1. What type of kinetics applies for alcohol in the body? Also, explain the clinical significance of this.

At a specific level of ethanol achieved in blood, the rate of oxidation follows zero-order kinetics. The typical adult can metabolize 7–10 g (150–220 mmol) of alcohol per hour. After ingestion of alcohol in the fasting state, peak blood alcohol concentrations are reached within 30 minutes. The presence of food in the stomach delays absorption by slowing gastric emptying. Distribution is rapid, with tissue levels approximating the concentration in blood. The volume of distribution for ethanol approximates total body water (0.5–0.7 L/kg). After an equivalent oral dose of alcohol, women have a higher peak concentration than men, in part because women have a lower total body water content and in part because of differences in first-pass metabolism. In the central nervous system (CNS), the concentration of ethanol rises quickly, since the brain receives a large proportion of total blood flow and ethanol readily crosses biologic membranes.

2. Give a brief summary of the metabolic pathways of ethanol metabolism.

There are 2 enzyme systems that metabolize ethanol to acetaldehyde:

• Alcohol dehydrogenase (ADH):

The NAD+, found mainly in the liver and gut, accounts for the metabolism of low to moderate doses of ethanol. Because of the limited supply of the co-enzyme NAD+, the reaction has zero-order kinetics, resulting in a fixed capacity for ethanol metabolism of 7-10g/h. Gastrointestinal metabolism of ethanol is lower in women than in men. Genetic variation in this system, affects the rate of ethanol metabolism.

• Microsomal ethanol-oxidizing system (MEOS):

At blood ethanol levels of 100 mg/L or higher, the liver microsomal mixed function oxidase system that catalyses most phase 1 drug-metabolizing reactions, contributes to ethanol metabolism. Chronic alcohol consumption induces CYT P450 enzyme synthesis and MEOS activity; this is partially responsible to the development of tolerance to ethanol. The primary isoform of CYT P450 induced by ethanol-2E1, converts acetaminophen to a hepatotoxic metabolite.

3. Which drugs can affect this metabolism and what are the effects thereof?

Disulfiram, Metronidazole, Cephalosporins and Hypoglycemic drugs inhibit aldehyde dehydrogenase so that acetaldehyde remains unchanged in the bloodstream. Side effects of sufficient acetaldehyde in the bloodstream include nausea & vomiting, headache, burning and general malaise.