Trimethaphan

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Trimethaphan
Clinical data
Routes of
administration
Oral, IM, IV
ATC code
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DrugBank
E number{{#property:P628}}
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Chemical and physical data
FormulaC22H25N2OS
Molar mass365.513 g/mol

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Trimethaphan is a drug that counteracts cholinergic transmission at the nicotinic receptors of the autonomic ganglia and therefore blocks both the sympathetic nervous system and the parasympathetic nervous system. It acts as a non-depolarizing competitive antagonist at the nicotinic acetylcholine receptor, is short-acting, and is given intravenously.

Effects

Trimethaphan is a quaternary amine and therefore carries a positive charge. Being charged, it cannot cross lipid cell membranes, such as those that comprise the blood-brain barrier. Due to this, trimethaphan does not have any effect on the central nervous system.

The ciliary muscle of the eye functions to round the lens for accommodation and is controlled mainly by parasympathetic system input. With administration of a ganglion-blocking drug, the ciliary muscle cannot contract (cycloplegia) and the patient loses the ability to focus their eyes.

Trimethaphan has a strong effect on the cardiovascular system. The size of blood vessels is primarily controlled by the sympathetic nervous system. Loss of sympathetic system input to the blood vessels causes them to get larger (vasodilation) which has the effect of lowering blood pressure. Postural hypotension is a common side effect of such drugs. Effects on the heart include a decreased force of contraction and an increase in heart rate (tachycardia). Although it is important to note that this reflexive tachycardia can be diminished or undetected due to the fact that Trimethaphan is also blocking the sympathetic ganglia innervating the heart.

The motility of the gastrointestinal tract is regulated by the parasympathetic system, and blockage of this input results in diminished motility and constipation.

Therapeutic Uses

The therapeutic uses of trimethaphan are very limited due to the competition from newer drugs that are more selective in their actions and effects produced. It is occasionally used to treat a hypertensive crisis and dissecting aortic aneurysm, to treat pulmonary edema, and to reduce bleeding during neurosurgery.

Adverse Effects

The adverse effects are due to its nonselective ganglion block and are described in the "Effects" section above. The side effects are severe enough to limit this drugs use to emergency and acute situations.

References

  • "Ganglion-blocking Drugs." Drug Benefits and Risks: International Textbook of Clinical Pharmacology. (2001). ISBN 0-471-89927-5
  • Katzung, Bertram G. Basic and Clinical Pharmacology, 9th ed. (2004). ISBN 0-07-141092-9