Midterm I

Question 1

1. Proton Pump inhibitors are known to reduce the oral bioavailability of tyrosine kinase inhibitors (TKIs) because:
   a. They induce CYP2C19 which is the main metabolic enzyme mediating first-pass metabolism of TKIs
   b. They inhibit OATP-mediated absorptive transport of TKIs at the intestinal mucosa
   c. They suppress gastric acid which results in very slow dissolution of the basic, poorly soluble TKIs in the stomach
   d. They slow gastric emptying and increase acid-catalyzed degradation of TKIs
   e. None of the above is correct

Answer 1

c. They suppress gastric acid which results in very slow dissolution of the basic, poorly soluble TKIs in the stomach

Question 2

2. The dose (concentration) of the precipitant drug is important to the potential for an interaction to cause harm to a patient because:
   a. A higher level means the patient is closer to toxicity before the interaction occurs
   b. The magnitude of effect will be determined by the dose (concentration)
   c. Slow metabolizers of the object drug will be affected to a larger degree
   d. It is inversely related to the dose of the object drug
   e. All the above are correct

Answer 2

b. The magnitude of effect will be determined by the dose (concentration)

Question 3

3. The reduction in itraconazole bioavailability by omeprazole can be reversed by:
   a. Giving each dose of itraconazole with 240mL of Coca-Cola
   b. Giving itraconazole solution
   c. Switching to ketoconazole
   d. A and B are correct
   e. All of the above are correct

Answer 3

d. A and B are correct

Question 4

4. Which of the following factors is/are expected to influence the nature, prevalence and severity of adverse drug interactions?
   a. Patient population (e.g. children, young adults, older adults)
   b. Clinical and practice setting (e.g. ambulatory clinic, in-hospital)
   c. Drug formulary
   d. All of the above
   e. None of the above

Answer 4

d. All of the above

Question 5

5. P-Glycoprotein (Pgp) inhibitors enhance the oral bioavailability of Pgp substrates to varying degrees because inhibition at the intestinal mucosa depends on:
   a. Dose of the Pgp inhibitor
   b. Potency of the Pgp inhibitor (Ki)
   c. Dissolution rate of the Pgp inhibitor
   d. Absorptive permeability of the Pgp inhibitor
   e. All of the above are correct

Answer 5

c. Dissolution rate of the Pgp inhibitor

Question 6

6. Concomitant disease can alter the risk of an adverse drug interaction outcome. For example the presence of renal dysfunction increases the risk of an adverse drug reaction when spironolactone and an ACE inhibitor are co-administered primarily because:
   a. Spironolactone is renally eliminated
   b. ACE inhibitors are renally eliminated
   c. Potassium is renally eliminated
   d. Patients with renal dysfunction are likely to have diabetes, which increases their sensitivity to the action of ACE inhibitors
   e. Sodium is renally eliminated

Answer 6

c. Potassium is renally eliminated

Question 7

7. The study by Singh et al. In 2000 showed that calcium carbonate as a calcium supplement can lower serum T4 significantly in some hypothyroid patient who had been stabilized on levothyroxine because:
   a. It chelates with levothyroxine to form a less permeable complex
   b. It acts as an antacid to neutralize gastric pH, thereby impeding levothyroxine dissolution
   c. It slows gastric emptying and promotes gastric degradation of levothyroxine
   d. It adsorbs levothyroxine and reduces the extent of gastrointestinal absorption
   e. None of the above is correct

Answer 7

d. It adsorbs levothyroxine and reduces the extent of gastrointestinal absorption

Question 8

8. Patients taking both diphenhydramine (allergy) and Tylenol with codeine (dental extraction) should be advised:
   a. That they should limit the Tylenol with codeine to a maximum of 4 doses daily to avoid
   hepatotoxicity
   b. That the diphenhydramine will not be very effective because the codeine will stimulate its elimination from the body
   c. To use cetirizine instead of diphenhydramine for their allergy
   d. Reduce their dose of Tylenol with codeine by 25%
   e. Reduce their dose of Tylenol with codeine by 50%

Answer 8

c. To use cetirizine instead of diphenhydramine for their allergy

Question 9

9. Which of the following is most likely to result in a patient being harmed by a drug interaction?
   a. The prescriber nor the pharmacists is aware of the interaction
   b. The precipitant drug has a narrow therapeutic range
   c. The object drug is metabolized by both CYP3A4 and CYP2D6
   d. The interaction is so strong it causes a split in the space-time continuum
   e. The patients baseline clearance of the object drug is very low

Answer 9

a. The prescriber nor the pharmacists is aware of the interaction

Question 10

10. The serum lithium concentration is often elevated in patient receiving concomitant thiazide diuretic and/or angiotensin converting enzyme (ACE) inhibitors because:
    a. Glomerular filtration of lithium ion is depressed by thiazide diuretics and ACE inhibitors
    b. Thiazide diuretics or ACE inhibitors block the proximal tubular secretion of lithium
    c. Renal clearance of lithium is sensitive to urine flow rate which is often elevated in patients taking thiazides and ACE inhibitors
    d. Thiazide diuretics and ACE inhibitors increases distal tubular reabsorption of lithium ion
    resulting in a decrease in renal clearance of lithium
    e. Both thiazide diuretics and ACE inhibitors can induce hypovolemia and elevate lithium level

Answer 10

d. Thiazide diuretics and ACE inhibitors increases distal tubular reabsorption of lithium ion
resulting in a decrease in renal clearance of lithium

Question 11

11. Rifampin precipitates drug interactions through a mix of mechanisms depending on its treatment regimen and timing of the interaction studies. Which of the following mechanisms is NOT known to be involved in rifampin-based drug interactions?
    a. Induction of efflux transport by Pgp at the intestinal mucosal
    b. Inhibition of efflux transport by Pgp at the intestinal mucosa
    c. Inhibition of uptake transport into the liver by MRP2 at the sinusoidal membrane
    d. Induction of CYP3A4 enzymes at the intestinal mucosa and the liver
    e. Inhibition of CYP3A4 enzymes at the intestinal mucosa and the liver

Answer 11

c. Inhibition of uptake transport into the liver by MRP2 at the sinusoidal membrane

Question 12

12. Which of the statement(s) below is(are) true regarding drug interactions involving inhibition of P-Glycoproteins (Pgp)?
    a. Pgp inhibitors consistently block renal proximal tubular secretion mediated by Pgp resulting in a significant lowering of renal drug clearance
    b. Inhibition of Pgp-mediated biliary drug clearance occurs occasionally, the best example being strong interaction between digoxin and talinolol
    c. Inhibition of intestinal Pgp results in increased oral drug bioavailability and is the principal effect of Pgp inhibitor in all cases
    d. A and B
    e. None of the above

Answer 12

e. None of the above

Question 13

13. Antacids are not all alike in their potential to precipitate drug interactions because they differ in which of the following characteristics:
    a. Absorptive capacity
    b. Al3+ and Mg2+ differ in their effects on gastrointestinal motility
    c. Stability of metal chelate differ between Al3+, Mg2+ and Ca2+
    d. None of the above applies
    e. All of the above are correct

Answer 13

e. All of the above are correct

Question 14

14. Which of the following is false for interactions triggered by elevation of stomach pH due to antacid neutralization action or suppression of gastric acid?
    a. Decrease of gastric degradation of acid-labile drugs and enhance their oral bioavailability
    b. Promotes premature release of drugs in the stomach from enteric-coated formulations
    c. Dissolution of acidic drugs is impeded, possibly leading to compromised oral bioavailability
    d. Significant reduction in oral bioavailability or poorly soluble, basic antifungals, such as
    ketoconazole and itraconazole
    e. Absorption of oral fluconazole is not affected because it is not very basic and reasonable
    soluble

Answer 14

c. Dissolution of acidic drugs is impeded, possibly leading to compromised oral bioavailability

Question 15

15. Orlistat (Alli, Xenical) can reduce the oral bioavailability of highly fat-soluble drugs (e.g. Cyclosporine) because:
    a. It irreversibly bind cyclosporine by the ion-exchange action
    b. It damages the intestinal mucosa resulting in malabsorption of some drugs like cyclosporine
    c. It disrupts the digestion of dietary fat and reduced the intestinal absorption fat-soluble drugs
    d. It accelerates intestinal motility, thereby reduces the bioavailability of particularly fat-soluble drugs
    e. The leading statement is false; i.e. Orlistat does not alter bioavailability of fat-soluble drugs

Answer 15

c. It disrupts the digestion of dietary fat and reduced the intestinal absorption fat-soluble drugs

Question 16

16. Which of the following statements(s) is (are) true regarding potential interactions between combination oral contraceptives and oral antibiotics?
    a. Significant interaction resulting in OC failure is expected with enzyme-inducing antibiotics, eg, rifampin
    b. Failure rate of OC in patients receiving non-enzyme inducing oral antibiotics is not any higher than the expected failure rate for typical use in the control population
    c. Pharmacokinetic studies have consistently failed to show that non-enzyme inducing oral
    antibiotics lower the AUC of ethinylestradiol or mestranol
    d. Potential interaction between OC and oral antibiotic resulting in unwanted pregnancy is a major concern in dental practice
    e. All of the above

Answer 16

e. All of the above

Question 17

17. Which of the following statement(s) concerning the interaction between metformin and cimetidine is (are) true?
    a. Cimetidine inhibits renal secretion of metformin mainly by blocking the uptake of metformin by OCT2 at the basolateral membrane of the tubular epithelium
    b. Cimetidine inhibits the efflux of metformin by MATEs at the apical membrane of the renal
    tubule, thereby inhibiting renal secretion of metformin
    c. Cimetidine’s inhibitory interaction with metformin also involves P-Glycoprotein
    d. A and B
    e. A and C

Answer 17

b. Cimetidine inhibits the efflux of metformin by MATEs at the apical membrane of the renal
tubule, thereby inhibiting renal secretion of metformin

Question 18

18. Which of the following mechanism(s) potentially apply (applies) to interactions between statins and cyclosporine?
    a. Cyclosporine inhibits intestinal CYP3A-mediated first-pass metabolism
    b. Cyclosporine inhibits CRP-mediated efflux transport at the intestinal mucosa
    c. Cyclosporine inhibits OATP-mediated hepatic uptake at the sinusoidal membrane
    d. None of the above
    e. All of the above

Answer 18

e. All of the above

Question 19

19. P-Glycoprotein is NOT expressed in which of the following tissue(s)?
    a. Liver
    b. Intestine
    c. Placenta
    d. Thyroid gland
    e. Kidneys

Answer 19

d. Thyroid gland

Question 20

20. The interaction between digoxin and diltiazem can result in patient harm. Assuming the prescriber is unaware of the interaction which of the following dosing scenarios would be most likely to result in patient harm.
    a. Diltiazem added to a patient taking digoxin for the last 10 months
    b. Both diltiazem and digoxin treatment started on the same day in a patient with atrial fibrillation
    c. digoxin prescribed to a patient who has been taking diltiazem for 4 months
    d. Lanoxicaps are prescribed for a patient who has been taking diltiazem for the past two years for hypertension
    e. All of these scenarios are equally likely to result in patient harm.

Answer 20

a. Diltiazem added to a patient taking digoxin for the last 10 months

Question 21

21. Addition of quinidine increases trough serum digoxin level because of.
    a. A decrease in the biliary excretion of digoxin due to inhibition of P-glycoprotein at the
    canalicular membrane of hepatocytes
    b. A decrease in the renal clearance of digoxin due to blockade of P-glycoprotein mediated tubular secretion
    c. A modest increase in the intestinal absorption of digoxin from inhibition of intestinal P-
    glycoprotein
    d. All of the above
    e. The leading statement is false; quinidine lowers trough serum digoxin level

Answer 21

d. All of the above

Question 22

22. The outcome of the interaction between rifampin and digoxin (i.e. whether an elevation or a lowering of AUC is observed) depends on the timing of the two drugs’ administration relative to each other and when the pharmacokinetic evaluation is conducted, because
    a. Rifampin slowly inactivates P-glycoprotein mediated absorption of digoxin the small intestine over a period of weeks
    b. Rifampin exerts dual effects of readily reversible inhibition and persistent induction of intestinal P-glycoprotein
    c. Rifampin sporadically induces choleresis, which interrupts enterohepatic circulation of digoxin
    d. A and B
    e. B and C

Answer 22

b. Rifampin exerts dual effects of readily reversible inhibition and persistent induction of intestinal P-glycoprotein

Question 23

23. A patient who is a poor metabolizer (PM) for a precipitant drug involved in a drug-drug interaction (DDI) will:
    a. Have a larger change in the object drug plasma concentration than that seen in a patient who is a rapid metabolizer of the precipitant drug
    b. Be at no risk of harm from the interaction
    c. Probably be on the large doses of the precipitant drug to get a therapeutic response
    d. Probably be on large doses of the object drug to get a therapeutic response
    e. None of the above are correct

Answer 23

a. Have a larger change in the object drug plasma concentration than that seen in a patient who is a rapid metabolizer of the precipitant drug

Question 24

24. Which following drug possesses anticholinergic effect that can potentially lower the oral bioavailability of L-DOPA as a result of an increase in its degradation by L-amino acid decarboxylase in the gastric mucosa?
    a. Metoclopramide
    b. Amitriptyline
    c. Donepezil
    d. Cisapride
    e. None of the above

Answer 24

b. Amitriptyline

Question 25

25. Ketoconazole has been demonstrated to increase the plasma concentration of omeprazole when they are co-administered. The effect of ketoconazole on omeprazole will be the largest in a. Patients who are extensive metabolizers for CYP2C19 b. Patients who take omeprazole at bedtime c. Patients who have very little or no CYP2C19 activity d. Patients who have the highest gastric pH e. None of the above effect the magnitude of this interaction

Answer 25

c. Patients who have very little or no CYP2C19 activity

Question 26

26. Which of the following factors can affect the magnitude of an interaction involving clearance inhibition, but only by influencing the object drug, not the precipitate drug? a. Dose b. Route of administration c. Patients genetic profile d. Alternative elimination pathways e. All of the above

Answer 26

e. All of the above

Question 27

27. High dose oral antibiotics can interfere with the efficacy of sulfasalazine in the treatment of ulcerative colitis because: a. Oral antibiotics damage intestinal mucosa and cause malabsorption of sulfasalazine b. Oral antibiotics suppress microflora in the large intestine responsible for the release of the active 5-aminosalicylic acid c. Oral antibiotics suppress pathogenic gut bacteria and decrease mucosal inflammation d. Oral antibiotics induce metabolic clearance of the active sulfapyridine metabolite in circulation e. None of the above is correct

Answer 27

b. Oral antibiotics suppress microflora in the large intestine responsible for release of the active 5-aminosalicylic acid

Question 28

28. Malabsorption of drugs induced by oral cytotoxic agents, mainly chemotherapy in cancer treatment can be minimized or avoided by which of the following strategy? a. Switch from solid dosage form to liquid formulation of the affected drug b. Switch to an alternate drug in the same class that has better bioavailability characteristics (i.e. no dissolution and/or permeability issues) c. Withdraw the affected drug(s) temporarily during the day(s) of chemotherapy and reinstate immediately afterwards d. A and B e. A and C

Answer 28

d. A and B

Question 29

29. Fluvoxamine (Luvox) is an inhibitor of CYP2C19. Which of the following is correct? a. Fluvoxamine will increase the AUC of omeprazole primarily in those who are CYP2C19 PMs b. Fluvoxamine will increase the AUC of omeprazole primarily in those who are CYP2C19 homozygote EMs c. Fluvoxamine will have little effect on omeprazole since its primarily metabolized by CYP3A4 d. Fluvoxamine will have little effect in patients who are rapid metabolizers of CYP2C19 e. None of the above is correct

Answer 29

b. Fluvoxamine will increase the AUC of omeprazole primarily in those who are CYP2C19 homozygote EMs

Question 30

30. OATs are examples of which of the following type of membrane transporters? a. Facilitative or equilibrative transporter b. Secondary active transporter driven by ion or proton gradient c. Primary active transporter driven by its own energy source (i.e. via ATP hydrolysis) d. Symporter, which is a form of primary active transport e. OAT is not a membrane carrier, but an ion channel for large organic solutes

Answer 30

b. Secondary active transporter driven by ion or proton gradient

Question 31

31. Sevelamer is a phosphate binder used to treat retention of phosphates in end-stage kidney disease. It can interfere with the oral absorption of some acidic and neutral drugs, such as warfarin and digoxin. a. True b. False

Answer 31

a. True

Question 32

32. Chelation interaction between Maalox and ciprofloxacin can be totally avoided by staggering the administration schedule, i.e. give ciprofloxacin two hours after the last dose of antacid and the next dose of antacid until two hours afterwards. a. True b. False

Answer 32

b. False

Question 33

33. The Drug Interaction Probability Scale (DIPS) is used to estimate the probability that the interaction will increase the object drugs plasma concentration by more than 25% above the baseline value. a. True b. False

Answer 33

b. False

Question 34

34. Clarithromycin has little to no effect of oral digoxin bioavailability in individuals who have the homozygous MDRI variant genotype that results in loss of P-glycoprotein efflux activity in the intestine. a. True b. False

Answer 34

a. True

Question 35

35. A pharmacokinetic drug interaction is more likely to cause a change in a patient’s response to the object drug than a pharmacodynamic interaction. a. True b. False

Answer 35

b. False