Mechanism of action
Ganglionic blockers block impulse transmission at the sympathetic ganglia. Neurotransmission within the sympathetic
and parasympathetic ganglia
involves the release of acetylcholine from preganglionic efferent nerves, which binds to nicotinic receptors on the
postganglionic efferent nerves. Ganglionic blockers inhibit autonomic activity by interfering with neurotransmission
within autonomic ganglia. This reduces sympathetic outflow to the heart, thereby decreasing cardiac output by
decreasing heart rate and contractility. Reduced sympathetic output to the vasculature decreases sympathetic vascular
tone, which causes vasodilation and reduced systemic vascular resistance, which decreases arterial pressure.
Parasympathetic outflow also is reduced by ganglionic blockers.
Clinical Use
Ganglionic blockers are not commonly used in the treatment of chronic hypertension largely because of their side
effects and because numerous more effective and safer antihypertensive drugs can be used. They are, however,
occasionally used for hypertensive emergencies.
The ganglionic blockers available for clinical use include trimethaphan camsylate and mecamylamine.
They are competitive antagonists at nicotinic acetylcholine receptors. Trimethaphan is a quaternary sulfonium ion and
cannot cross lipid cell membranes, whereas mecamylamine is a secondary amine. Therefore, trimethaphan is a shortacting peripheral direct vasodilator that must be given as an IV infusion, whereas mecamylamine can be given orally.
Mecamylamine rapidly disappears from the blood with a plasma half-life of 1 hour, and crosses the blood-brain barrier
into the CNS. Trimethaphan is rapidly excreted in unchanged form by the kidney. Mecamylamine is excreted by the
kidney much more slowly. Trimethaphan is the drug of choice for managing acute aortic dissection and for hypertensive
emergencies. Both drugs are of limited use, because of the availability of more specific acting vasodilators.
Mecamylamine has been used for labeling CNS nicotinic receptors and crosses into the CNS, where it can block
neuronal nicotinic acetylcholine receptors. Mecamylamine has been studied for use with nicotine for smoking
cessation.
Side effects
Side effects of trimethaphan include prolonged neuromuscular blockade and potentiation of neuromuscular blocking agents. It can produce excessive hypotension and impotence (because of its sympatholytic effect) as well as
constipation, urinary retention, and dry mouth (because of its parasympatholytic effect).
