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)

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

Three patients had neurologic signs due to isopropyl alcohol (IPA) intoxication. Over a several-week period, a known alcoholic developed apathy, confusion, ataxia, and hyperreflexia. During this period, there was no ethanol available to him, and he denied use of other intoxicants. He was found stuporous in the hospital after drinking IPA and admitted to IPA abuse during the preceding weeks. Two other men were admitted in a stupor after large ingestions of IPA. Intoxication with IPA has two different presentations: stupor in a known alcoholic and encephalopathy of unknown cause in individuals who hide their addiction. Ethanol, methanol, IPA, and ethylene glycol intoxications are associated with different clinical and laboratory findings.
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PMID:Isopropyl alcohol intoxication. 198 19

Ethanol withdrawal (ETX) in ethanol-dependent rats results in susceptibility to seizures, including generalized tonic-clonic audiogenic seizures (AGS). The inferior colliculus (IC) is strongly implicated in AGS initiation during ETX, but IC neuronal mechanisms subserving AGS are unclear. The present study examined IC (central nucleus) single neuronal firing during repeated (4 day) intragastric ethanol administration and during ETX. This involved microwire electrodes implanted chronically into freely moving rats and acoustic stimulation in intensities up to 105 dB SPL. During initial ethanol administration the animals were stuporous, and IC spontaneous neuronal firing and acoustically evoked firing at high stimulus intensities were significantly reduced. This firing reduction is consistent with the action of ethanol to enhance gamma-aminobutyric acid (GABA)-mediated inhibition, which is prominent in IC neurons at high stimulus intensities. During ETX the animals were agitated, and spontaneous IC neuronal firing and acoustically evoked firing at all stimulus intensities were significantly increased during the period of AGS susceptibility. Previous studies indicate that IC neuronal responses are tightly regulated by GABA and glutamate. The IC firing increases during ETX in the present study may involve the down-regulation of GABAA receptors and supersensitivity of glutamate receptors reported to occur during ETX. Previous studies also indicate that focal blockade of GABAA receptors or activation of glutamate receptors produces AGS susceptibility in normal rats. Therefore, the IC neuronal firing increases observed in the present study may play a critical role in initiation of AGS during ethanol withdrawal.
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PMID:Ethanol withdrawal induces increased firing in inferior colliculus neurons associated with audiogenic seizure susceptibility. 772 Aug 30

Methanol intoxication can be a challenge, in part because it is relatively uncommon but also because of the pharmacokinetics involved. A patient may not experience symptoms and thus may not present for treatment for several hours, or even a day or two, after exposure to the toxic substance. Yet, the interval between ingestion and treatment is one of the most important factors in determining patient outcome. Typical symptoms of methanol intoxication include lethargy, vertigo, vomiting, blurred vision, and decreased visual acuity. Treatment focuses on prevention of methanol conversion to its toxic metabolites, correction of metabolic acidosis, and elimination of the toxic substances from the system. Ethanol and bicarbonate administration and hemodialysis have been effective.
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PMID:Methanol intoxication. How to help patients who have been exposed to toxic solvents. 838 47

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