Direct-Acting Agonists
These drugs directly bind to and activate muscarinic or nicotinic receptors.
- Bethanechol
- Mechanism: Muscarinic agonist.
- Clinical Use: Post-op and neurogenic urinary retention; neurogenic ileus. Activates bladder smooth muscle.
- Mnemonic: “Bethany, call me to activate your bladder.”
- Pilocarpine
- Mechanism: Muscarinic agonist.
- Clinical Use: Glaucoma (both open-angle and closed-angle), Sjögren syndrome (for xerostomia/dry mouth). It increases salivary, sweat, and lacrimal secretions. In glaucoma, it contracts the ciliary muscle and pupillary sphincter, increasing aqueous humor outflow.
- Mnemonic: “You cry and drool on your pilow.”
- Carbachol
- Mechanism: Muscarinic and nicotinic agonist.
- Clinical Use: Used topically for glaucoma to induce miosis and reduce intraocular pressure.
- Varenicline
- Mechanism: Partial nicotinic receptor agonist.
- Clinical Use: Smoking cessation.
Indirect-Acting Agonists (Anticholinesterases)
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels
1. Centrally-Acting Agents
- Agents: Donepezil, Rivastigmine (available as transdermal patch), Galantamine. c
- Indications:
- Alzheimer Disease (AD): Mild-to-moderate and moderate-to-severe (provides modest symptomatic benefit; does not halt disease progression).
- Dementia with Lewy Bodies (DLB): Improves cognitive and psychiatric symptoms (visual hallucinations).
- Parkinson Disease Dementia (PDD): Rivastigmine is FDA-approved.
2. Peripherally-Acting Agents (Quaternary Amines)
- Pyridostigmine:
- Indication: 1st-line symptomatic maintenance for Myasthenia Gravis (MG).
- Clinical pearl: Improves skeletal muscle strength (ptosis, diplopia, bulbar weakness) by enhancing transmission at nicotinic receptors.
- Neostigmine:
- Indications:
- Reversal of non-depolarizing neuromuscular blockade (e.g., rocuronium, vecuronium) post-surgery.
- Must co-administer with an antimuscarinic (glycopyrrolate or atropine) to prevent severe reflex bradycardia, bronchospasm, and salivation.
- Acute Colonic Pseudo-obstruction (Ogilvie Syndrome): Used when conservative management fails and cecal diameter > 10–12 cm without mechanical obstruction.
- Reversal of non-depolarizing neuromuscular blockade (e.g., rocuronium, vecuronium) post-surgery.
- Indications:
- Edrophonium:
- Indication: Ultra-short-acting agent historically used in the Tensilon test to diagnose MG or differentiate myasthenic crisis from cholinergic crisis (largely replaced by anti-AChR Ab serologies and EMG/repetitive nerve stimulation).