Cholinergic Agonists (Parasympathomimetics)

Introduction

• Cholinergic System: Neurons release acetylcholine.
• Watch related video on cholinergic receptors for detailed physiology.

Parasympathetic Pathways

• Cranial Nerves with Parasympathetic Fibers:

  • Cranial Nerve 3 (Oculomotor Nerve): Supplies eye muscles, causes pupillary constriction (meiosis) and accommodation.
  • Cranial Nerve 7 (Facial Nerve): Innervates lacrimal and salivary glands; causes lacrimation and salivation.
  • Cranial Nerve 9 (Glossopharyngeal Nerve): Affects salivation through parotid glands.
  • Cranial Nerve 10 (Vagus Nerve): Influences heart (slows heart rate), bronchioles (constriction), and GI tract (increases secretion and motility).

• Sacral Parasympathetic Fibers (S2-S4): Affect lower GIT motility and bladder function.

Sympathetic Cholinergic Pathways

• Thoracolumbar Outflow (T1-L2):
  • Preganglionic fibers release acetylcholine, postganglionic usually release norepinephrine except in sweat glands.

Somatic Nervous System

• Nicotinic Receptors on Skeletal Muscles: Involved in muscle contraction.
• Muscarinic Receptors on Smooth/Cardiac Muscle and Glands: Various functions depending on receptor subtype (M1-M5).

Central Nervous System

• Cerebral Cholinergic Pathways: Role in cognitive function; deficits linked to Alzheimer's disease.

Pharmacology of Cholinergic Agonists

• Direct Agonists: Stimulate receptors directly (e.g., bethanecol, methacholine, pilocarpine, carbachol).

  • Bethanecol, Methacholine, Pilocarpine: Muscarinic receptors.
  • Carbachol: Both muscarinic and nicotinic receptors.

• Indirect Agonists: Inhibit acetylcholine breakdown (e.g., edrophonium, physostigmine, neostigmine, pyridostigmine).

  • Reversible Inhibitors: Short and long-acting varieties, some penetrate CNS (e.g., physostigmine).
  • Irreversible Inhibitors: E.g., sarin, organophosphates, ecothiopate.

Indications for Use

• Post-operative GI and Bladder Motility: Bethanecol and neostigmine.
• Bronchial Provocation Tests: Methacholine for asthma diagnosis.
• Glaucoma: Pilocarpine and carbachol for increasing aqueous humor drainage.
• Sjogren's Syndrome: Pilocarpine increases salivation and lacrimation.
• Myasthenia Gravis: Neostigmine and pyridostigmine to improve muscle strength.
• Alzheimer’s Disease: Donepezil, rivastigmine, galantamine to improve cognitive function.

Cholinergic Crisis

• Symptoms include diarrhea, urination, miosis, bradycardia, bronchospasm, salivation, sweating, muscle weakness, and CNS effects (agitation, convulsions).
• Mnemonic: Dumbbells.
• Treatment: Atropine and pralidoxime (for certain toxin exposures).

Exam Questions and Discussions

• Effects of botulinum toxin, management of post-op urinary retention, asthma improvement, eye exams, Alzheimer's treatment strategies, identifying cholinergic crisis, reversing neuromuscular blockers, managing xerostomia, and diagnosing myasthenia gravis with edrophonium.

Summary: Cholinergic agonists mimic or enhance acetylcholine action, affecting various systems and organs. Understanding receptor types and drug actions is crucial for targeted therapeutic use. These agents have specific clinical applications and potential adverse effects.