Alcohol Flashcards
What mediates Alcohol’s amnestic effects?
Inhibited NMDA receptor function
NMDA mediates memory and learning
What mediates Alcohol’s euphoric effect?
Increased dopamine release in the nucleus accumbens
What mediates Alcohol’s sedative effects?
Enhanced GABA-A receptor function
Chloride conduction
What mediate’s Alcohol causing coma/death?
Inhibiting voltage-sensitive calcium channels
Fluidizing cell membranes
What blood alc conc leads to the first signs of intoxication?
20 mg%
What blood alc conc leads to being legally impaired in many states?
50 mg%
What blood alc conc makes you 7x more likely to cause an accident?
100 mg%
What blood alc conc makes you 25x more likely to cause an accident?
150 mg%
What blood alc conc is lethal?
400 mg%
One drink per hour will lead to what blood alc conc?
30 mg%
What is the difference between first signs of intoxication and lethal dose?
20 fold difference
STEEP dose response curve
Why do we get easily dehydrated when we drink?
Alcohol inhibits ADH secretion; decreases renal reabsorption of water, we pee more
How is alcohol metabolized?
90-90% hepatic (mostly dehydrogenase, some CYP2E1), the rest is excreted unchanged by the lungs
How is ethanol metabolized in the liver?
Ethanol is metabolized by alcohol dehydrogenase (zero order kinetics) to acetaldehyde, using NADH to NAD+
Acetaldehyde is then metabolized by acetaldehyde dehydrogenase (first order kinetics) to Acetyl CoA, using NADH to NAD+
How does chronic alcohol use affect ethanol metabolism?
Upregulation of alcohol dehydrogenase
Down regulation of acetaldehyde dehydrogenase
How fast is alcohol metabolized?
7-10 g/hr or 14-20 mg%/hr
Avg drink has 14 g ethanol
How can you treat methanol intoxication?
Ethanol or fomepizol
Ethanol will use up the alcohol dehydrogenase
Fomepizol blocks gastric alcohol dehydrogenase
Methanol is metabolized to formic acid - bad!
What drugs inhibit acetaldehyde dehydrogenase?
1st generation oral hypoglycemics, cephalosporins (don’t drink while on these meds!)
Metronidazole may in some sub-populations
What drug inhibits alcohol dehydrogenase?
Aspirin
May promote NSAID-induced gastric bleeding (?)
How does ethanol use affect CYP2E1?
Initially competes for it, so acute ethanol use will decrease metabolism of drugs metabolized by CYP2E1 (increasing levels of drugs like theophylline, APAP, etc)
Chronic use results in induction of CYP2E1, so drug levels decrease because they are metabolized faster
What pharmacokinetic changes contribute to ethanol tolerance?
Increased activity of alcohol dehydrogenase
Increased induction of CYP2E1
What pharmacodynamic changes contribute to ethanol tolerance?
Glutamate receptor up-regulation
Decreased GABA-A receptor function
Increased membrane rigidity
In pts who are dependent on alcohol, what occurs 2-24 hours after they stop drinking?
Tremors, sleeplessness, irritability, seizures
In pts who are dependent on alcohol, what occurs 24-48 hours after they stop drinking?
Delirium, fever, vivid hallucinations
In pts who are dependent on alcohol, what occurs 3 days after they stop drinking?
Exhaustion, CV collapse
In pts who are dependent on alcohol, what occurs 5-7 days after they stop drinking?
Recovery, or 15% mortality
Have to treat alcohol w/d by giving GABA agonists such as BDZ’s
What is Protracted Withdrawal Symptom?
Prolonged symptoms of alcohol withdrawal
Symptoms include anxiety, drug cravings, anhedonia, and headache
Why does ethanol have such a high abuse liability?
It increases dopamine and taurine from mesolimbic areas
It alters endogenous opioid systems
Ethanol also thought to induce damage to the prefrontal cortex (kills part of the brain that says hey stop drinking)
Abuse liability increases with combined abuse (ie nicotine)
Which drug treatment for alcoholics punishes ethanol drinking?
Disulfuram - disulfuram reaction, inhibits acetaldehyde dehhydrogenase to increase acetaldehyde levels when they drink to increase bad effects
Which drug treatment for alcoholics decreases incidence of alcohol withdrawal seizures?
Diazepam - long acting BDZ, restores GABA activity
Which drug treatment for alcoholics decreases withdrawal-associated anxiety?
Ondansetron - 5HT3 antagonist
Which drug treatment for alcoholics decreases positive reinforcing effects?
Naltrexone (blocks endogenous opioids that are increased in alcoholics that causes cravings?)
Which drug treatment for alcoholics decreases positive and negative reinforcing effects?
Acamprosate
Which drug treatment decreases cravings and withdrawal anxiety (hint: intranasal)?
Oxytocin
Which drug treatment is an antiepileptic, decreases cravings, increases abstinence?
Topiramate
Alcohol toxicity can lead to serious neurological and mental disorder. What example did she give? What leads to this?
Wernicke-Korsakoff’s Psychosis
Atrophy of cerebellum, hippocampus, prefrontal cortex
What contributes to nutritional deficiency in alcoholics?
Ethanol decreases absorption of vitamins A, D, and thiamine
What GI tract damage is seen in alcoholics?
Esophageal reflux, gastritis, chronic diarrhea, pancreatitis
Why do alcoholics have enhanced APAP toxicity?
Glutathione depletion (they accumulate the active metabolite)
What causes cirrhosis in alcoholics?
Increased fat and protein accumulation in the liver
What causes necrosis and fibrosis in the liver?
Increased oxidative stress (think ethanol metabolism, they use NADH which is converted to NAD+)
Drinking during the three trimesters lead to what effects?
1st trimester = fetal alcohol syndrome
2nd trimester = spontaneous abortions
3rd trimester = low birth weight
What are the facial characteristics seen in FAS?
Epicanthal folds Flat midface Low nasal bridge Short nose Indistinct philitrum Thin upper lip Micrognathia
How much alcohol does it take to cause FAS?
75 mL/day (2.5-3 oz)
What consequence of drinking during pregnancy is there other than FAS?
If you drink during pregnancy, you’re essentially guaranteed to cause Alcohol-Related Neurodevelopmental DIsorder (ARND)
Poor motor skills and coordination
Auditory and visual processing problems
Cognitive deficits
Executive function decrease
