Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuroprotective role of P-glycoprotein, a multixenobiotic resistance transporter (ABCB1/MDR1), in the blood-brain barrier in fish was examined using behavioural toxicological assays. P-glycoprotein acts as cellular efflux pump to prevent substrates from accumulating in the brain, including environmental contaminants such as ivermectin, a common aquaculture pesticide and mammalian anti-parasitic drug. The behavioural toxicological assays were developed to determine the neuropathological effect of ivermectin in killifish (Fundulus heteroclitus). P-glycoprotein function and thus blood-brain barrier integrity can be compromised by chemosensitizers that inhibit transport activity. Fish treated with ivermectin and the P-glycoprotein inhibitor cyclosporin A were significantly more sensitive and succumbed more rapidly to tilting, lethargy, slowing of pectoral-fin movement and loss of haptic-reactivity compared to fish treated with ivermectin-only. P-glycoprotein inhibition is associated with significantly earlier onset and increased mortality in ivermectin-exposed fish. Our results suggest that P-glycoprotein confers resistance against ivermectin-induced behavioural neuropathology and mortality in fish. This assay provides us with a non-invasive tool to study P-glycoprotein function in the blood-brain barrier and evaluate the behavioural effects of potential environmental neurotoxins.
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PMID:Assessing neuroprotective P-glycoprotein activity at the blood-brain barrier in killifish (Fundulus heteroclitus) using behavioural profiles. 1788 28

A Chinese shar pei with a 2 yr history of episodic fever, lethargy, and shifting lameness was presumptively diagnosed with familial shar pei fever but had never been treated for the syndrome. After being presented for a superficial pyoderma with possible dermatophyte coinfection, treatment with a cephalosporin and ketoconazole were prescribed. One wk later, colchicine was initiated for familial shar pei fever using cautious dose escalation. Nevertheless, gastrointestinal toxicity, skeletal muscle myopathy, and hepatotoxicity developed within 2 wk. Abrupt resolution of gastrointestinal toxicity and myopathy followed drug withdrawal. However, escalating liver enzyme activity and hyperbilirubinemia led to liver biopsy to rule out an antecedent hepatopathy. Biopsy characterized canalicular cholestasis and colchicine-associated metaphase arrest and ring mitoses reflecting repression of mitotic spindle formation. Signs of illness completely resolved 3 mo after drug discontinuation. Although avoidable adverse interactions between ketoconazole and drugs reliant on cytochrome oxidase biotransformation and/or drug efflux mediated by multiple drug-resistant transporters are well documented in humans, these are rarely reported in veterinary patients. This case exemplifies an important and avoidable ketoconazole/colchicine drug interaction from which the patient completely recovered. The dog tested negative for the canine MDR1 loss of function mutation that also might potentiate colchicine toxicity.
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PMID:Adverse interaction between colchicine and ketoconazole in a Chinese shar pei. 2537 34

In high-dose intake of phenytoin, which is used frequently to treat epilepsy, nystagmus, diplopia, nausea-vomiting, lethargy, confusion, seizure, and coma can be observed. In recent studies on phenytoin intoxication, in which seizure and coma were observed in drug levels greater than 50 ug/mL. The serum phenytoin level of a patient, who consumed approximately 100 pcs of 100 mg phenytoin tablets in an effort to commit suicide, and who had no pathological finding in her neurologic examination, was 124 ug/mL. High drug level and the absence of toxic effect (or the absence of toxic effect correlated with the drug level) indicates that cytochrome P450 is functioning, but there can be a mutation in the MDR1 gene. In our case study, we report on phenytoin intoxication in a patient having a high level of phenytoin but no symptoms correlated with serum drug level, as supported by the findings in the literature.
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PMID:Phenytoin intoxication with no symptoms correlated with serum drug level: a case study. 2696 93