endothelial cells.
• Ionized or polar drugs generally fail to enter the CNS
because they are unable to pass through the endothelial
cells of the CNS, which have no slit junctions.
• These tightly juxtaposed cells form tight junctions that
constitute the so-called blood-brain barrier
 Blood-brain barrier
 To enter the brain, drugs must pass through
the endothelial cells of the capillaries of the
CNS or be actively transported.
 For example, a specific transporter for the
large neutral amino acid transporter
(protein pump) carries drugs into the brain.
By contrast, lipid soluble drugs readily
penetrate into the CNS because they can
dissolve in the membrane of the
endothelial cells.
 Ionized or polar drugs generally fail to enter
the CNS because they are unable to pass
through the endothelial cells (lipid layer)of
the CNS, which have no slit junctions. These
tightly juxtaposed cells form tight junctions
that constitute the so-called blood-brain
barrier.
blood–brain barrier is to protect against circulating
toxins or pathogens that could cause brain
infections, while at the same time allowing vital
nutrients to reach the brain.
• Placental barrier: a semipermeable membrane
made up of placental tissues and limiting the kind
and amount of material exchanged between
mother and fetus thiazides cross the placental
barrier and appear in cord blood.
 Drug structure
• The chemical nature of a drug strongly influences its
ability to cross cell membranes. Hydrophobic drugs,
which have a uniform distribution of electrons and no
net charge, readily move across most biologic
membranes. These drugs can dissolve in the lipid
membranes and, therefore, permeate the entire cell's
surface. The major factor influencing the hydrophobic
drug's distribution is the blood flow to the area.
• By contrast, hydrophilic drugs, which have either a
non-uniform distribution of electrons or a positive
or negative charge, do not readily penetrate cell
membranes, and therefore, must go through the
slit junctions.
 Plasma compartment
• If a drug has a very large molecular weight or binds
extensively to plasma proteins, it is too large to move out
through the endothelial slit junctions of the capillaries
and, thus, is effectively trapped within the plasma
(vascular) compartment. As a consequence, the drug
distributes in a volume (the plasma) that is about six
percent of the body weight or, in a 70-kg individual,
about 4 L of body fluid. Heparin shows this type of
distribution.
 Extracellular fluid
• If a drug has a low molecular weight but is hydrophilic, it
can move through the endothelial slit junctions of the
capillaries into the interstitial fluid.
• However, hydrophilic drugs cannot move across the lipid
membranes of cells to enter the water phase inside the
cell. Therefore, these drugs distribute into a volume that
is the sum of the plasma water and the interstitial fluid,
which together constitute the extracellular fluid.
• This is about twenty percent of the body weight, or
about 14 L in a 70-kg individual. Aminoglycoside
antibiotics show this type of distribution.
Other sites:
• In pregnancy, the fetus may take up drugs and thus
increase the volume of distribution. Drugs that are
extremely lipid-soluble, such as thiopental , may also
have unusually high volumes of distribution.
 Metabolism (biotransformation)
• Drugs are most often eliminated by
biotransformation and/or excretion into the
urine or bile. The process of metabolism
transforms lipophilic drugs into more polar
readily excretable products. The liver is the major
site for drug metabolism, but specific drugs may
undergo biotransformation in other tissues, such
as the kidney and the intestines. [Note: Some
agents are initially administered as inactive
compounds (pro-drugs) and must be metabolized
to their active forms.]
 Elimination
• Elimination Removal of a drug from the body occurs via a
number of routes, the most important being through the
kidney into the urine. Other routes include the bile, intestine,
lung, sweat tears ,skin, hair, or milk in nursing mothers. A
patient in renal failure may undergo extracorporeal dialysis,
which removes small molecules such as drugs.
• 1. Renal elimination of a drug: Drugs enter the kidney
through renal arteries, which divide to form a glomerular
capillary plexus.
• 2.Intestine: Some medications are eliminated through the
intestine by biliary excretion. After metabolism by liver the
metabolites are secreted into bile and passed into the
duodenum and eliminated with faeces.
• 3.Lungs:
• Most drugs removed by pulmonary rout are generally
intact and not metabolized. Agents such as gases and
volatile Liquids (General Anesthesia) that are
administers through the respiratory system usually are
eliminated by same system.
• 4. Sweat and salivary glands:
• Drug excretion through sweat and saliva is relatively
unimportant because the process depends on diffusion
of fat soluble drugs via epithelial cells of the glands.
• Excretion of drugs and metabolites in sweat may be
responsible for side effects such as dermatitis and
several other skin reactions.
 PHARMACO-DYNAMIC
• Pharmacodynamics is the study of the biochemical and
physiologic effects of drugs. The effects can include those
manifested within animals, microorganisms, or
combinations of organisms.
• It is the study of mechanism of drug action on living
tissues, the response of tissues to specific chemical
agents at various sites in the body. The effects of drug
can be recognized only by alterations of a known
physiological functions.
 Theories of drug interaction
1- Drug receptor interaction:
• It is known as the ability of drug to bind to its receptor. Structure
specificity is an essential postulate of the receptor theory the
drug action. This theory hypothesize that drugs are selectively
active substances that have a high affinity for a specific chemical
group (neuro-transmitters) or a particular constituent of cell.
• In essence the drug receptor interaction theory says that a
certain portion (active site) of a drug molecule selectively
combines or interacts with some molecular structure (a reactive
site on the cell surface or with a cell) to produce a biologic
effect. The relationship of a drug to its receptor has often been
linked to that of the fits of a key in a lock. Drug represents key
and receptor represents lock. These best fit will produce best
response from the cell.
• A drug may resemble an enzymes substrate so closely
that it can combine with the enzyme instead of with
the normal substrate.
• Drugs resembling enzyme substrate one known as
“antimetabolites” and can either block normal
enzymatic action or result in the production of other
substance with unique biochemical properties.
• The “antimetabolites” then became receptors.
However although enzymes may be receptors not all
receptors are enzymes.
 Conti…
2-Drug-enzyme interaction:
• (Also known as ability of drug to bind to its receptor)
• An interaction between drug and enzyme is the
second way by which drugs produce their effects.
• Enzymes are biologic catalysts that control all
biochemical reactions of the cell. Drugs can inhibit the
action of an enzyme and alter physiologic response.
• Drug that combine with enzymes are thought to do so
by virtue of their structural resemblance to an
enzyme substrate molecule (the substance acted on
by an enzyme).
 Conti…
3. Non- specific drug interaction: (intracellular)
• Some drugs demonstrate no structural specificity
and presumably act by more general effects on
cell membranes and cellular processes these
drugs may penetrate into cells or accumulate in
cellular membranes where they interfere by
physical or chemical means with some cell
functions or some fundamental metabolic
process.
 1-Agonist
• A drug that combines with receptors and initiates a sequence
of biochemical and physiological changes, possesses both
affinity and efficacy. Full agonist opioids activate opioids
receptors in brain fully resulting in the full opioids effect.
• e.g: heroin oxycodone, methadone, opium
• a- selective agonist: an endogenous agonist for a particular
receptor is a compound naturally that receptor. A selective
agonist is selective for a specific type of receptor
• e.g buspirone is a selective agonist for serotonin 5-HT1A
• b- Partial agonist: an agent that has affinity and some
efficacy but that may antagonize the action of other drugs
that have greater Efficacy.
 2. Antagonist
• An agent which interfere with or inhibit the
physiological actions of other drug.
• A. Competitive antagonist: an agent with an affinity
for the same receptor site as an agonist, it inhibits
the action of agonist. Its response is reversible by
increasing the concentration of agonist.
• B. Non-competitive antagonist: an agent that
combine with different part of receptor mechanism
and inactive the receptor so that agonist cannot be
effective regardless of concentration. Its effects are
irreversible.
 Summary
• Pharmacology is a branch of science that studies drug effects
with in a living organism. It deals with all the drugs used in the
society today, legal or ill-legal, street, prescription or
nonprescription.
• DRUG ACTION
• Most drugs enter systemic circulation after administration and
expose almost all tissues to possible effects of the drug .Most
drugs have an affinity for certain organs or tissues and exert
their greatest action at the cellular level on the specific areas
called target sites. Two main actions are :
• 1. Alteration in cellular environment:
• Some drug act on the body by changing the cellular
environment either physically or chemically.
 Conti…
• 2. Alteration in cellular function:
• Most drugs act on the body by altering cellular function.
• Theories of drug interaction
• 1. Drug receptor interaction: the ability of drug to bind to its
receptor. Structure specificity is an essential postulate of the receptor
theory the drug action.
• 2. Drug enzyme interaction: Drugs can inhibit the action of an
enzyme and alter physiologic response by combining with the
enzyme instead of with the normal substrate.
• 3. Non specific drug interaction: Some drugs demonstrate no
structural specificity and act by more general effects on cell
membranes and cellular processes, these drugs may penetrate into
cells or accumulate in cellular membranes and interfere by physical
or chemical means with some cell functions or some fundamental
metabolic process.
• MECHANISM OF DRUG ACTION
• The drug molecule must proceed from the point of
entry to the tissue with which they react.
• 1. Pharmaceutical phase: the study of the ways in
which various drug form influence pharmacokinetic
and pharmacodynamics activities.
• 2. Pharmacokinetic phase: examines the movement
of a drug over time through the body.
• 3. Pharmacodynamics phase: study of mechanism
of drug action on living tissues, the response of
tissues to specific chemical agents at various sites in
the body.