Drugs to Tx Fungal Infections Flashcards
What is the MOA for amphotericin B in the tx of many severe, invasive fungal infections?
Binds to the sterol component of a cell membrane leading to alterations in cell permeability and cell death
How can amphotericin B lead to cytotoxicity (in particular nephrotoxicity)?
It also binds to cholesterol component of the mammalian cells
Amphotericin B is indicated for what fungal organisms?
1) Cryptococcus neoformans
2) Blastomyces dermatitidis
Why is it imperative to prevent inadvertent overdosage of amphotericin B?
It may result in fatal cardiac arrest
What drug interaction is noted between amphotericin B and skeletal muscle relaxants/digitalis glycosides?
Hypokalemia
What black box warning is given for amphotericin B?
It should only be used for treating patients with life threatening fungal infections
What is the MOA of all azole drugs?
Stops the conversion of lanosterol to ergosterol via binding to fungal cytochrome P-450
Coadministration of what antihistamine is contraindicated in patients receiving fluconazole?
Terfenadine
What special population is fluconazole contraindicated for?
Pregnant women
Some azoles, including fluconazole, have been associated with what phenomenon seen on EKG?
QT prolongation
Azole antifungals also are both substrates and inhibitors of what cytochrome P450 family?
CYP3A4
Why are drugs such as cisapride, astemizole, erythromycin, pimozide, and quinidine are contraindicated in patients receiving fluconazole?
They also prolong QT interval and are metabolized via CYP3A4
Itraconazole has what black box warning for what patients?
Why?
1) Patients with heart failure
2) Due to its inotropic effects
Itraconazole is metabolized predominantly by?
CYP3A4
Voriconazole is contraindicated in patients with what conditions?
Why?
1) Hereditary Galactose Intolerance
2) Lapp Lactase Deficiency
3) Glucose-Galactose Malabsorption
4) Because voriconazole contains lactose
Voriconazole has the greatest affinity for which CYP isoenzyme?
CYP2C19
Which route of administration for voriconazole necessitates dose adaptation in cases of renal impairment?
Parenteral preparation
What drugs are a group of semisynthetic, cyclic lipopeptides with an N-linked acyl lipid side chain?
Echinocandins
What are the drugs that make up echinocandins?
1) Caspofungin
2) Micafungin
3) Anidulafungin
-Fungin
Echinocandins are approved for IV use with what infections?
Candida infections
What is the MOA of echinocandins?
Inhibition of β(1, 3)-D- glucan synthase which damages fungal cell walls
Which echinocandin is indicated in treatment of acute disseminated Candidiasis and prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation?
Micafungin
A “red man” syndrome associated with likely histamine release was first reported with which echinocandin?
Anidulafungin
What is a pyrimidine analogue that has activity against fungal species that interferes with purine and pyrimidine metabolism?
Flucytosine
The current use of flucytosine is mainly in combination with?
To treat?
1) Amphotericin B
2) Cryptococcal meningitis
Flucytosine should be used with extreme caution in patients with?
1) Renal impairment
2) Bone marrow depression
Flucytosine is contraindicated in what special populatoins?
1) Pregnant women
2) Women that are breastfeeding
