What are cytochrome P450 inducers?
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.
What do P450 enzymes do to drugs?
Cytochrome P450 enzymes also function to metabolize potentially toxic compounds, including drugs and products of endogenous metabolism such as bilirubin, principally in the liver. The Human Genome Project has identified 57 human genes coding for the various cytochrome P450 enzymes.
Which CYP450 enzyme is responsible for the majority of drug metabolism?
CYP3A subfamily CYP3A4 is the most abundantly expressed drug metabolizing enzyme in man responsible for the breakdown of over 120 different medications and is thus an important area for study with respect to enzyme based drug interactions.
Which TB drug is a powerful inducer of cytochrome P450?
Rifampin, for example, is a potent inducer of cytochrome P450 enzyme 3A, the enzyme subfamily responsible for metabolizing a large proportion of drugs currently on the market, as well as other cytochrome P450 enzymes.
What do enzyme inducers do?
An enzyme inducer is a type of drug that increases the metabolic activity of an enzyme either by binding to the enzyme and activating it, or by increasing the expression of the gene coding for the enzyme. It is the opposite of an enzyme repressor.
How does enzyme induction affects drug metabolism?
Enzyme induction refers to an increase in the rate of hepatic metabolism, mediated by increased transcription of mRNA encoding the genes for drug-metabolizing enzymes. This leads to a decrease in the concentrations of drugs metabolized by the same enzyme.
What are inducers and inhibitors?
This system can be inhibited or induced by drugs, and once altered can be clinically significant in the development of drug-drug interactions that may cause unanticipated adverse reactions or therapeutic failures. Drugs that cause CYP450 drug interactions are referred to as either inhibitors or inducers.
What effect does CYP450 inhibitors or inducers have on oral contraceptives?
Oral contraceptive hormones (OCs) are metabolized by the hepatic cytochrome p450 system; thus, inducers of the p450 system may increase OC metabolism. Whether decreased OC levels, associated with p450 inducer exposure, increase the risk of pregnancy is widely suspected but remains unknown.
How does enzyme induction occur?
Enzyme induction occurs when chemicals cause an increase in synthesis and activity of enzymes, thereby increasing the metabolism of drugs that are catalyzed by those enzymes. The parent drug is metabolized at an accelerated rate, leading to low potency and reduced effect.
What is the role of cytochrome P450 in drug metabolism?
Abstract. Cytochrome P450 is a family of isozymes responsible for the biotransformation of several drugs. Drug metabolism via the cytochrome P450 system has emerged as an important determinant in the occurrence of several drug interactions that can result in drug toxicities, reduced pharmacological effect, and adverse drug reactions.
How can I increase the bioavailability of cytochrome P-450 inhibitors?
Cytochrome P-450 enzyme inducers (e.g., rifampin, phenytoin, phenobarbital) decrease the bioavailability and increase the clearance of verapamil and diltiazem. Grapefruit juice, which inhibits some P-450 enzymes, has been found to increase the bioavailability of some dihydropyridine calcium antagonists.
How do cytochrome P-450 enzyme inducers affect the clearance of verapamil?
Cytochrome P-450 enzyme inducers (e.g., rifampin, phenytoin, phenobarbital) decrease the bioavailability and increase the clearance of verapamil and diltiazem.
How does aging affect the cytochrome P450 monooxygenase system?
The cytochrome P450 monooxygenase system is more affected by aging than any other metabolic pathway (3). Decreased biotransformation occurs in newborns due to underdevelopment of hepatic microsomal components (5). In the elderly, decreases in hepatic blood flow, enzyme activity, and liver mass result in reduced metabolic activity. Go to: