CYP450 Flashcards
Substrate, Inducer or Inhibitor: Rifampicin
CYP450 Inducer
Substrate, Inducer or Inhibitor: Statins
CYP450 Substrate
What is an Inducer?
Inducers increase the expression level of CYP450 enzymes resulting in increased metabolism of drugs and subsequently reducing the therapeutic concentration.
Therefore, potential changes in drug concentration may cause treatment failure. The effects usually develop over several days and may be slow to resolve depending on the half-life of the inducer.
What is a substrate?
Enzyme substrates are drugs or other substances that bind to and are metabolised by the CYP450 enzymes
What is an inhibitor?
Inhibitors prevent the CYP450 enzymes from working or reduce the rate of an enzyme-catalysed reaction. Consequently, this decreases drug metabolism in the body and increases the potential for toxicity. The effect often occurs quickly and is dose related.
Substrate, Inducer or Inhibitor: Theophylline
CYP450 Substrate
Substrate, Inducer or Inhibitor: Phenytoin
CYP450 Substrate
Substrate, Inducer or Inhibitor: Warfarin
CYP450 Substrate
Substrate, Inducer or Inhibitor: Selective serotonin reuptake inhibitors (SSRI): sertraline, citalopram, fluoxetine
CYP450 Substrate
Substrate, Inducer or Inhibitor: Amitriptyline
CYP450 Substrate
Substrate, Inducer or Inhibitor: Codeine
CYP450 Substrate
Substrate, Inducer or Inhibitor: Caffeine
CYP450 Substrate
Substrate, Inducer or Inhibitor: Nicotine/ Cigarette smoke
CYP450 Inducer
Substrate, Inducer or Inhibitor: Antibiotics: rifampicin, griseofulvin
CYP450 Inducer
Substrate, Inducer or Inhibitor: Steroids: dexamethasone, prednisolone, glucocorticoids
CYP450 Inducer
Substrate, Inducer or Inhibitor: Anticonvulsants: phenytoin, carbamazepine, phenobarbitone
CYP450 Inducer
Substrate, Inducer or Inhibitor: Alcohol
CYP450 Inducer
Substrate, Inducer or Inhibitor: St John’s Wort
CYP450 Inducer
Substrate, Inducer or Inhibitor: Antibiotics: sulfonamides, metronidazole, ciprofloxacin, chloramphenicol, macrolides, isoniazid
CYP450 Inhibitor
Substrate, Inducer or Inhibitor: Cimetidine
CYP450 Inhibitor
Substrate, Inducer or Inhibitor: Omeprazole
CYP450 Inhibitor
Substrate, Inducer or Inhibitor: Sodium valproate
CYP450 Inhibitor
Substrate, Inducer or Inhibitor: Azoles: ketoconazole, fluconazole
CYP450 Inhibitor
Substrate, Inducer or Inhibitor: Grapefruit
CYP450 Inhibitor
What should you consider before prescribing oral contraceptives for patients taking St John’s wort?
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
What should you consider when prescribing miconazole (for oral thrush) for patients taking warfarin
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
What is CYP450?
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
What are poor metabolisers?
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.
What are ultrarapid metabolisers?
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.
What are the 3 functions of CYPs?
- 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
Which types of reactions do CYPs undertake? (phase 1 metabolism)
Phase 1 reactions are ‘ catabolic ’
- Oxidation
- Reduction
- Hydrolysis
How do CYPs change drugs?
Non-polar -> polar
Lipid soluble -> water soluble
Polar and water soluble makes it easier to excrete
Which types of reactions occur in phase 2 metabolism? (not CYPs - transferase enzymes instead)
Phase 2 reactions are ‘ anabolic ’ (hence associated with conjugation)
- glucuronidation
- acetylation
- sulfation
Aim to make the drug even more water soluble and polar
Substrate, Inducer or Inhibitor:
Carbamazepine
CYP450 inducer
