Gamma hydroxybutyrate toxicity

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

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
  • Worse with other CNS depressants (alcohol, benzodiazepines, etc)
• 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

• 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
• Xylazine toxicity

Drugs of abuse

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

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

• 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

Disposition

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

See Also

• Sedative/Hypnotic