their action promoting accumulation of ach at muscarinic or nicotinic receptors is the basis of...
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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
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)
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)
Quaternary ammonium compounds do not cross the blood-brain barrier
For oral administration, high doses must be given
Carbamyl Inhibitors of AChE (4)
Neostigmine Carbamylates Acetylcholinesterase
Slow Hydrolysis of Carbamylated-AChE and Enzyme Liberation
Organophosphate Inhibitors of Acetylcholinesterase
Chemical characteristics
Promote accumulation of ACh at NM nicotinic receptor NN nicotinic receptor Muscarinic receptor
Organophosphate Inhibitors of Acetylcholinesterase (1)
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)
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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