Ganglion Blocking Drugs

Ganglion blocking drugs block nicotinic receptors on postganglionic neurons in both sympathetic and parasympathetic ganglia, which interrupts autonomic transmission at its relay point. They once treated severe hypertension and were used for controlled hypotension. Today they have almost no therapeutic role and mainly serve as research and teaching tools.

Classification. Quaternary agents: hexamethonium and pentolinium, poorly absorbed and erratic orally. Trimetaphan, a short-acting intravenous agent. Mecamylamine, a tertiary amine that is well absorbed and enters the brain.

Mechanism. They block the neuronal (Nn) nicotinic receptor channel, preventing depolarisation of postganglionic neurons. Blockade of the autonomic division that dominates tone at an organ determines the effect there. Vessels and sweat glands depend on sympathetic tone. The heart, gut, bladder, salivary glands and iris depend on parasympathetic tone.

Effects. Vasodilation with marked postural hypotension, tachycardia, dry mouth, constipation and ileus, urinary retention, mydriasis with cycloplegia, loss of sweating, and erectile and ejaculatory failure. Effects mimic autonomic denervation.

Pharmacokinetics. Hexamethonium and pentolinium are excreted unchanged by the kidney with poor oral bioavailability. Mecamylamine is excreted in urine, and excretion falls with alkaline urine, which prolongs effect.

Current relevance. Ganglionic blockade is used experimentally to measure autonomic contribution to blood pressure. Ganglion transmission is also impaired in autoimmune autonomic ganglionopathy, which produces the same pattern of autonomic failure.

• Hexamethonium: obsolete. Pulmonary fibrosis was reported with use, and it is not available clinically.
• Pentolinium: obsolete; erratic absorption.
• Trimetaphan: short-acting infusion for controlled hypotension and hypertensive emergencies; withdrawn in many countries. Also released histamine and has weak neuromuscular blocking effect.
• Mecamylamine: oral; licensed in some regions for moderately severe to severe hypertension; also studied for smoking cessation and other central nervous system uses. Central effects include tremor, confusion and seizures.

• Hypertension: mecamylamine 2.5 mg orally twice daily, increased by 2.5 mg at intervals of at least 2 days until blood pressure is controlled. Usual daily total is about 25 mg in 3 divided doses. It is used only when safer drugs have failed, and is rarely used.
• Hypertensive emergencies and aortic dissection: replaced by labetalol, esmolol, nicardipine, glyceryl trinitrate and sodium nitroprusside.
• Controlled hypotension in surgery: replaced by remifentanil, volatile agents, nitroprusside and beta blockers.
• Research and diagnosis: infusion to quantify autonomic support of blood pressure, mainly in specialist autonomic laboratories.
• Selection: no current first-line indication. Any patient with a ganglion blocker effect (extreme postural hypotension, anhidrosis, constipation, mydriasis, retention) should prompt a search for autoimmune ganglionopathy or another cause of autonomic failure.

Contraindications. Recent myocardial infarction, coronary insufficiency, uraemia or renal impairment, pyloric stenosis, glaucoma, hypovolaemia, and uncooperative patients who cannot be monitored for postural effects.

Adverse effects. Postural hypotension and syncope, constipation to paralytic ileus, urinary retention, blurred vision, dry mouth, impotence, tremor and seizures with mecamylamine, and rebound hypertension on abrupt withdrawal.

Interactions. Other antihypertensives, diuretics, alcohol, anaesthetics and sodium depletion all increase the hypotensive effect. Alkalinising agents (sodium bicarbonate, acetazolamide, some thiazides) reduce urinary excretion of mecamylamine and prolong effect. Antimuscarinics and sympathomimetics intensify tachycardia and urinary retention.

Monitoring. Supine and standing blood pressure before each dose change, bowel function, urinary output and renal function.

Special groups. Older adults: very high risk of falls and ileus. Renal impairment: accumulation is likely, so avoid. Pregnancy: avoid. Because of safer alternatives, use is generally not advised in any group.