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5.15 : Indirect-Acting Cholinergic Agonists: Pharmacological Actions

Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.

At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle twitching and fasciculations. Higher doses can lead to prolonged depolarization, resulting in a blockage of neuromuscular transmission, muscle weakness, and paralysis. These agents are commonly used to treat a condition called myasthenia gravis.

Anticholinesterases also activate cholinergic activity in postganglionic synapses of the parasympathetic nervous system. In the eye, they assist in the drainage of aqueous humor, which helps reduce intraocular pressure and is beneficial in treating glaucoma. In the cardiovascular system, they induce bradycardia (slowing heart rate) and hypotension (lowering blood pressure), making them helpful in treating supraventricular tachycardia. Furthermore, they cause contractions in smooth muscles of the gastrointestinal and urinary tracts, aiding in treating conditions such as post-surgical bowel atony and neurogenic bladder.

Anticholinesterases that can penetrate the blood-brain barrier enhance cholinergic transmission in the brain. They play a critical role in treating Alzheimer's disease, which involves disruptions in cholinergic transmission. Low doses of these agents in the brain produce an alerting response, while higher doses can lead to confusion, tremors, convulsions, coma, and respiratory failure.

Tags

Indirect acting Cholinergic AgonistsAnticholinesterasesPharmacological ActionsNeuromuscular JunctionAcetylcholineMyasthenia GravisGlaucoma TreatmentBradycardiaHypotensionGastrointestinal TractUrinary TractAlzheimer s DiseaseCholinergic Transmission

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