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5.14 : Indirect-Acting Cholinergic Agonists: Pharmacokinetics

Indirect-acting cholinergic agonists, or anticholinesterases, enhance the body's cholinergic activity by inhibiting acetylcholine's breakdown. They are categorized as reversible or irreversible agents based on their mechanism of action. They are further classified into short-acting, intermediate-acting, and long-acting agents based on their duration of action.

Reversible agents containing quaternary amines, such as neostigmine and edrophonium, are not easily absorbed orally because they are polar. These agents have limited ability to penetrate the eye and brain. On the other hand, agents like physostigmine, which carry a tertiary amine, are readily absorbed orally and can easily penetrate the eye and brain. Irreversible agents, such as dyflos, malathion, and sarin, are highly lipid-soluble, allowing them to be well absorbed through mucous membranes, eyes, lungs, and skin. They are easily distributed throughout the body and can cross the blood-brain barrier.

The duration of action varies for reversible anticholinesterases. Short-acting agents have effects that last for ten to twenty minutes due to rapid renal elimination. Intermediate-acting agents have effects that last from twenty minutes to six hours. Reversible agents with simple alcohol, such as edrophonium, are less stable and diffuse quickly, resulting in short-acting effects. Reversible agents with carbamate, like neostigmine, are slowly hydrolyzed, meaning they have an intermediate duration of action. On the other hand, organophosphates can gradually age to become resistant to hydrolysis, leading to their prolonged effects.

Anticholinesterases are broken down by cholinesterase enzymes in the liver, plasma, and skeletal muscles. The resulting byproducts are eliminated from the body through renal excretion.

Tags

Indirect acting Cholinergic AgonistsAnticholinesterasesAcetylcholine BreakdownReversible AgentsIrreversible AgentsPharmacokineticsQuaternary AminesTertiary AminesLipid soluble AgentsDuration Of ActionRenal ExcretionOrganophosphatesCholinesterase EnzymesNeostigminePhysostigmine

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