Pharmacokinetics: metabolism
Drug metabolism usually involves two types of biochemical reactions - phase I and phase II reactions
The majority of phase I and phase II reactions take place in the liver
This is a phenomenon where the concentration of a drug is greatly reduced before it reaches the systemic circulation due to hepatic metabolism. As a consequence much larger doses are need orally than if given by other routes. This effect is seen in many drugs, including:
Questions concerning zero-order kinetics and acetylator status are also common in the exam
Zero-order kinetics
Zero-order kinetics describes metabolism which is independent of the concentration of the reactant. This is due to metabolic pathways becoming saturated resulting in a constant amount of drug being eliminated per unit time. This explains why people may fail a breathalyser test in the morning if they have been drinking the night before
Drugs exhibiting zero-order kinetics
Acetylator status
50% of the UK population are deficient in hepatic N-acetyltransferase
Drugs affected by acetylator status
- phase I reactions: oxidation, reduction, hydrolysis. Mainly performed by the P450 enzymes but some drugs are metabolised by specific enzymes, for example alcohol dehydrogenase and xanthine oxidase. Products of phase I reactions are typically more active and potentially toxic
- phase II reactions: conjugation. Products are typically inactive and excreted in urine or bile. Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved
The majority of phase I and phase II reactions take place in the liver
First-pass metabolism
This is a phenomenon where the concentration of a drug is greatly reduced before it reaches the systemic circulation due to hepatic metabolism. As a consequence much larger doses are need orally than if given by other routes. This effect is seen in many drugs, including:
- aspirin
- isosorbide dinitrate
- glyceryl trinitrate
- lignocaine
- propranolol
- verapamil
- isoprenaline
- testosterone
- hydrocortisone
Questions concerning zero-order kinetics and acetylator status are also common in the exam
Zero-order kinetics
Zero-order kinetics describes metabolism which is independent of the concentration of the reactant. This is due to metabolic pathways becoming saturated resulting in a constant amount of drug being eliminated per unit time. This explains why people may fail a breathalyser test in the morning if they have been drinking the night before
Drugs exhibiting zero-order kinetics
- phenytoin
- salicylates (e.g. high-dose aspirin)
- heparin
- ethanol
Acetylator status
50% of the UK population are deficient in hepatic N-acetyltransferase
Drugs affected by acetylator status
- isoniazid
- procainamide
- hydralazine
- dapsone
- sulfasalazine