Structural Specificity of Drugs

Question 1

True or false: Polymorphism in drug targets affects drug efficacy

Answer 1

True

Question 2

Polymorphism in which receptor directly impacts an individual’s receptiveness to beta blockers in the treatment of HTN?

Answer 2

β1 adrenergic receptor gene (ADRB1)

Question 3

Two SNPs seen in ADRB1

Answer 3

Codon 49 (Ser49Gly)
Codon 389 (Arg389Gly)

Question 4

Codon 49 and Codon 389: Which is inside the cell and which is outside the cell?

Answer 4

Codon 49- outside

Codon 389- inside

Question 5

What is the target enzyme for warfarin?

Answer 5

Vitamin K epoxide reductase (VKOR)

Question 6

Which CYP enzyme plays a role in warfarin metabolism?

Answer 6

CYP2C9

Question 7

True or false: Patients that express low levels of Vitamin K 2,3-epoxide reductase would receive a high dose of warfarin

Answer 7

False. Low VKOR, low warfarin dose, high VKOR, high warfarin dose

Question 8

True or false: Drugs can target receptors and enzymes, not ion channels

Answer 8

False. All three are possible drug targets

Question 9

G6PD is crucial for the regeneration of what?

Answer 9

NADPH

Question 10

True or false: Decreased NADPH leads to decreased glutathione

Answer 10

True

Question 11

Glutathione (GSH) deficiency in red blood cells leads to what condition?

Answer 11

Hemolytic anemia

Question 12

NAT2 catalyzes what phase II reaction?

Answer 12

N-acetylation

Question 13

DPD deficiency is commonly seen in all of the following populations except:
East Indian
African Americans
Japanese
Korean

Answer 13

African Americans. DPD enzyme activity is lower compared to Caucasians but not deficient

Question 14

True or false: Very high expression of TPMT causes increased therapeutic effect of drug metabolized by this enzyme

Answer 14

False. High TPMT causes increased metabolism, which lowers therapeutic effect

Question 15

UGTs are highly responsible for catalyzing what type of reactions?

Answer 15

Glucuronidation

Question 16

True or false: UGT1A1*28 allele possesses lower enzyme activity than wild-type

Answer 16

True

Question 17

Where is OAT present? What is its function?

Answer 17

transports anions and are present in intestine, hepatocytes, kidneys and blood-brain barrier

Question 18

Which gene encodes for OAT polypeptide?

Answer 18

SLC01B1

Question 19

Which forms of SLCO1B1 have 100% activity?
1A
1B
5
15

Answer 19

1A and 1B

Question 20

At pH 7.4 (bloodstream, systemic circulation), are carboxylic acids positively charged, negatively charged or neutral?

Answer 20

Negative

Question 21

True or false: Atorvastatin’s hydrophobic character allows it to undergo passive uptake

Answer 21

True

Question 22

True or false: Polymorphism of OATP1B1 decreases the incidence of statin associated myopathy

Answer 22

False. Increases

Question 23

What is the benefit of formulating a drug in a salt form using a strong acid or strong base? (ex. warfarin SODIUM)

Answer 23

Increased water solubility

Question 24

By which two mechanisms do antacids decrease drug efficacy?

Answer 24

.Increase gastric pH

.Directly binding with the drug