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
- Neostigmine
- Can not cross the blood-brain barrier (quaternary amine)
- Thus cannot be used to treat atropine OD
- Myasthenia gravis
- Postoperative and neurogenic ileus and urinary retention
- Postoperative reversal of neuromuscular blockade
- Can not cross the blood-brain barrier (quaternary amine)
- Pyridostigmine
- Can not cross the blood-brain barrier (quaternary amine)
- Typically used with glycopyrrolate, hyoscyamine, or propantheline to control side effects
- Myasthenia gravis (longer action compared to neostigmine): improves muscle strength
- Physostigmine
- Lipophilic
- Can cross the blood-brain barrier (tertiary amine)
- Atropine overdose (antidote)