VPT 321: Veterinary Neuropharmacology (2+1) copy 1

IRREVERSIBLE ANTICHOLINESTERASE AGENTS

• These compounds are covalently bind to AChE and cause its inhibition irreversibly.
• Unlike carbamate and other reversible cholinesterase inhibitors, these do not posses cation group and thus react only with the esteratic site of ChE enzyme.
• The enzyme-substrate complex thus formed is highly stable and does not undergo spontaneous hydrolysis. Eg: Organophosphorus compounds.

Anticholinergic Drugs (Parasympatholytic/Cholinolytic)

• Conventionally drugs that block actions of ACh on muscarinic receptors are termed as anticholinergic drugs or parasympatholytics.
• Drugs that block actions of ACh on nicotinic receptors are designated as “Ganglionic blockers” and “Neuromuscular blockers” depending on their site of action.

Depending on the source, chemical nature and therapeutic uses, anticholinergic drugs are classified as:

• Non-selective muscarinic receptor antagonists (or) Non-selective antimuscarinic drugs.
• Selective muscarinic receptor antagonists (or) Selective antimuscarinic drugs   

Organophosphorus compounds (Phosphorylating agents)

• Organophosphorus compounds produce essentially irreversible inhibition of cholinesterase and new enzyme must be synthesized for recovery to occur.
• They are not important clinically for their therapeutic uses as they are for toxicity and poisoning.
• The organophosphorus compounds are highly lipid soluble (exception is echothiophate) and they have high vapour pressures (volatile).
• These characters make them extremely dangerous.
• Metabolism may activate (eg. Parathion to paraoxon) and deactivation is by hydrolysis in the liver.
• They are eliminated almost entirely as hydrolysis products in urine.