Pharmacology for Anaesthesia and Intensive Care

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Drug action

Mechanisms of drug action

Drugs may act in a number of ways to exert their effect. These range from relatively

simple non-specific actions that depend on the physicochemical properties of a

drug to highly specific and stereoselective actions on proteins in the body, namely

enzymes, voltage-gated ion channels and receptors.

Actions dependent on chemical properties

The antacids exert their effect by neutralizing gastric acid. The chelating agents

are used to reduce the concentration of certain metallic ions within the body.

Dicobalt edetate chelates cyanide ions and may be used in cyanide poisoning or

following a potentially toxic dose of sodium nitroprusside. The new reversal agent,

γ-cyclodextrin, selectively chelates rocuronium and reversal is possible from deeper

levels of block than can be effected with the anticholinesterases.

Enzymes

Enzymes are biological catalysts, and most drugs that interact with enzymes

are inhibitors. The results are twofold: the concentration of the substrate nor-

mally metabolized by the enzyme is increased and that of the product(s) of the

reaction is decreased. Enzyme inhibition may be competitive (edrophonium for

anticholinesterase), non-competitive or irreversible (aspirin for cyclo-oxygenase

and omeprazole for the Na+/H+ATPase). Angiotensin-converting enzyme (ACE)

inhibitors such as captopril prevent the conversion of angiotensin I to II and

bradykinin to various inactive fragments. Although reduced levels of angiotensin

II are responsible for the therapeutic effects when used in hypertension and heart

failure, raised levels of bradykinin may cause an intractable cough.

Voltage-gated ion channels

Voltage-gated ion channels are involved in conduction of electrical impulses associ-

ated with excitable tissues in muscle and nerve. Several groups of drugs have specific

blocking actions at these ion channels. Local anaesthetics act by inhibiting Na+chan-

nels in nerve membrane, several anticonvulsants block similar channels in the brain,

calcium channel blocking agents act on vascular smooth muscle ion channels and