Term
| blood concentration profile |
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Definition
elimination is zero order at concentrations above 10-20mg/dL
MEOS (CYP2E1) and role in elimination (>100mg/dL) |
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Term
|
Definition
10% from stomach, remainder from intestine
peak 30-90 minutes
limited by gastric emptying-slowed by food
food reduces alcohol reaching the systemic circulation |
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Term
|
Definition
distributed in total body water (58% men, 48% women)
-men dilute EtOH more
80mg/dL=0.08%
200mg/dL very drunk; 400-500mg/dL dead drunk
tolerance not considered for Legal Applications |
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Term
|
Definition
alcohol dehydrogenase
microsomal ethanol oxidizing system (MEOS) |
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Term
|
Definition
|
|
Term
| glucuronidation (0.5%-EtG test) |
|
Definition
test used to monitor alcohol consumption
metabolite has a very long half-life |
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|
Term
|
Definition
found in liver, brain, and stomach
ADH activity variation
men express higher levels of gastric ADH
polymorphisms of ADH in some Asian populations has reduced activity
Fomepizole inhibits ADH-use for ethylene glycol or methanol poisoning |
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Term
| microsomal ethanol oxidizing system |
|
Definition
mixed function oxidase
inducible with [ethanol]>100mg/dL
includes CYP450 2E1, 1A2, 3A4
consumes STP and dissipates heat |
|
|
Term
|
Definition
found mainly in liver
heterozygous ALD2H*2--reduced metabolic activity, flushing and warm feeling, can stil consume alcohol
homozygous ALDH2*2--deficient in ability to metabolize acetaldehyde, consumption of alcohol results in hangover effect, decreased incidence of alcoholism
disulfram inhibits ALDH |
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|
Term
| effects on ligand-gated ion channels |
|
Definition
GABA-modulated GABA-A receptors-->enhance Cl- influx
Glutamate-antagonize NMDA receptor |
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|
Term
| neurotransmitters/enzymes |
|
Definition
prostaglandins
enkephalins
dopamine
norepinephrine
serotonin
adenylate cyclase
phospholipase
Ca2+ |
|
|
Term
|
Definition
analgesia (as little as 2oz)
CNS stimulation (50mg/dL)
progressive CNS depression (100-200mg/dL)
Coma-death (respiratory paralysis)=300-500mg/dL |
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Term
|
Definition
| vasodilation, warmth, CV depression with high doses |
|
|
Term
|
Definition
positive-moderate use decreases coronary disease-HDL
negative-cardiomyopathy, arrhythmias(withdrawal), hypertension |
|
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Term
|
Definition
| hypothermia, moderate in man |
|
|
Term
|
Definition
EtOH is a secretagogue (increases HCl secretion)
Appetite stimulant (low dose)=too much is a depressent
contraindicated with peptic ulcer disease
irritant at high concetrations (>40%) |
|
|
Term
|
Definition
fatty liver leading to cirrhosis is common in abusers
increased NADH:NAD+ ratio
vitamin deficiencies;glutathione reduced
increased fat metabolism (promotes triglyceride synthesis from FFA) |
|
|
Term
| inhibition of pituitary ADH secretions |
|
Definition
|
|
Term
|
Definition
|
|
Term
| endocrine and electrolyte balance |
|
Definition
alterations in steroids balance; gynecomastia
ascites, edema, effusions |
|
|
Term
|
Definition
| increase rate of infection |
|
|
Term
|
Definition
| mouth, pharynx, larynx, esophagus, liver |
|
|
Term
|
Definition
acute tolerance (one episode)=intoxication is greater when BAC is ascending rather than descending
chronic tolerance |
|
|
Term
| drug disposition tolerance (MEOS) |
|
Definition
| however, magnitude of tolerance does not explain observed tolerance |
|
|
Term
|
Definition
|
|
Term
|
Definition
mild;insomnia, vivid dreams (REM rebound), tremors, anxiety, motor agitation
severe;delerium tremens (DTs), sweating, nausea, vomiting, diarrhea, fever, tonic-clonic convulsions, hallucinations |
|
|
Term
|
Definition
intensity depends on level and duration of intoxication
treatment: benzodiazepines, phenytoin for seizures, electrolytes
requires months for complete recovery |
|
|
Term
|
Definition
hepatic disease
peptic ulcer disease
epilepsy |
|
|
Term
| drug interactions- CNS depressants |
|
Definition
| opioids, antipsychotics, antidepressants, anti-histamines, sedative-hypnotics |
|
|
Term
| drug interactions-aldehyde dehydrogenase inhibitors |
|
Definition
| antabuse, MAOIs, metronidazole, griseofulvin, some cephalosporins, chloramphenicol |
|
|
Term
|
Definition
| increases toxic metabolites (i.e. NAPQI) |
|
|
Term
|
Definition
| insulin and oral hypoglycemics |
|
|
Term
|
Definition
external disinfectant=sponges
vehicle for liquid preparations
internal=cold, sedative properties, appetite stimulant
treatment of ethylene glycol or methanol poisoning (IV infusion 5-10%)--cost effective (vs fomepizole-ADH inhibitor) |
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|
Term
| management of acute intoxication |
|
Definition
| prevent respiratory depression, aspiration of vomit, and metabolic alterations |
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|
Term
| teratology (fetal alcohol syndrome) |
|
Definition
facial dysmorphology
low birth weight
decreased brain size
mental retardation
unknown mechanism |
|
|
Term
| medical problems in alcoholics |
|
Definition
fatty liver and cirrhosis
encephalopathy
chronic gastritis
vitamin deficiency
cardiovascular disorders
immunosuppression
withdrawal |
|
|
Term
|
Definition
*psychosocial therapy with drugs appears to be best
alcoholics anonymous (AA)
disulfiram:ALDH inhibitor
naltrexone:opiod receptor antagonist
acamprosate:NMDA antagonist
SSRI(fluoxetine):mixed results, may be better in depressed patients
others: serotonin partial agonists (buspirone), 5HT antagonist (ondansetron, ritanserin), dopamine antagonist, CB1 antagonist (acomplia) |
|
|
Term
| "tackling alcoholism with drugs" |
|
Definition
disulfram (antabuse)--interferes with alcohol metabolism
naltrexone (depade, revia, vivitrol)--blocks opioid receptors
acamprosate (campral)--inhibits glutamate signaling
topiramate (topamax)--inhibits glutamate signaling, enhances GABA signaling
ondansetron (zofran)--blocks 5HT3 receptors
baclofen (baclofen)--stimulates GABAb receptors
varenicline (chantix)--weakly activates nicotinic ACh receptors |
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