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Carbamyl Inhibitors of AChE (1)

Their action promoting accumulation of ACh at muscarinic or nicotinic receptors is the basis of their pharmacological, therapeutic, and toxic actions Are derivatives of carbamic acid Bind covalently to the esteratic site of AChE, resulting in carbamylation of the enzyme.

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Carbamyl Inhibitors of AChE (1)

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  1. Their action promoting accumulation of ACh at muscarinic or nicotinic receptors is the basis of their pharmacological, therapeutic, and toxic actions Are derivatives of carbamic acid Bind covalently to the esteratic site of AChE, resulting in carbamylation of the enzyme Carbamyl Inhibitors of AChE (1) Carbamic acid Carbamic acid ester

  2. Quaternary compounds bind to the ionic binding site of AChE Their induce accumulation of AChE at nicotinic and muscarinic sites, producing pharmacological responses qualitative to cholinergic stimulation Inhibition of AChE is reversible, in the order of hours Are metabolized in the plasma by plasma esterases Carbamyl Inhibitors of AChE (2)

  3. High doses produce skeletal muscle weakness due to depolarizing blockade at the end plate of the neuromuscular junction High doses produce a profound fall in cardiac output and blood pressure Their inhibition of AChE is not reversed by pralidoxime Carbamyl Inhibitors of AChE (3)

  4. Quaternary ammonium compounds do not cross the blood-brain barrier For oral administration, high doses must be given Carbamyl Inhibitors of AChE (4)

  5. Neostigmine Carbamylates Acetylcholinesterase

  6. Slow Hydrolysis of Carbamylated-AChE and Enzyme Liberation

  7. Organophosphate Inhibitors of Acetylcholinesterase

  8. Chemical characteristics Promote accumulation of ACh at NM nicotinic receptor NN nicotinic receptor Muscarinic receptor Organophosphate Inhibitors of Acetylcholinesterase (1)

  9. Their action promoting accumulation of ACh at the muscarinic receptor of the ciliary muscle is the basis of their therapeutic effectiveness in open angle glaucoma Only two of these agents are used for therapeutics Echothiophate for glaucoma Diisopropylflurophosphate (DFP) for glaucoma (?) Organophosphate Inhibitors of AChE (2)

  10. Inhibition of AChE by these agents is irreversible New enzyme synthesis is required for recovery of enzyme function They also inhibit pseudocholinesterase Metabolized by A-esterases (paroxonases) present in plasma and microsomes. They are metabolized by CYP450. Organophosphate Inhibitors of AChE (3)

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