Drug Interactions between guanethidine and Phenergan VC

MONITOR: Sympathomimetic amines may decrease the hypotensive effect of postganglionic adrenergic blocking agents, while the latter may potentiate the pharmacologic effects of direct-acting sympathomimetic amines (e.g., dobutamine, epinephrine, methoxamine, norepinephrine) but inhibit those that are primarily indirect-acting (e.g., mephentermine). Postganglionic adrenergic blocking agents such as guanadrel, guanethidine, and rauwolfia alkaloids work by depleting catecholamine stores from adrenergic nerve endings. Therefore, they may sensitize adrenergic receptors to direct-acting sympathomimetics, but blunt the effects of indirect-acting agents whose activity is mediated through the release of catecholamines. Guanethidine and reserpine have been reported to attenuate the pharmacologic effects (mydriasis, pressor response) induced by ephedrine and dopamine, both of which exhibit direct and indirect sympathomimetic activities (i.e., mixed-acting). However, guanethidine intensified the mydriasis produced by phenylephrine, which is also thought to be mixed-acting. Conversely, ephedrine has been shown to partially reverse the hypotensive effect of guanethidine.

MANAGEMENT: Due to their pressor effect, sympathomimetic amines should be used cautiously in patients with hypertension. Alternatives to postganglionic adrenergic blocking agents should be considered if patients are treated with sympathomimetic amines, since effects of the latter may be intensified or diminished depending on whether they are direct- or indirect-acting. Most agents with indirect sympathomimetic activity are mixed-acting, thus it may be difficult to predict how they will be affected by postganglionic adrenergic blocking agents. If the combination is used, blood pressure and heart rate should be monitored.

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GENERALLY AVOID: Phenothiazines may inhibit the antihypertensive effect of guanethidine, probably through inhibition of guanethidine neuronal uptake. No data are available for guanadrel, but a similar interaction is suspected. Other adrenergic neurone blockers may also interact.

MANAGEMENT: This combination should generally be avoided. An alternative antihypertensive regimen may be necessary for patients who must take phenothiazine antipsychotics. If patients do receive a phenothiazine with an adrenergic neurone blocker, their blood pressure should be monitored closely. The dosage of the antihypertensive may require adjustment.

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