mechanism of drug action

1. Mechanism of drug action
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2. Introduction
• A drug may produce its effects by a number of mechanisms
like combination with enzymes , cell membrane or other
components of a cell.
• The action either be physical or chemical and are classified at
four levels :
Molecular– Receptor, ion channel, enzyme, carrier molecules
Cellular– Transduction e.g., G protein, ion channel, enzyme
Tissue– Contraction, secretion, metabolic activity,
proliferation
System– CNS, CVS , etc.
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3. Types of effects
Local Effect
• When the drug effect occurs in immediate vicinity of
application, this is known as local effect.
Systemic Effect
• When the drug effect occurs away from the site of
administration, this is known as systemic effect.
Primary effect:
• Primary effect is the effect for which the drug is administered
or the treatment of the disease for which the drug is given.
Side effect:
• All other effects occurring in addition are known as secondary
effects. When the secondary effects are undesirable by the
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4. Mechanisms:
• Most drugs act by altering the various body control systems,
which may be receptors, enzymes or ion channels.
• These various mechanisms include:
1. Physical mechanisms
2. Chemical mechanisms
3. Drug- receptor interactions
4. Drug- enzyme interactions
5. Drug- channel interactions
6. Miscellaneous mechanisms
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5. Mechanism of Drug Action -
Physical Mechanisms
• When the drug does not produce any chemical
reaction or change in the cells of the body and the effect
is only physical, the mechanisms involved are called
physical mechanisms.
• These includes:
 Local Application– Emollients, Counter irritants, Massagers,
pastes
 Physically acting antacids– Milk, Mucin
 Bulk forming purgatives– Bran, Ispaghula, Magnessium
sulphate
 Mannitol
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6.  Liquid paraffin
 Activated charcoal
 General Anesthetics
 Rubfacients
 Astringents
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7. Mechanism of Drug Action -
Chemical Mechanisms
• In chemical mechanisms, drugs act by producing chemical
reactions in the body.
• These include:
 Chemically acting antacids– NaHCO3
 Chelating agents– Dimercaprol, penicillamine,
desferrioxamine
 Pralidoxime
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8. Mechanism of Drug Action -Drug
Receptor Interaction
• Receptor:
Macromolecules protein in nature which are target sites
for drugs.
Most drugs have to bind receptors to produce effects.
Receptors are located mostly on the cell membrane but
certain intracellular receptors are found as well.
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11. • The binding of drug with receptor may by of two types:
 Reversible binding
 Irreversible binding
• In reversible binding, the bond between the drug and
receptor is very weak ionic, hydrogen or van der wall. This the
effect is short lived.
• In irreversible binding, very strong covalent bonds are
present, which prolongs the effects of drug. The effect
continues until the drug is excreted or new receptor is
generated.
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12. There are three forms of binding to receptors:
• Agonists
• Antagonists
• Partial agonists
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14. Ligands
• Ligands are the endogenous substances, molecules or
compounds which bind with receptors present in the
body.
• e.g. acetyl choline, adrenaline, noradrenalin,
neurotransmitters like glutamate, aspartate and GABA.
• They produce various effects and interfere with the flow
of ions through channels called ligand gated channels.
• Their action may:
 Resemble with natural ligand
 Block the natural ligand
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15. Agonists
• They are the drugs which when bind receptors, cause
activation of receptors.
• They have the capacity to produce chain reactions in the
receptors which ultimately bring about the effects.
• Agonists have two properties:
 Affinity for receptor
 Capability to produce chain reactions in the cells having
capability of intrinsic activity or efficacy
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16. Types of Receptors:
• Ligand gated ion channels
• G-protein coupled receptors
• Kinase linked receptors
• Nuclear receptors
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18. • When drug binds the receptor, activation occurs, and the
response gradually increases until it reaches the peak, then
the response decreases, although agonist still binds.
• This is due to desensitization of receptors, which might be
overcome by removing the agonists from the receptor.
• Example includes suxamethonium (succinyl choline), which
produces relaxation of skeletal muscles
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19. • Prolong contact of tissues with the agonists results in
decreased number of receptors in the tissues called down
regulation of receptors.
• Example includes the patients suffering from bronchial
asthma, in whom by prolong usage of beta agonists down
regulation occurs.
• This the effect is reduced.
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21. Antagonists:
• A substance which interferes with or inhibits the
physiological action of another.
• They have two properties:
 Affinity
 Do not have efficacy or intrinsic activity
• Examples include atropine, which is antagonist of acetyl
choline. Propanolol is antagonist of beta receptors.
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22. • The binding of antagonist with receptor is of two types:
 Reversible binding
 Irreversible binding
• Reversible binding is also known as competitive
antagonism. E.g. atropine.
• Irreversible antagonism occurs when binding effect of
antagonist is prolonged until drug is excreted or new
receptor is generated.
• Example includes phenoxy benzamine, which non-
competitively blocks action of catecholamines at beta
receptors.
• Second generation H1 histamines are also non-
competitive blockers.
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23. Partial antagonists
• They have intermediate levels of efficacy.
• They bind with the receptors but have very small
intrinsic activity and efficacy.
• Examples include beta blockers like pindolol and
oxpranolol.
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24. • Drugs having agonist effect at receptors have positive efficacy.
• Drugs having inverse agonist effect at receptors have negative
efficacy.
• Drugs having antagonist effect at receptors have zero efficacy.
Efficacy
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25. Mechanism of Drug Action -Drug
Enzyme Interactions
• Drug enzyme interaction is similar to drug receptor
interactions.
• The drugs resemble the natural substrates, bind enzymes and
cause change in their activity.
• This may take place by:
 Activation of enzymes
 Inhibition of enzymes
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26. • This combination of drugs with the enzyme may be:
 Competitive
 Non competitive
• Non competitive response is irreversible until new enzyme is
generated
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27. Examples of Competitive Inhibition
• ACE inhibitors e.g., captopril
• Carbidopa——-Levodopa
• Ethanol———-Methanol
• Reversible anticholinestrases e.g., Neostigmine,
physostigmine
• Disulfiram——Alcohol
• Allopurinol
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28. Non Competitive Inhibition
• The effects of non competitive inhibition are prolonged. These
include:
• Irreversible anticholinestrases e.g., Organophosphate
compounds
• Aspirin
• MAO Inhibitors e.g., Iproniazid, Phenelzine
• Proton Pump Inhibitors e.g., Omeprazole, Esomeprazole
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29. Mechanism of Drug Action -Drug
Channel Interactions
• In drug channel interaction, drug interfere with the flow
of ions through the channels specific for these ions.
• These include the Na+, K+,Ca++ and Cl- channels.
Examples include:
 Sodium Channels:- Quindine Procainamide, Local
anesthetics
 Calcium channels:- Nifedipine, Verapamil, Diltiazem
 Potassium Channels:- Amiodarone, sulfonylureas
 Chloride Channels:- Benzodiazepines
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30. Mechanism of Drug Action -
Miscellaneous Mechanisms
• Certain drugs do not act through any of the mechanisms
already mentioned, they are categorized as miscellaneous.
• These include:
 Colchicines, vinca alkaloids
 Ionizing radiation
 Levamisole
 Immunosuppressive:- Cyclosporine
 Therapeutic antibodies
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