What is the cytochrome P450 CYP system?
Cytochrome P450 (CYP) is a hemeprotein that plays a key role in the metabolism of drugs and other xenobiotics (Estabrook, 2003). Understanding the CYP system is essential for advanced practitioners (APs), as the consequences of drug-drug interactions can be profound.
How do I memorize CYP450?
Cytochrome P450 (CYP450) enzymes can be inhibited or induced by some drugs, resulting in significant drug interactions that can cause unanticipated adverse reactions or therapeutic failures. An easy way to remember the mnemonic is; CRAP GPs spend all day on SICKFACES.com.
How many CYP450 enzymes are there?
Cytochrome P450 enzymes are essential for the metabolism of many medications. Although this class has more than 50 enzymes, six of them metabolize 90 percent of drugs, with the two most significant enzymes being CYP3A4 and CYP2D6.
What is the Flockhart table?
The Flockhart Table(TM) only catalogs drug-drug interactions that are mediated by CYPs. Drug-drug interactions caused via other enzymes (e.g., UGTs) are not included in this table. In addition, some of the drugs listed here could be substrates of uptake and efflux drug transporters.
What do cytochrome P450 enzymes do?
Cytochrome P450 enzymes are present in most tissues of the body, and play important roles in hormone synthesis and breakdown (including estrogen and testosterone synthesis and metabolism), cholesterol synthesis, and vitamin D metabolism.
Where are cytochromes P450 found?
liver cells
Cytochrome P450 enzymes are primarily found in liver cells but are also located in cells throughout the body. While a large body of knowledge exists on the role of CYP450s in xenobiotic metabolism, recent studies have begun to reveal the endogenous functions carried out by this important superfamily of enzymes.
What are inducers of CYP450?
Cytochrome P-450 enzyme inducers (e.g., rifampin, phenytoin, phenobarbital) decrease the bioavailability and increase the clearance of verapamil and diltiazem. Conversely, the enzyme inhibitor cimetidine increases the bioavailability and decreases the clearance of calcium antagonists.
How many CYP enzymes are there?
Of the 30 CYP enzymes, only 6 have a major role in drug metabolism. These are CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. Some of the drugs metabolized by these CYP enzymes are presented in Table 6.1 and representative drugs which can induce or inhibit the functions of these CYP are listed in Table 6.2.
How many CYP genes are there?
57 genes
There are 18 mammalian cytochrome P450 (CYP) families, which encode 57 genes in the human genome.
Which GI drugs interact with CYP450?
Clinical example of P450-based interactions
- Terfenadine. Terfenadine is the first non-sedating H1-antihistamine drug.
- Cimetidine. Cimetidine inhibits antihistamine H2-receptor binding and is used in the treatment of gastric ulcers.
- Grapefruit juice.
- Omeprazole.
- Erythromycin.
- Cyclosporin.
- Rifampicin.
What happens when CYP450 is inhibited?
IRREVERSIBLE INHIBITION In some cases, CYP450 inhibition is irreversible. The formation of a stable complex, between a drug and the metabolizing enzyme, is one mechanism that can result in irreversible inhibition. The inhibitor can be a drug or one of its metabolites.
What are cytochrome P450 (CYP) enzymes?
cytochrome P450 system is comprised of about 40-50 isoenzymes.
Is cyanide a competitive inhibitor?
Cyanide acts as competitive inhibitor to the enzyme cytochrome c oxidase . This prevents the electron transport chain (the last part of cellular respiration) from working, meaning that the cell can no longer produce ATP for energy.
What is cytochrome P450?
Cytochrome P450. Cytochromes P450 (CYPs) are the principal enzymes responsible for the oxidation of the wide and complex array of drugs and foreign chemicals to which the body is exposed.