Cholinergic Agonists

The parasympathetic ("rest-and-digest") branch of the autonomic nervous system runs the body’s calm, housekeeping functions — and it signals through one neurotransmitter: acetylcholine (ACh) acting on muscarinic receptors. When ACh fires, the body slows the heart, constricts pupils, and stimulates the gut, bladder, and glands (saliva, tears, sweat).

Cholinergic agonists boost that ACh signal. They’re used where a body function is under-active: a hypotonic bladder that won’t empty (urinary retention), dry mouth/eyes, glaucoma (constricting the pupil improves outflow), and the muscle weakness of myasthenia gravis.

Direct agonists (bethanechol, pilocarpine) *are* ACh-like molecules that bind muscarinic receptors themselves — bethanechol targets the bladder/GI tract (urinary retention, ileus), pilocarpine the eye and salivary glands. Indirect agonists work by blocking the enzyme acetylcholinesterase, which normally breaks ACh down — so ACh piles up and its effect is amplified everywhere.

The indirect cholinesterase inhibitors (neostigmine, pyridostigmine) are the mainstay of myasthenia gravis (more ACh at the neuromuscular junction restores strength) and are used to reverse non-depolarizing neuromuscular blockers after surgery. (Their CNS-penetrating cousins — donepezil, rivastigmine — are used in Alzheimer disease.)

Push cholinergic effect too far and every parasympathetic action fires at once — a cholinergic crisis. The picture is captured by SLUDGE: Salivation, Lacrimation, Urination, Diarrhea, GI cramping, Emesis — plus bradycardia, bronchospasm/bronchorrhea, and miosis (tiny pupils). The same syndrome is what organophosphate (pesticide/nerve-agent) poisoning produces.

The antidote is atropine (an anticholinergic that blocks the muscarinic receptors) — the mirror-image drug in this system. For a myasthenia patient, distinguishing cholinergic crisis (too much drug) from a myasthenic crisis (too little) is critical because the treatments are opposite.