Drugs to Tx Fungal Infections

Question 1

What is the MOA for amphotericin B in the tx of many severe, invasive fungal infections?

Answer 1

Binds to the sterol component of a cell membrane leading to alterations in cell permeability and cell death

Question 2

How can amphotericin B lead to cytotoxicity (in particular nephrotoxicity)?

Answer 2

It also binds to cholesterol component of the mammalian cells

Question 3

Amphotericin B is indicated for what fungal organisms?

Answer 3

1) Cryptococcus neoformans

2) Blastomyces dermatitidis

Question 4

Why is it imperative to prevent inadvertent overdosage of amphotericin B?

Answer 4

It may result in fatal cardiac arrest

Question 5

What drug interaction is noted between amphotericin B and skeletal muscle relaxants/digitalis glycosides?

Answer 5

Hypokalemia

Question 6

What black box warning is given for amphotericin B?

Answer 6

It should only be used for treating patients with life threatening fungal infections

Question 7

What is the MOA of all azole drugs?

Answer 7

Stops the conversion of lanosterol to ergosterol via binding to fungal cytochrome P-450

Question 8

Coadministration of what antihistamine is contraindicated in patients receiving fluconazole?

Answer 8

Terfenadine

Question 9

What special population is fluconazole contraindicated for?

Answer 9

Pregnant women

Question 10

Some azoles, including fluconazole, have been associated with what phenomenon seen on EKG?

Answer 10

QT prolongation

Question 11

Azole antifungals also are both substrates and inhibitors of what cytochrome P450 family?

Answer 11

CYP3A4

Question 12

Why are drugs such as cisapride, astemizole, erythromycin, pimozide, and quinidine are contraindicated in patients receiving fluconazole?

Answer 12

They also prolong QT interval and are metabolized via CYP3A4

Question 13

Itraconazole has a black box warning for what patients?

Why?

Answer 13

1) Patients with heart failure

2) Due to its inotropic effects

Question 14

Itraconazole is metabolized predominantly by?

Answer 14

CYP3A4

Question 15

Voriconazole is contraindicated in patients with what conditions?

Why?

Answer 15

1) Hereditary Galactose Intolerance
2) Lapp Lactase Deficiency
3) Glucose-Galactose Malabsorption

4) Because voriconazole contains lactose

Question 16

Voriconazole has the greatest affinity for which CYP isoenzyme?

Answer 16

CYP2C19

Question 17

Which route of administration for voriconazole necessitates dose adaptation in cases of renal impairment?

Answer 17

Parenteral preparation

Question 18

What drugs are a group of semisynthetic, cyclic lipopeptides with an N-linked acyl lipid side chain?

Answer 18

Echinocandins

Question 19

What are the drugs that make up echinocandins?

Answer 19

1) Caspofungin
2) Micafungin
3) Anidulafungin

-Fungin

Question 20

Echinocandins are approved for IV use with what infections?

Answer 20

Candida infections

Question 21

What is the MOA of echinocandins?

Answer 21

Inhibition of β(1, 3)-D- glucan synthase which damages fungal cell walls

Question 22

Which echinocandin is indicated in treatment of acute disseminated Candidiasis and prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation?

Answer 22

Micafungin

Question 23

A “red man” syndrome associated with likely histamine release was first reported with which echinocandin?

Answer 23

Anidulafungin

Question 24

What is a pyrimidine analogue that has activity against fungal species that interferes with purine and pyrimidine metabolism?

Answer 24

Flucytosine

Question 25

The current use of flucytosine is mainly in combination with?

To treat?

Answer 25

1) Amphotericin B

2) Cryptococcal meningitis

Question 26

Flucytosine should be used with extreme caution in patients with?

Answer 26

1) Renal impairment

2) Bone marrow depression

Question 27

Flucytosine is contraindicated in what special populations?

Answer 27

1) Pregnant women

2) Women that are breastfeeding