Pharmacology of Ethanol Flashcards
Where is ethanol absorbed and what affects its rate of absorption?
Ethanol is absorbed throughout the GI tract, but most rapidly in the small intestine. More rapid ingestion leads to more rapid absorption due to concentration gradient. The presence of food slows absorption by delaying passage to the small intestine (may decrease Cp max by 30%)
How is alcohol excreted from the system?
90-98% is metabolized in the liver. The remainder is excreted in expired air (.05% of BAC) and urine (130% of BAC)
How does the liver metabolize ethanol?
Two pathways: Dehydrogenases and CYP2E1. DEHYDROGENASE PATHWAY (non-induced, zero order kinetics) Ethanol is converted to acetaldehyde by alcohol dehydrogenase, and acetaldehyde is converted to acetic acid by aldehyde dehydrogenase. CYP450 PATHWAY (Induced by ETOH, first order kinetics) CYP2E1 converts alcohol to acetaldehyde, which is then converted to acetic acid by aldehyde dehydrogenase.
How does the metabolism of ethanol result in excess NADH and what does this excess cause?
NADH is created by both alcohol dehydrogenase and aldehyde dehydrogenase (2:1 NADH:ETOH). Increased NADH can cause:
Inc Blood Acetate -> acidosis, behavioral disturbances
Inc Mg2+ excretion -> can lead to convulsions
Inc AcetylCoA -> Inc fat synth & dec fat use -> Fatty Liver
Dec Krebs activity -> dec glucogenesis -> hypoglycemia
Dec uric acid excretion -> gout attacks
What drug category is alcohol in and how does it act in this manner (not MOA)?
Alcohol is a CNS depressant that produces sedative-hypnotic effects. The prime site of action is in the CNS and its effects are proportional to the blood alcohol concentration. It is not a stimulant at any dose and its effects are similar to barbiturates, however, it depresses inhibitory cortical neurons first, resulting in a brief stimulatory phase prior to depressive actions.
What is alcohol’s MOA?
The MOA may include specific perturbations of membrane proteins (including Cl- channels) and relatively non-specific non-receptor mediated disruption of neuronal plasma membranes. Low doses interact with GABA (+) and Glutamate receptor coupled ion channels. High doses inhibit neurons without GABA mediation.
What is the rate of alcohol metabolism?
Metabolism occurs at a constant rate (zero-order kinetics) of 7-10 grams per hour. This correlates to a BAC reduction of 0.015-0.020% per hour. Maximum rate ~220g/day. These all may increase by up to 50% in chronic alcoholics.
What is the site of action of Antabuse (Disulfiram) and what are the physical symptoms that result?
Disulfiram (Antabuse) blocks the action of aldehyde dehydrogenase, causing the accumulation of acetaldehyde. This results in vasodilation, headache, nausea, vomiting, respiratory difficulties, chest pains, and orthostatic hypotension.
What are the anti convulsive effects of alcohol?
Alcohol has good anti convulsive effects, but withdrawal produces CNS hyper excitability and may precipitate convulsions. Contraindicated in epilepsy.
What are the sleep effects of alcohol?
Alcohol causes the suppression of Stage IV and REM sleep, with REM rebound on withdrawal from alcohol. Similar to those effects of barbiturates.
What are the effects of alcohol on the liver?
Initially reversible damage (increased fatty acid/lipid deposition -> hepatitis), eventually cell death and replacement by collagen (Cirrhosis). Regeneration and enlargement of the liver cause pressure on the veins -> dec venous return, ascites, esophageal varicosities; possible decreased synthesis of clotting proteins -> inc bleeding time.
What are the effects of alcohol on the GI tract?
Alcohol is an irritant to the GI tract, inducing gastric secretions and possible gastric ulceration (esp with aspirin). Effects may range from gastritis to actual hemorrhage. Increased digestive secretions can produce pancreatitis. High doses can decrease absorption of amino acids, glucose, folic acid, thiamine, & B12.
What are the heart and cardiovascular effects of alcohol?
Alcohol is a direct vasodilator and block response to cold, inc risk of hypothermia (think flushed face). May also cause direct damage to cardiac muscle and lead to higher systolic and diastolic pressure (>3-5 drinks/day). Moderate (1-2 drinks/day) intake may have protective effect due to increased HDL and decreased platelet adhesiveness.
What are the renal effects of alcohol?
Alcohol exerts a diuretic effect by inhibiting the secretion of antidiuretic hormone. This effect only occurs when the BAC is rising, stable or decreasing BAC may cause an antidiuretic effect.
What is the criteria and major effects by trimester in fetal alcohol syndrome?
Criteria for FAS: Pre- or post-natal growth retardation AND altered morphogenesis (esp facial) AND CNS involvement (often mental retardation). Major effects by trimester 1: Major morphologic abnormality; 2: Increased risk of spontaneous abortion; 3: Decreased fetal growth.
