Gamma hydroxybutyrate toxicity

Background

• Abbreviation: GHB
• Central nervous system depressant
• Abused for:
  • Body building or sleep enhancement
  • euphoric, sexual, stimulant, and relaxant effects
  • Surreptitious drugging to facilitate sexual assault

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
• 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

• 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

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

Drugs of abuse

• Cocaine
• Ecstasy
• Marijuana
• Amphetamines
• Alcohol
• Synthetic cannabinoids
• Bath salts
• Heroin
• 25C-NBOMe‎
• Inhalant abuse
  • Hydrocarbons
• Gamma hydroxybutyrate (GHB)
• Phencyclidine (PCP)
• Psilocybin (magic mushrooms)

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
• physostigmine may reverse coma but if have coingestant is dangerous-may lower seizure threshold

See Also

• Sedative/Hypnotic

References

Authors

Ross Donaldson, Neil Young, Daniel Ostermayer, Claire