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HY points followed by a quiz at the end
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What are cholinergic receptors?
- Called cholinergic because they bind acetylcholine.
- Muscarinic and nicotinic types.
- Nicotinic are located at most preganglionic nerve terminals and at skeletal muscle.
- USMLE focuses probably 49 times out of 50 Qs on muscarinic, which stimulate the GI tract, urinary bladder, and sweat glands.
- USMLE cares most that you know the parasympathetic nervous system agonizes muscarinic receptors.
- USMLE also wants you to be aware of pro- vs anti-cholinergic drugs and what effects they’ll have.
What does cholinergic vs anti-cholinergic mean?
- Cholinergic agents either: 1) agonize cholinergic receptors directly, or 2) increase the potentiation of ACh binding to its receptors by inhibiting acetylcholinesterase (the enzyme that breaks down ACh).
- If an agent is cholinergic, it will cause DUMBBELSS signs/symptoms –> Diarrhea, Urination, Miosis, Bradycardia, Bronchoconstriction, neuromuscular Excitation, Lacrimation, Salivation, Sweating.
- Anti-cholinergic agents block cholinergic receptors directly. They will cause the opposite of DUMBBELSS –> Constipation, Urinary retention, Mydriasis, Tachycardia, Not bronchodilation (β2 agonism, but not M antagonism, will bronchodilate), Skeletal muscle relaxation, Dry eye, Dry mouth, Anhydrosis.
Muscarinic receptor agonists
Bethanechol
- Answer for neurogenic bladder (hypocontractile bladder), classically in diabetes.
- 49F + T2DM + can’t feel her feet or ankles + HbA1c of 11 + urinary studies show post-void volume of 300 mL; drug to Tx her condition? –> answer = bethanechol –> stimulates detrusor muscle.
Carbachol
- Carbachol is used to constrict the pupil and lower intraocular pressure in open-angle glaucoma.
- Don’t confuse with bethanechol, which is used for neurogenic bladder.
Pilocarpine
- Answer for closed angle glaucoma when needing to lower intraocular pressure acutely and fast.
- Constricts the pupil.
- Very powerful agent.
- 38M + left eye is painful and red + pupil is fixed and slightly dilated; which potent mitotic agent is most appropriate for this patient?–> answer = pilocarpine.
Methacholine
- Used to diagnose asthma.
- Muscarinic agonist that can induce bronchoconstriction and reproduce asthma symptoms in those with asthma.
- Never use during acute episodes (clearly).
- USMLE wants you to know the MOA is muscarinic receptor agonist.
Acetylcholinesterase inhibitors
- Acetylcholinesterase is the enzyme in the synaptic cleft that breaks down acetylcholine. So if you block this enzyme, you increase the amount of ACh available in the synaptic cleft –> increased binding to cholinergic receptors.
Donepezil
- Used to treat Alzheimer.
- Alzheimer is characterized by ↓ ACh-producing neurons in the basal forebrain (nucleus basalis of Maynert).
- 69M + one-year Hx of worsening cognitive decline + MMSE is 22/30 + neurologic exam shows no abnormalities; which drug is most appropriate for this patient? –> answer = donepezil.
Rivastigmine, Galantamine
- Slightly lower yield than donepezil, but also used to treat Alzheimer.
Edrophonium (aka Tensilon)
- Short-acting.
- Tensilon test can help diagnose myasthenia gravis.
- A patient with MG gets improvement of muscle weakness with edrophonium administration.
- However, if the USMLE asks how to diagnose myasthenia gravis, choose antibodies against post-synaptic ACh receptors over Tensilon test.
Pyridostigmine
- Treatment for myasthenia gravis.
- 40F + worsening diplopia and ptosis by the time she finishes work late-afternoon; Tx? –> answer = pyridostigmine.
Physostigmine
- Known to have good blood-brain barrier penetration.
- Treatment for atropine overdose (atropine is a muscarinic receptor antagonist).
Super-HY points about agents that cause cholinergic side-effects
Organophosphates
- Organophosphates act as acetylcholinesterase inhibitors –> cause DUMBBELSS in patient working on fruit farm or who “drank fluid” attempting to commit suicide.
- Pralidoxime will kick out the phosphate group from the organophosphate that’s bound to and inhibiting the acetylcholinesterase –> regenerates active acetylcholinesterase.
- 20F + working on fruit farm + has constricted pupils + bradycardia + drooling; what’s the Tx for this patient’s condition? –> answer = atropine, followed by pralidoxime.
- Atropine blocks muscarinic receptors directly. This is the answer before pralidoxime. If the USMLE Q lists both answers, choose atropine first.
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