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Gamma Hydroxybutyrate


Presentation

  • METHODS: A toxicology database was used to identify patients presenting with a history suggestive of withdrawal from GHB and analogues.[ncbi.nlm.nih.gov]
  • Emergency physicians must consider withdrawal from these agents when patients present with clinical features suggestive of a sedative-hypnotic withdrawal syndrome.[ncbi.nlm.nih.gov]
  • Gamma-hydroxybutyrate (GHB) withdrawal syndrome is increasingly encountered in emergency departments among patients presenting for health care after discontinuing frequent GHB use.[ncbi.nlm.nih.gov]
  • We report two cases from Kansas City where the patients presented in, or developed profound coma.[ncbi.nlm.nih.gov]
  • I present a case report of a death following the use of gamma-hydroxybutyrate (GHB) in combination with alcohol; this was the third death reported in the UK, with, to date, at least 27 deaths in America.[ncbi.nlm.nih.gov]
Falling
  • Small doses produce relaxation, tranquility and drowsiness which make it extremely easy to fall asleep naturally. Higher doses increase the drowsiness effect and decrease the time it takes to fall asleep.[diagnose-me.com]
  • CAUTION GHB's dose/response curve is similar to that of alcohol : At higher doses, users fall unconscious and are temporarily unable to be awakened (coma). It may also dangerously depress breathing. Avoid Mixing With Alcohol.[erowid.org]
Nocturnal Awakening
  • The meta-analysis showed that GHB reduced cataplexy attacks both on a daily (weighted mean difference (WMD) -1.10; 95% confidence interval (CI) -1.29/-0.90, p 0.00001) and a weekly basis (WMD -7.04; 95% CI -12.45/-1.63, p 0.01), subjective nocturnal awakenings[ncbi.nlm.nih.gov]
Dyspnea
  • Respiratory depression Cocaine (70) Death from respiratory arrest, irregular (Cheyne-Stokes) respiration Ecstasy (MDMA a,b ) *,(71) Respiratory depression Ethanol a,(72) Respiratory depression Heroin/Opiate (73) Respiratory depression Methamphetamine *, (74) Dyspnea[ualberta.ca]
Vomiting
  • Other effects were headache, nausea, vomiting, myoclonic jerking, and short-term coma. There have been no reported deaths. If product use is discontinued, full recovery with no long-term side effects is universal.[ncbi.nlm.nih.gov]
  • The observed clinical symptoms ranged from confusion, disorientation, vomiting, and nystagmus to ataxia, sinus bradycardia, unconsciousness, and apnea.[ncbi.nlm.nih.gov]
  • The girl had had persistent vomiting and a seizure. Urine metabolic screening tests were positive for gamma-hydroxybutyrate (GHB). Samples from toy beads ingested by both children contained 1,4-butanediol, which is metabolised to GHB in humans.[ncbi.nlm.nih.gov]
  • Diaphoresis, nausea, and vomiting occurred less frequently. The onset of withdrawal symptoms in these patients was rapid (1 to 6 hours after the last dose) and symptoms were prolonged (5 to 15 days).[ncbi.nlm.nih.gov]
  • Adverse events included 2 instances of hypotension and 6 episodes of vomiting with GHB-plus-ethanol ingestion.[ncbi.nlm.nih.gov]
Nausea
  • Other effects were headache, nausea, vomiting, myoclonic jerking, and short-term coma. There have been no reported deaths. If product use is discontinued, full recovery with no long-term side effects is universal.[ncbi.nlm.nih.gov]
  • Baclofen was well tolerated; patients reported mild side effects such as fatigue, nausea, dry mouth, excessive sweating, and depressive feelings.[ncbi.nlm.nih.gov]
  • Diaphoresis, nausea, and vomiting occurred less frequently. The onset of withdrawal symptoms in these patients was rapid (1 to 6 hours after the last dose) and symptoms were prolonged (5 to 15 days).[ncbi.nlm.nih.gov]
  • Effects clumsiness , diarrhoea , dizziness , drowsiness , euphoria , headache , increased sex drive , lowered heart rate , lowered inhibitions , lowered temperature , memory lapses , nausea , urinary incontinence .[adf.org.au]
  • At higher doses, GHB may cause dizziness, loss of coordination, nausea, and vomiting. Coma and respiratory depression may also occur. Combining GHB and any other sedative, especially alcohol, is extremely dangerous.[merckmanuals.com]
Seizure
  • Coma and seizures have been reported following abuse of GHB, but dependence liability has received little attention.[ncbi.nlm.nih.gov]
  • Administration of gamma-hydroxybutyrate (GHB) to animals induces electroencephalographic and behavioral changes that resemble petit-mal seizures.[ncbi.nlm.nih.gov]
  • Furthermore, these GHB-induced electroencephalogram-behavioral changes can be blocked by anticonvulsant drugs, which are specific in their action against petit-mal seizures.[jpet.aspetjournals.org]
  • This manifested as delirium, tremor, and seizures despite only small decreases in GHB dose and treatment with benzodiazepines.[ncbi.nlm.nih.gov]
  • We report a case of withdrawal from 1,4-BD lasting 6 days and complicated by new onset of seizures and rhabdomyolysis.[ncbi.nlm.nih.gov]
Insomnia
  • This withdrawal syndrome includes insomnia, anxiety and tremor; withdrawal symptoms resolve in 3-12 days. GHB has the potential to cause a significant incidence of abuse and adverse effects.[ncbi.nlm.nih.gov]
  • The most common patient symptoms were tremor (67%), hallucinations (63%), tachycardia (63%) and insomnia (58%). Seizures and rhabdomyolysis each occurred in 7% of cases, but only 1 death occurred.[ncbi.nlm.nih.gov]
  • The withdrawal syndrome was accompanied initially by symptoms of anxiety, insomnia, and tremor that developed soon after GHB discontinuation. These initial symptoms may progress to severe delirium with autonomic instability.[ncbi.nlm.nih.gov]
  • Features include auditory and visual hallucinations, tremors, tachycardia, hypertension, sweating, anxiety, agitation, paranoia, insomnia, disorientation, confusion, and aggression/combativeness.[doi.org]
  • 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.[ncbi.nlm.nih.gov]
Tremor
  • This manifested as delirium, tremor, and seizures despite only small decreases in GHB dose and treatment with benzodiazepines.[ncbi.nlm.nih.gov]
  • Previous attempts at cessation reportedly resulted in diaphoresis, tremors, and agitation.[ncbi.nlm.nih.gov]
  • This withdrawal syndrome includes insomnia, anxiety and tremor; withdrawal symptoms resolve in 3-12 days. GHB has the potential to cause a significant incidence of abuse and adverse effects.[ncbi.nlm.nih.gov]
  • The most common patient symptoms were tremor (67%), hallucinations (63%), tachycardia (63%) and insomnia (58%). Seizures and rhabdomyolysis each occurred in 7% of cases, but only 1 death occurred.[ncbi.nlm.nih.gov]
  • The withdrawal syndrome was accompanied initially by symptoms of anxiety, insomnia, and tremor that developed soon after GHB discontinuation. These initial symptoms may progress to severe delirium with autonomic instability.[ncbi.nlm.nih.gov]
Confusion
  • The observed clinical symptoms ranged from confusion, disorientation, vomiting, and nystagmus to ataxia, sinus bradycardia, unconsciousness, and apnea.[ncbi.nlm.nih.gov]
  • Common negative consequences included oversedation, loss of consciousness, motor incoordination, and mental confusion. Nine subjects reported that they would use GHB again, some despite severe negative consequences.[ncbi.nlm.nih.gov]
  • Vomiting Irregular or shallow breathing Confusion, irritation and agitation Hallucinations Blackouts and memory loss Unconsciousness that can last for 3 to 4 hours Death 2 Long-term effects Little is known about the long-term effects of GHB use.[adf.org.au]
  • Features include auditory and visual hallucinations, tremors, tachycardia, hypertension, sweating, anxiety, agitation, paranoia, insomnia, disorientation, confusion, and aggression/combativeness.[doi.org]
  • Common side-effects were confusion, sleepiness, and dizziness; euphoria and change of vital functions were not observed. GHB is extensively metabolized and rapidly eliminated in urine and oral fluid.[ncbi.nlm.nih.gov]
Amnesia
  • Among the possible described side-effects after the continued consumption of GHB are amnesia and deterioration of memory. Likewise, recent studies indicate the existence of neurotoxicity in certain brain regions after its prolonged treatment.[ncbi.nlm.nih.gov]
  • Negative effects may include sweating, loss of consciousness, nausea, hallucinations, amnesia, and coma, among other side effects.[drugs.com]
  • In higher dosages it may induce amnesia, drowsiness, nausea, agitation, visual problems, unconsciousness, and even death.[about-addiction.com]
  • However, GHB has serious side effects including abrupt, intense drowsiness, decreased body temperature, vomiting, slow and deep respiration, temporary amnesia, interference with mobility and verbal coherence, diarrhea, seizures, decreased heart rate,[newjerseycriminallawattorney.com]

Treatment

  • Questionnaires will be administered during 12 weeks of baclofen treatment and at follow-up (six months after the start of treatment).[ncbi.nlm.nih.gov]
  • Benzodiazepine treatment of life-threatening gamma-hydroxybutyrate (GHB) withdrawal is frequently unsatisfactory. Animal studies suggest strongly that treatment with GABA(B) agonists, such as baclofen, will be a more effective strategy.[ncbi.nlm.nih.gov]
  • The MSLTs indicated that the narcolepsy patients had a marginally increased sleep latency mean during GHB versus placebo treatment (p 0.074) and significantly increased total stage 0 (wakefulness) on day 29 of GHB versus day 29 of placebo treatment (p[ncbi.nlm.nih.gov]
  • We aim, through this overview, to explore the neurobiological pathways causing GHB dependency and withdrawal, and their implications for treatment choices.[ncbi.nlm.nih.gov]
  • Providing treatment for patients' mental health issues is vital for ensuring treatment compliance, avoiding relapse and improving the patients' quality of life.[ncbi.nlm.nih.gov]

Prognosis

  • Prognosis With isolated use of GHB, prognosis is normally good. Spontaneous recovery of consciousness is usual, within 2-6 hours. [ 23 ] With repeated use, evidence exists for the development of tolerance and physical dependence.[patient.info]
  • Prognosis The prognosis varies. Although most patients live until adulthood, neuropsychiatric symptoms can be disabling, decreasing quality of life. Early mortality, including sudden unexpected death in epilepsy patients (SUDEP), has been reported.[orpha.net]

Etiology

  • […] metabolized to CO 2 ). 2 Gas chromatography mass spectrometry will detect GHB up to 6-8 hours post administration, however, this form of advanced analysis is rarely available onsite. 2 Patients with 6 hours of CNS depression evaluate for alternative etiologies[emdocs.net]
  • Etiology SSADH deficiency is due to mutations in the ALDH5A1 gene (6p22), encoding mitochondrial succinate-semialdehyde dehydrogenase, a protein involved in amino-acid degradation.[orpha.net]
  • Grace, The depolarization block hypothesis of neuroleptic action: implications for the etiology and treatment of schizophrenia, Advances in Neuroscience and Schizophrenia, 10.1007/978-3-7091-9211-5_6, (91-131), (1992).[doi.org]

Epidemiology

  • Epidemiology. There is limited information regarding statistical trends on world-wide use of GHB and its analogs.[doi.org]
  • Department of Health and Human Services: National Institute on Drug Abuse Epidemiologic Trends in Drug Abuse, Volume I: Highlights and Executive Summary, June 2001, Community Epidemiology Work Group. www.drugabuse.gov/PDF/CEWG/EXSUMJune01.pdf Epidemiologic[web.archive.org]
Sex distribution
Age distribution

Pathophysiology

  • Some considerations on the pathophysiology of generalized bilaterally synchronous spike and wave discharge. Epilepsia 9, 249-263 (1968). 32.[books.google.com]
  • Our understanding of the pathophysiological mechanisms of ASs has been greatly advanced by the availability of genetic and pharmacological models, in particular the γ-hydroxybutyrate (GHB) model which, in recent years, has been extensively used in studies[ncbi.nlm.nih.gov]
  • Emmanuel Mignot, Narcolepsy: Genetic Predisposition and Pathophysiology, Narcolepsy, 10.1007/978-1-4419-0854-4_1, (3-21), (2008). P.S. van Nieuwenhuijzen, I.S. McGregor and G.E.[doi.org]
  • Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev. Available online at . Accessed June 2016.[labtestsonline.it]

Prevention

  • […] of GHB compared to benzodiazepines and Chlormethiazole for AWS prevention.[ncbi.nlm.nih.gov]
  • While the drug treatment literature has a wealth of information to draw upon, GHB-specific information may greatly assist relapse prevention. . American Academy of Addiction Psychiatry.[ncbi.nlm.nih.gov]
  • Nevertheless, in clinical practice, there is no known medical treatment to support GHB relapse prevention.[ncbi.nlm.nih.gov]
  • GHB withdrawal, which can be severe, is better prevented or attenuated by daily medical monitoring and adjustment of treatment dosage.[ncbi.nlm.nih.gov]
  • Objectives: To evaluate the efficacy and safety of GHB for the treatment of AWS and the prevention of relapse.[cochrane.org]

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