Gamma hydroxybutyrate toxicity

Background

  • Abbreviation: GHB
  • Central nervous system depressant
  • GABA-B agonist (as opposed to GABA-A agonists - alcohol, benzodiazepines, etc)
  • Abused for:
    • Body building or sleep enhancement
    • euphoric, sexual, stimulant, and relaxant effects
    • Surreptitious drugging to facilitate sexual assault
  • Also used therapeutically in the treatment of narcolepsy[1]

Pharmacokinetics

  • effect starts in 15-20min, peaks in 30-60 min,
  • lipid soluble, no protein binding so crosses BBB readily
  • elimination is dose-dependent with half life of 20-50 min
  • The duration of GHB's clinical effects depends upon the dose, and ranges from 2.5 to 4 hours

Pharmacology

  • Is a metabolite and precursor of GABA
  • Interacts with GHB-specific receptors and also acts as a direct agonist of GABA-B receptors
  • Affects multiple neurotransmitter systems, including those of opioids, dopamine, serotonin, glutamate, and acetylcholine
  • Gamma butyrolactone (GBL) and 1,4 butanediol (BD) are GHB analogs that are rapidly metabolized to GHB after ingestion, with the same toxic and recreational effects

Clinical Features

Classic Presentation: Young adult presents comatose and is intubated for airway protection and subsequently awakens while in the emergency department. When awake, can be safely discharged

  • CNS and respiratory depression
  • also cardiac and GI symptoms
  • often found to have co-intoxicants
  • usually young white male from nightclub
  • may present with nausea and vomiting, respiratory depression, bradycardia, seizure
  • may also have ataxia, nystagmus, somnolence and aggression
  • respiratory/CNS depression resolves abruptly
  • respiratory depression worse with other CNS depressants (alcohol, benzodiazepines, etc)
  • periods of apnea and hyperventilation
  • decreases respiratory rate but tidal volume increases so minute volume stable
  • can also have seizure but EEG shows no epileptiform changes
  • bradycardia, hypotension
  • ekg change occasionally but rare
  • also get vomiting, hypothermia

Clinical Course

  • recover in 2-6 hrs
  • may be extubated and sent home
  • if longer than 6hr, look for other cause
  • can have cross tolerance with other drugs-alcohol and others that effect liver p450 cytochome oxidase system

Differential Diagnosis

Sedative/hypnotic toxicity

Drugs of abuse

Evaluation

  • Not detectable on routine toxicology screens

Management

  • supportive
  • look for coingestants and occult trauma
  • charcoal not helpful since rapidly absorbed and since can vomit and aspirate
  • protein bound so can use dialysis*but so short course usually do not need.

Antidotes

  • flumazenil/ narcan helps in animals but not in humans[citation needed]
  • physostigmine may reverse coma, but if co-ingestant present, may be dangerous-potential to lower seizure threshold

See Also

References

  1. Mamelak M, Scharf MB, Woods M. Treatment of narcolepsy with gamma-hydroxybutyrate. A review of clinical and sleep laboratory findings. Sleep. 1986;9(1 Pt 2):285-289. doi:10.1093/sleep/9.1.285
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