Gamma hydroxybutyrate toxicity: Difference between revisions

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== Background ==
{{GHB background}}
- ghb is natural analog of gaba
 
- used as dietary supplement, recreational drug
 
- gives ams, resp depression, recover in 6 hrs
 
- ghb withdrawal like sedative/ hypnotic/ alcohol wd
 
- gaba is cns inhibitor neuroxmtter
 
- 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
 
<br>
 
===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==
 
''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 and resp depression
*CNS depression; ataxia, nystagmus, somnolence, seizure, coma
 
**EEG may show no epileptiform changes
- also cardioa and gi sxs
*Respiratory depression; may also alternate between periods of apnea and hyperventilation
 
**Worse with other CNS depressants ([[alcohol]], [[benzodiazepines]], etc)
- many times have cointoxicants
*Bradycardia, hypotension; ECG changes are rare
 
*Nausea and vomiting GI symptoms
- usually young white male from nightclub
*Hypothermia
 
*Often found to have co-intoxicants
- can have n/v, resp deprsn, bradycardia, sz
*Usually young white male from nightclub
 
*CNS and respiratory depression can resolve abruptly within minutes
- get euphoria s hang over
**Patients may become aggressive upon waking
 
- 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 resp rate but tidal vol increases so minute vol stable
 
- can also have sz but eeg shows no epileptiform changes
 
- bradycardia, hypotension- ekg change occasionally but rare
 
- also get vomitting, hypothermia
 
===Clinical Course===
===Clinical Course===
 
*Recover in 2-6 hours
- recover 2- 6 hrs
*May be extubated and sent home  
 
*If longer than 6 hours, look for other cause  
- may be extubated and sent home  
*Can have cross tolerance with other drugs-alcohol and others that effect liver [[p450]] cytochrome oxidase system
 
- 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==
==Differential Diagnosis==
{{Sedatve/hypnotic toxicity types}}
{{Sedatve/hypnotic toxicity types}}


== Diagnosis ==
{{Drugs of abuse types}}
 
== Treatment ==
 
- 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 don't need.
 
Antidotes
 
- flumazenil/ narcan helps in animals but not in humans
 
- physostigmine may reverse coma but if have coingestant is dangerous- may lower sz threshold
 
== GHB Withdrawal ==
 
- like alcohol
 
- tremor, agitation, hallucinations, tachy, htn,


- wd only if have long term use, not episodic binging
==Diagnosis==
*Not detectable on rapid urine drug screens
*Definitive diagnosis requires gas chromatography
*ED physicians are not accurate in diagnosing clinically


- tx c benzos, neuroleptics, bb, chloral hydrate, barbs
==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.


- need v large dose of benzos
===Antidotes===
*[[Flumazenil]]/ [[Narcan]] helps in animals but not in humans{{Citation needed|reason=Reliable source needed|date=January 2021}}
*[[Physostigmine]] may reverse coma, but if co-ingestant present, may be dangerous-potential to lower [[seizure]] threshold


- wd sxs occur few hours p ghb
==Disposition==
*May consider discharge if symptoms improve after observation for several hours
*Consider admission if symptoms do not improve or worsen


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


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


[[Category:Tox]]
[[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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