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)