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Cholinergic Receptors — Muscarinic vs Nicotinic
TEXTPharmacology II · 10 min read
Two completely different receptor families, both responding to acetylcholine. The clinical drugs all live at one or the other.
After this lesson you can
2 min read8 sections- Distinguish nicotinic vs muscarinic receptors.
- Recall acetylcholine synthesis + breakdown.
- Match anticholinergics to clinical context.
- Predict cholinergic crisis features.
Muscarinic receptors M1-M5
M1 (CNS, gastric parietal cells) — Gq ↑IP3/Ca.
M3 (smooth muscle, glands) — Gq contraction + secretion.
M4 (CNS).
M5 (CNS, eye).
Activation by ACh causes bradycardia, bronchoconstriction, bronchorrhea, salivation, miosis, increased GI motility, urinary contraction.
Nicotinic receptors
Pentameric structure.
Two main subtypes: N(M) at neuromuscular junction (2α/β/δ/ε in adult, 2α/β/δ/γ in fetal — relevance to extrajunctional receptor upregulation in burns/denervation).
N(N) at autonomic ganglia + adrenal medulla.
Acetylcholine life cycle
Packaged in vesicles, released by Ca²⁺-dependent exocytosis.
Binds postsynaptic receptor for milliseconds.
Hydrolyzed by acetylcholinesterase (AChE) to acetate + choline; choline reuptake recycles.
AChE inhibition (neostigmine, pyridostigmine, edrophonium, physostigmine) increases synaptic ACh — used clinically for NMB reversal.
Anticholinergic drugs
Atropine: tertiary amine, crosses BBB central anticholinergic effects (delirium in elderly).
Glycopyrrolate: quaternary, doesn't cross BBB preferred for antisialagogue + bradycardia.
Scopolamine: tertiary, motion sickness patch — also crosses BBB (delirium risk).
All block M1-M5 indiscriminately at clinical doses.
Pediatric dosing matters (atropine 0.02 mg/kg, min 0.1 mg).
Neostigmine + glycopyrrolate pairing
30-50 mcg/kg IV reverses non-depolarizing NMB by raising synaptic ACh.The ACh excess also stimulates muscarinic receptors — bradycardia, bronchospasm, salivation, bowel contraction.
Pair with glycopyrrolate 7-15 mcg/kg to block muscarinic effects while sparing nicotinic.
Atropine sometimes used instead (faster onset, shorter duration; CNS-active).
Sugammadex skips the entire pathway by directly encapsulating roc/vec.
Central anticholinergic syndrome
- agitation
- confusion
- hallucination
- hyperthermia
- tachycardia
- mydriasis
- dry mucous membranes ("mad as a hatter, hot as Hades, blind as a bat, dry as a bone")
Elderly + cognitively impaired most vulnerable.
Treatment: physostigmine 1-2 mg IV slowly — only AChE inhibitor that crosses BBB.
Caution in seizure history + heart block.
Organophosphate poisoning + irreversible AChE inhibition
Pesticides, sarin/VX nerve agents bind AChE covalently massive ACh excess at all cholinergic synapses SLUDGE (Salivation, Lacrimation, Urination, Diarrhea, GI cramping, Emesis) + miosis, bronchorrhea, bradycardia, bronchospasm, fasciculations, weakness, seizures, death.
Treatment: atropine 2-5 mg IV q5 min titrated to drying secretions (large total doses often needed — 50+ mg), pralidoxime (2-PAM) 1-2 g IV (regenerates AChE before 'aging' makes binding irreversible — give early, within hours).
Decontamination + supportive ventilation.
CRNA awareness: relevant for mass-casualty + agricultural exposures.
Echothiophate eye drops + succinylcholine prolongation
Patients on echothiophate have prolonged succinylcholine block (sometimes hours).
Same for organophosphate exposure.
Check medication list for cholinesterase inhibitors before sux.
Mivacurium also affected.
Bambuterol (prodrug of terbutaline) similar effect.
If sux used in these patients: be prepared to ventilate for extended period until cholinesterase activity recovers.
⚠ Common pitfalls
- Atropine in atrial fibrillation — paradoxical AV block can happen.
- Glycopyrrolate vs atropine confusion — glyco doesn't cross BBB (less CNS effect).
- Treating cholinergic crisis with more reversal — patient needs decreased cholinergic, not more.
- Sux + atropine vs ED50 in peds — anti-bradycardia is real, give the atropine.
💎 Clinical pearls
- Nicotinic at NMJ + autonomic ganglia; muscarinic at end-organ smooth muscle/glands.
- Neostigmine + glycopyrrolate is the classic reversal pairing — glycopyrrolate counteracts the muscarinic effects.
- Atropine = anti-muscarinic, CNS-crossing; glyco = anti-muscarinic, peripheral only.
- Pseudocholinesterase deficiency: sux duration measured in hours, not minutes — wait it out, continue ventilation.
Recap
- Nicotinic at NMJ + autonomic ganglia; muscarinic at end-organ smooth muscle/glands.
- Neostigmine + glycopyrrolate is the classic reversal pairing — glycopyrrolate counteracts the muscarinic effects.
- Atropine = anti-muscarinic, CNS-crossing; glyco = anti-muscarinic, peripheral only.
- Pseudocholinesterase deficiency: sux duration measured in hours, not minutes — wait it out, continue ventilation.
Mark each section done to complete the module.