Ganglionic Blockers

Ganglionic Blockers Chemische Eigenschaften,Einsatz,Produktion Methoden

• 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.

• Nebenwirkungen

  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).