Gamma hydroxybutyrate toxicity: Difference between revisions
 
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== Background ==
{{GHB background}}
*Abbreviation: GHB
*Central nervous system depressant, natural analog of GABA
*Abused for:
***Body building or sleep enhancement 
**euphoric, sexual, stimulant, and relaxant effects
**Surreptitious drugging to facilitate sexual assault
 
===Metabolism===
*exists naturally in brain*also heart, liver, kidney, muscle, brown fat
*ghb eliminated by Krebs cycle and expired as co2, also by liver and very little by urine
 
===Pharmacokinetics===
*effect starts 15*20min, peaks in 30*60 min,
*lipid soluble, no protein binding so crosses BBB readily
*elimination is dose dependant with half life of 20*50 min
 
===Pharmacology===
*cns depression is main effect
*novel ghb receptor exists in brain*as synaptosomal membrane
*at pons and hippocampus as well as cortex and caudate
*ghb also binds to gaba receptor but with lower affinity
*ghb receptor assoc with dopaminergic neurons
*increases formation and release of dopamine
*also affects acetylcholine and 5*hydroxytryptamine and cns opiods


==Clinical Features==
==Clinical Features==
*cns and resp depression
''Classic Presentation: Young adult presents comatose and is intubated for airway protection and subsequently awakens while in the emergency department. When awake, typically can be safely discharged.''
*also cardioa and gi sxs
*CNS depression; ataxia, nystagmus, somnolence, seizure, coma
*many times have cointoxicants
**EEG may show no epileptiform changes
*usually young white male from nightclub
*Respiratory depression; may also alternate between periods of apnea and hyperventilation
*can have n/v, resp deprsn, bradycardia, sz
**Worse with other CNS depressants ([[alcohol]], [[benzodiazepines]], etc)
*get euphoria s hang over
*Bradycardia, hypotension; ECG changes are rare
*can also get ataxia, nystagmus, somnolence and aggression
*Nausea and vomiting GI symptoms
*resp/ cns deprrsion resolves abruptly
*Hypothermia
*resp depression worse with other cns depressants-alcohol  
*Often found to have co-intoxicants
*periods of apnea and hyperventilation-is periodic breathing
*Usually young white male from nightclub
*decreases resp rate but tidal vol increases so minute vol stable
*CNS and respiratory depression can resolve abruptly within minutes
*can also have sz but eeg shows no epileptiform changes
**Patients may become aggressive upon waking
*bradycardia, hypotension*ekg change occasionally but rare
*also get vomitting, hypothermia
===Clinical Course===
===Clinical Course===
*recover 2-6 hrs
*Recover in 2-6 hours
*may be extubated and sent home  
*May be extubated and sent home  
*if longer than 6hr, look for other cause  
*If longer than 6 hours, look for other cause  
*can have cross tolerance with other drugs-alcohol and others that effect liver p450 cytochome oxidase system  
*Can have cross tolerance with other drugs-alcohol and others that effect liver [[p450]] cytochrome oxidase system


==Differential Diagnosis==
==Differential Diagnosis==
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{{Drugs of abuse types}}
{{Drugs of abuse types}}


== Diagnosis ==
==Diagnosis==
*Not detectable on routine toxicology screens
*Not detectable on rapid urine drug screens
*Definitive diagnosis requires gas chromatography
*ED physicians are not accurate in diagnosing clinically


== Treatment ==
==Management==
*supportive
*Supportive
*look for coingestants and occult trauma  
*Look for co-ingestants and occult trauma  
*charcoal not helpful since rapidly absorbed and since can vomit and aspirate
*Charcoal not helpful since rapidly absorbed; patients may vomit and are at risk for aspiration
*protein bound so can use dialysis*but so short course usually don't need.  
*Protein bound so can use dialysis but so short course usually do not need.  


===Antidotes ===
===Antidotes===
*flumazenil/ narcan helps in animals but not in humans  
*[[Flumazenil]]/ [[Narcan]] helps in animals but not in humans{{Citation needed|reason=Reliable source needed|date=January 2021}}
*physostigmine may reverse coma but if have coingestant is dangerous-may lower sz threshold  
*[[Physostigmine]] may reverse coma, but if co-ingestant present, may be dangerous-potential to lower [[seizure]] threshold


== GHB Withdrawal ==
==Disposition==
*like alcohol
*May consider discharge if symptoms improve after observation for several hours
*tremor, agitation, hallucinations, tachy, htn,
*Consider admission if symptoms do not improve or worsen
*wd only if have long term use, not episodic binging
*tx c benzos, neuroleptics, bb, chloral hydrate, barbs
*need v large dose of benzos
*wd sxs occur few hours p ghb


==See Also==
==See Also==
*[[Sedative/Hypnotic]]
*[[Sedative/Hypnotic]]


== Source ==
==References==
<references/>


[[Category:Toxicology]]
[[Category:Toxicology]]

Latest revision as of 16:53, 24 April 2021

Background

  • Abbreviation: GHB
  • Frequently referred to as the "date rape drug"
  • 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

  • Effects start in 15-20 minutes, peak in 30-60 minutes,
  • Lipid soluble, readily crosses the blood brain barrier
  • Elimination is dose-dependent; half-life of 20-50 minutes
  • The duration of GHB's clinical effects depends upon the dose, and ranges from 2.5-4 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, typically can be safely discharged.

  • CNS depression; ataxia, nystagmus, somnolence, seizure, coma
    • EEG may show no epileptiform changes
  • Respiratory depression; may also alternate between periods of apnea and hyperventilation
  • Bradycardia, hypotension; ECG changes are rare
  • Nausea and vomiting GI symptoms
  • Hypothermia
  • Often found to have co-intoxicants
  • Usually young white male from nightclub
  • CNS and respiratory depression can resolve abruptly within minutes
    • Patients may become aggressive upon waking

Clinical Course

  • Recover in 2-6 hours
  • May be extubated and sent home
  • If longer than 6 hours, look for other cause
  • Can have cross tolerance with other drugs-alcohol and others that effect liver p450 cytochrome oxidase system

Differential Diagnosis

Sedative/hypnotic toxicity

Drugs of abuse

Diagnosis

  • Not detectable on rapid urine drug screens
  • Definitive diagnosis requires gas chromatography
  • ED physicians are not accurate in diagnosing clinically

Management

  • Supportive
  • Look for co-ingestants and occult trauma
  • Charcoal not helpful since rapidly absorbed; patients may vomit and are at risk for aspiration
  • Protein bound so can use dialysis but so short course usually do not need.

Antidotes

Disposition

  • May consider discharge if symptoms improve after observation for several hours
  • Consider admission if symptoms do not improve or worsen

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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