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

Peak alcohol levels are reached within 30minutes and distribution happens very fast. The presence of food in the stomach delays the absorption of alcohol. In the CNS, the concentration of ethanol rises quickly because the brain receives the most blood and ethanol readily crosses biologic membranes. 

More than 90% of alcohol consumed is oxidized in the liver, the rest is excreted by the lungs and in the urine. The rate of oxidation follows zero-order kinetics thus it is independent of time and concentration of the drug. An adult can metabolize 7-10g (150-220ml) of alcohol per hour which is approximately 300ml beer or 105ml wine   

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

1. Alcohol dehydrogenase pathway: the primary pathway of alcohol metabolism involves the enzyme called ADH which catalyzes the conversion of alcohol to acetaldehyde. These enzymes are usually found in the liver and small amounts are found in the stomach and brain. Thus, metabolism can occur in the stomach, more in men than in female. 

2. Microsomal ethanol-oxidizing system: this system is also known as the mixed function oxidase system and uses the co-factor NADPH in the metabolism of ethanol. It consists primarily of cytochrome P450 2E1, 1A2 and 3A4. If alcohol is being misused/ chronically consumed, MEO system is induced. 

3. Acetaldehyde metabolism:   much of acetaldehyde is oxidized in the liver in a reaction catalyzed by mitochondrial NAD-dependent aldehyde dehydrogenase (ALDH). Acetate is the product of this reaction and is further metabolized to CO2 and water. 

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

Alcohol dehydrogenase are inhibited by the drug Fomepizole, which blocks the metabolism of ethanol. 

Oxidation of acetaldehyde is inhibited by Disulfiram. Acetaldehyde accumulates and causes the person to experience nausea, vomiting, dizziness and headache. 

Drugs such as metronidazole, trimethoprim and cefotetan inhibit ALDH and has the same reaction as disulfiram.