Gamma hydroxybutyrate toxicity: Difference between revisions
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== Background == | == Background == | ||
- ghb is natural analog of gaba | - ghb is natural analog of gaba | ||
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- ghb can be used for absence sz model | - ghb can be used for absence sz model | ||
- ghb has tissue protective effects for MI, cva, | - ghb has tissue protective effects for MI, cva, sepsis, bowel ischemia, shock, radiation, o2 free radicals, general anesthetic | ||
sepsis, bowel ischemia, shock, radiation, o2 free | |||
radicals, general anesthetic | |||
- ghb like benzos for etoh wd | - ghb like benzos for etoh wd | ||
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<br> | <br> | ||
Metabolism | ===Metabolism=== | ||
kidney, muscle, brown fat | - exists naturally in brain- also heart, liver, kidney, muscle, brown fat | ||
- ghb eliminated by Krebs cycle and expired as co2, | - ghb eliminated by Krebs cycle and expired as co2, also by liver and very little by urine | ||
===Pharmacokinetics=== | |||
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 | - lipid soluble, no protein binding so crosses BBB readily | ||
- elimination is dose dependant with half life of 20- 50 min | |||
===Pharmacology=== | |||
Pharmacology | |||
- cns depression is main effect | - cns depression is main effect | ||
- novel ghb receptor exists in brain- as synaptosomal | - 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 also binds to gaba receptor but with lower | |||
affinity | |||
- ghb receptor assoc with dopaminergic neurons | - ghb receptor assoc with dopaminergic neurons | ||
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- increases formation and release of dopamine | - increases formation and release of dopamine | ||
- also affects acetylcholine and 5- hydroxytryptamine | - also affects acetylcholine and 5- hydroxytryptamine and cns opiods | ||
and cns opiods | |||
Drug of Abuse | Drug of Abuse | ||
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- date rape drug | - date rape drug | ||
==Clinical Features== | |||
== | |||
- cns and resp depression | - cns and resp depression | ||
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- get euphoria s hang over | - get euphoria s hang over | ||
- can also get ataxia, nystagmus, somnolence and | - can also get ataxia, nystagmus, somnolence and aggression | ||
aggression | |||
- resp/ cns deprrsion resolves abruptly | - resp/ cns deprrsion resolves abruptly | ||
- resp depression worse with other cns depressants- | - 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 | |||
- bradycardia, hypotension- ekg change occasionally | |||
but rare | |||
- also get vomitting, hypothermia | - also get vomitting, hypothermia | ||
===Clinical Course=== | |||
Clinical Course | |||
- recover 2- 6 hrs | - recover 2- 6 hrs | ||
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- if longer than 6hr, look for other cause | - if longer than 6hr, look for other cause | ||
- can have cross tolerance with other drugs- alcohol | - can have cross tolerance with other drugs- alcohol and others that effect liver p450 cytochome oxidase system | ||
==Differential Diagnosis== | |||
{{Sedatve/hypnotic toxicity types}} | |||
== Diagnosis == | |||
== Treatment == | == Treatment == | ||
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- look for coingestants and occult trauma | - look for coingestants and occult trauma | ||
- charcoal not helpful since rapidly absorbed and | - charcoal not helpful since rapidly absorbed and since can vomit and aspirate | ||
since can vomit and aspirate | |||
- protein bound so can use dialysis- but so short course usually don't need. | |||
Antidotes | Antidotes | ||
- flumazenil/ narcan helps in animals but not in | - flumazenil/ narcan helps in animals but not in humans | ||
humans | |||
- physostigmine may reverse coma but if have coingestant is dangerous- may lower sz threshold | |||
== GHB Withdrawal == | == GHB Withdrawal == | ||
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- wd only if have long term use, not episodic binging | - wd only if have long term use, not episodic binging | ||
- tx c benzos, neuroleptics, bb, chloral hydrate, | - tx c benzos, neuroleptics, bb, chloral hydrate, barbs | ||
barbs | |||
- need v large dose of benzos | - need v large dose of benzos | ||
- wd sxs occur few hours p ghb | - wd sxs occur few hours p ghb | ||
==See Also== | ==See Also== | ||
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== Source == | == Source == | ||
[[Category:Tox]] | [[Category:Tox]] | ||
Revision as of 16:44, 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
- 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