Anticholinergic Drugs

Anticholinergic Drugs, Atropine, Substitutes & Cholinergic Agonists

1. Definition, scope & terminology

• Cholinergic agonists (cholinomimetics, parasympathomimetics) produce actions similar to acetylcholine (ACh), either by directly interacting with cholinoceptors (cholinergic agonists) or indirectly by raising ACh availability via cholinesterase inhibition (anticholinesterases) (KDT 8e Ch.7, p.114).
• Anticholinergic drugs are conventionally restricted to agents that block ACh actions on autonomic effectors and in the CNS exerted through muscarinic receptors — synonyms: muscarinic receptor antagonists, atropinic, parasympatholytic (KDT 8e Ch.8, p.124).
  • Nicotinic-receptor antagonists also block ACh actions but are separately termed ganglion blockers (autonomic ganglia) and neuromuscular blockers (skeletal muscle) (KDT 8e Ch.8, p.124).
  • Katzung prefers the term "antimuscarinic" over "parasympatholytic," since these drugs block the effects of parasympathetic autonomic discharge (Katzung Ch.8, p.129–30).
• Atropine is the prototype antagonist — highly selective for muscarinic receptors, with much lower potency at nicotinic receptors and clinically undetectable action at non-muscarinic receptors (Katzung Ch.8, p.132; KDT 8e Ch.8, p.124).
  • Selectivity is demonstrable on guinea-pig ileum: atropine blocks ACh-induced contractions without affecting those from histamine, 5-HT or other spasmogens; selectivity is lost at very high doses (KDT 8e Ch.8, p.124).
• All anticholinergics are competitive (surmountable) antagonists — blockade by a small dose can be overcome by raising the agonist concentration (KDT 8e Ch.8, p.124; Katzung Ch.8, p.130).
• This topic spans both arms of muscarinic pharmacology — the agonists (choline esters + cholinomimetic alkaloids) and the antagonists (belladonna alkaloids + synthetic/semisynthetic substitutes) — because G&G presents them together as the two faces of the same receptor target (G&G 14e Ch.11, pp.207–20).