PHARMACOLOGY-1

FINAL ASSINGMENT SPRING-2020

Submitted to, Submitted by,

Ms. ZARIN TASNIM GIAS SUMAIYA ZAMAN PROME
LECTURER, ID:1822001649
NORTH SOUTH UNIVERSITY COURSE:214.5
SECTION: 05

June 7, 2020
DEPARTMENT OF PHARMACEUTICAL SCIENCES
[Company address]
1. Explain the pharmacokinetics of analgesic drugs in the human body.
(Instruction: Your answer should include the concept of ADME of analgesic drugs
in general. Then, you must select a specific analgesic drug as an example to explain
the ADME of that particular drug.)
Ans Pain can be described as “an unpleasant sensory and emotional experience associated with
actual and potential tissue damage.” [1]
Mechanism of pain:
When an immune cell is damaged it produces a cytokine

Cytokine helps to triggers the production of prostaglandin Sensory nerve surrounding the area
will response to Prostaglandin

The sense will be relayed to the dorsal cord of the spine by the nerve system also known as first-
order neurons. With the release of “substance P”, the first-order neuron will transfer the sense to
second-order neuron
The second-order neuron will be ascending the sense through the spinothalamic tract (spinal
cord, medulla, pons, and midbrain)

In the thalamus, the second-order neurons will pass the sense to the third-order neuron and these
neurons will transfer the sense in the region of the brain which is correlated with injury

The cortex of that region will interpret the sense as PAIN

Analgesic drug: Drugs that relieve pain and depress CNS. There are two type of analgesic drug.
narcotic analgesic and non-narcotic analgesic. Narcotic analgesic drugs (Morphine) are used for
severe pain and non-narcotic drugs (Aspirin) are used for moderated pain. In general, mostly as
an analgesic drug, the non-narcotic drug is suggested. The narcotic drug can reduce severe pain
but most of them have seductive and many toxic effects on the body. Seductive effect of this
drug can make addicted to it. That is why NSAIDs are highly preferable to reduce pain,
inflammation and fever.

Reference:
(1. Merskey, 2002.) 2. (Cuny, "Pharmacokinetics of salicylates in elderly.", (1979) (Tripatti, 2019)
(www.medlineplus.gov) (Friedel, H. A., Langtry, H. D., & Buckley, M. M. (1993)
Pharmacokinetics of analgesic drug in general :

Analgesic drug drug is carried by all analgesic drug All drugs are

Metabolism
Distribution

Excretion
Absorption

are mostly blood and other are metabolised in mainly excreted

absored by body fluids ( like liver and conver by urine .almost
GIT ,intestine and plama) to the into active 80% is excreted
rectal mucosa .if destination.in form .Without by urine and less
the drug molecule that site there are metabolism it can than 10% are
is highly special receptor not produce any excreted by
lipophilic it can in the cell which pharmacological sweats and faces
be absored by binds with the action
blood-brain drug molecule.
barrier

Pharmacokinetics of an analgesic drug:

Aspirin:
Aspirin is a weak organic acid. Aspirin is acetylsalicylic acid. It a product after drug intake it
covert into salicylic acid. It is one of the oldest analgesics which is still in use.

(taken from internet)

Aspirin is a non-narcotic analgesic drug.it is used for moderate pain. it is also used as an anti-
inflammatory drug.
Pharmacokinetics property of Aspirin:
Absorption :
Aspirin is a weakly acidic drug. It rapidly absorbed in the lining of the stomach and intestine.
Distribution :
Aspirin rapidly distributes into the body fluids. Salicylic acid binds to albumin which is present
in blood plasma (aspirin being capable of irreversibly acetylating many proteins), and are
distributed in the synovial cavity, central nervous system, and saliva.[2]
Metabolism:
 phase -1

Reference:
(1. Merskey, 2002.) 2. (Cuny, "Pharmacokinetics of salicylates in elderly.", (1979) (Tripatti, 2019)
(www.medlineplus.gov) (Friedel, H. A., Langtry, H. D., & Buckley, M. M. (1993)
Aspirin is hydrolyzed rapidly by plasma and tissue esterases to acetic acid and the active
metabolite salicylic acid. 

Phase-2
Salicylic acid also metabolized by the liver.

Salicylic acid Glucuronic acid Glucuronide

+ =

Salicylic acid + Glycine = Salicyluric acid

+ acid oxidized Genesic acid

Salicylic

Salicylic acid metabolized in hepatic conjugation with glucuronic acid and forms glucuronide.
salicylic acid also conjugates with glycine and form salicyluric acid. salicylic acid also oxidized
to genesic acid. These metabolized products are easily excretable from the body.
Excretion:

Reference:
(1. Merskey, 2002.) 2. (Cuny, "Pharmacokinetics of salicylates in elderly.", (1979) (Tripatti, 2019)
(www.medlineplus.gov) (Friedel, H. A., Langtry, H. D., & Buckley, M. M. (1993)
Excretion of unmetabolized salicylic acid increased the body pH above 8. So salicylic acid gets
ionized in the kidney which decreases its reabsorption and also increases the absorption from the
body.[2]
2. Describe how the body responses to anti-inflammatory drugs once they are taken
to reduce inflammation in the body. (Instruction: Your answer should describe the
pharmacodynamics of anti-inflammatory drugs.)
Ans: inflammation is a protective response to our body's immune system. Inflammation can be
caused by the entry of pathogens ( like a virus, bacteria, micro-organism, etc) inside the body,
physical trauma, thermal trauma, hypersensitivity, etc. To reduce the inflammation most use anti-
inflammatory drugs are NSAIDs (Non-Steroidal Anti-inflammatory Drug).
Mechanism of action of inflammation:
When our body comes in the exposure of any pathogen it shows certain symptoms like redness,
an increase of swelling, pain, fever, etc are known as inflammatory symptoms. These symptoms
are facilitated by Prostaglandin, Histamin, leukotriene, serotonin, bradykinin, etc . these are the
mediators of inflammation. Every inflammatory mediator has a specific function.
Prostaglandin: mediate fever, pain, inflammation
Histamine: vasodilation, tissue congestion, and swelling
Leukotriene: Principle mediator of asthma, increase vascular permeability
Serotonin: vasodilation, increase vascular permeability.

Reference:
(1. Merskey, 2002.) 2. (Cuny, "Pharmacokinetics of salicylates in elderly.", (1979) (Tripatti, 2019)
(www.medlineplus.gov) (Friedel, H. A., Langtry, H. D., & Buckley, M. M. (1993)
Prostaglandin is responsible for fever, pain, and inflammation. Prostaglandin is 20carbons
containing unsaturated essential fatty acids.it includes a ring structure. The synthesis mechanism
of inflammation is discussed below:
Chemical or mechanical stimuli disrupts the cell membrane and membrane phospholipid coverts
into arachidonic acid with the help of phospholipase A enzyme. Then arachidonic acid divides
into two pathway cyclooxygenase and lipoxygenase.
In the cyclooxygenase pathway, it generates eicosanoids with a ring structure.[3] All tissues
have COX can form unstable Prostaglandin G (PGG) and Prostaglandin H2 (PGH 2). These
Prostaglandin H2 (PGH2) again converted into Prostaglandin E2 (PGE2), Prostacyclin (PGI2),
Thromboxane A2(TXA2).COX-1 and COX-2 ( isomers of cyclooxygenase) both isoforms
catalyzed the same reactions.COX-1 participates in physiological changes as reduction of gastric
HCl, increase secretion of mucus in the stomach, responsible for the homeostatic function. On
the other hand, COX-2 is responsible for pain, fever & inflammation.[3]
Mode of action of anti-inflammatory drug :

The NSAIDs (Non-Steroidal Anti Inflammatory Drug). are a group of chemically dissimilar
agents that have similar pharmacological activities such as antipyretic, analgesic, and anti-
inflammatory activities. NSAIDs is commonly used as an anti-inflammatory drug.
When NSAIDs are taken to reduce inflammation, the NSAIDs interrupt the mechanism of
inflammation Mechanism of action of NSAIDs as an anti-inflammatory agent is given below ;

Which causes release of

stimulation of
disrupts cell membrane the phospholipid cell
inflammation
membrane

NASIDs (non-selective)
reduce the synthesis of
blocks COX1 7 COX2 which is coverted into
prostaglandins that
enzyme ARACHODONIC Acid
mediate inflammation

thus reduce
inflammation

Reference:
(1. Merskey, 2002.) 2. (Cuny, "Pharmacokinetics of salicylates in elderly.", (1979) (Tripatti, 2019)
(www.medlineplus.gov) (Friedel, H. A., Langtry, H. D., & Buckley, M. M. (1993)
Arachidonic acid produces Prostaglandin E2 (PGE2), Prostacyclin (PGI2), Thromboxane
A2(TXA2) by cyclooxygenase which exists in COX-1 and COX-2 isoforms. Most t NSAIDs
blocks the COX-1 and COX-2 nonselective as most are nonselective COX inhibitor. Because of
that, the production of prostaglandin is reduced. As the production of prostaglandin is low the
inflammatory effect is also reduced.
This is known as the Pharmacodynamics action of Anti-inflammatory drugs.[3]
.

3. Describe in details the role of prostaglandin as autacoid.

Ans: Autacoids are heterogeneous substances have widely differing structures and
pharmacologic activity. Autacoids all have a common feature of being formed by the tissue in
which they act on. These work as a local hormone but they are produced by tissue rather than in
the specific endocrine system. Example of autacoids is histamine, prostaglandin etc.
Prostaglandin:
Prostaglandin is unsaturated fatty acid derivatives that act on the tissues in which they are
synthesized and rapidly metabolized to inactive the product at the site of action.[3]
Roles of Prostaglandin:
Prostaglandin is produced by the biotransformation of arachidonates. There is a wide variety of
prostaglandin found depending on their pharmacological action on tissues (prostaglandin E 2,
Prostaglandin F2 α, Prostacyclin ). Prostaglandins may have different potency and may have
different side effects. Prostaglandin is produced by all cell and used as mediators of many
physiological and pathological process.[4]
Reference:
(1. Merskey, 2002.) 2. (Cuny, "Pharmacokinetics of salicylates in elderly.", (1979) (Tripatti, 2019)
(www.medlineplus.gov) (Friedel, H. A., Langtry, H. D., & Buckley, M. M. (1993)
Roles of Prostaglandin Derivatives given below :
1.Cardiovascular System :

 Prostaglandin E2 causes vasodilation. It also causes a fall in blood pressure.

 Prostaglandin F2 α causes vasocontraction of larger veins and arteries.
 Prostacyclin causes vasodilation. It is more hypotensive then Prostaglandin E2.
 Prostaglandin E2 and Prostaglandin F2 α works as weak inotropic
Prostaglandin on blood vessel :
Prostaglandin E2 Prostaglandin F2 α Prostacyclin

Causes vasodilation Causes vasocontraction Causes vasodilation

Causes blood pressure falls Have little effect on blood Causes blood pressure falls
pressure more than Prostaglandin E2
Weak inotropic Weak inotropic

2.Platelets :
 Prostaglandin E2 has pro-aggregation and anti-aggregation effect.
 Prostacyclin is a potent inhibitor of platelet aggregation.
Prostaglandin on platelet :
Prostaglandin E2 Prostaglandin F2 α Prostacyclin
Have pro-aggregation and Have potent inhibition of
anti-aggregation effect on platelet aggregation
platelet
3.Bronchi, Uterus, GIT:
 Prostacyclin causes bronchial muscle dilation (mild) and Prostaglandin E 2 is a powerful
bronchodilator. It also inhibits histamine release.
 Prostaglandin F2 α causes bronchoconstriction.
 Prostaglandin E2 and Prostaglandin F2 α cause contract human uterus.
 Prostaglandin E2 relaxed the stomach muscles and Prostaglandin F2 α contract the stomach
muscles.
 Prostaglandin E2 and Prostacyclin reduces the secretion of acid in the stomach
Prostaglandin on Bronchi, Uterus, GIT:
Prostaglandin E2 Prostaglandin F2 α Prostacyclin

Reference:
(1. Merskey, 2002.) 2. (Cuny, "Pharmacokinetics of salicylates in elderly.", (1979) (Tripatti, 2019)
(www.medlineplus.gov) (Friedel, H. A., Langtry, H. D., & Buckley, M. M. (1993)
 Bronchial muscle Powerful Brochoconstrictors Bronchodilator
Bronchodilator
Uterus Contract uterus in Contract uterus in
pregnant in non- pregnant in non-
pregnant pregnant
Stomach Reduces acid Reduces acid
secretion and secretion and causes
causes relaxation in a contraction in GIT
GIT muscle muscle

4.Kidney :
 Prostaglandin E2 and Prostacyclin increase H2O, Na+ and K+ excretion; it causes renal
vasodilation and inhibits tubular reabsorption.
 Prostaglandin E2 and Prostacyclin inhibit ADH action and renin secretion.
5. CNS:
 Prostacyclin induces fever.
 Prostaglandin E2 produce variety effect
Prostaglandin E2 Prostaglandin F2 α Prostacyclin
Produce fever, seduction, induce fever
rigidity and behavioural
change

6. Intestine, Endocrine system and metabolism:

 Prostaglandin E2 contracts the longitudinal muscle and relax the circular
muscle. Prostaglandin E2 also increase peristalsis and Cl- and water secretion.
 Prostaglandin F2 α increases fluids and electrolyte secretion in the intestine
 Prostacyclin inhibits toxin fluids secretion in the intestine
 Prostaglandin E2 release the anterior pituitary hormone, steroids and insulin in
the endocrine system.
 Prostaglandin E2 give insulin-like action during metabolism.
Prostaglandin E2 Prostaglandin F2α Prostacyclin
Intestine contracts increases fluids inhibits toxin
longitudinal and and electrolyte fluids
relax circular secretion secretion
Reference:
(1. Merskey, 2002.) 2. (Cuny, "Pharmacokinetics of salicylates in elderly.", (1979) (Tripatti, 2019)
(www.medlineplus.gov) (Friedel, H. A., Langtry, H. D., & Buckley, M. M. (1993)
 muscle
Endocrine system release the anterior
pituitary hormone,
steroids and insulin
metabolism give insulin-like
action
These are the role of Prostaglandin as autacoids in the body.
4. Describe the mechanism of action, dose, duration, side effects and indications of
specific NSAID assigned to you. (NABUMETONE)
Ans: The NSAIDs are a group of chemically dissimilar agents that have similar
pharmacological activities such as antipyretic, analgesic, and anti-inflammatory activities.
NSAIDs have some classification according to their pharmacological action.

Nabumetone is a white, crystalline powder, insoluble in water and sparingly soluble in ethanol.
Nabumetone is a nonsteroidal anti-inflammatory drug.

Indication:

Reference:
(1. Merskey, 2002.) 2. (Cuny, "Pharmacokinetics of salicylates in elderly.", (1979) (Tripatti, 2019)
(www.medlineplus.gov) (Friedel, H. A., Langtry, H. D., & Buckley, M. M. (1993)
Nabumetone is a well-known pain relief drug. It is a partial COX-1 and preferable COX-2
inhibitor. It is used to reduce pain, swelling, stiffness caused by osteoarthritis (arthritis caused by
a breakdown of the lining of the joints) and rheumatoid arthritis (arthritis caused by swelling of
the lining of the joints). [4]
Mechanism of action of Nabumetone : (Pharmacological property)
Nabumetone is a nonsteroidal anti-inflammatory drug which possesses analgesic, anti-
inflammatory and antipyretic properties and it is used to treat osteoarthritis and rheumatoid
arthritis. Its pharmacokinetics and pharmacodynamic activities are given below:[5]
Pharmacokinetics property:

nebutamol the pro-drug is it undergoes the metabolized

Absorption

Metabolism
Distribution

Excretion
primarily distributed by the metabolism in the nebutamol is
absorbed in body fluid to the liver and covert excreated 80% by
into,active 6- urine and 9% by
dudenum . it is liver for methoxy-2-
absorbed as non- metabolism. the faces
naphthylacetic acid
ionized pro-drug (6-MNA) which
diffuse into fluid
and tissue and
inhibit those
prostaglandin which
mediate inflamation

Pharmacodynamics property :
Nabumetone is taken as a pro-drug form
absorbed in dedendum of the intestine
It carried to the liver by body fluid for the first-pass metabolism
where is converted into the active compound, 6-methoxy-2-naphthyl acetic acid (6-MNA)?
This compound rapidly absorbed by the tissue and fluid.
, 6-methoxy-2-naphthyl acetic acid inhibit 2 cyclooxygenase isoenzymes COX-1 and
COX-2
It inhibits chemotaxis, alter lymphocyte activity and inhibit pro-inflammatory cytokine activity
prostaglandins responsible for inflammation cannot produce
relief pain[5]

Reference:
(1. Merskey, 2002.) 2. (Cuny, "Pharmacokinetics of salicylates in elderly.", (1979) (Tripatti, 2019)
(www.medlineplus.gov) (Friedel, H. A., Langtry, H. D., & Buckley, M. M. (1993)
Dose and Dosage form : Nabumetone is an oral drug. It is available in 500 mg and 750 m
osteoarthritis patients are suggested to take 1000 mg/day after the meal; two times rheumatoid
arthritis patients are suggested to take 1000 mg/day after meal ; two times
Duration of action :
The drug gives a slow and sustained relief effect. The duration of action of Nabumetone is 6-8
hours.
Side effect:

Headache Dyspesia

Abdomin
Edema Vomiting Diarrhea
al pain

NABUME NABUME
TONE TONE

Stomatiti
Fatigue Nausea sweating
s

Tinnitus Gastritis

Nabumetone has less adverse effect than other NSAIDs. It can cause ulcers, gastric erosion and
dedendum erosion.[4]
Precaution and warning :
Not for patients with cardiovascular disease; can cause hepatic impairment; pregnant women's
are not suggested to take it as the effect on infant is unknown.[4]

Reference:
(1. Merskey, 2002.) 2. (Cuny, "Pharmacokinetics of salicylates in elderly.", (1979) (Tripatti, 2019)
(www.medlineplus.gov) (Friedel, H. A., Langtry, H. D., & Buckley, M. M. (1993)