Pharmacogenetics

Question 1

Pharmacogenetics

Answer 1

The study of differences in drug response due to allelic variation at individual genes affecting drug metabolism, efficacy, and toxicity

Question 2

Pharmacogenomics

Answer 2

The study of alleles at many polymorphic loci for their affect on the outcome of drug therapy

Question 3

Pharmacokinetics

Answer 3

The rate at which the body Absorbs, Distributes, Metabolizes, or Excretes drugs (ADME); describes whether or how much drug reaches the target

Question 4

Pharmacodynamics

Answer 4

Describes the relationship between the concentration of a drug at its site of action and the observed biological effects

Question 5

Phase I drug metabolism

Answer 5

Attach a polar group onto the compound to make it more soluble; usually hydroxylation

Question 6

Phase II drug metabolism

Answer 6

Attach a sugar/acetyl group to detoxify the drug and make it easier to excrete

Question 7

Cytochrome P450 (CYP450)

Answer 7

Liver & intestinal enzymes that metabolize a wide number of drugs; CYP families CYP1, CYP2, and CYP3 are involved in the Phase I metabolism (inactivation) of 90% of all commonly used medications

Question 8

CYP-mediated drug activation

Answer 8

Most CYPs function to inactive drugs; rarely, CYPs are needed for drug activation

Ex: CYP2D6 converts codeine (inactive) into morphine (active)

Question 9

CYP3A

Answer 9

Substrate: Cyclosporin
Inhibitors: Ketoconazole (anti-fungal), Grapefruit Juice
Inducers: Rifampin

Question 10

CYP2D6

Answer 10

Substrates: Tricyclic antidepressants, Codeine
Inhibitors: Fluoxetine, Paroxetine

Question 11

CYP2C9

Answer 11

Substrates: Warfarin

Question 12

N-acetyltransferase (NAT) gene

Answer 12

NAT enzyme is important for Phase II metabolism; rate of acetylation is determined by polymorphism in the NAT1 and NAT2 genes

Substrate: Isonaizid for tuberculosis

Question 13

Thiopurine methyltransferase (TPMT) gene

Answer 13

TPMT enzyme important in the metabolism of 6-mercaptopurine and 6-thioguanine; giving children with deficient TPMT enzyme activity and ALL standard doses of these drugs will kill them due to hyperimmunosuppression

Question 14

Glucose-6-Phosphate Dehydrogenase (G6PD) gene

Answer 14

G6PD is a common, X-linked enzymatic deficiency disorder; G6PD deficienc individuals are susceptible to hemolytic anemia following drug exposure

Substrate: Sulfonamide antibiotics

Question 15

Vitamin K Epoxide Reductase Complex (VKORC1) gene

Answer 15

VKORC1 protein reduces & recycles Vitamin K so that it can contribute to the carboxylation (activation) of clotting factors; deficient individuals at greater risk for severe bleed with anticoagulants

Warfarin’s anticoagulant effect inhibits this pathway

Question 16

CYP3A4

Answer 16

Especially active member of the CYP450 family; participates in Phase I metabolism of over 405 of commonly used meds

Question 17

4 main approaches to treatment of genetic disease at the level of mutant protein

Answer 17

Cofactor administration, replace extracellular protein (Factor VIII in Hemophilia A, A1-AT), replace intracellular protein, target intracellular protein (Gaucher disease, Fabry disease)