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22 Cards in this Set
- Front
- Back
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AChE loci
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RBC, placenta, vascular tissue
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Fcn butycholinesterase
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breaks down succinyl, propyl, & butylcholine. Nonspecific
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Diff b/w BUCHE & AChE to diisopropylphosphate
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BUCHE is more sensitive to DHP
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Structure & fcn of AChE
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Ser, Glu, His in active site. Trp & Tyr in choline bing site. Ammonium binds @ choline site & acetyl binds a @ triad
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Process after binding
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release choline 1st leaves acetyl. Then acetate released 2nd
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What are the noncovalent inhibitors
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edrophonium, tacrine, donepezil
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edrophonium: absorption, distribution, MA
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(4amine) but water soluble, need large oral dose clinically. Short half life
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Tacrine & Donepezil: absorption, distribution, MA
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3amines. Metabolized by CYP450
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Carbamates
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(Reversible) neostigamine (4amine), pyridostigmine (4amine), physostigmine (3amine), & rivastigmine (3amine)
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Carbamate Mech of action
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React w/ serine in active site & forms carbamate AChE that is more stable than acetylated AChE
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Absorption of neo & pyridostigamine
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(4amine) but can be over come w/ large dose
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Organophosphates
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Diisopropylfluorophosphate (DFP), Echothiophosphate, parathion, & malathion
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Organophosphate mech action
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Irreversible inhibitor. Makes very stable intermediate. Enzyme recovery takes days.
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Organophosphate absorption, distribution, elimin
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Highly lipid soluble. Absorbed through skin, enter CNS. Thiophosphates must be meta to phosphates in the body
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Pharm effects of AChE
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Potentiates & prolongs actions of cholineric & muscarinic stim
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Clinical use in reversal of nondepol NMJ blockade
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Neostigamine. Inc levels of Ach to overcome competitive antag
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AChE clinical use in myasthenia gravis
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Disease results from the dec in nic receptors. iv edrophonim used to diagnose b/c of short duration Neo, pyridostigamine, & ambenonium to treat. Corticosteriods & cyclosporine added in resistant cases
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AChE use in glaucoma
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Closed angle need surgery. Open angle: use pilocarpine (miotic) or timolol (dec production) initially. Physostigmine used occassionally. Long acting demecarium or echothiophate if all else fails
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AChE clinical use in Alzheimer's Disease
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Disease due to a loss of cholinergic neurons. Tacrine no longer used due to toxicity & short duration. Donepezil high selective, very long half life, & little toxicy. Rivastigmine long half life, transdermal patch w/ low peak is better tolerated, no p450
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Rx for acute AChE inhibitor poisoning
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Atropine + pralidoxime, decontaminate, ventilate, diazepam for convulsions
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What is mech of atropine + pralidoxime
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Pralidoxime (2-PAM) causes phosphorylation & reactivation of AChE in the periphery (notCNS). Must give atropine w/i min or enzyme will rephosphorylate. Soman poisoning is not treated w/ 2-PAM (must give in min
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What is sig of giving pyridostigmine prophylaxis
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Soldiers given in anticipation of chemical warfare w/ nerve gas (soman). Forms carbamoyl-AChE to preent organos from reacting w/ AChE
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