| What are the factors affecting the effect of a drug use? | age, gender, underlying disease, genetic variation (interindividual genes of targets transporters and enzymes) |
| What are the variations in enzymes of drug metabolism? | Genetic polymorphism in enzymes of phase I and II
In phase I (most common is CYP3A5 (CCB, cyclosporine), CYP2C8 (retinoic acid), CYP2C9 (NSAIDs, phenytoin, warfarin), CYP2C19 (omeprazol, phenytoin, propranolol)
So most important active ones are CYP2C, CYP2D, CYP3A subfamilies |
| What is pharmacogenetics and pharmacogenomics? | Genetics (on how a single genetic variation affects the drug response)
Genomics (on all genes and their influence)
Three types of variations (pharmacokinetic variation, pharmacodynamic variation, genetic variations associated with idiosyncratic drug effects. |
| What are variations in enzymes of drug metabolism? | Occur in enzymes of phase I or II |
| What are examples of variations of enzymes in phase I? | Most important ones are CYP2C, 2D and 3A, expressed in GI
CYP3A5 affect CCB, cyclosporines...
CYP2C8 affects retinoic acid
CYP2C9 affects NSAIDs, phenytoin, warfarin
CYP2C19 affects omepraazole, phenytoin, propranolol. |
| What are examples of variations in phase II? | N-acetyl transferases, Sulfotransferases.
Thiopurine S-methyl transferase affecting mercaptopurine |
| What are the variations in drug targets (pharmacodynamics)? | ex: ACE variations affecting ACE inhibitors (lisinopril)
ApoE affecting statins (pravastatin) |
| Talk about Debrisoquine drug. | Anti-HTN drug, used for phenotyping CYP2D6 drug metabolizing enzyme.
most subjects metabolize it extensively while some do rapidly and some poorly |
| What are idiosyncratic drug reactions? | Not known, neither dynamics or kinetics, interactions between medication and a unique aspect of physiology.
Ex: deficiency in glucose-6-phosphate dehydrogenase affecting drug reactions (pentose phosphate pathway difference producing NADPH) this NADPH is used in oxidation of glutathionone drug.
Can cause acute hemolytic anemia known as favism (fawwal, after eating fava beans, ID, drugs in G6PD deficient pt) |
| Give an example of indiosycratic drug reaction. | Medications causing stress on RBCs as a side effect, drugs like sulfonamides, antimalarial, analgesics (acetaminophen and ibuprofen).
Individuals with G6PD deficiency exposed to these drugs cause severe hemolytic anemia |
