Clinical Pharmacology

Question 1

What must be checked prior to use of abacavir?

Answer 1

HLA-B5701 - risk of hypersensitivity, DRESS.

Question 2

What HLA subtype increases risk of SJS/TENS in Han Chinese with carbamazepine use?

Answer 2

HLA-B1502. Also avoid phenytoin.

Question 3

What HLA subtype increases risk of SJS/TENS/DRESS in caucasians/Japanese with carbamazepine use?

Answer 3

HLA-A3101

Question 4

When should you not use allopurinol in Han Chinese?

Answer 4

HLA-B5801 -> SJS/TENS/DRESS

Question 5

HLA-B3505 increases risk of SJS with what drug?

Answer 5

Nevirapine (HIV)

Question 6

What HLA subtype increases risk of liver failure with flucloxacillin?

Answer 6

HLA-B5701

Question 7

What CYP does tamoxifen require to become activated, and what are clinical implications?

Answer 7

CYP2D6 - Fluoxetine and paroxetine inhibit this, therefore lower activity of tamoxifen

Question 8

What are some P-glycoprotein inhibitors?

Answer 8

Verapamil, macrolides, amiodarone, CNIs, ketoconazole

Question 9

What are some P-glycoprotein inducers?

Answer 9

St John’s wort, Rifampicin, carbamazepine, phenytoin

Question 10

Enzyme inducers

Answer 10

CBZ, phenytoin, phenobarbitones, alcohol, sulfonamides, rifampicin

Question 11

CYP metabolising warfarin?

Answer 11

CYP2C9. Metabolism inhibited by omeprazole, amiodarone, metronidazole, cimetidine.

Question 12

What CYP is substrate for clopidogrel metabolism?

Answer 12

CYP2C19 - inhibited by PPIs

Also acts as an inhibitor of CYP2C19

Question 13

What classes of antibiotics dependen on time above MIC?

Answer 13

Lincosamides, beta lactam

Question 14

Which class of antibiotics depends on Cmax?

Answer 14

Aminoglycosides

Question 15

Which class of antibiotics depend on total exposure above MIC?

Answer 15

Vancomycin

Question 16

Mechanism of action of indapamide?

Answer 16

Thiazide like diuretic, inhibits Na-Cl in DCT and also inhibits response to pressor stimuli

Question 17

Mechanism of action of amiloride?

Answer 17

Inhibits ENaC in late DCT, potassium sparing

Question 18

Which factors DO affect the bioavailability of an orally administered drug?

Answer 18

1st pass metabolism, rate of GI transit; presence of other drugs in GIT; lipid solubility of drug

Question 19

What factor DOES NOT affect bioavailability of an orally administered drug?

Answer 19

dose

Question 20

acidic drugs like phenytoin bind primarily to which plasma protein?

Answer 20

albumin

Question 21

how is lithium cleared?

Answer 21

100% renally

Question 22

which PD factor is most important in determining the efficacy of beta lactams and lincosamides?

Answer 22

time the concentration is above the MIC (should be at least 40-50% of the dosing interval)

Question 23

The proportion of drug reabsorbed in the renal tubule depends on the

Answer 23

urine pH

Question 24

MOA of Ivabradine for stable angina

Answer 24

slows heart rate

Question 25

During a constant rate of IV infusion of Taz, which factor determines the steady state drug concentration?

Answer 25

dose rate

Question 26

PD factor important in determining efficacy of aminoglycosides and quinolones

Answer 26

ratio of the max concentration over the MIC (maximum plasma drug concentration at the binding site)

Question 27

Diuretic that inhibits renal K secretion at the distal nephron by mineralocorticoid-independent mechanism

Answer 27

Amiloride

Question 28

Diuretic that inhibits the apical DCT epithelium Na-Cl co-transporter and decreaeses PVR

Answer 28

Indapamide

Question 29

Drugs that are important for albumin binding

Answer 29

Warfarin, Digoxin, NSAID, benzodiazepines, phenytoin

Question 30

What drug is dependent on the total exposure of the body to the antibiotic to MIC?

Answer 30

Vancomyin (as indicated by the ratio of the Area under the concentration-time curve during a 24hour period AUC0-24)

Question 31

CYP 2C9 inhibitors

Answer 31

Omeprazole, Metronidazole, Cimetidine, Amiodarone

Question 32

Tacrolimus MOA

Answer 32

engages FKBP12 -> forms complex that inhibits calcineurin phosphatase and T cell activation

Question 33

Ciclosporin MOA

Answer 33

engages cyclophilin -> forms complex that engages calcineurin which normally dephosphorylates NFATc -> moves to nucleus of T cell and increases genes for IL2 and related cytokines