Mechanism of drug action

and
dose response relationship

Dr. Satabdi Ghosh

MBBS, MD
Assistant Professor
Department of Pharmacology & Therapeutics
Pharmacodynamics

• Definition: This is the branch of pharmacology which deals

with the mechanism of action and pharmacological effects of
drugs.
Pharmacological effects

1. Desired effect / Therapeutic effects

2. Undesired effect/Adverse Drug Reaction
How do drugs act?
• Most of the drugs act by binding with specific target proteins.

• Target protein:
Receptor
Enzyme
Ion channel
Carriers
 Cont..

• Few drugs act without being bound to any tissue constituent, it is

called non-specific drug action.
Exam:
Osmotic diuretics: Mannitol.
Bulk purgatives: Dietary fibres, Isphagula.
Antacids: Aluminium hydroxide/ magnesium tricillicate.
Heavy metal chelating agents: Desferrioxamine
 Cont..

• Receptors: are regulatory proteins (macromolecular) which bind

to endogenous mediators and or drugs (ligands) and produce
response.
• Endogenous mediator: neurotransmitter, hormones or autacoids.

• Ligand: They are chemical substance which can combine with

receptors like drug molecule, hormone. When drug is radioactive
and the pathway of drug is traced these drugs are called ligand.
 Cont…

• Location of receptor: Most are located on cell surface, few within the
cell cytoplasm or nucleus.

• Function of receptor: Receptors have two essential functions

1) recognition of the specific ligand molecule

2) Transduction of the signal into a response.

Classify receptors
• According to mechanism of action
Receptor

Classical receptor
(physiological receptor) Non classical receptor

Ion channel coupled receptor Enzyme as receptor

G- Protein coupled receptor
Tyrosine kinase coupled receptor
DNA coupled receptor
Transport protein as receptor
Voltage gated ion channel
Structural protein as receptor
Nucleic acid as receptor
 Cont..
• According to location:
1. Membrane/ cell surface receptors:
- alfa and beta adrenoceptors, cholinergic receptors
2. Cytoplasmic receptors:
- Steroid hormone receptors
3. Nuclear receptors:
- Thyroid hormone receptors.
Consequences of drug-receptor interaction
• The events that occur after binding of drug with the receptor and
which are responsible for the ultimate drug response are called post-
receptor events or receptor effector coupling.

[D] + [R] ─── [DR]

Conformational change in receptor

Response
Examples
1. Post receptor events of ion channel coupled receptor:
- Opening of ion channel
- Closing of ion channel
2. Post receptor events of G-protein coupled receptors
- Formation of 2nd messengers
- Inhibition of 2nd messengers
- Ca++ release
- May open/close receptor operated ion channel
3. Post-receptor events of tyrosine kinase receptors
- Phosphorylation of proteins
 Cont..

4. Post receptor events of nuclear receptor:

- gene transcription

Binding of drugs to receptor

Drugs binding to receptor may be
- Agonists
- Antagonists
- Partial agonists
- Inverse agonists
Definition
Affinity:
Tendency of a drug to bind with receptor is called affinity.

Efficacy:
Ability of a drug to activate the receptor after binding with it and produce an
effect that refers to maximum effect is called efficacy.
Exam:
Amiloride cause 5% Na+ excretion: Low efficacy
Thiazide cause 10% Na+ excretion: Moderate efficacy
Frusemide cause 25% Na+ excretion : High efficacy
Potency
It is the amount of drugs (weight) in relation to its effects. It is expressed in w/w.

Exam:

Dexamethasone 0.5 mg and Hydrocortisone 5 mg produce maximum and equal

therapeutic effect.

So, Dexamethasone is more potent than hydrocortisone

Bumetanide 1 mg and Frusemide 50 mg produce maximum and equal diuretic
effect.

So, Bumetanide is more potent

Between potency and efficacy which is important?
Agonist
Drugs having affinity as well as efficacy are called agonist.

Drug that binds to the receptors and activate the receptors to produce effects.

affinity efficacy
[D] + [R] [DR] [DR] Response

Exam:
- Acetylcholine agonist of cholinergic receptor
- Adrenaline agonist of  and  receptor
- Histamine agonist of H1 receptor
Antagonist
Drug having affinity but lacking of efficacy is called antagonist.

Drugs that binds with receptors but do not activate the receptors, thereby
preventing the natural agonist from exerting its effects.
affinity
[D] + [R] [DR] No response

Exam:
- Propanolol antagonist of  receptor
- Chlorpheniramine antagonist of H1 receptor
- Naloxone antagonist of  receptor
Partial agonist
 Drug having affinity and low efficacy is called partial agonist.

 The drugs that combines with its specific receptor and produce some degree of
activation or weak responses and will block the action of natural agonist.

 Individually it acts as a weak agonist but in presence of potent agonist it act as an

antagonist.
Exam: Nalorphine has morphine like activity and also effective against morphine.

Acute morphine poisoning – nalorphine act as antagonist (High dose)

Chronic morphine poisoning – nalorphine act as agonist (Low dose)
Inverse agonist

Drug have affinity but produce effects that are specially opposite to those of the
agonist.

Exam: beta carbolines bind with the benzodiazepine receptor of the CNS and
produce stimulation, anxiety, increased muscle tone and convulsion. These effects
of beta carbolines are opposite to the actions of benzodiazepines. So, beta carboline
is considered as inverse agonists.
Summery

Agonist= Affinity + efficacy

Antagonist= Affinity + no efficacy
Partial agonist= Affinity + weak efficacy
Inverse agonist= Affinity + inverse efficacy
Physical interaction of receptor with drug bonds
1. Hydrogen bond
2. Ionic bond
3. Vander wall’s bond
4. Covalent bond
Receptor regulation
 Receptor number is regulated by two factors.
1. Receptor down regulation
2. Receptor up regulation

Receptor down regulation/adaptation/ refractoriness/ desensitization:

 Prolonged high concentration of agonist cause a reduction in the number of

receptors available for activation is called receptors down regulation.

 Greater degradation of receptor than the formation. The vanishing receptors are
taken into the cell by endocytosis.
 Cont..

Exam : Insulin medication.

Mechanism of down regulation: Due to long time medication with agonist

1. Internalization of receptor degradation

2. Decrease synthesis and increase destruction of receptor
3. Phosphorylation of receptor
4. Desensitization of receptor (receptors become fatigue)
Receptor up regulation

Def: Prolong exposure of receptor with the antagonist leads to changes in receptor
occupancy and affinity and an increase in sensitivity and number of receptor is
called receptor up regulation.

 Formation of receptors is greater than degradation.

 Exam: Sudden withdrawal of  blocking drugs may cause rebound

hypertention and angina attack due to up regulation of adrenergic receptors
(prolong blocking cause the receptor up regulation and sensitization)
 Cont..

 So sudden withdrawal of drug, many number of receptors become suddenly

become accessible to the normal NT ( Nor-adrenaline and Adrenaline)

 Mechanism of receptor up regulation

1. Unmasking of the receptors

( formation of receptor and degradation of receptors)

2. Increase sensitization of receptor to agonist

( development of withdrawal syndrome)

1st messenger

The chemical substances that directly cause the physiological/pharmacological

effects, after binding with the receptor are called 1 st messenger.

Exam: Drug, hormone, neurotransmitter.

Second messengers

The chemical substances that are found after binding of receptor with 1 st messenger
(drug/hormone/neurotransmitter) and later are responsible for the ultimate
physiological/pharmacological effects.

Exam: 1. cAMP (cyclic adenosine monophosphate)

2. cGMP (cyclic guanosine monophosphate)

3. IP3 (inositol triphosphate)

4. DAG (Diacyl glycerol)

5. Ca++ ion
IV
Ion channel coupled receptor
When a drug/ligand binds with
N an ion-channel receptor (like nAChR)
a
+

a conformational change occurs in the receptor

central transmembrane ion channel open

transmembrane conduction of relevant ions (like Na +/Cl-)

Alteration of the electrical

N potential across the membrane
a
+

Pharmacological effects occur

Example of ligand gated ion channel receptors
1) Nicotinic Acetylcholine receptor (nAChR)

2) Gamma amino butyric acid-type A (GABAA) receptor

3) 5 Hydroxy tryptamine, type-3 (5HT3) receptor

Mechanism of nAChR
Ach binds with its binding site on nAChR

Conformational change occur in receptor

Opening of central transmembrane Na+ ion channel

Transmembrane conduction of Na+ along conc. gradient

depolarization

action potential
Clinical importance of ion channel
Blocking of Na+ channel

 Local anaesthetic : Lidocaine block voltage gated Na+ channel

block depolarization no action potential no transmission of pain

sensation anesthetic action

 Anti-epileptic drug : Phenytoin, Carbamazepine etc

 Anti-arrhythmic drug: Quinidine

 Cont..
• Blocking K+ channel : Amiodarone, Sotalol block voltage sensitive K +
channel prolongs phase 3 repolarization of action potential
anti-arrhythmic effect

Blocking of Ca++ channel : Captopril, Verapamil, Diltiazem (anti-hypertensive and

anti-arrhythmic drug)

Opening Cl- channel: Sedative and hypnotic drugs (e.g. benzodiazepine,

Barbiturate etc)
G-protein coupled receptor
(GPCR)
G- protein coupled receptor

 G-Protein coupled receptors are called so because of their interaction with the
guanine nucleotides GTP and GDP. They use the common molecular
mechanism that involves binding and hydrolysis of GDP.

 They are sometimes called metabotropic receptors.

 Structure:

All the monomers comprising 7 membrane-spanning segments.

(Vascular, bronchial)
Mechanism of action of tyrosine kinase coupled receptor
When a drug binds with the tyrosine kinase receptor in the extracellular domain

a conformational change occurs in the receptor

two monomer of the receptor bind with each other

dimeric stage is formed

enzymatic activation of intracellular domain and the tyrosine kinase domain and
phosphorylate one each other

activated receptor then catalyzes the phosphorylation of tyrosine residue on different signaling
mechanism.
 Cont..
 Inactive stage: remains in monomeric form
 Active form: It converts into a dimeric form

Exam:
1. Insulin receptor
2. Epidermal growth factor (EDEF) receptor
3. Platelet derived growth factor (PDEF) receptor
4. Atrial natriuretic peptide (ANP) receptor
5. Transforming growth factor (TNF-ꞵ) receptor

Function: mainly involved in events controlling cell growth and differentiation.

Structure of DNA-coupled receptor
 DNA coupled receptor has 3 distinct domains
- Ligand binding domain
- Transcription activating domain
- DNA- binding domain

 Inactive forms of receptor: A heat shock protein (hsp 90) binds with the
receptor in absence of the ligand and prevent folding into the active conformation
and make the receptor inactive.
Mechanism of DNA coupled receptor
Drug or ligand enters into the cytosol and binds with receptor

A receptor-ligand activated complex is formed

that is actively transported into the nucleus

DNA binding domain of the receptors binds with the gene

transcription activating domain regulates transcription by RNA polymerase

resulting mRNA is exported to cytoplasm to synthesis protein

response
 Cont..
Example of DNA-coupled receptor
1. Receptors for steroid hormones.
e.g: - Corticosteroids
- Mineralocorticoids
- Sex steroids
- Vitamin D

2. Thyroid hormone receptor

Non-classical receptor
1) Enzyme as receptor
a) drug action by enzyme stimulation: GTN (anti-angina drug)
GTN NO stimulate guanyl cyclase

GTP cGMP

b) drug action by enzyme inhibition:

i. reversible or competitive
ii. Irreversible or Non-competitive
 Cont..

Competitive
1. Physostigmine & neostigmine act by inhibiting cholinesterase
accumulation of Ach and produce effect.
2. ACE inhibitor (angiotensin converting enzyme inhibitor Captopril)
inhibit angiotensin I convert to angiotensin II

Non-competitive
1. Organophosphorus compound irreversely inhibit cholinesterase enzyme
accumulation of ach and produce action.
3. Aspirin irreversely inhibit cyclo oxygenase enzyme and inhibit formation of
prostaglandin and TXA2 produce anti-platelet effect.
 Cont..
c) Drug action by false substrate mechanism:
[Substrate: is the metabolic product having a definite configuration on which
enzyme act. It is essential for normal activity or metabolic activities of the cell.
Drugs that act on substrate have structural activity to that substrate.]

exam: -methyl dopa. Drug is converted to other substrate that is less active
than true substrate.
-methyl Dopa
Dopa decarboxylase

-methyl dopamine (false substrate)

(Here, true substrate is dopa)
 Cont..

2.Transport protein/ carrier protein as receptor

Na+- K+ ATP-ase pump as receptor for cardiac glycosides.

 Proton-pump (H+- K+ ATP-ase) as receptor for proton pump inhibitor.

3. Voltage gated ion channel

 Voltage gated Na+ channel
 Voltage gated Ca++ channel
 Voltage gated K+ channel
 Cont..
4. Structural protein as receptor
e.g. Colchicine blocks tubulin receptor inhibit mitotic cell division of
inflammatory cell suppression of inflammation relief from gouty
arthritis.

5. Nucleic acid as receptor

e.g: Alkylating anticancer drug e.g. Cyclophosphamide, Melphalan etc.
Alkylating drugs conjugate with nucleic acid alkylation of nucleic acid
destruction of nucleic acid inhibition of uncontrolled cell division
cancer cell anticancer activity.
Non-receptor mechanism of drug action

A) by altering physiochemical property of cell:

 Drugs donot act on specific site. Receptors are not involved
 All drugs act by this mechanism are lipid soluble. e.g: general anasthetics,
hypnotics, alcohol, anticoagulant.
 Drugs may accumulate in the cell membrane or penetrate the cell membrane
and inhibit influx of ion.

e.g. Halothane (highly lipid soluble drugs) bind with the lipids of cell
membranes through hydrophobic bond disrupt neuronal cell membrane
disrupt Na+ , Ca++ channel but Cl- channel intact hyperpolarization
causes unconsciousness general anesthesia.
 Cont..
B) Direct chemical interaction
1) Chelation: Antacids chelate tetracycline
2) Neutralization:
- Antacid neutralizes gastric acid.
- Heparin is electronegative, Protamine sulphate is electropositive. So,
Protamin sulphate inhibit heparin action.
Dose-response relationship
Some basic concepts

Dose: it is amount of drug that is administered in the patient.

e.g: If a patient is taken 500 mg of paracetamol, so dose is 500 mg.

Response: effect shown by the body to a particular drug.

e.g: Paracetamol is antipyretic drug so response is it should bring body temperature

to normal.
How drug response is obtained
Drug + receptor Drug-receptor complex

Response
Dose-response relationship

 The pharmacological effect of a drug depend on the concentration at the site

of action, which in turn determined by the dose of drug administered. Such a
relationship is called dose-response relationship.

 Dose-response relationship is described by a curve, is called dose-response

curve.

 Dose: plotted in horizontal axis

 Response: plotted on vertical axis

Fig:
Types
1. Graded dose-response relationship
2. Quantal dose-response relationship

Forms of graded dose response curve

 Arithmetic form
 Log scale form
Why log dose response curve?

• We convert the X axis values (doses) from arithmetic to logarithm scale, for best
plotting of dose-response curve, so that if we plot the arithmetic values then these
values will go out of the paper and we can not be able to plot all values in small
paper. So it is important for best interpretation of results.
Advantage of log dose response curve
1. Easy to calculate the response
2. Short paper is needed
3. Large number of figure can be accumulated
4. We can perform a valid comparison as the middle portion of curve is
straight line
5. Can compare the efficacy of one drug with other.
Graded dose-response relationship

 Gradation of response in relation to gradation of dose is called dose response

relationship.

 As the concentration of a drug increases, its pharmacologic effect also

gradually increases until all the receptors are occupied (the maximum effect).

 Explanation: Upto certain limit, the response of a drug is proportionate to

the dose (e.g: dose response). So, it means an increase in the drug
response due to increase dose. (anaesthethic and sedative-hypnotic drug)
Fig:
Exam of graded dose-response relationship
 Cont..
 Shape of the curve: Elongated S or sigmoid shaped

 Information from the graded dose response curve

1. Maximal efficacy
2. Potency
3. Selectivity of a drug
4. Types of drug antagonism
5. Potential variability of responsiveness among individual
Information from graded dose response curve
Quantal dose response relationship/ percent-dose relationship/ all or
none relationship

 Certain pharmacological effects which can not be quantified but can

only be said to be present or absent (all or none).

 This relationship presents individual variation of response at a

fixed dose.

 Fixed dose is required to produce response, but below this there is

no response.

 Shape of the curve: Hyperbola

Importance of quantal dose-response relationship
 Used for acute toxicity test and for safety margin of drugs.
 Fig:
Therapeutic index (TI)

 Therapeutic index of a drug is the ratio of the dose that produces

toxicity in half of the population (TD 50) to the dose that produces a

clinically desired or effective response (ED 50) in half of the population.

TD50
TI = ED50 [Human]

Here,
TD50 = is the dose which produce toxicity in 50% population
ED50 = is the dose which produce half maximal response
 Cont..
Incase of lower animals
LD
TI = 50

ED50

LD50 = is the dose which causes death in the 50% experimental animal

If TD50 more and ED50 relatively low TI is high

If TD50 low and ED50 relatively high TI is low
Information we get from TI
1. The more the TI, the more the safe drug
2. For safer therapeutic application of a drug, its TI must be > 1.
3. TI = 1 for poison
4. A drug may have different TI depending upon its clinical use; e.g:
Aspirin
In headache: TI is high
In rheumatoid arthritis: TI is low
5. For application of new drug, TI has greater significance.
6. If TI of a drug is low, it should be used with care.
 Cont..
High therapeutic index
1. Antibiotics: Penicillins, Sulfonamide
2. Diuretics: Thiazide diuretics
3. NSAIDs: Paracetamol
4. Proton pump inhibitor: Omeprazole, pantoprazole, Oesmoprazole

Low therapeutic index

1. CVS drug: Warferin, Digoxin 5. Anti-cancer drugs
2. Anti-convulsant: Phenytoin, Valproate 6. Carbamazepine
3. Antibiotics: Gentamicin (aminoglycosides) 7. Theophyline
4. Lithium
Therapeutic window

Def: Therapeutic window is the well defined range of drug’s serum

concentration at which a desired effect occurs, below which there is little

effect, above which toxicity occurs.

 More specifically, it is the range between the ED 50 and the starting

point of TD50 curve.

 Cont..

Exam: Medication with a small pharmaceutical window such as Carbamazepine

must be administered with care and control. By frequently measuring blood
concentration of the drug, since it gives easily adverse effects like agranulocytosis.

Clinical importance:

1. It can help to avoid most of the potential side effects

2. Therapeutic window is believed to be more reliable than the TI.

Drug interaction
Drug interaction

 When two or more drugs are given simultaneously, the effect of

one drug may be altered by another drug.

Drug interaction can be occur in vitro or in vivo.

 result in either beneficial or harmful effect.

Site of drug interaction
1) Outside the body
2) During absorption
3) During distribution
4) At the receptor level
5) During biotransformation
6) During excretion
Pharmacokinetic interaction
 These occur when one drug alters the absorption, distribution,
metabolism or excretion of another drug.

During absorption:

 Antacids containing Al, Mg or Ca form causes chelation with

tetracycline and form unabsorbable complexes. Thereby reduces the
bioavailability of tetracycline.

 Some drug affect absorption of other drugs by altering

gastrointestinal motility.
 Cont..
During distribution
 A drug which is extensively bound to plasma protein can be displaced
from its binding site by another drug which has greater affinity for the
same binding site. So, rising free concentration of displaced drug.

e.g: Drug like Aspirin competes with warfarin for the same protein
binding site. Aspirin displaces warfarin from binding site resulting in
increasing adverse effects of Warferin ( bleeding tendency)
 Cont..
During metabolism

 Enzyme induction: by drugs which accelerates biotransformation of

drugs and is a cause of therapeutic failure.

Contraceptives + Refampicin Failure of contraception

 Enzyme inhibition: by drugs that inhibits biotransformation of drugs

and cause acceleration of therapeutic action.

Warferin + Metronidazole Haemorrhage

 Cont..

During excretion

 Probenecid competes with penicillins for active transport at the

kidney and prolongs the action of penicillins, which is beneficial.

e.g: Penicillin + Probenecid excretion of penicillin

blood concentration of penicillin and its action is increased .
Pharmacodynamics interaction

The interaction is due to action of drugs on receptor or physiological

system. This may result either additive, synergistic or antagonistic
effect.

 The interaction may result harmful effect.

 Synergism: When the therapeutic or toxic effects of two drugs are

greater than the effect of individual drug, called synergism.
Two types: 1. Addition
2. Potentiation
 Cont..

Summation/Addition:

The combined effect of two or more drugs is equal to the sum of their
individual effect.

Effect of drug A+B = effect of drug A + effect of drug B

e.g: the combination of thiazide diuretic and a beta adrenergic blocking

drug is used for treatment of hypertention.
 Cont..
 Potentiation

When the net effect of two drugs used together is greater than the
sum of the individual drug effects, the drugs are said to have potentiation
effect.

Effect of drug A+B  Effects of drug A + Effects of drug B

e.g: Levodopa + Carbidopa

Acetylcholine + Physostigmine
Drug antagonism

 The effects of one drug can be reduced or abolished by the presence of

another drug and this effect is termed drug antagonism.

 Drug antagonism is of three types: 1. Chemical
2. Physiological
3. Pharmacological

 Physiological and pharmacological antagonism involve an interaction

of an agonist and antagonist.
Chemical antagonism
 When a drug antagonizes the effect of another drug by simple
chemical reaction without action on the receptor.

For example, antacid neutralizes gastric acid.

Physiological antagonism

When the physiological effect of one drug is antagonized by another

drug by acting on two different types of receptor.
 Opposite effect of two drugs on same function.
 Two drugs act on two different types of receptor and antagonize
action of each other.

e.g: Acetylcholine causes contraction of intestinal smooth muscle by

acting on muscarinic cholinoceptors. That action is antagonized by
adrenaline (act on adrenoceptors) which causes relaxation of intestinal
smooth muscle.
Pharmacological antagonism
• 2 types

• Pharmacological antagonism

Competitive/ Non-competitive/
Reversible / Irreversible/ Non-
Surmountable surmountable
antagonism antagonism
Characteristics of competitive antagonism / Reversible antagonism
1. Both the agonist and antagonist compete for the same receptor to displace each
other from the receptor site.

2. An antagonist bind with the receptor thereby preventing the agonist from
binding and initiating a response.

3. It is reversible. It is totally dependent on the concentration of agonist and

antagonist.

4. The dose-response curve remains parallel but shifted to the right with
maintaining its maximum efficacy.
Clinical use of competitive reversible antagonism

1. Atropine in OPC poisoning

2. Nalorphine in morphine poisoning

Non-competitive/ Irreversible antagonism
1. In this type, agonist and antagonist bind with different binding
sites of the same receptor.
2. Since binding sites are different, there is no competition for
binding with receptor
3. Antagonist bind with receptor and changes the structure of
receptor
4. As a result, agonist can not bind with receptor
5. The dose-response curve does not maintain parallel pathway .
Fig: different binding sites of the same receptor.
Example

The bond between the drug and receptor is permanent

covalent bond. So, increase concentration of non-bound drug
can not displace the bound drug.

 Phenoxybenzamine binds covalently with  receptor and

antagonize irreversely so that high concentration of
catecholamine does not displace phenoxybenzamine.
Difference
Competitive between
antagonismcompetitive and non-competitive antagonism
Non-competitive antagonism
1. Both the agonist and antagonist compete for 1. No competition of drug to reach the site of
the same site of receptor to displace each receptor
other from the receptor site.
2. The same maximum response can be 2. Maximum response cannot be
obtained by increasing conc. of agonist. It is obtained. It is non-surmountable.
surmountable.
3. The dose-response curve remains parallel 3. The dose-response curve does not
but shifted to the right with maintaining its maintain parallel pathway.
maximum efficacy.

4. Exam: Atropine in OPC poisoning 4. Exam: Phenoxybenzamine binds with 

receptor
Nalorphine in morphine poisoning
5. Intensity of response depends on conc. of 5. Response only depends on conc of
agonist and antagonist. antagonist.
Prolongation of drug action
Prolongation of drug action by
1. By prolonging absorption from site of administration
a) in oral route:
- Sustained release tablets
- Controlled release tablet/ capsules
- Coating of drug particles with resins, plastic materials
b) Parenteral route:
 IM injection along with vasoconstrictor substance. e.g: Adrenaline with local
anaesthetics
 The SC and IM injection of drug in insoluble form prolong the drug action. e.g:
Benzathene penicillin.
 Cont..
c) Transdermal drug delivery system:
- The impregnated in adhesive patches applied on skin is becoming
popular.
e.g: GTN.

2. By increasing plasma protein binding:

- Drug congeners those are highly bound to plasma protein and slowly
released in the free active form. e.g: Sulfadoxine.
 Cont..
3. By producing rate of metabolism:

 small chemical modification: addition of an ethinyl group to estradiol. e.g: OCP

 Inhibition of specific enzyme: Allopurinol inhibits the degradation of 6-

Mercaptopurine.

4. By reducing renal excretion:

Probenecid binds with the same acidic transport protein for excretion with that
of penicillin Probenecid excretion Penicillin excretion
 Cont..

5. others:
 By increasing the dose of the drug

Advantage of prolongation of drug action

1. Frequency of administration can be reduced.

2. It is more convenient for the patient cost effective.

3. Improved patient compliance.

4. Drug effect could be maintained overnight without disturbing sleep.

Questions
1. Define of pharmacodynamics.
2. What is receptor? Functions of receptor.
3. Classify receptor.
4. Consequence of drug-receptor interaction.
5. Definition with example: Affinity, efficacy, potency, agonist, antagonist,
partial agonist, inverse agonist.
6. What is receptor down and up regulation?
7. What is 1st and 2nd messenger?
8. Difference between 4 types of receptor families.
9. What is receptor? Drugs that act by binding with a receptor may be agonist,
antagonist, partial agonist or reverse agonist. Differentiate between them
and give examples.
Questions
10. What is receptor-effector linkage? Classify receptor according to
types of receptor-effector linkage.
11. What are G- protein coupled receptors? How do they operate? What
are the second messengers are what are their role?
12. Give examples of non-protein drug action i.e drugs donot bind to
receptor.
13. Describe about non-classical receptor.
14. Describe an intracellular receptor (for example: a steroid receptor)
15. What type of receptor-effector linkage occurs with insulin receptor.
16. What is dose response relationship? What are types?
17. What is graded dose response relationship? What information is
Questions
18. What is the important of quantal dose response relationship? What
information we get from it?
19. What is therapeutic index? Give example and importance of it.
20. What is therapeutic window? Importance of it.
21. What happens when two drugs we given together. Given example in
each case.
22. Define and classify drug antagonism. Differentiate between competitive
and non-competitive antagonism. Give example in each case.
23. Short note: Physiological and Pharmacological antagonism.
24. What are the methods of prolongation of drug action and importance of
it?
Previous 5 years question
1. Define receptor and classify them according to receptor effector linkage.
Briefly describe the receptor mediated drug action. (May- 2022, May- 18)
2. Define second messenger. Illustrate the role of G-protein on second
messenger system. (May – 2020)
3. Mention the molecular targets for drug action. Discuss briefly the receptor
mediated drug action with example. (Nov- 2020)
4. Mention the molecular target of drug action. Explain drug-enzyme
interaction. (May-2019)
5. Name the target protein to which drug bind for producing action, give
example (Nov- 17)
6. Define agonist, antagonist, partial agonist with example. Write down
difference between up regulation and down regulation of receptor. (Nov 18)
 Cont….
7. Define agonist and antagonist with example. Explain with example of ion
channel mechanism of drug action. (Jan- 17)
8. Compare between potency and efficacy of drugs. (May – 17)
9. Short note: Agonist (July 17)
10. Explain the transporter (carrier) mechanism of drug action. (Nov- 17)
11. Short note: Physiological and pharmacological antagonism (May- 2019,
May 2020)
THANK YOU