Review Question - QID 100808

Headache, hypotension, anemia, and uremia are known side effects of intravenous amphotericin B therapy.

Amphotericin B is an anti-fungal which targets fungal cells by preferentially binding ergosterol, a molecule unique to fungal membranes. Upon binding to ergosterol, amphotericin B forms pores in the fungal membrane, allowing leakage of electrolytes. It is clinically used to treat systemic mycoses including Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, and Mucor. Despite this drug being fairly selective to the ergosterols in fungal membranes, it is also known to bind cholesterol in mammalian cell membranes to some degree, which can cause widespread adverse effects, including: fever, chills, hypotension, nephrotoxicity, anemia, IV phlebitis, as well as electrolyte abnormalities including hypomagnesemia and hypokalemia (the basis of this drug being known as Ampho-terrible).

Incorrect Answers:
Answer 1: The adverse effects of fluconazole are explained primarily by its inhibition of cytochrome P450 enzymes.
Answer 2: Flucytosine functions by inhibiting DNA synthesis after its conversion to 5-fluorouracil. Its side effects are similar to some anti-cancer chemotherapeutics: nausea, vomiting, diarrhea, and bone marrow suppression.
Answer 4: Terbinafine inhibits the fungal enzyme: squalene epoxidase which is used to synthesize ergosterol in the fungal membrane.
Answer 5: Griseofulvin acts through its binding of microtubular proteins thus disrupting mitosis. Adverse effects include teratogenicity, carcinogenicity, confusion, and headaches.