Parasympathomimetic Drugs

 

3.1. Parasympathomimetic drugs

Parasympathetic nerves use ACh as a neurotransmitter. Cholinomimetic drugs mimic the action of ACh at its receptors. Knowledge of the distribution of receptor subtypes (muscarinic or nicotinic) helps in predicting drug response.

Cholinergic   site

Receptor subtype

Neuroeffector junctions

Muscarinic

ganglionic synapses

Nicotinic

3.2. Classification of Cholinomimetics1. Direct-acting (receptor agonists)
muscarinic receptors
nicotinic receptors
2. Indirect-acting (cholinesterase inhibitors)
reversible
irreversible3.3. Direct-acting Cholinergic Receptor Agonistsa) Muscarinic receptor agonists
drugs that mimic Ach at neuroeffector junctions of PNS
Mechanisms :
Cholinergic receptors are coupled to G proteins (intramembrane transducers that regulate second messengers):
agonist  ----> increase in cGMP ----> activation of IP3, DAG cascade
  DAG opens smooth muscle Ca2+ channels
IP3 ----> release of Ca2 +  from sarcoplasmic reticulum
agonist  selectivity is determined by muscarinic receptor subtype and G protein in cell.
Types of direct acting muscarinic receptor agonists:
a) Esters of choline (e.g. acetylcholine, pilocarpine, carbachol, bethanechol chloride)
-poorly absorbed, -variable susceptibility to hydrolysis by cholinesterase-affects duration of action
b) Alkaloids (e.g. muscarine)
-well absorbed, not used clinically-mushroom poisoning (Amanita muscaria)
Acetylcholine
-highly susceptible to hydrolysis-IV bolus lasts 5-20 seconds-limited use in topical application in ophthalmology Pilocarpine
-acts on smooth muscles of eye to constrict the pupil (miosis)-used to treat glaucoma-contracts ciliary muscles by stimulating muscarinic receptors-rapid penetration (15-30 min) and long duration (8 hrs.)- increased aqueous outflow Carbachol
-carbamylate of choline-used mainly in ophthalmology for cataract surgery (causes rapid miosis)-decreases intraocular pressure by opening drainage angle of anterior chamber of eye - .: used in glaucoma (when resistant to pilocarpine or physostigmine)
Bethanechol Chloride
-choline ester-persistent effects because it is resistant to cholinesterase's-selectively stimulates urinary and gastrointestinal tracts-facilitates emptying of neurogenic bladder in patients after surgery or parturition or with spinal cord injury

Cholinergic   site	Receptor subtype
Neuroeffector junctions	Muscarinic
ganglionic synapses	Nicotinic