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 pathogenesis of the rare hypernatremia, usually described in the literature as "neurogenic" or "essential" hypernatremia, consists of defective thirst mechanism either alone or in combination with impaired osmoregulation of ADH release. As etiology, disturbances of the neoplastic, vascular and degenerative type and malformations in the hypothalamic area are known. In patients with the hypodipsia-hypernatremia syndrome, dysfunction of the anterior pituitary lobe, obesity, abnormal regulation of body temperature, psychomotor retardation and episodic muscular weakness are frequently encountered as additional abnormalities. A 6-year-old patient is described with hypodipsia-hypernatremia syndrome manifest for 3 years. Besides hypernatremia, hypodipsia and the relative insensitivity of the osmoreceptors regulating ADH release, elevated body temperature, polyphagia and obesity, partial hypothalamic-hypophyseal dysfunction, lethargy and psychomotor retardation are the principal findings. An inflammatory lesion or one occupying an intracranial space was not demonstrable until now. Under forced water intake and hypocaloric diet the patient has progressed well with nearly complete normalization of the hypernatremia, body temperature and obesity.
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PMID:Hypodipsia-hypernatremia syndrome. 42 94

Ethylene glycol (EG) is a toxic chemical found in antifreeze and heat exchangers. Standard therapy for EG intoxication in administration of ethanol (ETOH) to inhibit its metabolism by alcohol dehydrogenase (ADH). Studies indicate 1,3-butylene glycol (BG) binds to ADH more efficiently than EG and is orally less toxic than EG or ETOH. Male rats were divided into 5 groups of 6 animals. Groups received by oral intubation a single dose of EG (32 mmole/kg), BG (39 mmole/kg) initially and every 6 h up to 72 h, ETOH (39 mmole/kg) initially and every 6 h up to 72 h, or EG initially and then either BG or ETOH every 6 h up to 72 h. Administration of ETOH produced hepatotoxicity and pulmonary pathology as indicated by changes in clinical chemistry, urinalysis, and histopathology, while BG did not. Neither ETOH nor BG produced any apparent nephrotoxicity. ETOH produced ataxia, lethargy and central nervous system depression while BG did not. BG produced a higher concentration of urinary EG indicating a better inhibition of ADH metabolism of EG. Ethanol produced a higher EG blood concentration than BG. Ethanol's higher EG blood concentration may be partially attributed to dehydration and a decreased urine output as well as inhibition of ADH metabolism. Ethanol produced mortality in all animals prior to 72 h. The EG/ETOH combination produced mortality more quickly due to additive toxicity of the combination. Lack of any significant toxicity produced by BG and the production of significant toxicities by ETOH indicates that BG is potentially a better antidote than ETOH.
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PMID:The toxicokinetics of 1,3-butylene glycol versus ethanol in the treatment of ethylene glycol poisoning. 162 60

Many psychiatric patients have polydipsia and polyuria without identifiable underlying medical causes. Hyponatremia develops in some polydipsic patients and can progress to water intoxication with such symptoms as confusion, lethargy, psychosis, and seizures or death. This syndrome is sometimes called "compulsive water drinking," "psychogenic polydipsia," and "self-induced water intoxication." Although the underlying pathophysiology of the syndrome is unclear, several factors have been implicated in producing polydipsia and symptomatic hyponatremia. These include a possible hypothalamic defect, the syndrome of inappropriate secretion of ADH (SIADH), and neuroleptic medication. Evaluation of psychiatric patients with polydipsia includes a search for other medical causes of polydipsia, polyuria, hyponatremia, and SIADH. Treatment modalities currently available include fluid restriction and medications.
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PMID:Polydipsia and hyponatremia in psychiatric patients. 328 1

2-Chloroacetaldehyde (CAA) formed during the metabolism of the anti-cancer drug ifosfamide (IP) has been implicated in ifosfamide-related neurotoxicity during chemotherapy but the neurotoxic mechanisms are unknown. We have found that IP (900 mg kg-1, p.o.) caused lethargy and mild hind limb paralysis after 6 h. Neurotoxicity and IP-induced mortality was markedly enhanced in mice pretreated with either phenobarbital or dexamethasone to induce cytochrome P4503A. Cerebral glutathione (GSH) levels were also markedly depleted in these pretreated mice. 2-Chloroethanol (92 mg kg-1, i.p.) (CE) also caused a 50% reduction in cerebral GSH 6 h after administration to mice. At this time maximum lethargy and unresponsiveness to touch was apparent in CE-treated mice. Severe hind limb paralysis developed and death ensued 12-18 h later. Prior depletion of cerebral GSH with 2-cyclohexene-1-one greatly accelerated the onset of CE-induced neurotoxicity suggesting that cerebral GSH status is an important determinant of CE-induced neurotoxicity. Furthermore, pretreatment with N-acetylcysteine delayed both CE-induced neurotoxicity and cerebral GSH depletion. Induction of cerebral but not hepatic CYP2E1 by ethanol before CE challenge also potentiated CE-induced cerebral GSH depletion and neurotoxicity. Hepatic GSH depletion was unaffected suggesting that CE-induced paralysis is dependent on a cerebral but not a hepatic CYP2E1 catalysed oxidation of CE to CAA. Ethanol was neuroprotective even if given 60 min after CE and prevented further cerebral GSH depletion. 4-Methylpyrazole, a CYP2E1 and alcohol dehydrogenase inhibitor, prevented both CE-induced hepatic and cerebral GSH depletion and paralysis. This suggests that the neurotoxicity associated with IP chemotherapy involves activation of chloroethanol by cerebral CYP2E1 to chloroacetaldehyde which mediates cerebral GSH depletion. Neurotoxicity may be prevented by restoring cerebral GSH status and/or by preventing activation of CE by CYP2E1 with ethanol.
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PMID:2-Chloroacetaldehyde-induced cerebral glutathione depletion and neurotoxicity. 876 99