Drug Metabolism Flashcards
Give an example of a drug that is chemically activated from an inactive drug to its active substrate
Enalapril to enalaprilat
Codeine to morphine
Sites for drug metabolism
Liver, lungs, kidney, skin , GIT
Outcome of drug metabolism
Inactivation, active metabolite, active drug
What types of enzymes are involved in drug metabolism
Microsomal enzymes
Non microsomal enzymes
Another name for phase 1 reactions
Functionalization/ non synthetic
List reactions that occur in phase 1
1) oxidative
2) reductive
3) hydro lyric rxns
Others are cyclization and decyclization
Another name for phase 2 rxns
Conjugation rxns
List the endogenous substances in phase 2 rxns
Glucoronide, sulphate, amino acid , acetate, glycine etc
Location of microsomal enzymes
In the smooth endoplasmic reticulum of the liver, lungs, kidneys and intestinal mucosa
Location of non microsomal enzymes
Cytoplasm, mitochondria, plasma
List the microsomal enzymes
Monooxygenases, Cytochrome P450, UGT, epoxide hydroxylases
List non microsomal enzymes
Esterases and amidases
Microsomal enzymes are found in what phase
Phase 1 and 2
Cytochrome P450 enzymes are cytoplasm bound T or F
F
They are membrane bound, heme containing proteins
CYP families contain how many genes, families and sub families
57 genes, 18 families and 44 subfamilies
Examples of CYP enzymes
CYP2D6, CYP2C19, CYP296, CYP3A4, CYP3A5
Which CYP is involved in significantly higher number of drug metabolism compared to other enzymes
CYP3A4
What does modification include
1) induction of drug metabolizing enzymes
2) inhibition of drug metabolizing enzymes
Biological factors related to modification
Species/ strain differences (slow or fast acetylators)
Genetics
Disease state
Sex differences (M or F)
Circadian rhythm
Age
Diet
Pregnancy
List drugs that inhibit CYP enzymes
CIG POKER
Cimetidine
Isoniazid
Grapefruit
Phenelzine
Omeprazole
Ketoconazole
Erythromycin
Retonavir
List drugs that induce CYP enzymes
BRCC
Barbiturates
Rifampicin
Carbamazepine
Cyclophosphamide
T or F testosterone is an enzyme inhibitor
F it is an enzyme inducer
T or F felodipine is inhibited by grape fruit
T
T or F progesterone is an enzyme induced
T
Drugs with extensive first pass effect include
Lidocaine, propranolol, nitroglycerin, morphine
Other factors that may affect first pass effect
Increased bioavailability in liver disease
Effects of other drugs
Individual variation in oral drug absorption
