The document discusses the mechanisms of drug action, summarizing that most drugs produce their effects by interacting with specific protein targets in the body. It identifies the main categories of protein targets as enzymes, ion channels, transporters, and receptors. For each category, examples are given of drugs that act through these mechanisms, such as enzymes being stimulated or inhibited, drugs blocking ion channels, inhibiting transporters, and acting through receptor occupation and receptor subtypes.

1. MS. SHIVANGI MISTRY
M.PHARM (PHARMACOLOGY)
ASSISTANT PROFESSOR
BHAGWAN MAHAVIR COLLEGE OF PHARMACY

2. MECHANISM OF DRUG ACTION
• Drug action : Drug action is the initial interaction of a drug with cells at the
site of action & the resultant physiological & biochemical consequences
are the drug effect.
• Majority of drugs produce their effect by interacting with a discrete target
biochemolecule, which usually is protein .
• Protein that are targets of drug action can be grouped into four major
categories :
1. Enzyme
2. Ion channel
3. Transporters
4. Receptor

3. 1. ENZYME

4. • Drugs can either increase or decrease the rate of enzymatically
mediated reactions.
• Enzyme stimulation : it is increase affinity for the substrate .
• enzyme stimulation is relevant to some natural metabolites only ,
e.g. pyridoxine acts as a co- factor & increase decarboxylase activity.
• Several enzyme are stimulated through receptor & second
messenger, e.g. adrenaline stimulates hepatic glycogen
phosphorylase through beta- receptor & second messenger.
• Enzyme inhibition :
• (A) Non-specific inhibition : They alter the tertiary structure of any
enzyme with which they come in contact & thus inhibit it.
• E.g. Heavy metal salts, strong acid & alkalies, alcohol, formaldehyde,
phenol.

5. • (B) specific inhibition : (a) competitive inhibition :
• Equilibrium type : The drug being structurally similar with the normal
substrate for catalytic binding site of enzyme so that the product is not formed
or non-functional product is formed.
• E.g . - physostigmine & neostigmine compete with Ach for cholinesteras.
- sulfonamide compete with PABA for bacterial folate synthetase.
• Non-equilibrium type : it’s type of enzyme inhibition can also occur with drug
which react with same catalytic site of enzyme but either form strong covalent
bonds or have such high affinity for enzyme that normal substrate is not able
to displace the inhibition.
• E.g. - Organophosphate react covalently with esteretic site of the enzyme
cholinesteras.
- Methotrexate has 50,000 time higher affinity for dihydrofolate
reductase than normal substrate DHFA.

6. • (b) Non-competitive : The inhibitor reacts with adjacent & not with
catalytic site, but alter enzyme in such a way that it loses it’s catalytic
property.
• E.g - Omeprazole :- H+ k+ ATPase.
- Digoxin :- Na+ K+ ATPase.
• 2. ION CHANNEL :
• Protein which acts as ion selective channels participate in
transmembrane signaling & regulate intracellular ionic composition.
• Drugs can affect ion channel either through specific receptor ( ligand gated ion channels, G-
protein operated ion channels) or by directly binding channels & affecting ion movement.
• E.g. - quinine block myocardial Na+ channel.
- dofetilide & amiodarone bolck myocardial delayed rectifier K+ channels.

9. 3. TRANSPORTERS :
• Several substrate are translocated across membrane by binding
to specific transporters.
• Many drugs produce their action by directly interacting with
carrier of transpoter protein to inhibit going physiological
transport of metabolites.
• E.g. - amphetamine selectively block dopamine reuptake in
Brian neurons by vesicular amine transporter.
- reserpine block granular reuptake of noradrenaline &
5-HT by vesicular amine transporter.

10. 4. RECEPTOR

13. • (A) Receptor occupation theory : Clark (1937) propounded theory of
drug action based on occupation of receptor by specific drugs & that
pace of cellular function can be altered by interaction of receptor with
drug.
• Agonist :- it’s have both affinity & max. intrinsic activity.
- E.g. adrenaline, histamine, morphine.
• Competitive antagonist :- it’s have affinity but no intrinsic activity.
- E.g. propranolol, atropine.
• Partial agonist :- it’s have affinity & submax. Intrinsic activity.
- E.g. pentazocine.
• Inverse agonist :- it’s have affinity but negative intrinsic activity.
- E.g. benzodiazepine receptor.

14. (B) The two-state receptor model :-
• The receptor is believed to exit in two interchangeable state :
Ra(active) & Ri(inactive) which are in equilibrium.

16. (C) NATURE OF RECEPTOR :

17. (D) RECEPTOR SUBTYPE :

18. RELATIONSHIP BETWEEN DRUG CONC. & EFFECT :