Mechanism of Drug Action
The basic mechanism of drug action can be classified into four categories –
- Physical Action
- Chemical Action
- Through Receptors
- Through Enzymes
The physical properties of the drug is responsible for its action; e.g.
Mass of the Drug: Bulk laxatives (isabgool, agar) produces laxative effect because of swelling in presence of water.
Osmotic Activity: Mannitol and magnesium sulphate produces purgative effect due to their osmotic activity.
Adsorptive Property: Kaolin, charcoal is used to adsorb gastric poison.
Demulcent Effect: Liquid paraffin produces a smooth coating over the lumen of the intestine. This is responsible for its purgative effect.
Radio-Activity: Radio-active isotopes used for the treatment of cancer produce their effect by emitting ionising radiations.
Radio-Opacity: Barium sulphate and urografin are used for diagnosis as radio-opaque contrast media.
Electrical Charge: Heparin, an anticoagulant drug produces its effect due its negative charge.
The chemical properties and reactions are responsible for their action.
Acidity and Alkalinity: Dilute HCL is effective in the treatment of hypochlorhydria. Sodium bicarbonate acts as an antacid by neutralising HCL in stomach.
Chelation: Chelating agents like dimercaprol(B.A.L.) combine with metals like arsenic and form water soluble complexes. This helps in the easy elimination of metal through urine.
Oxidization: Oxidizing agents like potassium permanganate, iodine are germicidal and inactivate ingested alkaloids.
Receptor is a specific binding site of drug, which is situated on the surface or inside the effector cell. A large number of drugs act through these receptors. The action of drug is produce by activating or inhibiting the receptor activity.
Agonist: It activates pharmacological action after combining with the receptor. E.g. adrenaline,histamine.
Antagonist: It inhibitthe action of an agonist on a receptor but does not have any effects of its own. E.g. atropine,naloxone, propranolol.
Receptor Occupation Theory
The interactions between the two molecular (drug & receptor) species are to be direct by the law of mass action. The effect to be a direct function of the drug- receptor complex formed.
Where, D is the drug, R is the receptor, E is the effect, DR is the drug-receptor complex. According to above theory :
i) The intensity of response is proportional to the fraction of receptors occupied by a drug, and maximal response occurs when all receptor are occupied.
ii) Drugs have an all or none response on each receptor, i.e. either a receptor is fully activated or not at all, there is no partial activation.
iii) A drug and its receptor have matching structural relationship and stand in rigid ‘lock and key relationship.
The above concepts are partially correct, so, Ariens and Stephenson modified that. All receptors need not to be occupied for a maximal response. There was a number of spare receptors are present. Different drugs had different capacities to induce response. They also mentioned that it should be possible to partially activate a receptor and ‘all or none ’response is not essential.
(S = Strength of stimulus imparted to the cell by activation of the receptor.)
Depending on the agonist, DR could generate a stronger or weaker S.
Functions of Receptors:
i ) To transmit regulatory signals from outside to within the effector cell.
ii) They intensify the signals.
iii) To incorporate various regulatory signals.
Maximum biological reactions are occurred under catalytic influence of enzymes. So, they are very important target for drug action. Drugs can either increase or decrease the rate of enzymatically mediated reactions.
Stimulation: Stimulation of an enzyme increases its affinity for the substrate so that rate constant of the reaction decreases. E.g. adrenaline stimulates adenylyl cyclise.
Inhibition: Inhibition of enzymes is a widespread mode of drug action. There are two types of inhibition one is nonspecific and another is specific. Heavy metal salts, alcohol, strong acid, strong alkali, phenol inhibit enzymes non-specifically. Many drugs inhibit a specific enzyme by competitive or non-competitive manner. E.g. sulphonamides compete with PABA for bacterial folate-synthetase (competitive inhibition), disulfirum inhibit the enzyme aldehyde dehydrogenase( noncompetitive inhibition).
Antagonism: When one drug decreases or inhibits the action of another, they are said to be antagonistic. E.g. charcoal used in alkaloidal poisoning and chelating agents (EDTA) complex with metals.
Synergism: When the action of one drug is increased by other, they are said to be synergistic. In a synergistic pair both the drugs can have action in the same direction or given alone one may be inactive but still enhance the action of other when given together.
Synergisms are two types—
Additive: The effect of two drugs are in the same direction and simply add up
e.g. aspirin + paracetamol——————analgesic/antipyretic.
Ephedrine + Theophylline —————– bronchodilator.
Potentiation: The effect of combination is greater than the individual effect of components. Effect of drug (A+B) Effect of A + Effect of B.
e.g. Acetylcholine + Physostigmine——— inhibition of breakdown.
Levodopa + Carbidopa ——————– -inhibition of peripheral metabolism.
Captopril + diuretics ———————- antihypertensive.