Mechanisms

An overview of the mechanisms of drug action shows that drugs act on the cell membrane by:

• Action on specific receptors,1 e.g. agonists and antagonists on adrenoceptors, histamine receptors, acetylcholine receptors

• Interference with selective passage of ions across membranes, e.g. calcium entry (or channel) blockers

• Inhibition of membrane bound enzymes and

1 A receptor mediates a biological effect, e.g. adrenocoeptor; a binding site, e.g. on plasma albumin, does not.

pumps, e.g. membrane bound ATPase by cardiac glycoside; tricyclic antidepressants block the pump by which amines are actively taken up from the exterior to the interior of nerve cells.

Drugs act on metabolic processes within the cell by:

• Enzyme inhibition, e.g. platelet cyclo-oxygenase by aspirin, cholinesterase by pyridostigmine, xanthine oxidase by allopurinol

• Inhibition of transport processes that carry substances across cells, e.g. blockade of anion transport in the renal tubule cell by probenecid can be used to delay excretion of penicillin, and to enhance elimination of urate

• Incorporation into larger molecules, e.g. 5-fluorouracil, an anticancer drug, is incorporated into messenger-RNA in place of uracil

• In the case of successful antimicrobial agents, altering metabolic processes unique to microorganisms, e.g. penicillin interferes with formation of the bacterial cell wall, or by showing enormous quantitative differences in affecting a process common to both humans and microbes, e.g. inhibition of folic acid synthesis by trimethoprim.

Drugs act outside the cell by:

• Direct chemical interaction, e.g. chelating agents, antacids

• Osmosis, as with purgatives, e.g. magnesium sulphate, and diuretics, e.g. mannitol, which are active because neither they nor the water in which they are dissolved are absorbed by the cells lining the gut and kidney tubules respectively.

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