U01.05.019 Cholinomimetic agents

Cholinomimetic agents mimic the effects of Acetylcholine (ACh) by directly activating muscarinic receptors or inhibiting Acetylcholinesterase (AChE). These agents can be classified into direct and indirect agonists, each with distinct pharmacologic effects and clinical applications.

Key Points to Remember

Cholinomimetic agents can exacerbate conditions such as COPD, asthma, and peptic ulcers.
Direct agonists activate muscarinic receptors directly.
Indirect agonists (anticholinesterases) prevent the breakdown of ACh, increasing its levels.

Direct Agonists (Cholinergic Receptor Agonists)

These agents directly activate muscarinic receptors.

Drug	Mechanism of Action	Clinical Application	Mnemonic/Note
Bethanechol	Activates bladder smooth muscle; resistant to AChE. No nicotinic activity.	Used for urinary retention.	“Bethany, call me to activate your bladder.”
Carbachol	Carbon copy of acetylcholine but resistant to AChE.	Constricts pupil and relieves intraocular pressure in open-angle glaucoma.
Methacholine	Stimulates muscarinic receptors in the airway when inhaled.	Challenge test for diagnosing asthma.
Pilocarpine	Contracts ciliary muscle of the eye and pupillary sphincter; resistant to AChE.	Open-angle and closed-angle glaucoma, xerostomia (Sjögren syndrome). Stimulates sweat, tears, and saliva.	“You cry, drool, and sweat on your ‘pilow.’”

Indirect Agonists (Anticholinesterases)

These agents inhibit Acetylcholinesterase, increasing acetylcholine levels at synapses.

Drug	Mechanism of Action	Clinical Application	Mnemonic/Note
Donepezil, Rivastigmine, Galantamine	Increase ACh. First-line treatment for Alzheimer’s disease.	Improve cognition in Alzheimer’s disease.	“Dona Riva dances at the gala.”
Edrophonium	Increases ACh.	Used historically to diagnose myasthenia gravis (now replaced by anti-AChR antibody test).
Neostigmine	Increases ACh. Does not cross the blood-brain barrier (quaternary amine).	Postoperative and neurogenic ileus, urinary retention, myasthenia gravis, reversal of neuromuscular junction blockade.	“Neo CNS = No CNS penetration.”
Physostigmine	Increases ACh. Crosses the blood-brain barrier (tertiary amine).	Antidote for anticholinergic toxicity, e.g., atropine overdose.	“Phreely crosses the blood-brain barrier.”
Pyridostigmine	Increases ACh; enhances muscle strength.	Long-acting treatment for myasthenia gravis, does not penetrate CNS.	“Pyridostigmine gets rid of myasthenia gravis.”

Clinical Applications of Cholinomimetic Agents

Urinary Retention: Bethanechol is commonly used for its ability to activate the bladder.
Glaucoma: Both Carbachol and Pilocarpine are effective in managing open-angle and closed-angle glaucoma by constricting the pupil and reducing intraocular pressure.
Asthma Diagnosis: Methacholine is used as a challenge test for diagnosing asthma by stimulating airway muscarinic receptors.
Alzheimer’s Disease: Donepezil, Rivastigmine, and Galantamine are essential in improving cognitive function in Alzheimer’s patients by increasing ACh levels in the brain.
Myasthenia Gravis: Neostigmine and Pyridostigmine help improve muscle strength by inhibiting ACh breakdown at neuromuscular junctions.

Points to Remember for USMLE Step 1

Direct vs. Indirect Agonists: Direct agonists (e.g., Bethanechol) activate muscarinic receptors, while indirect agonists (e.g., Neostigmine) increase ACh levels by inhibiting AChE.
Cholinergic Toxicity: Be aware of the potential for cholinergic toxicity, especially in conditions like COPD, asthma, and peptic ulcers. Watch for excessive salivation, sweating, and bradycardia in vulnerable patients.
Mnemonic for Cholinergic Agents: Remember “Dona Riva dances at the gala” for the first-line Alzheimer’s agents and “Bethany, call me to activate your bladder” for Bethanechol.

USMLE Step 1 Review Series

Curriculum