Week 3 Lect 19 Drugs

Question 1

Isoniazid

Answer 1

N-acetyltransferase 2 (NAT 2) genetic polymorphism
Catalyzes acetylation of isoniazid

Slow acetylators (homozygous for AD alleles)- high blood drug levels, prone to toxicity

Sxs: neuropathy and hepatotoxicity

Question 2

Succinylcholine

Answer 2

Butyrylcholinesterase Polymorphism (AR)

Neuromuscular blocker, binds to nicotinic receptor and acts like acetylcholine cause depolarization of end plate

If genetic polymorphism- cannot metabolize succinylcholine. Membrane remains depolarized - flaccid paralysis

Question 3

Debrisoquine

Answer 3

CYP2D6 polymorphism

Marker (anti-HTN drug)

Poor metabolizers homozygous recessive
Ultra metabolizers have multiple copies of CYP2D6

Similar drug: Metoprolol- B2 brochiodilate, dec HR
Codeine needs CYP2D6 to convert into morphine. Ultrametabolizers need higher dose but can have overdose- respiratory arrest

Question 4

6-mercatopurine and azathiopurine

Answer 4

Thiopurine S-methyl transferase (TPMT)

Catalyzes S-methylation of anticancer thiopurines.
Homozygous - low TPMT activity means myelosuppression. Patients need 1/10 of normal dose.

Question 5

Gefitinib

Answer 5

Mutation in Epidermal Growth Factor

EGFR overexpressed in nonsmall cell lung cancer (NSCLC)

Getitinib inhibits tyrosine kinase EGFR
Pts with mutation on ATP-binding site of TK receptors respond better to the drug

Question 6

Warfarin

Answer 6

Narrow therapeutic window, racemic mixture

S config 3-5x more potent than R, CYP2C9
Gives 6-hydroxywarfarin and 7-hydroxywarfarin

R warfarin, CYP1A1, CYP1A2, CYP3A4 gives meatbolites.

Warfarin inhibites Vit K Eposxide Reductase. VKORC1 gene

If mutation in CYP2C9 or VKORC1 pts given lower dose

Question 7

Sulfonamides, antimalarials, cloramphencol with G6PD def

Answer 7

G6PD required to make NADPH

If G6PD def, decreased NADPH, decrease cellular detox, increased free radials and peroxides

Can cause hemolytic anemia