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 euphoric, sexual, stimulant, and relaxant effects
 
 
 
*gives ams, resp depression, recover in 6 hrs
 
 
*ghb can be used for absence sz model
*ghb has tissue protective effects for MI, cva, sepsis, bowel ischemia, shock, radiation, o2 free radicals, general anesthetic
*ghb like benzos for etoh wd
*ghb fda approved for narcolepsy tx
===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
 
===Drug of Abuse===
*touted for body building or sleep enhancement
*date rape drug


==Clinical Features==
==Clinical Features==
*cns and resp depression  
*cns and respiratory depression  
*also cardioa and gi sxs
*also cardioa and gi symptoms
*many times have cointoxicants  
*many times have cointoxicants  
*usually young white male from nightclub  
*usually young white male from nightclub  
*can have n/v, resp deprsn, bradycardia, sz
*can have nausea and vomiting, respiratory deprsn, bradycardia, seizure
*get euphoria s hang over  
*get euphoria s hang over  
*can also get ataxia, nystagmus, somnolence and aggression  
*can also get ataxia, nystagmus, somnolence and aggression  
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*resp depression worse with other cns depressants-alcohol  
*resp depression worse with other cns depressants-alcohol  
*periods of apnea and hyperventilation-is periodic breathing  
*periods of apnea and hyperventilation-is periodic breathing  
*decreases resp rate but tidal vol increases so minute vol stable  
*decreases respiratory rate but tidal vol increases so minute vol stable  
*can also have sz but eeg shows no epileptiform changes  
*can also have seizure but eeg shows no epileptiform changes  
*bradycardia, hypotension*ekg change occasionally but rare  
*bradycardia, hypotension*ekg change occasionally but rare  
*also get vomitting, hypothermia  
*also get vomitting, hypothermia  
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*may be extubated and sent home  
*may be extubated and sent home  
*if longer than 6hr, look for other cause  
*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  
*can have cross tolerance with other drugs-alcohol and others that effect liver [[p450]] cytochome oxidase system


==Differential Diagnosis==
==Differential Diagnosis==
{{Sedatve/hypnotic toxicity types}}
{{Sedatve/hypnotic toxicity types}}


== Diagnosis ==
{{Drugs of abuse types}}
 
==Evaluation==
*Not detectable on routine toxicology screens
*Not detectable on routine toxicology screens


== Treatment ==
==Management==
*supportive  
*supportive  
*look for coingestants and occult trauma  
*look for coingestants and occult trauma  
*charcoal not helpful since rapidly absorbed and since can vomit and aspirate  
*charcoal not helpful since rapidly absorbed and since can vomit and aspirate  
*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  
*physostigmine may reverse coma but if have coingestant is dangerous-may lower sz threshold  
*[[physostigmine]] may reverse coma but if have coingestant is dangerous-may lower [[seizure]] threshold


== GHB Withdrawal ==
==Disposition==
*like alcohol
*tremor, agitation, hallucinations, tachy, htn,
*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]]

Revision as of 23:02, 10 September 2016

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

  • cns and respiratory depression
  • also cardioa and gi symptoms
  • many times have cointoxicants
  • usually young white male from nightclub
  • can have nausea and vomiting, respiratory deprsn, bradycardia, seizure
  • get euphoria s hang over
  • can also get ataxia, nystagmus, somnolence and aggression
  • resp/ cns deprrsion resolves abruptly
  • resp depression worse with other cns depressants-alcohol
  • periods of apnea and hyperventilation-is periodic breathing
  • decreases respiratory rate but tidal vol increases so minute vol stable
  • can also have seizure but eeg shows no epileptiform changes
  • bradycardia, hypotension*ekg change occasionally but rare
  • also get vomitting, hypothermia

Clinical Course

  • recover 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

Disposition

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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