≈ neostigmine; duration of action 3-6 hours (more suitable in chronic treatment of myasthenia gravis).
≈ neostigmine; duration of action 10-20 min (used in diagnosis of myasthenia gravis, or as curare antidote).
Newer centrally acting agents (tacrine, donepezil, galanthamine, rivastigmine) – used in treatment of Alzheimer disease (žr. S11 p.)
- covalently bind to acetylcholinesterase& pseudocholinesterase.
enzyme molecule is inactivated (activity restoration requires synthesis of new enzyme molecules); “aging” – inactivated enzyme molecule slowly releases alkyl group and so becomes permanently inactivated (impossible to reactivate).
extremely toxic synthetic agents:
military nerve agents (convulsions, breathing muscle paralysis); newer military agents “age” in minutes ÷ seconds.
clinical features – general cholinergic effects (muscarinic + nicotinic + CNS);
toxicity manifests when > 50% acetylcholinesterase is inactivated.
garlic-like / petroleum-like odor in patient’s breath.
1-3 weeks after initial exposure, organophosphate-induced delayed polyneuropathy (OPIDP) may develop - distal dying back axonopathy - cramping muscle pain in legs, paresthesias, motor weakness (e.g. foot drop, weakness of intrinsic hand muscles, absent ankle jerk, weakness of hip and knee flexors).
erythrocyte (true) cholinesterase – gold standard (reflects enzyme activity in neural tissues) – below 70% of normal.
plasma (pseudo) cholinesterase – levels affected by many other conditions.
urine screen for metabolites.
ABCDo not use morphine, aminophylline!
benzodiazepines for seizures
decontamination (avoid self-contamination - wear protective clothing, masks, gloves!) – gastric lavage with charcoal, skin flushing with water and soap.
atropine in high doses (1-2 mg IM q1h) can reverse many muscarinic and CNS effects.
tachycardia is not contraindication.
end point for atropine administration is drying of bronchial secretions.
Acetylcholinesterase reactivation – pralidoxime (PAM) 1 g IV:
effective only if given before “aging” (but late presentation does not preclude administration).
acts at nicotinic receptors; cannot reverse CNS effects (drug molecule has charged group).