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

Alcohol is a small water-soluble molecule that is rapidly absorbed from the GIT. Due to the high lipophilicity of alcohol allows for a rapid distribution occurs across the blood brain barrier into the central nervous system. Peak alcohol levels in the blood can be seen within 30 minutes after consumption in fasting state. The total fluid in the body has an important role in the distribution of alcohol, the more body fluids, the longer the alcohol will take for the concentration to reach toxic levels. Alcohol is mainly metabolized by the liver (90%) by means of 2 enzyme systems, namely Alcohol Dehydrogenase and the MEOS (mixed function oxidases).

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

The 2 enzyme systems responsible for the metabolism of alcohols (ethanol) in the liver namely the Alcohol Dehydrogenase System and MEOS .

• •  The Alcohol Dehydrogenase system which catalyses the conversion of alcohol to Acetaldehyde using zero-order kinetics, resulting in the pathway becoming  saturated and independent on the concentration of ethanol. This pathway  metabolizes low to moderate amounts of alcohol [7-10g/h] and is dependent on NAD as a co-enzyme.
  • The Microsomal Ethanol-oxidising system (MEOS) is responsible for metabolizing ethanol at higher concentrations [>100mg/dL] to Acetaldehyde. Its activity can be induced with chronic consumption of alcohol.
  • Once alcohol is converted to Acetaldehyde, Aldehyde-dehydrogenase converts it to Acetate which is thereafter broken down be to Carbon Dioxide and water to be excreted through the urine or used to from Acetyl Co-A.
• Which drugs can affect this metabolism and what are the effects thereof?

Drugs that influence the metabolism of alcohol include: Disulfiram, Metronidazole, Cephalosporin and Hypoglycaemic drugs. These drug result in the inhibition of Aldehyde Dehydrogenase leading to the accumulation of Acetaldehyde in the body. The increased concentrations of Acetaldehyde in the body will cause the same negative effects experienced with excessive drinking such as nausea, vomiting, ataxia, headaches.