Drugs to Treat Fungal Infections (J-Staud)

Question 1

When is it appropriate to give Amphotericin B?

Answer 1

Due to toxicity, it is reserved for severe, life-threatening invasive fungal infections

or

People who are unable to tolerate alternative antifungal agents.

Question 2

Amphotericin B is delivered in what type of drug delivery system?

Answer 2

Liposome

Question 3

What is Amphotericin B’s MOA

Answer 3

Binding to the sterol component of a cell membrane, leading to alterations in cell permeability and cell death.

Question 4

How does Amphotericin B lead to renal cytotoxicity?

Answer 4

On top of binding to the fungal sterol component, it also binds to the cholesterol component of mammalian cells.

Question 5

What two major fungal species did Dr. Staudinger want us to know Amphotericin B can treat?

Answer 5

Cryptococcus neoformans

Blastomyces dermatitidis

Question 6

Amphotericin B warnings and precautions?

Answer 6

Prevent inadvertent over dosage -> fatal cardiac or cardiopulmonary arrest.
Verify product name and dosage, especially if dose is over 1.5 mg/kg

Precautions: Anaphylaxis, first dose should be administered under close observation.

May require use of a phenothiazine (promethazine)

Question 7

Drug Interactions of Amphotericin B? (6)

Answer 7

Aminoglycosides
Cyclosporine
Antineoplastic agents

Skeletal muscle relaxants and digitalis glycosides can lead to hypokalemia

Amphotericin B may increase the toxicity of flucytosine

Pregnancy category B

Question 8

What is the MOA of Fluconazole (azole drugs)?

Answer 8

Interruption of the conversion of lanosterol to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes.

Question 9

Coadministration of which drug/drug class is contraindicated in patients receiving fluconazole?

Answer 9

Terfenadine (specifically listed)

Any drug known to prolong the QT interval and are metabolized via CYP3A4

Examples - Cisapride, astemizole, erythromycin, pimozide, and quinidine

Question 10

What is the MOA of Itraconazole?

Answer 10

Interruption of the conversion of Ianosterol to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes

Question 11

Warnings and Precautions of Itraconazole?

Answer 11

Symptoms of liver disease

Question 12

Itraconazole black box warning?

Answer 12

Due to its inotropic effects, patients with heart failure

Question 13

Metabolism of Itraconazole?

Answer 13

CYP3A4! lots of drug interactions

Question 14

What is the MOA of Voriconazole?

Answer 14

Interruption of the conversion of Ianosterol to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes

Question 15

Warning an Precautions for Voriconazole?

Answer 15

Patients with hereditary galactose intolerance, Lapp Lactase deficiency, or glucose-galactose malabsorption.

(Voriconazole contains lactose)

Question 16

Voriconazole Metabolism?

Answer 16

CYP2C19,

Oral is not affected by renal failure

parenteral preparation is solubilized in a compound that is secreted by the kidneys, so you have to adjust dose in IV in cases of renal impairment

Question 17

List the three drugs in the Echinocandins class. What are they used for?

Answer 17

Caspofungin
Micafungin
Anidulafungin

Approved for IV use in systemic Candida infections

Question 18

Echinocandins MOA?

Answer 18

Inhibition of beta(1, 3)-D-glucan synthase.

This enzyme is necessary for integrity of the fungal cell wall.

Leads to fungal cell walls being damaged.

Question 19

Micafungin indication?

Answer 19

Candidemia
Candidiasis

Prophylaxis of Candida Infections in patients undergoing hematopoietic stem cell transplantation

Question 20

Adverse effects of Echinocandins?

Answer 20

Red man syndrome

Question 21

Black box warning of Micafungin?

Answer 21

Potential Liver fxn/tumor

Not by US, by Europe

Question 22

MOA of Flucytosine?

Answer 22

noncompetitive inhibitor of thymidylate synthetase, interferes with DNA synthesis.

Question 23

Which drugs has Flucytosine successfully been used in combination with?

Answer 23

Ketoconazole
fluconazole
liposomal amphotericin B
itraconazole

Question 24

Which drug is flucytosine mainly used in combination with? For what infection?

Answer 24

liposomal amphotericin B

Cryptococcal meningitis

Question 25

Blackbox warnings for flucytosine?

Answer 25

Renal impairment

Hepatic impairment should be monitored closely

Pregnancies

Women that are breastfeeding

Extreme caution with bone marrow depression (toxicity can be irreversible and may lead to death in immunosuppressed patients)

Question 26

Flucytosine elimination?

Answer 26

Renal elimination; up to 96% may be eliminated as unchanged drug