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

Alcohol is lipophilic and therefore has a rapid distribution and absorption from the digestive tract to the rest of the body. Due to it being lipophilic it also moves through the blood-brain barrier. In fasting conditions, the peak levels can be reached within 30 min. Total body water has an effect on the volume of distribution and therefore women (with less body water) reach their peak faster than men. 90% of the metabolism of alcohol takes place in the liver while the rest takes place in the lungs and urine. Adults metabolize 1g / h for every 10kg of body mass. The clinical significance of this is that if a person ingests more alcohol than he can metabolize and excrete, dangerous central nervous system side effects can be experienced and can lead to coma, respiratory depression and even death. Also it can cause sedation, as well as feeling of well-being.

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

Occurs due to 2 enzyme systems, depending on the amount ingested:

• Alcohol dehydrogenase: Occurs in low and moderate amounts of ethanol. There is a limited amount of NAD (coenzyme), so zero-order kinetics are followed, so the rate of degradation of the ethanol remains constant regardless of the amount of ethanol ingested. It metabolizes ethanol constantly at 7-10g per hour.

• Microsomal ethanol oxidation: Occurs at high concentrations (more than 100mg / dL). The MEOS activity increases as chronic use of ethanol. Ethanol is oxidized to acetaldehyde in the endoplasmic reticulum, so it can be induced and can cause tolerance. The end product is therefore Acetaldehyde.

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

To further metabolize acetaldehyde to acetate, the enzyme aldehyde dehydrogenase was required. If this enzyme is inhibited, acetate will not form. Drugs that inhibit this enzyme include: Disulfiram, Metronidazole, Hypoglycemic drugs (metformin)and Cephalosporin. Effects are that all the drugs therefore suppress aldehyde dehydrogenase, which causes the acetaldehyde to accumulate and not metabolize to convert to acetate, which can lead to nausea, headaches, vomiting, palpitations, flushing and dizziness