Oxime therapy and chronic organophosphate neurotoxicity
THE CONTEXT
The passage continues pralidoxime treatment, explains the limits of oxime therapy and describes delayed neurological effects of repeated organophosphate exposure.
Pralidoxime administration and timing
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The loading dose is followed by a continuous infusion of 8–10 mg/kg/hour until recovery.
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Pralidoxime produces more marked cholinesterase reactivation in skeletal muscle than at autonomic sites. It does not reactivate central cholinesterase because it does not penetrate the brain.
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Treatment should begin as early as possible, within a few hours, before phosphorylated enzyme undergoes aging and becomes resistant to hydrolysis.
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Doses may be repeated as needed, with a stated maximum of 12 g in the first 24 hours. Lower doses according to symptoms may continue for 1–2 weeks.
Role and variability of oxime therapy
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Oximes are adjuncts to atropine, which remains the primary antidote.
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Clinical benefit varies with the organophosphate involved, its aging rate, the amount of poison absorbed, the delay before treatment and the oxime dose.
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Other oximes mentioned are obidoxime, which is more potent than pralidoxime, and diacetyl-monoxime, which is lipophilic.
Chronic organophosphate poisoning
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Repeated exposure to certain fluorine-containing and triaryl organophosphates causes polyneuritis and demyelination after a latent period of days to weeks.
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Sensory disturbances occur first, followed by muscle weakness, tenderness, depressed tendon reflexes and lower motor neuron paralysis.
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In a second phase, spasticity and upper motor neuron paralysis gradually develop. Recovery may take years.
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The mechanism is unknown but is not due to cholinesterase inhibition. There is no specific treatment.
Myasthenia gravis presentation
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The clinical case describes double vision, drooping eyelids, difficulty chewing and limb weakness accentuated by exercise, with symptoms fluctuating over time; a provisional diagnosis of myasthenia gravis is made.