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Download 2/10/2015 Ethanol Pharmacokinetics – Absorption
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2/10/2015 Ethanol Pharmacokinetics – Absorption Ethanol – fully water soluble yet hydrophobic enough to diffuse across cell membranes. EtOH is readily absorbed, primarily through the small intestine. Some absorption (ca. 20%) occurs through stomach. Factors Affecting Ethanol Absorption Food slows ethanol absorption and decreases amount absorbed. 1. Gastric emptying delayed – hence, alcohol resides in stomach longer 2. Enzymes in the GI metabolize alcohol, so decreasing the rate of absorption results in lower blood alcohol content (BAC). Carbonation speeds up alcohol absorption Carbonation forces fluids into small intestine more rapidly. 1 2/10/2015 Alcohol Pharmacokinetics – Distribution Ethanol is more water soluble than fat soluble, so distributes more into aqueous environments. Alcohol crosses all membranes in the human body, including the BBB and placenta. Alcohol Pharmacokinetics – Metabolism Approximately 95% of ethanol is metabolized Approximately 95% of ethanol is metabolized. 85% of metabolism occurs in liver; 15% of metabolism occurs in GI tract. 5% is excreted unchanged via the lungs. Breathalyzer analyzes for ethanol (not metabolite(s)). 2 2/10/2015 Alcohol Metabolism Alcohol metabolism follows zero‐order (linear) kinetics. 10‐14 mL ethanol / hour metabolized ‐ roughly 1 drink per hour. NAD+ cofactor supply limits ethanol metabolism. Acetaldehyde metabolite is toxic – buildup can cause nausea, vomiting, headache, flushing Alcohol Metabolism Gender Differences Considering men and women of similar age, weight and fitness: Men: Higher percentage of water in the body, so more dilute BAC Women: Higher body fat; since fat is less vascularized, more concentrated BAC Men: Greater amount of ALD enzyme in GI tract, hence, increased metabolism 3 2/10/2015 Denatured Alcohol Methanol added to industrial ethanol to discourage recreational use. Denatured alcohol is labeled as such, and a dye may be added to the solution. Denatured alcohol is tax exempt. Toxicity of Denatured Alcohol Metabolites of methanol are toxic. Treatment for methanol poisoning? 4 2/10/2015 Toxicity of Denatured Alcohol Alcohol dehydrogenase oxidizes several alcohols (non‐specific enzyme). Administer ethanol – block methanol from metabolism by enzyme. or Administer alcohol dehydrogenase inhibitor. Cofactors in Biochemical Redox Reactions NAD+ NADP+ Nicotinamide adenine dinucleotide Nicotinamide adenine dinucleotide phosphate NAD+ = oxidizing agent NADH = reducing agent NADP+ = oxidizing agent NADPH = reducing agent FAD Flavin adenine dinucleotide FAD = oxidizing agent FADH2 = reducing agent 5 2/10/2015 Draw Arrows to Show Flow of Electrons In vivo oxidation of ethanol to acetaldehyde 6
