Exam Facts

Question 1

Which (3) drugs are weak bases that require an acidic medium for drug dissolution and absorption and therefore have interactions with PPIs and H-2 blockers?

Answer 1

1. Ketoconazole (Nizoral®)
2. Itraconazole (Sporanox®)
3. Atazanavir (Reyataz®)

Management w/ PPIs and H2-blockers
For ketoconazole and itraconazole:
Try to avoid PPI/H2 blockers if possible, but if not possible take with acidic beverage (cola)

For Atazanavir:
If Tx-experienced, avoid all together
If Tx-naive, limit prilosec (or equiv) to 20mg daily and give atazanavir 10-12 hrs after H2/PPI

Question 2

What effect does NSAIDs have on Lithium?

Answer 2

NSAIDs can increase Li++ concentrations by 25-50%.

Prostaglandins cause renal vasodilation and promote renal perfusion. NSAIDs inhibit prostaglandin synthesis which can decrease GFR and renal elimination of some drugs (like lithium)

Question 3

The clinical significance of drug interactions from changes in urinary pH is only relevant for drugs excreted unchanged in urine with NTI. What weak base(s) and weak acid(s) were affected by changes in urinary pH?

Answer 3

Weak Base
1. Quinidine

Weak bases will be non-ionized in acidic urine and be reabsorbed. Weak bases will be ionized in alkaline urine and be excreted. Urine can be alkalinized by antacids, Na bicarb, acetazolamide.

Weak Acid

1. Methotrexate
2. ASA

Question 4

What 4 tissues is P-gp efflux protein located in?

Answer 4

small intestine
kidney
liver
brain

Question 5

T/F - P-gp and CYP3A4 have common substrates?

Answer 5

True

Ex. rifampin decreases cyclosporin levels by 3A4 induction (increased metabolism) and P-gp induction (decrease absorption)

Question 6

Which of the following NOACs is/are substrates of both P-gp and CYP3A4?

A. Xarelto®
B. Pradaxa®
C. Eliquis
D. A & B
E. A & C

Answer 6

E. A & C

Rivaroxaban (Xarelto®) and apixaban (Eliquis®) are substrates of both P-gp and CYP3A4 while dabigatran (Pradaxa®) is only a substrate of P-gp. A new NOAC approved in January 2015, Edoxaban (Savaysa®) is also only a P-gp substrate.

Remember, less chance of drug interactions with Xarelto® and Eliquis® b/c 2 modes of elimination compared to only 1

Question 7

List the dosing recommendations for all NOACs when combined with P-gp inducer (rifampin, phenytoin, St. John’s Wort, Carbamazepine)

Answer 7

Avoid use across the board

Apixaban (Eliquis®)
Rivaroxaban (Xarelto®)
Dabigatran (Pradaxa®)
Edoxaban (Savaysa®)

Question 8

T/F - Inhibition of OAT1B1 uptake transporter results in decreased risk of statin toxicity?

Answer 8

False - OAT1B1 transports statins from portal blood into hepatocytes for metabolism (and where statins accomplish their MOA). By inhibiting uptake of statins into hepatocytes, more statin concentration in plasma and increased risk of toxicity (rhabdomyolysis)

Question 9

Which of the following are inhibitors of OATP?

A. Rifampin
B. Cyclosporin
C. Gemfibrozil
D. B & C
E. All of the above

Answer 9

E. All of the above are inhibitors of OATP

Rifampin is actually an INHIBITOR of OATP not inducer like it is for most everything else.

Lopinavir/ritonavir (Kaletra®) is another inhibitor of OATP

Question 10

Since ALL statins are substrates of OATP, what are the only 3 statins and at what dose when given in combination with an OATP inhibitor cyclosporin?

Answer 10

1. Rosuvastatin (Crestor®) 5mg
2. Pravastatin (Pravachol®) 20mg
3. Fluvastatin (Lescol®) 20mg