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

Ethanol is a small water soluble molecule which produces fast absorption, due to the lipophilic properties fast distribution also occurs especially across the blood brain barrier and into the central nervous system. When alcohol is consumed on an empty stomach blood plasma peeking results within 30 minutes as opposed to the stomach being lined with food that will decrease the stomach emptying time and allow gastric enzymes to help metabolize ethanol molecules before reaching the liver. Total body fluids also play a major role in distribution time where the more body fluids ( 0.5-0.7L/KG) you poses the longer it will take for your blood alcohol concentration to reach toxic levels because dissolution and increased amounts of volume dilutes this concentration. Metabolism of ethanol is mainly through the liver (90%) and the rest will be excreted through the lungs and urine.

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

2 enzymes systems in the liver are responsible for ethanol metabolism.

Through zero order kinetics which means that the pathway can become saturated and is not dependent on the concentration of ethanol nor time exposure. Alcohol dehydrogenase metabolizes low to moderate amounts of alcohol (7-10g/h) and is dependent on the co-enzyme NAD. Microsomal Ethanol-Oxidizing System -MEOS- metabolizes ethanol In higher concentrations (>100mg/Dl). Both these metabolic pathways metabolises ethanol to acetaldehyde where aldehyddehidrogenase will convert it further into acetate that is ultimately broken down into carbon dioxide and water for excretion.

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

Disulfiram, Metronidazole, cephalosporin & hypoglycemics

These drugs interfere/inhibit the actions of aldehyddehidrogenase and thus cause an increase in the accumulation of acetaldehyde in the body. These abnormal concentrations will precipitate the negative side effects of a night out drinking including nausea, vomiting, ataxia etc. and are typically used in individuals with high alcohol tolerance or disulfiram to treat alcoholism. Patient taking these medications should always be warned of the possible side effects and advise to not consume any alcohol during their treatment period.

 

Katzung, B.G., 2018. Basic & Clinical Pharmacology. 14th ed. United States of America: McGraw-Hill Education.

Brand, L. 2021. Sedative Hypnotic drugs. Study Unit 2[PowerPoint Presentation]. Unpublished lecture notes on eFundi, FKLG 312. Potchefstroom, NWU.