Gamma hydroxybutyrate toxicity
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
- Absinthe
- Barbiturates
- Benzodiazepines
- Chloral hydrate
- Gamma hydroxybutyrate (GHB)
- Baclofen toxicity
- Opioids
- Toxic alcohols
- Xylazine 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