Flashcards in Antifungals Deck (28)
Amphotercin B mech
Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes. "amphoTERicin 'tears' holes in the fungal membrane by forming pores
Amphotercin B Clinical Use
Serious, systemic mycoses. Cryptococcus (amphotercin B with/without flucytosine for cryptococcal meningitis), Blastomyces, Coccidioides, Histoplasma, Candida, Mucor. Intrathecally for fungal meningitis. Supplement K+ and Mg+2 because of altered renal tubule permeability.
Amphotercin B Toxicity
Fever/chills ('shake and bake'), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis ('amphoterrible').
What can decrease the nephrotoxicity of Amphotercin?
Same as amphotercin B.
Is Nystatin Oral, IV, IM Topical, Inhaled?
Topical! too toxic for systemic use
Nystatin clinical use
'Swish and Swallow' for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis
What are the Azoles?
Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole
Mech of Azoles
Inhibit fungal sterol (ergosterol) synthesis, by inhibiting the CYP-450 enzyme that converts lanosterol to ergosterol
Clinical use of Azoles
Local and less serious systemic mycoses
Which Azole is used for chronic suppression of cryptococcal meningits in AIDS patients and candidal infections of all types?
Which Azole do you treat Blastomyces, Coccidioides, Histoplasma with?
Which Azole do you use to treat topical fungal infections?
Clotrimazole and miconazole
Where are the toxicities/SE of the Azoles?
Testosterone synthesis inhibition (gynecomastia, esp with ketoconazole), liver dysfunction (inhibits CYP 450)
Inhibits DNA and RNA biosynthesis by conversion to 5-FU by cytosine deaminase
Clinical use of Flucytosine
Systemic fungal infection (esp. meningitis caused by Cryptococcus) in combination with Amphotercin B
Toxicity of Flucytosine
Bone Marrow Suppression
What are the Echinocandins?
Caspofungin, micafungin, anidulafungin
What is the mechanism of the Echinocandins?
Inhibits cell wall synthesis by inhibiting synthesis of beta glucan
What is the clinical use of Echinocandins?
Invasive Aspergillosis, Candida
What is the toxicity of Echinocandins?
GI upset, flushing (by histamine release)
Inhibits the fungal enzyme squalene epoxidase
Clinical use of Terbinafine
Dermatophytoses (especially onychomycosis - fungal infection of finger or toe nails). Tinea fungi
GI upset, headaches, hepatotoxicty, taste disturbance
Interferes with microtubule function; disrupts mitosis. Deposits in keratin containing tissues (i.e nails)
Clinical use of Griseofulvin
Oral treatment of superficial infection; inhibits growth of dermatophytes (tinea, ringworm)