CYP450 Flashcards

Question

What should you consider before prescribing oral contraceptives for patients taking St John’s wort?

Answer 1

St John’s wort is a CYP450 3A4 and 3A5 enzymes inducer. It increases the metabolism and clearance of oral contraceptive pills such as levonorgestrel, norethisterone, ethinylestradiol and desogestrel from the body. As a result, patients may experience breakthrough bleeding and potential contraceptive failure. St John’s wort should not be taken concurrently with oral contraceptive pills or patients should use alternative methods such as barrier methods, depots and intrauterine devices (IUD). For patients who require emergency contraception, a copper IUD is preferred over levonorgestrel. However, in cases where a contraindication arises for a copper IUD, 3 mg of levonorgestrel should be given as a single dose during and within 28 days after stopping St John’s wort

Answer 2

Miconazole is a CYP450 2C9 enzyme inhibitor. It inhibits the metabolism and clearance of warfarin, subsequently causing a rapid and extensive increase in warfarin concentration in the body. As a result, the anticoagulant effect of warfarin is increased, measured by an increase in the international normalised ratio (INR). Miconazole should not be prescribed concurrently with warfarin. If necessary, monitor INR and reduce a patient’s warfarin dose accordingly. Patients should be advised to seek immediate medical attention if they experience any signs of bleeding, which include unexplained bruising, nose bleeds, or blood in their urine

Answer 3

Cytochrome P450 (CYP450) are a group of enzymes encoded by the P450 genes and responsible for the metabolism of most drugs seen in clinical practice. 90% of drugs are metabolised by CYP3A5, CYP3A4, CYP2D6, CYP2C19, CYP2C9 and CYP1A2. CYP3A4 and CYP2D6 are the most important of these enzymes

Answer 4

Poor metabolisers (PM) are characterised by the inability to metabolise drugs via the CYP2D6 metabolic pathway, resulting in an increased risk of adverse effects and toxicity. The reverse applies to prodrugs. Poor metabolisers fail to convert the prodrug into its active form leading to a lack of therapeutic response. PM phenotype affects up to 10% of Caucasians and 30% of the Chinese population.

Answer 5

Ultrarapid metabolisers metabolise the drug rapidly, resulting in a lack of therapeutic response in these individuals. The reverse applies to prodrugs. Ultrarapid metabolisers rapidly convert the prodrug to its active form, causing potential toxicity. Ultrarapid metaboliser phenotypes are most prevalent in the North African, Ethiopian and Arab populations, affecting 16% – 28% of the populations. In the rest of the world, the prevalence of ultrarapid metaboliser phenotypes is estimated to be 1% in the Chinese, Japanese and Hispanic populations and 5.5% in Western Europe.

Answer 6

- Convert a toxic metabolite into a non-toxic metabolite - Convert a pro-drug into an active drug - Convert an active drug into an inactive drug

Answer 7

Phase 1 reactions are ‘ catabolic ’ - Oxidation - Reduction - Hydrolysis

Answer 8

Non-polar -> **polar** Lipid soluble -> **water soluble** Polar and water soluble makes it easier to excrete

Answer 9

Phase 2 reactions are ‘ anabolic ’ (hence associated with conjugation) - glucuronidation - acetylation - sulfation Aim to make the drug even more water soluble and polar

Answer 10

CYP450 inducer