1. Alcohol undergo zero-order kinetics in the body. This is due to the limited amount of NAD (nicotinamide adenine dinucleotide), the co-enzyme influencing the conversion of alcohol (ethanol) to acetaldehyde, by alcohol dehydrogenase. When there are not enough NAD left to help with the metabolism of alcohol (usually due to a high alcohol intake), the rest of the alcohol will also be metabolized by the Microsomal Ethanol-Oxidizing System (MEOS). When high alcohol consumption occurs regularly the MEOS system will be used regularly leading to the induction of this system. This system consists primarily of cytochrome P450 enzymes and the metabolism and clearance of other drugs, not only alcohol, that are metabolized by cytochrome P450-enzymes. Toxic byproducts of this cytochrome P450 reactions also increase, due to the induction of this enzymes. The induction of this enzymes also plays a part in the development of tolerance for alcohol (Brand, 2021; Katzung, 2018).
2. There are 2 metabolic pathways (enzyme-systems) for  the metabolism of ethanol.
   1. Alcohol Dehydrogenase pathway

This is the primary pathway for the metabolism of moderate to low amounts of ethanol, which takes place in the liver, primarily. Ethanol (alcohol) is converted to acetaldehyde by the enzyme alcohol dehydrogenase which catalyse this conversion. With this conversion, nicotinamide adenine dinucleotide also known as NAD⁺ (an co-enzyme), is also converted to NADH. This pathway is dependent on this co-enzyme and thus follows zero-order kinetics (Brand, 2021; Katzung, 2018).

Note: Small amounts of alcohol dehydrogenase is found in the stomach and brain (Katzung, 2018).

1. 2. Microsomal Ethanol-Oxidizing System (MEOS) a.k.a. Mixed function oxidase system

Ethanol is converted to acetaldehyde with MEOS. With this conversion, NADPH (co-factor) and oxygen is also converted to NADP⁺ and water (Katzung, 2018)

Both these pathways forms acetaldehyde which are then further converted to acetate with the enzyme aldehyde dehydrogenase and the co-enzyme NAD⁺, which is in turn converted to NADH (Katzung, 2018).

3. The drugs that can influence the metabolism of ethanol is as follow:

• Fomepizole can inhibit the enzyme, alcohol dehydrogenase, at the Alcohol Dehydrogenase pathway (Katzung, 2018).

The effect of this inhibiting will cause the accumulation of ethanol in the body due to the fact that it cannot be converted acetaldehyde.

• Aldehyde dehydrogenase can be inhibited by the drugs: cephalosporins, disulfiram, hypoglycemic drugs and metronidazole.

The effect of the inhibition of aldehyde dehydrogenase: Acetaldehyde cannot be converted to acetic acid and accumulates in the body (Brand, 2021). Acetaldehyde is toxic to the body’s cells and liver. The result of ethanol use together with these drugs, causes the patient to have symptoms of: nausea, hypotension, throbbing, confusion, flushing, headache, sweating and vomiting (Katzung, 2018).  

Reference list

Katzung, B.G. 2018. Basic & Clinical Pharmacology. 14th ed. International: Mc Graw Hill Education.

Brand, L. 2021. Alcohols. SU 3 [pdf]. Unpublished lecture notes on eFundi, FKLG 312. Potchefstroom: NWU.