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CLONIDINE: A WORTHWHILE ADDITION TO ANTIHYPERTENSIVE THERAPY

Oonidine ('Catapres'), recently released in the USA, is a new antihypertensive for the treatment of moderate or severe hypertension. It causes less orthostatic hypotension than ganglionic blockers, monoamine oxidase inhibitors, and sympathomimetic neuron blocking agents like guanethidine and bethanidi.ne, and probably less than methyldopa. Its hypotensive action is additive to other agents, and it can be highly effective when combined with a diuretic in selected pa iienls.

Therapy should start with a daily dose of O.l-0.2mg which should be increased at weekly intervals by 0.1-0.2mg. By increasing the dose gradually, and by giving the major portion of the daily dose at night, sedation, an annoying side-effect of clonidine therapy, can be minimised. Patients engaged in hazardous activities should be warned about the possibility of sedation while on clonidine. As occurs with other non-diuretic antihypertensive agents, fluid and salt retention may occur. This can be prevented by the simultaneous administ ration of a diuretic. Onset of antihypertensive action is usually 30 minutes after oral administration and reaches a maximum within 2- 4 hours. Antihypertensive action usually disappears within 24- 36 hours, possibly within 4-6 hours in some individuals. More pharmacokinetic information is needed in order to improve therapeutic regimens and to reduce the side-effects of clonidine therapy.

Withdrawal syndrome rf chronic clonidine therapy is abruptly discontinued, a withdrawal syndrome, characterised by overactivity of the sympathetic nervous system and elevation of blood pressure, may result. Deaths due to hypertensive encephalopathy have reportedly followed sudden clonidine discontinuation. Patients should be warned not to stop their medication suddenly. The withdrawal syndrome can be avoided by gradually reducing the clonidine dose over 2-4 days. Treatment of a withdrawal syndrome involves either readrninistration of clonidine or the 13·blocker, propranolol. An o:·blocker phentolamine or phenoxybenzamine, can be added for control of blood pressure.

Drug interactions Tricyclic antidepressants can interfere with clonidine's antihypertensive action . Insulin-induced hypoglycaemia can be potentiated by clonidine, and so patients receiving hypoglycaemic agents should be monitored carefully. Tolazoline can be used to reverse the toxicity of clonidine overdosage. (22 references)

Pettinget, W.A.: New England Journal of Medicine 293: l l79-li&O (4 Dec 1975)

INPHARMA 6th December, 1975 p16