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Principal and mechanism of drug action

Principles and Mechanisms of Drug Action

Principles

Drugs do not create any new functions to any physiological system but can only increase, decrease or replace existing functions by following one of the following principles:
• Stimulation
There is increase in level of physiological activity of specialised cells or physiological system; e.g. Pilocarpine may stimulate salivary secretion and induce contraction of pupil; adrenaline may stimulate heart and induce glycogenolysis.
• Depression
There is a decrease in the level of activity of specialised cells or physiological systems; e.g. general anaesthetics depress CNS; quinidine depresses the heart.

• Replacement
There is replacement of deficient substances, either endogenous (insulin in diabetes mellitus, thyroxine in myxoedema) or exogenous (vitamin B12 in pernicious anaemia, iron in microcytic anaemias, vitamin C in beriberi.)
• Chemotherapy
It involves selective targeting of invading microorganisms with minimal effect on the host cells; e.g. use of Rifampicin/Isoniazid in tuberculosis, use of quinine in malaria.

Mechanism of Drug Action

Following mechanisms operate in the manifestations of drug action:
• Physical action
Some drugs act on the basis of a given physical property, e.g. adsorbent action by charcoal, kaolin; osmotic activity by osmotic purgatives and diuretics; bulk mass given by bulk laxatives like psyllium husk; radioopacity given by diagnostic contrast media.
• Chemical action
Some drugs act by participating in a specific chemical reaction, e.g. gastric antacids neutralise gastric activity: aluminium hydroxide/magnesium hydroxide; chelating agents form complexes with metals: penicillamine with copper; dimercaprol with mercury; desferrioxamine with iron; acidifying agents like ammonium chloride; alkalinising agents like sodium bicarbonate and antioxidants like vitamin C, sylimarin, curcumin.
• Action through enzymes
Enzymes can be important targets of drug action since many body functions are mediated through activity of certain enzymes. Enzyme induction and inhibition has been discussed under section 1.2.6 and 1.2.7 respectively. Enzyme stimulation also is a mechanism of drug action; e.g. adrenaline stimulates adrenaline cyclase while pyridoxine stimulates dopa decarboxylase.
• Action through ion channels
A number of drugs influence transmembrane ion channels like sodium, potassium, calcium and chloride. They may open up or close such channels. The net effect depends on how specific channels are affected. Sodium or calcium channel blockers alter generation of action potentials. Potassium channel blockers or openers alter membrane repolarisation. Chloride channel openers induce hyperpolarisation. Irreversible blocker of sodium channel like tetrodotoxin is one of the most dangerous poison.
• Action through receptors
Receptors for various neurotransmitters like acetyl choline, nor-adrenaline, adrenaline, serotonin (5-HT), dopamine etc. are discussed separately.
• Action by replacement
Drugs can be used to replace deficient endogenous or exogenous factors e.g. treatment of anaemia. Replacement of deficient genes in the form of gene therapy has been used successfully in some genetic disorders. Some common disorders requiring gene therapy are listed below in table

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• Chemotherapy
Drugs can be used in antimicrobial and cancer chemotherapy by selective targeting of invading microorganisms or cancer cells, with minimal action on host cells.