Drug Metabolism Flashcards
What is drug metabolism?
A biochemical modification of pharmaceutical substances by living organisms; usually through specialised enzyme activity
What is a prodrug?
Drugs activated following metabolism
Give two examples of prodrugs
Codeine and enalapril
What are the effects of drug metabolism?
- Loss of pharmacological activity
- Decrease in activity (some metabolites show activity)
- Increasing activity (as is the case with prodrugs)
- Production of toxic metabolites
What types of toxicity are there?
Direct toxicity, carcinogenesis and teratogenesis
What three processes are part of Phase I Drug metabolism?
Oxidation, reduction and hydrolysis
What is the general outcome of Phase I Drug Metabolism?
Polar groups are expressed/introduced to a molecule to provide an active site for Phase II to occur
What is the most important superfamily of enzymes in drug metabolism?
Cytochrome-P450 superfamily
What are the there most important CYP enzymes?
CYP3A4, CYP2D6 and CYP1A2
What is the action of CYP3A4?
Major constituent of liver enzymes in metabolism of a wide range of drugs
What is the action of CYP2D6?
Responsible for the metabolism of some antidepressants, antipsychotics and conversion of codeine to morphine
What are some interesting features of CYP2D6?
Reduced or absent expression in 5-10% of the population
Induction by cigarette smoking may be important in psychiatric patients (also theophylline)
What is the outcome of Phase II Drug Metabolism?
Involves conjugation - attachment of glucuronic acid, glutathione, sulphate, acetate
Enzymes can be induced by things which increases metabolism of drugs; what effect will this have on drug activity?
Decreased drug activity
What are the two most common enzyme inducers?
Alcohol and smoking
