Fungal Pharm

Question 1

Amphotericin B

Answer 1

polyene via Strep nodosus

binds sterol of cell membrane of extracellular and intracellular fungi–>increase perm and death

also binds to cholesterol of mammalian cells–> nephrotoxicity

injection: single bilayer liposomes (less than 100nm diameter) formed by micro-emulsification of multi-lamellar vesicles as homogenizer

use in aspergillus, candida, cryptococcus and blastomyces

overdose–> fatal cardiac arrest

anaphylaxis

N, V, chills, rigors

may require promethazine use

only used to treat life-threatening fungal infections

interacts with SM relaxants and digitalis glycosides–>hypokalemia and nephrotoxicity

Question 2

Fluconazole

Answer 2

bis-triazole antifungal that interrupts conversion of lanosterol to ergosterol–>binds CYP450 in fungus and disrupts membrane

treats candida

don’t give same time as terfenadine or with drugs that prolong QT interval (erythromycin, pimozide, quinidine)

hepatic injury, anaphylaxis, fetal harm

prolong QT interval

hypokalemia and cardiac failure–> life-threatening ventricular arrhythmias and torsades

increase cardiotoxicity with erythromycin

inhibits CYP450

don’t use with CCB, immunosuppressants, chemo, benzos, antidipressants, macrolides, SSRI

Question 3

Itraconazole

Answer 3

potent inhibitor of CYP450

take with food–>acidic stomach increases absorption

aspergillus, sporothrix, alternaria, bipolaris, curvularia

don’t use in pregnancy, LV dysfunction, CHF

liver disease

black box–>heart failure

Question 4

Voriconazole

Answer 4

triazole antifungal–> inhibits CYP450 mediated lanosterol demethylation

candida, aspergillosis, fusarium, scedosporium

hepatic toxicity, arrhythmias, QT prolong, fetal toxicity, anaphylaxis, photosensitivity

parenteral dose requires dose adjustment in cases of renal impairment, however excretion of oral dose not affected by renal failure

Question 5

Caspofungin

Answer 5

echinocandin–> IV Candida

inhibit glucan synthase (key integrity of cell wall)

use with caution in hepatic impairment

red man syndrome

first drug approved

Question 6

Micafungin

Answer 6

echinocandin–> IV Candida

inhibit glucan synthase (key integrity of cell wall)

red man syndrome

use with caution in hepatic impairment

hepatocellular tumors

Question 7

Anidulafungin

Answer 7

echinocandin–> IV Candida

inhibit glucan synthase (key integrity of cell wall)

red man syndrome

hypotension and bradycardia

Question 8

Flucytosine

Answer 8

pyrimidine analogue prodrug–>interferes with purine and pyrimidine metabolism

noncompetitive inhibitor of thymidylate synthetase

use in combo with ketoconazole, fluconazole, liposomal amphotericin B, itraconazole

use mainly with liposomal amphotericin B to treat cryptococcal meningitis

only use in severe infections

renal disease, failure, impairment

bone marrow suppression

hepatotoxicity

fetal harm and breastfeeding