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

Prodrugs of GHB

- gbl like ghb

- also 1,4 butanediol

- 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

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

Source

Mistry