Antifungals Flashcards
What predisposes patients to fungal infection?
Name some organisms responsible for systemic and superficial mycoses.
Immunocompromisation, use of broad-spectrum Abx, and presence of indwelling catheters.
Systemic eg Aspergillus, Candida, Histo/Blasto/Coccidiodes.
Superficial eg Candida, Tricho/Dermatophyton and microsporum.
Amphotericin B
What is its mechanism of action?
What are its indications?
What are its adverse effects?
Amphotericin B
It binds ergosterol in the cell membrane (sometimes forms pores).
It is effective (“gold-standard”) against many serious systemic mycoses. Effectiveness is variable for Aspergillus/Mucor/Rhizopus/Fusarium.
N/V, fever/chills, headaches, hypotension, hypokalemia, tachypnea, nephrotoxicity, and “hypochromic anemia”. Dependent on total cumulative dose.
Flucytosine
What is its mechanism of action?
What are its indications?
What are its adverse effects?
Flucytosine
It is activated by a fungal deaminase to form 5-FU–blocks DNA synthesis.
Used in serious infections eg Candida/Cryptococcus and in conjunction with Amphotericin B.
N/V/D and enterocolitis, leuko/thrombocytopenia, hepatic enzyme elevation. Contraindicated in patients with renal insufficiency or bone marrow depression.
What is the mechanism of action of imidazoles and triazoles?
What are their side effects and contraindications?
Inhibition of 14-α-sterol demethylase; blocks ergosterol synthesis.
They cause N/V/D, rash, headache, and hepatotoxicity. They also inhibit CYP3A/2C–this can cause cardiotoxicity(?) with some drugs if they are metabolized by those enzymes.
Fluconazole
Describe its efficacy in treating Candida.
What other mycoses is it used for?
What are its specific side effects?
Fluconazole
Covers only a few species of Candida, but penetrates widely (CNS/urine).
Cryptococcal meningitis.
Mildest CYP3A inhibition and hepatotoxicity, eosinophilia and thrombocytopenia.
Itraconazole
Describe its efficacy in treating Candida.
What other mycoses is it used for?
What are its specific side effects?
Itraconazole
It covers more species than fluconazole (including Krusei in vitro), but is only useful for esophageal/pharyngeal infections.
Blastomyces, Histoplasma, Aspergillus.
Worst CYP3A inducer. Hypokalemia, heart failure, dizziness/weakness/vertigo and impotence.
Voriconazole
Describe its efficacy in treating Candida.
What other mycoses is it used for?
What are its specific side effects?
Voriconazole
Covers all species (including glabrata/krusei) but does not help with urinary infections.
Aspergillus, fusarium, scedosporium.
Visual disturbances and photosensitive rash.
Caspofungin
What is its mechanism of action?
What are its indications?
What are its adverse effects?
Caspofungin
Blocks synthesis of glucans in the cell wall.
Invasive Aspergillus, esophageal/systemic Candida.
Well-tolerated, with some N/V, fever, flushing, and phlebitis.
What drugs are used to treat superficial mycoses?
(non-dermatophytes)
Nystatin, Natamycin, Fluconazole, Miconazole, Ketoconazole (not discussed), Clotrimazole, Itraconazole.
Miconazole
What is its mechanism of action?
What are its indications?
What are its adverse effects?
Miconazole
Same as the other azoles; block ergosterol synthesis.
Vaginal Candida (creams/suppositories).
Burning/itching at site.
Clotrimazole
What is its mechanism of action?
What are its indications?
What are its adverse effects?
Clotrimazole
Same as the other azoles; block ergosterol synthesis.
For Candida, as a topical or oral troche.
Irritation (topical), abnormal LFT (oral troche).
Nystatin
What is its mechanism of action?
What are its indications?
What are its adverse effects?
Nystatin
Similar to amphotericin B (bind ergosterol in cell wall)
Topical and GI use for Candida.
Well-tolerated as a topical, some GI distress when taken orally (also tastes gross).
Natamycin
What is its mechanism of action?
What are its indications?
What are its adverse effects?
Natamycin
Similar to amphotericin B; bind ergosterol in cell wall.
As an ophthalmic solution, used for conjunctivitis/blepharitis/keratitis due to Fusarium, Cephalosporium, and Aspergillus (not really Candida!).
Conjunctival chemosis and hyperemia. Hypersensitivity.
What drugs are used to treat dermatophytic mycoses?
Miconazole/Clotrimazole, Tolnaftate (tinactin), Terbinafine, Ciclopirox and others.
Ciclopirox
What is its mechanism of action?
What are its indications?
Ciclopirox
Not really clear, seems to deprive fungi of metals.
For nail infections (it’s a nail lacquer!)
