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

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

• Absinthe
• Barbiturates
• Benzodiazepines
  • Flunitrazepam (Rohypnol)
• Chloral hydrate
• Gamma hydroxybutyrate (GHB)
• Baclofen toxicity
• Opioids
  • Lomotil toxicity
  • Loperamide toxicity
• Toxic alcohols
  • Ethanol
  • Ethylene glycol
  • Isopropyl alcohol
  • Methanol

Drugs of abuse

• 25C-NBOMe‎
• Alcohol
• Amphetamines
• Bath salts
• Cocaine
• Ecstasy
• Gamma hydroxybutyrate (GHB)
• Heroin
• Inhalant abuse
  • Hydrocarbon toxicity
  • Difluoroethane (electronics duster)
• Marijuana
• Phencyclidine (PCP)
• Psilocybin ("magic mushrooms")
• Synthetic cannabinoids

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

• Sedative/Hypnotic