Pharmacogenetics

Question 1

NAT2 polymorphism (N-acetyltransferase 2)

Answer 1

Defect: decreased activity of NAT2
Problem: slow acetylators are
prone to toxicity of drugs metabolized by acetylation
Examples: Isoniazid, Hydralazine, Procainamide, Sulfonamides

Question 2

Hydralazine / Procainamide

Answer 2

NAT2 polymorphism

ROS: SLE-like syndrome

Question 3

Sulfonamides

Answer 3

NAT2 polymorphism

ROS: HS rxn, hemolytic anemia, SLE-like syndrome

Question 4

Succinylcholine

Answer 4

Butyrylcholinesterase polymorphism

ROS: prolonged paralysis

Question 5

Codeine

Answer 5

Poor metabolizers (CYP2D6): codeine cant be converted to morphine so its useless
Ultra rapid metabolizers (CYP2D6): can overdose from standard doses of codeine

Question 6

6-mercaptopurine / Azathioprine

Answer 6

Thiopurine S-methyltransferase polymorphism

Problem: methylated causing inactivation

Question 7

Gefitinib

Answer 7

Mutation in ATP-binding site [of the TK domaine of the epidermal growth factor receptor (EGFR) in nonsmall cell lung cancer] responds better to gefitinib

Question 8

Warfarin

Answer 8

Metabolism: CYP2C9
Problem: pt w/ variant alleles require decreased doses to achieve anticoagulant effect (they have increased risk for hemorrhage)
Target: vitamin K epoxied reductase (gene VKORC1) has polymorphism so the dosing varies d/t this as well

Question 9

Chloroquine / Primaquine / Sulfonamides / Cloramphenicol

Answer 9

G6PD polymorphism
Problem: decreased formation of NADH results in inability to detoxify free radicals and peroxides in the cell
ROS: hemolytic anemia d/t oxidative stress on RBCs

Question 10

Isoniazid

Answer 10

NAT2 polymorphism

ROS: neuropathy and hepatotoxicity

Question 10

Butyrylcholinesterase Polymorphism

Answer 10

Defect: BCHE gene (AR transmission)
Problem: decreased rate of metabolizing depolarizing NM blockers (succinylcholine)

Question 11

CYP2D6 Polymorphism (poor metabolizers)

Answer 11

Problem: may suffer adverse effects when treated with standard doses of drugs like Metoprolol
*codeine is rendered useless bc the CYP2D6 is needed to convert it to morphine

Question 12

CYP2D6 Polymorphism (ultrarapid metabolizers)

Answer 12

Problem: require high dose of drugs metabolized by CYP2D6

**SE: can OD on codeine causing respiratory depression or arrest in response to standard doses

Question 13

Thiopurine S-methyltransferase Polymorphism

Answer 13

Problem: methylates anticancer thiopurines, inactivating them
**thiopurines have narrow therapeutic index and some pts suffer from life-threatening myelosuppression