๐Ÿง  Acetylcholine and Cholinergic Drugs for USMLE Step 1: Direct & Indirect Agonists, Receptor Actions, and Toxicities

Acetylcholine (ACh) is a cornerstone neurotransmitter in both the central and peripheral nervous system, and the target of numerous drugs and toxins.

On Step 1, youโ€™ll encounter it in:

  • Pharmacology

  • Toxicology

  • Neuro and GI systems

Understanding the types of receptors, drug classes, and clinical applications will help you reason through complex vignettes.

๐Ÿง  Acetylcholine and Cholinergic Drugs for USMLE Step 1: Direct & Indirect Agonists, Receptor Actions, and Toxicities

๐Ÿ”ฌ ACh Receptors: Muscarinic vs Nicotinic

Receptor Type Location Mechanism Effects
Muscarinic (M1โ€“M5) Parasympathetic target organs G-protein coupled SLUDGE effects
Nicotinic (Nn, Nm) Ganglia, NMJ, adrenal medulla Ligand-gated ion channel Sympathetic activation, muscle contraction

๐Ÿง  Step 1 loves receptor type-to-organ and drug matchups

๐Ÿ’Š Cholinergic Agonists

Drug Type Use
Bethanechol Direct Urinary retention
Pilocarpine Direct Glaucoma, dry mouth
Neostigmine Indirect Myasthenia, ileus
Physostigmine Indirect Anticholinergic toxicity

โ˜ ๏ธ Cholinergic Toxicity

SLUDGE-M Mnemonic

  • Salivation

  • Lacrimation

  • Urination

  • Diarrhea

  • GI cramps

  • Emesis

  • Miosis, Muscle fasciculations

Organophosphates (e.g., parathion, sarin gas)

  • Irreversibly inhibit AChE โ†’ toxic ACh buildup

๐Ÿงช Step 1 Case Clue: Farmer exposed to pesticide with pinpoint pupils, wheezing, bradycardia

๐Ÿ’‰ Antidote: Atropine + Pralidoxime

Drug Mechanism Notes
Atropine Muscarinic antagonist Treats SLUDGE; no effect on nicotinic symptoms
Pralidoxime Regenerates AChE Effective before enzyme aging in organophosphate poisoning

๐Ÿง  Step 1 Clinical Clue

A patient treated for myasthenia with neostigmine presents with diarrhea, salivation, and miosis. How do you distinguish cholinergic crisis from MG worsening?

โœ… Give edrophonium

  • If improves: MG exacerbation

  • If worsens/no change: Cholinergic crisis

๐Ÿง  Mnemonics

  • โ€œHot as a hare, dry as a bone, blind as a batโ€ฆโ€ โ†’ Atropine toxicity

  • โ€œDUMBELSโ€ for organophosphate symptoms

    • Diarrhea, Urination, Miosis, Bradycardia, Emesis, Lacrimation, Salivation

๐ŸŽฏ Final Review Table

Drug Class Examples Main Uses
Direct agonists Bethanechol, Pilocarpine Stimulate bladder, saliva, and eye drainage
AChE inhibitors Neostigmine, Donepezil Myasthenia gravis, Alzheimerโ€™s
Anticholinergics Atropine, Scopolamine Bradycardia, motion sickness, GI cramping

๐Ÿ“˜ Call-to-Action

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