cholinergic drugs

• Locations of different cholinergic receptors:

  • Muscarinic receptors:
  • M1: CNS/ENS
  • M2: Heart
  • M3: EG, MP, AC, BB
  • Nicotinic receptors:
  • NMJ, Nm (muscular) and autonomic ganglia Nn (neuronal)
• Responses mediated through different nicotinic and muscarinic cholinergic receptors at various sites:

  • Muscarinic Actions of Acetylcholine:
  • Cardiovascular system:
  • Heart: Ach stimulates M2 receptors of the heart, opens K+ channels → hyperpolarization, reducing SA and AV nodal activity
  • Blood vessels: ACh stimulates M3 receptors of vascular endothelial cells, leading to vasodilatation and a fall in blood pressure
  • Smooth muscles:
  • Gastrointestinal tract
  • Urinary bladder
  • Bronchi
  • Exocrine glands
  • Eye
• Important pharmacokinetic features of acetylcholine:

  • ACh is rapidly hydrolysed to choline and acetic acid by cholinesterases
  • Two types of cholinesterase: True cholinesterase (AChE) found in cholinergic neurons, ganglia, RBCs, and NMJ; Pseudocholinesterase or butyrylcholinesterase found in plasma, liver, and glial cells
• Classification of cholinomimetic or parasympathomimetic drugs based on their mechanism of action:

  • Directly acting (Cholinergic agonists): Pilocarpine, Cevimeline, Bethanechol, Carbachol
  • Indirectly acting (Anticholinesterases):
  • Reversible: Physostigmine, Neostigmine, Pyridostigmine, Edrophonium, Galantamine, Donepezil, Rivastigmine
  • Irreversible: Organophosphates like parathion, malathion, ecothiophate
• Therapeutic uses of pilocarpine and cevimeline:

  • Pilocarpine:
  • Used as a sialagogue to augment salivary secretion
  • In xerostomia, Sjogren’s syndrome, and open-angle glaucoma
  • Cevimeline:
  • Treats xerostomia and dry eyes
  • Long-acting with fewer side effects compared to pilocarpine
• Adverse effects of pilocarpine:

  • diarrhea
  • urination
  • miosis
  • paralysis
  • bronchospasm
  • bradycardia