Alcohol (lec 1) Flashcards
Alcohol abuse vs Alcoholism?
Abuse = social life impaired ≥ 1 mo
Ism = tolerance/dependence resulting from long-term use
Genetic factors for alcoholism?
↑↑ β-endorphins in DA-reward pathway
Alcohol absorbed where?
Distributes?
stomach, small intest
evenly thru body and across BBB and placenta
Peak blood alcohol content (BAC) occurs when?
30 - 90 min post drinking
Alcohol metabolized how?
Uses what co-factor?
alcohol dehydrogenase -> acetaldehyde -> aldehyde DH -> acetate
NAD+ (saturation occurs at low levels of alcohol),
byproduct is NADH
NAD+ use by alcohol results in?
inability of other enzymes to use NAD+ ->
accumulation of lactate/acetyl-CoA ->
FA synth/lactic acidosis
Alcohol metabolism rate?
Zero-order, rate independent of concentration
~10g/hr
Women less tolerant of alcohol, why?
fewer alcohol dehydro in GI tract ->
metabo more slowly than men
Microsomal-ethanol oxidizing system (MEOS) is?
Result of?
Alternate metabo of alcohol to acetaldehyde,
Uses NADPH, byproduct is NADP+
chronic alcohol consumption
Alcohol affects other drugs how?
competes for metabolism
induces CYP2E1
Alcohol ↑ metabolism of what type of drugs?
CYP450-metabolized drugs
e.g. phenytoin (seizures),
hypoglycemics
Alcohol-induction of CYP2E1 has what effect on acetaminophen?
↑↑ hepatotoxicity
Alcohol inhibits breakdown of what drugs?
pheonthiazine
benzodiazepine
barbiturate
TCA
Aldehyde DH deficiency results in?
Esp common in what group?
acetaldehyde accumulates -> flushing, HA, N
Asians
Pharmacokinetic Alcohol Tolerance from?
ETOH-induced CYP2E1/MEOS ->
metabolism ↑ in chronic users
Pharmacodynamic Alcohol Tolerance from?
Down-reg GABA receptors and
Up-reg NMDA receptors
**withdrawal is result of pharmacodynamics
Cross tolerance is?
↑ tolerance to ETOH causes ↑ tolerance to benzodiaz/barbitu
Alcohol action on GABA?
CNS depressant: binds GABAa recep -> ↑ Cl- influx -> inhibits GABA transmission -> ↓ DA in mesolimbic path, down reg of GABA recept
Alcohol action on NMDA?
inhibits glutamine effect on NMDA recept ->
upreg of NMDA recept
NMDA involved w/ learning/memory, seizures
Alcohol effects: low [ ]?
higher [ ]?
disinhibition
depressant/sedation of mood, motor, etc
Anterograde amnesia is?
blackout from NMDA recpt blockade
ETOH effects: smooth mm?
vasodilator
hypothermia
relax uterus
ETOH effects: heart?
kidney?
↓ myocard contractility
↓ ADH = diuretic
Acute ETOH toxicity results in?
V, stupor, coma, resp depression
metabolic/e- ∆s
hypothermia
↓ BP/CO
Acute ETOH toxicity-induced seizure tx?
benzos, anticonvulsants
Chronic ETOH abuse effects on liver/GI?
Nutrition?
Lowers [glutathione] = ox stress tissue damage,
FA prdxn = fibrosis
folate/thiamine deficiency
Chronic ETOH abuse effects on CNS?
Wernicke-Korsakoff Synd (thiamine deficiency),
Korsakoff’s Psychosis,
Peripheral neuropathy
Wernicke-Korsakoff Synd presentation?
eye mm paralysis,
ataxia,
confusion,
coma/death
Korsakoff’s Psychosis presentation?
chronic memory loss
Chronic ETOH abuse effects on CV?
Cardiomyopathy (direct toxicity of acetaldehyde),
Arrhy
HTN
↑ CV dz
Chronic ETOH abuse effects on tobacco?
↑ carcinogenicity of tobacco
Naltrexone (ReVia) action?
Used for?
S/E?
opoid recpt antagonist:
blocks etoh from stim reward path
↓ craving for eoth
liver damage
Acamprosate (Campral EC) action?
Used for?
GABA analogue:
normalizes balance of GABA/Glutamine
eoth cessation support
NOT liver toxic (kidney metab)
Disulfiram (Antabuse) action?
aldehyde DH inhibitor:
actealdehyde build-up = severe toxic s/e
ETOH w/drawal presentation:
Mild?
Severe?
anxiety, irritab, N, tachy
hallucination, delirium/tremors, seiz, arrhy, hypoTN
ETOH w/drawal tx?
Diazepam/Chlordiaz: prevent DTs, seizures
Lorazepam: stop seiz
Phenytoin: 2nd line stop seiz
Methanol Poisoning presentation?
Visual disturb (snowstorm)
Formaldehyde breath
Bradycard, coma
Methanol Poisoning action?
methanol metab to toxic aldehydes/oxalates ->
transient CNS stim ->
severe metabolic acidosis
Methanol Poisoning tx?
resp support
lavage
alkalization
Fomepizole
Fomepizole (Antizol) action?
alcohol DH inhibitor
