ACTIONS AND PHARMACOLOGY This is a ganglionic blocking agent that inhibits both sympathetic and parasympathetic discharge by occupying receptor sites, thus stabilizing postsynaptic membranes from the effects of acetylcholine. This blockade results in vasodilation, improved blood flow to some vascular beds, and a decrease in blood pressure. The heart rate may rise in response to the decrease in peripheral vascular resistance. Cardiac output, stroke volume, and left ventricular work decrease. It has a rapid onset of action, and its effects are of short duration.

INDICATIONS Historically, trimethaphan had been the drug of choice for acute aortic dissection, especially of the descending type. However, because it causes a number of serious side effects, it has been replaced by the combination of nitroprusside and b blockade as the therapy of choice. It continues as a second-line agent in this setting.

USE Trimethaphan is given by intravenous infusion at a rate of 0.3 to 3.0 mg/min. It is sometimes used in combination with propranolol (1 to 3 mg IV or 10 to 40 mg orally qid) to reduce the velocity and force of left ventricular ejection.

SIDE EFFECTS AND CONTRAINDICATIONS A number of serious side effects can occur including bladder atony with urinary retention, ileus, gastric atony, cycloplegia, severe postural hypotension from blockade of circulatory reflex pathways, and even respiratory arrest. Tolerance develops with continued use; therefore, it is mainly useful for short-term administration such as in patients awaiting surgery or in inoperable patients until oral therapy with another agent can be started.

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