pralidoxime and Nervous-System-Diseases

Organophosphate poisoning by oral or inhalation routes is characterized by a typical time-course of clinical features.. We report a case of subcutaneous chlorpyrifos self-injection leading to a delayed cholinergic phase, prolonged coma, and severe permanent neurologic injury with electrophysiological patterns suggestive of overlapping intermediate syndrome and distal peripheral neuropathy. Time-course and severity of clinical features were not altered by either atropine or pralidoxime administration. Due to prolonged and severe alteration in consciousness, we used brain multimodal nuclear magnetic imaging and auditory cognitive event-related potentials to assess the patient's potential for awakening. Electrophysiological testing used to monitor muscle weakness showed the coexistence of 20 Hz-decremental responses in proximal muscles and severe denervation in distal muscles. Red blood cell acetylcholinesterase activity progressively normalized on day 60, while plasma butyrylcholinesterase activity remained low until day 100. Chlorpyrifos was detectable in serum until day 30 and urine metabolites for up to three months, supporting the hypothesis of a continuous chlorpyrifos release despite repeated surgical debridement. We suggest that adipose and muscle tissues acted as a chlorpyrifos reservoir. At one-year follow-up, the patient exhibited significant neuromuscular sequelae.. Subcutaneous chlorpyrifos self-injection may result in severe toxicity with prolonged neurologic injury, atypical overlapping electrophysiological patterns, and a poor final outcome.

Topics: Antidotes; Atropine; Brain; Chlorpyrifos; Humans; Injections, Subcutaneous; Insecticides; Magnetic Resonance Imaging; Male; Muscarinic Antagonists; Nervous System Diseases; Poisoning; Pralidoxime Compounds; Suicide, Attempted; Treatment Outcome; Young Adult

This investigation compared the efficacy of diazepam and the water-soluble prodiazepam-avizafone-in sarin poisoning therapy. Guinea pigs, pretreated with pyridostigmine 0.1 mg/kg, were intoxicated with 4LD(50) of sarin (s.c. route) and 1 min after intoxication treated by intramuscular injection of atropine (3 or 33.8 mg/kg), pralidoxime (32 mg/kg) and either diazepam (2 mg/kg) or avizafone (3.5 mg/kg). EEG and pneumo-physiological parameters were simultaneously recorded. When atropine was administered at a dose of 3 mg/kg, seizures were observed in 87.5% of the cases; if an anticonvulsant was added (diazepam (2 mg/kg) or avizafone (3.5 mg/kg)), seizure was prevented but respiratory disorders were observed. At 33.8 mg/kg, atropine markedly increased the seizure threshold and prevented early respiratory distress induced by sarin. When diazepam was administered together with atropine, seizures were not observed but 62.5% of the animals displayed respiratory difficulties. These symptoms were not observed when using avizafone. The pharmacokinetic data showed marked variation of the plasma levels of atropine and diazepam in different antidote combination groups, where groups receiving diazepam exhibited the lowest concentration of atropine in plasma. Taken together, the results indicate that avizafone is suitable in therapy against sarin when an anticonvulsant is judged necessary.

Topics: Animals; Anticonvulsants; Atropine; Brain; Chemical Warfare Agents; Cholinesterase Inhibitors; Diazepam; Dipeptides; Drug Interactions; Electroencephalography; Guinea Pigs; Histocytochemistry; Muscarinic Antagonists; Nervous System Diseases; Pralidoxime Compounds; Prodrugs; Pyridostigmine Bromide; Respiratory Insufficiency; Sarin; Seizures

Organophosphate insecticides strongly inhibit both true cholinesterase and pseudocholinesterase activities. In this report, we have reported a patient who injected himself a strong organophosphate compound, methamidophos, and showed the typical clinical picture of organophosphate intoxication. As far as we know, this is the first case of intoxication by intravenous (i.v.) injection. With the appropriate therapy, his symptoms disappeared in a few days.

Topics: Adult; Antidotes; Atropine; Cholinesterase Inhibitors; Cholinesterase Reactivators; Humans; Injections, Intravenous; Insecticides; Male; Muscarinic Antagonists; Nervous System Diseases; Organothiophosphorus Compounds; Pralidoxime Compounds; Schizophrenia; Suicide, Attempted

Reflex sympathetic dystrophy or Sudeck's atrophy is a syndrome that can usually be followed by a traumatic insult. This disorder is accompanied by signs and symptoms of vasomotor instability, trophic skin changes, and rapid development of bony demineralization. This report presents a case with reflex sympathetic dystrophy syndrome secondary to organophosphate intoxication induced neuropathy. The patient was threated with calcitonin well.

Topics: Action Potentials; Adult; Atropine; Bone and Bones; Calcitonin; Cholinesterase Reactivators; Dimethoate; Electromyography; Follow-Up Studies; Humans; Male; Median Nerve; Motor Neurons; Muscle, Skeletal; Nervous System Diseases; Pralidoxime Compounds; Radiography; Radionuclide Imaging; Reflex Sympathetic Dystrophy; Ulnar Nerve

The ability of a supralethal dose of chlorpyrifos to produce delayed neuropathy was examined using assessments of clinical signs, electromyography (EMG), motor nerve conduction velocity (MNCV), lymphocyte neuropathy target esterase activity (LNTE), and histologic changes in nervous system tissues. Cats were exposed to a single, im injection of corn oil (vehicle control), DFP (positive control) at 5.0 mg/kg, or chlorpyrifos at 300 mg/kg and observed for 60 days. Atropine and 2-PAM were administered to chlorpyrifos exposed cats one to two times a day for 14 to 24 days in response to the appearance of cholinergic signs. Anorectic cats during the acute toxicosis were force fed by hand and hydration was maintained by administering fluids sc. Onset of ataxia (mean +/- SD) for the positive control and chlorpyrifos exposed cats were 16.2 +/- 1.8 days (range of 14-19 days) and 19.0 +/- 1.4 days (range of 17-21 days), respectively. Functional deficits for both groups were confined to the hindlimbs and characterized by a crouched-waddling gait, hypermetria, and proprioceptive deficits. Maximal inhibition of LNTE activity was 96% at 24 hr postdosing in the positive control group and 46% at 7 days postdosing in the chlorpyrifos group. No EMG or MNCV abnormalities were detected in any of the treatment groups. Axonal degeneration was similar for the positive control and chlorpyrifos exposed cats. Ascending tracts of the cervical spinal cord and descending tracts of the thoracic and lumbar spinal cord were most severely affected and peripheral nerves were only mildly affected. The clinical and histologic effects produced indicate that chlorpyrifos can cause delayed neuropathy in the domestic cat. The moderate but prolonged inhibition of LNTE produced by chlorpyrifos is atypical of classic organophosphorus delayed neurotoxicants.

Topics: Animals; Antidotes; Atropine; Carboxylic Ester Hydrolases; Cats; Chlorpyrifos; Cholinesterases; Diazepam; Electromyography; Isoflurophate; Lymphocytes; Male; Motor Neurons; Nervous System Diseases; Neural Conduction; Pralidoxime Compounds; Time Factors

The efficacy of oxime (HI-6, toxogonin or PAM Cl) therapy against GF (cyclohexyl methylphosphonofluoridate) poisoning was assessed in mice. It was found that the combinations of atropine and either toxogonin or HI-6 were effective therapies against GF poisoning. PAM therapy was ineffective. HI-6 was the only oxime which reactivated GF inhibited acetylcholinesterase. This might explain the reason why the HI-6 treated mice appeared to recover more quickly from the incapacitating effects following GF poisoning.

Topics: Animals; Antidotes; Atropine; Chemical Warfare Agents; Cholinesterase Reactivators; In Vitro Techniques; Lethal Dose 50; Male; Mice; Mice, Inbred Strains; Nervous System Diseases; Obidoxime Chloride; Organophosphate Poisoning; Organophosphorus Compounds; Oximes; Pralidoxime Compounds; Pyridinium Compounds

Topics: Animals; Antidotes; Atropine; Carboxylic Ester Hydrolases; Chickens; Dose-Response Relationship, Drug; Female; Insecticides; Lethal Dose 50; Male; Nervous System Diseases; Organothiophosphorus Compounds; Pralidoxime Compounds; Rats; Rats, Inbred Strains