Neuropharmacology of Alcohol Flashcards
How many grams of alcohol are in a “unit”?
14g
By how much does one unit of alcohol raise BAC, on average?
0.03 percentage points (but this varies so much as to be almost useless)
Why is alcohol able to partially eliminated by exhalation?
It’s soluble in water, but has a high diffusion coefficient, so it crosses the alveolar membrane easily. (and it’s volatile)
Why can alcohol get pretty much everywhere in the body?
It’s both hydrophilic and lipophilic, giving it a high volume of distribution and access to all compartments of the body.
Where is alcohol best absorbed? Is it active or passive transport?
In the small intestine.
Passive diffusion.
What 4 variables affect the rate of absorption of alcohol?
Concentration: shot faster than beer
Food in stomach
Type of food (fatty food delays absorption more).
How frequently the individual drinks. (habitual drinkers absorb EtOH more quickly)
Into what tissue does EtOH enter most slowly?
Fat
2 distribution-related reasons for why women get a higher BAL for a given dose of EtOH?
Women have higher fat content and lower body water content.
What percentage of EtOH is metabolized?
90%
What are 2 ways in which EtOH is converted to acetaldehyde?
Microsomal ethanol oxidizing system (MEOS), using especially CYP 2E1. Alcohol dehydrogenase (ADH).
What’s a metabolic reason for why men get a lower BAL than women from the same dose of EtOH?
Men have more ADH in their stomach cells.
Where is ADH?
Mainly liver. Also in brain and stomach.
When is MEOS used?
When ADH is saturated (and NAD is depleted)
What enzyme converts acetaldehyde to acetate? What happens if yours doesn’t work very well?
Acetaldehyde dehydrogenase.
If it doesn’t work, acetaldehyde build up causes flushing, vomiting, dizziness.
Which enzyme does disulfiram target?
Acetaldehyde dehydrogenase.
By what kinetics is alcohol metabolized?
At low levels, up to 100mg/dL, first order.
At higher levels, ADH is saturated, and EtOH is eliminated at a constant rate of about 8g /hr.
Is CYP 2E1 the only thing that gets induced by regular EtOH consumption?
No, other P450 molecules are upregulated, such as 3A4, often resulting in faster metabolism of drugs, reducing their effectiveness / increasing production of toxic metabolites of acetominophen.
Why is a BAL of 100 - 199mg / 100ml the danger zone?
Because people fall asleep and you can’t see worsening symptoms easily.
4 effects of chronic alcohol abuse on the CNS?
Loss of white and grey matter (esp. frontal lobe).
Reduced brain metabolism.
Wernicke’s / Korsakoff syndrome.
Neuropathy
3 acute cardiovascular effects of EtOH?
Vasodilatation
Reduced myocardial contractility
Atrial and ventricular arrhythmias (via higher catecholamine levels)
3 chronic cardiovascular negative effects of EtOH?
Increased BP.
Dilated cardiomyopathy
Increased triglyceride levels.
3 cardioprotective effects of moderate EtOH?
Raised HDL??
Antioxidant content??
Increases tPA
3 effects of EtOH on the kidney?
Decreased ADH (anti-diuretic hormone) -> diuresis and K+ loss
Vasodilation -> diuresis
Decreased uric acid excretion -> gout
5 effects of EtOH on the GI tract?
Stimulates gastrin, pepsin, histamine, and gastricacid.
Peptic ulcers.
Emesis.
Pancreatitis.
Gastric and esophageal cancers (maybe via acetaldehyde)
Is EtOH consumption a risk factor for lots of different cacners?
Yep. GI tract stuff, liver, breast.
4 effects of chronic EtOH on hematopoeisis and immune function?
Reduced platelets
Reduced folate stores / absorption -> macrocytosis
Reduced PMN function
Reduced T-cell function
Effect of EtOH on sleep?
Reduces sleep latency and time to REM, but reduces sleep quality overall.
Increases number of apneic episodes.
Chronic effects of EtOH on endocrine function (esp in men)?
Testicular atrophy
Gynecomastia
Acute effects of EtOH on endocrine function?
Hypoglycema (why late-night burritos are delicious)
Hypokalemia -> vomiting, diarrhea
Effects of EtOH on sexual performance?
“…provokes desire, takes away performance…” is probably enough. (but this happens for both sexes.
Why can’t fetuses handle EtOH?
It crosses the placenta easily, and they don’t have metabolic machinery (no ADH) to break it down.
Fetal alcohol syndrome is no good.
