Antifungals

Question 1

amphotericin B mechanism

Answer 1

• binds ergosterol (unique to fungi)- forms membrane pores that allow leakage of electrolytes

Question 2

amphotericin B clinical use

Answer 2

• serious, systemic mycoses
• cryptococcus, coccidiodes, histoplasma, candida, mucor
• intrathecally for fungal meningitis
• supplement K and Mg because of altered renal tubule permeability

Question 3

amphotericin B toxicity

Answer 3

• fevers/chills “shake and bake”, hypotension, nephrotoxic (dose-dependent), arrhythmias (hypoMg, hypoK), anemia, IV phlebitis
• hydration decreases nephrotoxicity, liposomal amphotericin decreases tox

Question 4

nystatin mechanism and use

Answer 4

• same mech as amphotericin B, topical form because too toxic for systemic use
• “swish and swallow” for oral canidiasis, topical form for diaper rash or vaginal candidiasis

Question 5

azoles mechanism

Answer 5

mech - inhibit fungal sterol (ergosterol) synthesis by inhibiting cytochrome P450 enzyme that converts lanosterol to ergosterol

Question 6

azoles clinical use

Answer 6

local and less serious systemic mycoses

• fluconazole for suppression for cryptococcal meningitis in AIDS pts and candidal infections of all types
• itraconazole for blastomycoses, coccidioides, histoplasma
• clotrimazole and miconazole for topical fungal infections

Question 7

azoles toxicity

Answer 7

testosterone synthesis inhibition (gynecomastia), liver dysfunction

Question 8

flucytosine

Answer 8

• mech: inhibits DNA and RNA biosynthesis by conversion to 5FU by cytosine deaminase
• use: systemic fungal infections (esp cryptococcal meningitis) in combo with amphotericin B
• tox: BM suppression

Question 9

echinocandins

Answer 9

• caspofungin, micafungin, anidulafungin
• mech: inhibits cell wall synthesis by inhibiting synthesis of b-glucan
• used for invasive aspergillosis, candida
• tox: GI upset, flushing

Question 10

terbinafine

Answer 10

• mech: inhibits the fungal enzyme squalene epoxidase - inhibits ergosterol synthesis
• use: dermatophytoses (esp onychomycoses)
• tox: GI upset, headaches, hepatotoxicity, taste disturbance

Question 11

griseofulvin

Answer 11

• interferes with microtubule function, disrupts mitosis, deposits in keratin-containing tissues (nails)
• used for oral treatment of superficial infections, inibits growth of dermatophytoses
• tox: teratogenic, carcinogenic, confusion, headaches, inc P450 metabolism

Question 12

antiprotozoan therapy

Answer 12

• pyrimethamine (toxo), suramin and melarsoprol (typanosoma brucei), nifurtimox (t. cruzi), sodium stibogluconate (leishmaniasis)

Question 13

chloroquine

Answer 13

• blocks detoxification of heme into hemozoin
• heme accumulates and is toxic to plasmodia
• used for treatment of plasmodial species other than falciparum (they have resistance due to membrane pump)
• for life-threatening malaria, treat with quinidine or artesunate
• tox: retinopathy, pruritis

Question 14

antihelminthic therapy

Answer 14

• mebendazole, pyrantel pamoate, ivermectin, diethylcarbamazine, praziquantel
• immobilize helminths
• use praziquantel against flukes (trematodes) like schistosoma