Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gamma-hydroxybutyrate (GHB) is encountered in biological specimens as an endogenous neuromodulator, recreational drug, or therapeutic agent. Clinically, the drug is useful for the treatment of cataplexy. Illicit doses are typically 2-4 g, and the onset of action is rapid, occurring 15-30 min following oral ingestion. Dose-dependent effects include drowsiness, euphoria, dizziness, vomiting, respiratory depression, coma, and death. GHB was isolated from biological samples using a simple liquid-liquid extraction. The trimethylsilyl derivative (GHB-di-TMS) was analyzed using gas chromatography-mass spectrometry with positive chemical ionization. Deuterated internal standard and selective ion monitoring were used throughout. We report a GHB fatality involving a 35-year-old male who was partying with friends. Subjects at the party ingested unknown quantities of wine and GHB. A female companion at the party reported seeing the male alive before she herself passed out. She awoke to find the decedent cold and stiff. Postmortem specimens were submitted for comprehensive toxicology testing. No alcohol or common drugs of abuse were detected. A targeted analysis revealed GHB in urine, brain, vitreous fluid, femoral blood, heart blood, and liver at concentrations of 1665 mg/L, 102 mg/kg, 48 mg/L, 461 mg/L, 276 mg/L, and 52 mg/kg, respectively. Concentrations of the drug in urine and vitreous fluid are important in death investigations because of significant postmortem production of GHB in blood specimens. The cause of death was attributed to GHB intoxication, and the manner of death was accidental.
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PMID:Distribution of GHB in tissues and fluids following a fatal overdose. 1610 69

gamma-Hydroxybutyrate (GHB) is an endogenous short chain fatty acid and a, mostly oral, pharmacological compound that has been utilised in a variety of ways. Endogenously, GHB is synthesised locally within the CNS, mostly from its parent compound GABA. Sodium oxybate is the sodium salt of GHB and is used for the exogenous oral administration of GHB. It is likely that supraphysiological concentrations of GHB from exogenous administration produce qualitatively different neuronal actions than those produced by endogenous GHB concentrations. Evidence suggests a role for GHB as a neuromodulator/neurotransmitter. Under endogenous conditions and concentrations, and depending on the cell group affected, GHB may increase or decrease neuronal activity by inhibiting the release of neurotransmitters that are co-localised with GHB. After exogenous administration, most of the observed behavioural effects appear to be mediated via the activity of GHB at GABA(B) receptors, as long as the concentration is sufficient to elicit binding, which does not happen at endogenous concentrations. Endogenous and exogenous GHB is rapidly and completely converted into CO(2) and H(2)O through the tricarboxylic acid cycle (Krebs cycle). Sodium oxybate has been observed to modulate sleep in nonclinical study participants, and sleep and wakefulness in clinical populations, including groups with insomnia, fibromyalgia and narcolepsy. In narcolepsy, sodium oxybate has shown dose-related effects on various properties of sleep, including increases in slow-wave sleep duration and delta power, and a reduced number of night-time awakenings. Furthermore, multiple measures of daytime sleepiness and cataplexy demonstrated consistent short- and long-term improvement in response to night-time sodium oxybate therapy. The most common reported adverse events include dose-related headache, nausea, dizziness and somnolence.
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PMID:gamma-Hydroxybutyrate/sodium oxybate: neurobiology, and impact on sleep and wakefulness. 1714 Feb 79

(1) Narcolepsy is characterised by sudden, overwhelming daytime drowsiness, sometimes associated with cataplexy (more or less complete loss of muscle tone during an emotional reaction). (2) Modafinil moderately reduces daytime drowsiness but has no effect on cataplexy. Methylphenidate, an amphetamine psychostimulant, seems to act on both drowsiness and cataplexy, although its clinical evaluation is limited to observational series. (3) Oxybic acid, long used in general anaesthesia, but also misused for recreational and criminal purposes (chemical or drug-induced submission), has been approved to treat adults with both narcolepsy and cataplexy, in the form of an oral solution of sodium oxybate. (4) The rationale behind the use of sodium oxybate is to re-establish a near-normal pattern of the different phases of sleep. Because of its short-lasting action, sodium oxybate has to be taken once at bedtime and then again 2.5 to 4 hours later. (5) Clinical evaluation mainly consists of 4 double-blind placebo-controlled trials of sodium oxybate. Three short-term trials, involving 136 patients treated for 4 weeks and 228 and 270 patients treated for 8 weeks, showed that sodium oxybate at a dose of 4.5 g to 9 g a day reduced the number of cataplexy attacks but that a dose of at least 6 g was needed to reduce daytime drowsiness. A trial involving 56 patients who had been taking sodium oxybate for nearly 2 years, assessed the effects of stopping versus continuing treatment. The results suggest that sodium oxybate is effective in the long term. (6) During clinical trials, 61% of patients had adverse effects attributed to sodium oxybate. These included gastrointestinal disorders (nausea (18%)), neurological disorders (dizziness (15%), headache (6%)), confusion (3%), and enuresis (7%). (7) Altered consciousness and respiratory depression occurred after a single intake of a dose two or three times higher than the recommended dose. (8) Misuse, especially to obtain chemical or drug-induced submission (i.e. as a 'date rape' drug), is facilitated by the odourless and colourless nature of the oral solution. (9) In practice, for some patients who are seriously affected by persistent episodes of cataplexy or drowsiness, despite treatment of narcolepsy, sodium oxybate is preferable to methylphenidate, which has been less thoroughly evaluated. However, the risks of misuse and overdose mean that this drug should only be proposed to patients in whom the benefits are likely to outweigh the risks.
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PMID:Sodium oxybate: new drug. Fewer attacks of cataplexy in some patients. 1758 23