Acetylcholinesterase inhibitors antidotes

ACh receptors are destroyed by endocytosis via coated pits and proteolysis in lysosomes. In myasthenia gravis, the receptors are crosslinked by antireceptor antibodies, which facilitate the rate-limiting endocytosis step receptor destmction occurs in less than half the normal time, resulting in net receptor loss. The chronic disease is characterized clinically by such muscular weakness and abnormal fatigue that patients cannot even keep their eyes open. Acetylcholinesterase inhibitors increase the ACh concentration and excitation of the neuromuscular junction, resulting in increased strength and endurance. As expected, AChE inhibitors are also potent curare antidotes because the increased ACh levels displace the blocker more readily. 

Galantamine (Razadyne) [Cholinesterase Inhibitor] Uses Alzheimer Dz Action Acetylcholinesterase inhibitor Dose 4 mg PO bid, T to 8 mg bid after 4 wk may T to 12 mg bid in 4 wk Caution [B, ] T Effect w/ suc-cinylcholine, amiodarone, dildazem, verapamil, NSAIDs, digoxin X- effect w/ anticholinergics, T risk of death vs placebo Contra Severe renal/hepadc impair Disp Tabs, soln SE GI disturbances, wt loss, sleep disturbances, dizziness, HA Interactions T Effects W/ amitriptyline, cimeddine, erythromycin, fluoxetine, fluvoxamine, ketoconazole, paroxetine, quinidine EMS Use succinylcholine w/ caudon, may need a reduced dose monitor ECG for induced conduction abnormalities OD May cause cholinergic Sxs (SLUDGE), muscle weakness, resp depression, and Szs atropine may be used as antidote... 

Marginally easier to break are some covalent bonds that link atoms other than carbon, although a swamping excess of the reagent is usually required. Two examples the restoration by mercaptan antidotes of cells poisoned by arsenicals (exchange of one As—S bond for another), and rescue of a victim poisoned by an acetylcholinesterase inhibitor, using an oxime antidote (exchange of one P—O bond for another), as described in Sections 12.0 and 12.3 respectively. 

The antidotes cannot be used to cure poisoning by carbamates because they may react with the carbamate and make a more potent inhibitor. The easy methods available for determining the potency of inhibitors make it possible to test the relationship between structure and activity, and to try to find inhibitors that work better for insect acetylcholinesterase than for the mammalian enzyme. 

Atropine is the primary antidote for poisoning due to inhibitors of acetylcholinesterase, including carbamate (eg, physostigmine) and organophosphate insecticides (eg, malathion). Prali-doxime may be administered to regenerate inactivated enzyme in poisoning due to insecticides. The answer is (J). 

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