Parasympathomimetic drugs (Cholinomimetic drugs)

Parasympathomimetic drugs activate the parasympathetic nervous system (PSNS). As the neurotransmitter of the PSNS is acetylcholine, parasympathomimetics are also called cholinomimetic agents. These are classified according to whether they act as direct agonists of acetylcholine receptors (ACh) or indirect agonists of ACh (also called anticholinesterase). While direct agonists act by binding directly to muscarinic or nicotinic ACh receptors, indirect agonists prolong the action of endogenous acetylcholine by inhibiting acetylcholinesterase. Direct agonists of ACh are used topically in ophthalmology to induce miosis, while indirect agonists are used to treat, e.g., postoperative ileus or urinary retention and myasthenia gravis.

• Mechanism of action
  • Direct parasympathomimetics: bind to muscarinic or nicotinic ACh receptors
  • Indirect parasympathomimetics: inhibit acetylcholine esterase

Drug	Indications
Direct parasympathomimetics (direct agonist)
Bethanechol	Postoperative and neurogenic ileus and urinary retention
Carbachol	Alleviation of intraocular pressure Miosis
Pilocarpine	Induces sweat, tears, and saliva production Open-angle and closed-angle glaucoma
Methacholine	Diagnosis of bronchial hypersensitivity → See bronchial challenge test.
Indirect parasympathomimetics (indirect agonist)
Neostigmine	Postoperative ileus and urinary retention Myasthenia gravis Postoperative reversal of neuromuscular blockade
Pyridostigmine	Myasthenia gravis
Edrophonium	Used to diagnose myasthenia gravis in the past
Physostigmine	Glaucoma Antidote for atropine overdose
Donepezil Rivastigmine Galantamine	Alzheimer's disease

Effects of parasympathomimetics

ACh receptors	Organ/Tissue	Effects
M1, M4, M5	Central nervous system	Influences neurologic functions (e.g., memory)
M2	Heart	↓ Heart rate and atrial contractility Slows down AV conduction → possibly AV block
M3	Smooth muscle	↑ Intestinal peristalsis ↑ Bladder contraction (increases detrusor muscle tone, relaxes the internal urethral sphincter) Airway Bronchoconstriction ↑ Bronchial secretions Eye Miosis Accommodation Blood vessels: vasodilation
	Exocrine glands	↑ Secretions: sweat, gastric acid
Nicotinic	Skeletal muscle	↑ Muscle contraction and tone

References:^[1]

Direct parasympathomimetics

• Local side effects (e.g., application to eyes: blurred vision due to miosis)
• If applied systemically: side effects identical to those of indirect parasympathomimetics

Indirect parasympathomimetics

• Cardiovascular symptoms: bradycardia, hypotension
• Gastrointestinal symptoms: ↑ salivation, diarrhea, abdominal pain, uncontrolled urination
• Increased sweating, salivation, and gastric secretion
• Nausea
• Ocular symptoms: miosis, lacrimation
• CNS-related symptoms: restlessness, anxiety, ataxia, tremor possibly culminating in coma
• Musculoskeletal symptoms: fasciculations, weakness; , spasms, paralysis → peripheral neuromuscular respiratory failure
• Cholinergic crisis (cholinergic syndrome)
  • Cause: in most cases as a result of poisoning with organophosphates
  • Clinical presentation: severe and life-threatening constellation of side effects of indirect parasympathomimetics
  • Antidotes: antimuscarinic agents atropine, pralidoxime

DUMBBELLSS for clinical features of cholinergic syndrome = Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Emesis, Lacrimation, Lethargy, Sweating, and Salivation!

References:^[2]

We list the most important adverse effects. The selection is not exhaustive.