• Watter tipe kinetika ondergaan etanol in die liggaam?  Verduidelik ook wat die kliniese betekenis hiervan is.

Zero-orde kinetika- daar is ‘n beperkte hoeveelheid ko-ensiem NAD teenwoordig in die liggaam wat veroorsaak dat die alkoholdehidrogenase ensiemsisteem versadigbaar is. Dus sal dit slegs lae en matige hoeveelhede alkohol kan hanteer (Brand, 2021). Indien die alkohol te veel is, kan toksiese newe-effekte ontstaan as gevolg van die opeenhoping.

By vlakke etanol wat gewoonlik in die bloed bereik word, volg die tempo van oksidasie zero-orde kinetika, dit wil sê dit is onafhanklik van tyd en konsentrasie van die middel (Katzung, 2018:397).

• Gee ‘n kort opsomming van die metaboliese weë van etanolmetabolisme.
• Give a brief summary of the metabolic pathways of ethanol metabolism.

Alcohol Dehydrogenase Pathway

This is the primary pathway for alcohol metabolism. Cystolic enzymes catalyze the conversion of alcohol to acetaldehyde mainly in the liver (also brain and stomach). The genetic variation in ADH enzymes affects the rate of ethanol metabolism and can also alter vulnerability to alcohol-abuse disorders. Conversion of ethanol by ADH to acetaldehyde takes place, and a hydrogen ion is transferred from ethanol to the cofactor nicotinamide adenine dinucleotide (NAD+) to form NADH. Alcohol oxidation generates an excess of reducing equivalents in the liver (NADH) as net result. This can contribute to metabolic disorders that accompany chronic alcoholism and lactic acidosis and hypoglycemia that regularly accompany acute alcohol poisoning (Katzung, 2018:397).

This is the metabolism for low and moderate amounts of alcohol. There is a restricted amount of NAD involved  and zero-kinetics are followed.(Brand, 2021).

Microsomal Ethanol-Oxidizing System (MEOS)

Also known as mixed function oxidase system. It uses NADPH as a cofactor in ethanol metabolism and consists primarily of cytochrome P450.

With chronic consumption of alcohol, MEOS activity is induced. This causes a significant increase in ethanol metabolism and clearance of other drugs eliminated by CYP450’s that constitute the MEOS system and in generation of the toxic byproducts of cytochrome P450 reactions (toxins, free radicals, H2O2) (Katzung, 2018:397-398).

The increased MEOS activity (metabolism for higher concentrations of alcohol bigger than 100mg/dl) can be partly responsible for tolerance. As in Alcohol Dehydrogenase Pathway, the end product is also acetaldehyde (Brand, 2021).

• Watter geneesmiddels kan hierdie metabolisme beïnvloed en wat is die effekte daarvan?
• Which drugs can affect this metabolism and what are the effects thereof?

Fomepizole- inhibits alcohol dehydrogenase. It prevents the conversion of methanol and ethylene glycol to toxic metabolites (Katzung, 2018: 406)

Cephalosporins, metronidazole, disulfiram and hypoglycemic drugs  can inhibit Aldehyde dehydrogenase. When these drugs are given with alcohol, aldehyde enzyme activity can be reduced, causing accumulation of acetaldehyde in the body (Brand, 2021).

Disulfiram inhibits oxidation of acetaldehyde and is used to stop drinking by patients with alcohol dependence. When ethanol is used with disulfiram, acetaldehyde accumulates and causes facial flushing, nausea and vomiting, dizziness, and headache.

Metronidazole, cefotetan, trimethoprim – these drugs inhibit ALDH and can cause disulfiram-like reactions in combination with ethanol (Katzung, 2018:398).

Reference list

Brand, L. 2021. Pharmacology FKLG312 2021.  Study unit 3 [PDF]. Unpublished lecture notes on eFundi, FKLG312. Potchefstroom: NWU.

Katzung, B.G.  2018.  Basic & Clinical Pharmacology.  14th ed. New York: McGraw-Hill Education.