Gamma hydroxybutyrate toxicity: Difference between revisions

Revision as of 16:47, 12 March 2015

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

Source

Authors:

@@ Line 1: / Line 1: @@
 == Background ==
-- ghb is natural analog of gaba
+*ghb is natural analog of gaba
+*used as dietary supplement, recreational drug
-- used as dietary supplement, recreational drug
+*gives ams, resp depression, recover in 6 hrs
+*ghb withdrawal like sedative/ hypnotic/ alcohol wd
-- gives ams, resp depression, recover in 6 hrs
+*gaba is cns inhibitor neuroxmtter
+*ghb can be used for absence sz model
-- ghb withdrawal like sedative/ hypnotic/ alcohol wd
+*ghb has tissue protective effects for MI, cva, sepsis, bowel ischemia, shock, radiation, o2 free radicals, general anesthetic
+*ghb like benzos for etoh wd
-- gaba is cns inhibitor neuroxmtter
+*ghb fda approved for narcolepsy tx
-- 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
-<br>
 ===Metabolism===
+*exists naturally in brain*also heart, liver, kidney, muscle, brown fat
-- 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
-- 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,
-- 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
-- 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
-- cns depression is main effect
+*novel ghb receptor exists in brain*as synaptosomal membrane
+*at pons and hippocampus as well as cortex and caudate
-- novel ghb receptor exists in brain- as synaptosomal membrane
+*ghb also binds to gaba receptor but with lower affinity
+*ghb receptor assoc with dopaminergic neurons
-- at pons and hippocampus as well as cortex and caudate
+*increases formation and release of dopamine
+*also affects acetylcholine and 5*hydroxytryptamine and cns opiods
-- 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
+*touted for body building or sleep enhancement
+*date rape drug
-- date rape drug
 ==Clinical Features==
+*cns and resp depression
-- cns and resp depression
+*also cardioa and gi sxs
+*many times have cointoxicants
-- also cardioa and gi sxs
+*usually young white male from nightclub
+*can have n/v, resp deprsn, bradycardia, sz
-- many times have cointoxicants
+*get euphoria s hang over
+*can also get ataxia, nystagmus, somnolence and aggression
-- usually young white male from nightclub
+*resp/ cns deprrsion resolves abruptly
+*resp depression worse with other cns depressants-alcohol
-- can have n/v, resp deprsn, bradycardia, sz
+*periods of apnea and hyperventilation-is periodic breathing
+*decreases resp rate but tidal vol increases so minute vol stable
-- get euphoria s hang over
+*can also have sz but eeg shows no epileptiform changes
+*bradycardia, hypotension*ekg change occasionally but rare
-- can also get ataxia, nystagmus, somnolence and aggression
+*also get vomitting, hypothermia
-- 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
-- recover 2- 6 hrs
+*may be extubated and sent home
+*if longer than 6hr, look for other cause
-- may be extubated and sent home
+*can have cross tolerance with other drugs-alcohol and others that effect liver p450 cytochome oxidase system
-- 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==
@@ Line 102: / Line 58: @@
 == 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.
-- supportive
+===Antidotes ===
+*flumazenil/ narcan helps in animals but not in humans
-- look for coingestants and occult trauma
+*physostigmine may reverse coma but if have coingestant is dangerous-may lower sz threshold
-- 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
-- like alcohol
+*tremor, agitation, hallucinations, tachy, htn,
+*wd only if have long term use, not episodic binging
-- tremor, agitation, hallucinations, tachy, htn,
+*tx c benzos, neuroleptics, bb, chloral hydrate, barbs
+*need v large dose of benzos
-- wd only if have long term use, not episodic binging
+*wd sxs occur few hours p ghb
-- tx c benzos, neuroleptics, bb, chloral hydrate, barbs
-- need v large dose of benzos
-- wd sxs occur few hours p ghb
 ==See Also==