Withdrawal Reactions Following Cessation of Central a-Adrenergic Receptor Agonists

Interruption of long-term treatment with a2-adrenergic receptor agonists may be associated with reversal of their hemodynamic effects, clinical and biochemical evidence of increased peripheral sympathetic activity, and behavioral responses similar to those seen after narcotic or alcohol withdrawal. Reactions are most commonly observed after short-acting imidazoline drugs such as clonidine and tiamenidine. Reactions are less common after longer acting agents such as guanfacine. A new management approach to withdrawal has been evaluated, which uses a combination of a,blockade (prazosin) and cardioselective /3-blockade (atenolol) together with a benzodiazepine (chlordiazepoxide). Withdrawal reactions were not observed in eight patients in whom clonidine was withdrawn under cover of these agents. The mechanism of the withdrawal reaction may involve agonist-induced down regulation of a2-adrenergic receptor affinity, number, or both. Experimental studies with the irreversible a-antagonist phenoxybenzamine on the turnover of a2-receptors suggest that recovery of receptor number may be much slower in the brain than in the periphery. (Hypertension 6 (Suppl II): II-71-II-75, 1984)