The document discusses the principles of drug action and mechanisms of drug-receptor interactions. It explains that drugs can stimulate, depress, irritate or replace cellular functions. It also describes the different types of drug-receptor binding including agonists that activate receptors, antagonists that block receptor activation, and partial agonists that weakly activate receptors. The document outlines the concepts of affinity, intrinsic activity, competitive and non-competitive antagonism, and how these principles underlie drug action at the molecular level through interactions with cellular receptors.

1. PHARMACODYNAMICSPHARMACODYNAMICS
Principles of Drug ActionPrinciples of Drug Action

For a drug to act, there are following principles
1) Stimulation- Increase in rate of functional activity
or increase secretion from the gland.
E.g. Adrenaline stimulates heart,
pilocarpine stimulates salivary glands,
Caffeine stimulates CNS.
2) Depression- It is reduction in such functional activity
e.g. Barbiturates, alcohol depress CNS

2. 3) Irritation- The drug act by irritating cells.
e.g. Liniments to relieve pain.
Mild irritation may stimulate associated function
viz: (Bitters saliva secretion) but
strong irritation results in inflammation, necrosis and
morphological damage resulting in loss of function.
viz: (acids)
4) Replacement- This is use of natural metabolites,
hormones in deficiency states
viz:. levodopa in parkinsonism, insulin in diabetes.
5) Cytotoxic Action- Selective cytotoxic action is
utilized for cure of infection and neoplasms
viz: penicillin, chloroquine etc.

3. Mechanism of Drug ActionMechanism of Drug Action
1) Physical Action-
A Physical property of drug is responsible for its action
e.g.
I. Mass- Agar and bran seeds absorb water when administered
orally and swell in size acting as laxatives
II. Smell- volatile oils like peppermint oil mask taste of bitter
III. Taste- bitters increase flow of HCL in stomach & improve
appetite e.g. quassia, gentian
IV. Osmolarity-Diuretics like mannitol, purgatives like Mg.
sulphate

4. V Adsorption- kaolin & activated charcoal adsorbs gasses
and poison in GIT .
Vi Soothing-demulcent- Syrups are used as pharyngeal
demulcents in treatment of cough.
Vii Electrical charge- Heparin is negatively charged
acidic compound used as anticoagulants

5. 2) Chemical Action- A drug reacts extracellularly according to
simple chemical reaction
Acidity or alkalinity- .
 Antacids neutralize gastric HCL,
 Acidifying and alkalinizing agents react buffers in plasma and
alter pH of urine.
3) Drug acting on Enzymes
Almost all biological reactions are carried out under catalytic
influence of enzymes.
Enzyme stimulations- It is relevant to many endogenous
mediators and modulators e.g. Adrenaline stimulates adenylyl
cyclase.
Enzyme inhibition-
A) Non specific inhibition- Many chemicals and drugs are
capable of denaturing proteins, they alter tertiary structure of
any enzyme and inhibit it.
E.g. Heavy metals salts, strong acids and alkalies

6. B) Specific inhibition- Many drugs inhibit a particular enzyme without
affecting others. Such inhibition is either competitive or non competitive
1) Competitive-
A) Reversible:
The drug competes with the normal substrate or coenzyme
so that new equilibrium is achieved in presence of drug.
• Enzyme activity is regained
VIZ: Neostigmine inhibits anticholinesterase
viz:. Sulfonamides compete with PABA for bacterial folate synthetase.
B) Irreversible:
The drug forms a covalent bond with enzyme so normal
substrate is unable to bind to it.
• Enzyme activity is lost bcz covalent bond is strong.
viz: Organophosphates inhibits anticholinesterase

8. VIZ. Aspirin- cyclooxygenase,
2) Non competitive- The inhibitor reacts with an adjacent site and not with
the catalytic site but alters the enzyme in such a way that It loses its
catalytic property.

9. 4. Drug action through Receptor4. Drug action through Receptor
RECEPTOR
•Receptors are the macromolecular component of the cell to which a drug bind to
produce its effect.
•“ molecular reaction partners” (Receptor --- “specific binding site with functional
correlate” )
• Receptors are situated on the surface or inside the effectors cell.
Functions of the receptors :
•Propagation of signal from outside to inside the cell.
•Amplify the signal.

11. The categories of drugs act at any receptor
A) Agonist
B) Antagonist
C) Partial agonist
D) Inverse agonist

12. A) Agonist It activates a receptor to produce an effect similar to that of the
physiological signal.
• It has both affinity and intrinsic activity.
 Eg : Adrenaline (epinephrine) - β- receptors - Bronchodilation
B) Antagonist(Receptor Blocker) It prevents the action of an agonist on a receptor
 It has affinity but no intrinsic activity
 Eg : propranolol - β- receptors - Bronchoconstriction
C) Partial agonist It activates a receptor to produce submaximal (weak) effect.
 Morphine- opioid receptors - Maximum analgesia
Nalorphine(PA)- opioid receptors - Less analgesia
D) Inverse agonist It activates a receptor to produce an effect in the opposite direction to
that of the well recognized agonist.
Viz: BZDs - GABA receptors – anti-anxiety
DMCM - GABA receptors - anxiety
Affinity: It is the ability of the drug to bind to the receptors
Intrinsic activity: It is the ability of a drug to activate the receptor and produce the
response.
Ligand (Latin-Ligare- to bind)
•Selectively attaches to specific sites/receptors

13. Partial agonist
Partial agonist act as
competitive antagonist
in presence of an
agonist
Morphine – full Agonist
Nalorphine – Partial
Agonist

14. Inverse agonistInverse agonist

15. Binding of drugs to receptorBinding of drugs to receptor
suggests..suggests..
1)1) The reaction obeys law of mass actionThe reaction obeys law of mass action
D + R DR EffectsD + R DR Effects
2) At equilibrium, receptor occupancy is related with drug2) At equilibrium, receptor occupancy is related with drug
concentration.concentration.
3)3) If two drugs compete for same receptor, each has effectIf two drugs compete for same receptor, each has effect
of reducing other’s.of reducing other’s.
4)4) Spare receptor (Full agonist not needed to bind allSpare receptor (Full agonist not needed to bind all
receptors)receptors)
5)5) Drug action through receptor introduced the concept ofDrug action through receptor introduced the concept of
a) Affinitya) Affinity
b) Efficacy (intrinsic activity)b) Efficacy (intrinsic activity)

16. Agonists have both affinity and maximal intrinsic
activity (IA=1) e.g. Adrenaline, histamine.
Competitive antagonists have affinity but no intrinsic
activity (IA=0)
e.g. propranolol, atropine.
Partial agonist have affinity and submaximal intrinsic
activity (IA=0.5)
e.g. Nalorphine.
Inverse agonists have affinity but intrinsic activity
with a minus sign (IA = 0 to -1)

17. AntagonismAntagonism
Types of antagonism
Physical antagonism
e.g. Charcoal
adsorbs
alkaloids
Chemical
antagonism
e.g. Kmno4 oxidizes
Alkaloids, use for
gastric
lavage
Physiological/
Functional
antagonism
e.g. Glucagon &
insulin
Receptor
antagonism
Competitive
Antagonism
e.g. ach &atropine
Non-competitive
Antagonism
e.g. diazepam-
bicuculline

18. Competitive AntagonismCompetitive Antagonism
• Two drugs (agonist and antagonist )
compete with each other for binding
same receptor, a receptor can bind
only one drug molecules at a time.
• So at a given agonist concentration,
agonist’s occupancy will be reduced
in presence of antagonist.
• However, because two are in same
concentration and competition it is
necessary to raise agonist’s
concentration in order to restore
agonist occupancy and elicit
response.
• E.g. Acetylcholine antagonizes action
of Atropine at Muscarinic receptor

19. COMPETITIVE
1. Antagonist binds with the same
receptor as the agonist
2. Antagonist resembles chemically
with the agonist
3. The same maximal response
can be attained by increasing
dose of agonist
4. The antagonist apparently
reduces affinity of the agonist or
appears to have inactivated a
certain no. of agonist molecules
NON COMPETITIVE
1. Antagonist binds to another site
of receptor
2. Does not resemble
3. Maximal response is suppressed
4. The antagonist apparently
reduces efficacy of the agonist
or appears to have inactivated a
certain no. of receptor
5.
6.
Intensity of response depends
on concentration of both agonist
and antagonist
Example-Ach-Atropine
Morphine-Naloxone
5.
6.
Intensity of response depends
only on the concentration of
antagonist
Example Diazepam-Bicuculline

20. Importance of antagonistImportance of antagonist
1. Correcting adverse effects-
e.g. ephedrine and phenobarbitone
2. Treating drug poison-
e.g. morphine with naloxone