Gamma hydroxybutyrate toxicity: Difference between revisions

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== Source ==
== Source ==


[[Category:Tox]]
[[Category:Toxicology]]

Revision as of 16:23, 22 March 2016

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

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

  • cns and resp depression
  • also cardioa and gi sxs
  • many times have cointoxicants
  • usually young white male from nightclub
  • can have n/v, resp deprsn, bradycardia, sz
  • 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 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

  • 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

Diagnosis

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
  • tx c benzos, neuroleptics, bb, chloral hydrate, barbs
  • need v large dose of benzos
  • wd sxs occur few hours p ghb

See Also

Source