chapsixteenpharm

Cholinesterase is an enzyme necessary for the breakdown of acetylcholine into choline and acetic acid. This hydrolysis reaction causes the inactivation of ACh. Cholinesterase inhibitors, therefor, would prevent the inactivation of ACh. Think of all the junctions that use ACh as a transmitter. ACh is the transmitter at all junctions between motor neurons and skeletal muscle, as well as at preganglionic junctions of the parasympathetic and sympathetic nervous systems. ACh is also the transmitter at all postganglionic junctions of the parasympathetic nervous system. That means that these drugs will have little selectivity.

Chemistry	Positively charged so cannot directly penetrate cell membranes.
Mechanism of Action	These drugs tie up ChE for a long time, preventing it from catalyzing the hydrolysis reaction of ACh.
Pharmacologic Effects and Therapeutic Use	Therapeutic use of ChE inhibitors usually affects only muscarinic receptors and nicotinic receptors of the neuromuscular junction. The muscarinic effects are identical to the effects of muscarinic agonists. Effects on skeletal muscle are dose dependent (therapeutic doses increase the force of muscle contraction and toxic doses decrease the force of contraction). Treatment of myasthenia gravis is the principal indication for neostigmine. Also used to reverse effects of a nondepolarizing neuromuscular blockade.
Adverse Effects	Excessive muscarinic stimulation and neuromuscular blockade can be caused by accumulation of ACh. Toxicity results in cholinergic crisis, and causes excessive muscarinic stimulation and respiratory depression.
Drug Interactions	ChE inhibitors can be used to overcome blockade by muscarinic antagonists (atropine) and by nondepolarizing neuromuscular blockers (tubocurarine). ChE inhibitors will intensify effects of depolarizing neuromuscular blockers (succinylcholine).
Nursing Implications	Contraindicated for patients with mechanical bowel or urinary tract obstruction. When used as treatment for myasthenia gravis, teach patients to manage dosage adjustment and recognize symptoms of under- or over- dosing. Encourage patient to wear Medic Alert bracelet.