L7 Drug Metabolism Flashcards
Pharmacokinetics
Absorption
Excretion
Distribution
Metabolism
The conversion of the drug into a
more Water soluble compound.
Metabolism
Family number
Subfamily
Isoenzyme numberThe main site of drug metabolism is
the …….
liver
Family number
Subfamily
Isoenzyme number
CYP 3A4
drugs or environmental pollutants can enhance the activity of hepatic metabolizing enzymes.
Enzyme inducers
Increasing biotransformation of drugs
Enzyme inducers
decreasing their plasma concentrations & pharmacologic effect.
Enzyme inducers
N.B. if the metabolite is active, the drug activity is increased = prodrugs
Enzyme inducers
Factors that inhibit hepatic metabolizing enzyme, Decreasing drug biotransformation
Enzyme Inhibitors
leads to higher levels and greater potential for toxic effects with drugs
Example erythromycin, ketoconazole, Natural substances (grapefruit)
Enzyme Inhibitors
Neonates
Starvation
Cancer
Liver disease
Enzyme inhibitors
Enzymatic inhibition
Environmental Contaminants as insecticides/pesticides
, Smoking
Enzymatic induction
Drugs affecting activity of metabolizing enzymes
Enzyme inducers:
- Phenobarbitone
*Phenytoin
*Rifampicin
*Carbamazepine
Drugs affecting activity of metabolizing enzymes
Enzyme inhibitors
*Erythromycin
*Ketoconazole
*Grapefruit
*Cimetidine
*Clarithromycin
The rate of drug metabolism and elimination is directly proportional to
the concentration of free drug, (Most drugs)
first-order kinetics (Linear kinetics):
The mechanisms of metabolism and excretion are SATURABLE (At high drug concentration)
zero-order (non-linear kinetics):
The mechanisms of metabolism and excretion are SATURABLE (At high drug concentration)
zero-order (non-linear kinetics):
the rate of metabolism and excretion is constant. (does not depend on the drug concentration) e.g. aspirin in high doses
zero-order (non-linear kinetics):
Mechanisms of hepatic drug metabolism
1. Phase I:
• reduction, oxidation, hydrolysis.
• may increase, decrease, or have no effect on pharmacologic activity.
• If the metabolite is sufficiently polar, it is excreted by the kidneys.
• many phase I metabolites are still too lipophilic to be excreted, they need phase-II.
Mechanisms of hepatic drug metabolism
2. Phase-2
• conjugation reactions with an endogenous substrate, (glucuronic acid, sulfuric acid, acetic acid, or an amino acid)
• Some Drugs may enter phase II directly without prior phase I metabolism.
• It results in more water-soluble compounds that are often therapeutically inactive, then excreted by the kidney or in bile.
