Antifungal Therapy Flashcards
1
Q
Amphotericin B
mechanism
A
Amphotericin “tears” holes
- binds ergosterol
- forms membrane pores
- allows leakage of electrolytes
2
Q
Amphotericin B
clinical use
A
- serious, systemic mycoses
- Cryptococcus
- Blastomyces
- Coccidioides
- Histoplasma
- Candida
- Mucor
- intrathecally for fungal meningitis
- supplement K+ & M2+(altered renal tubule permeability)
3
Q
Amphotericin B
toxicity
A
- fever/chills (“shake & bake”)
- hypotension
- nephrotoxicity
- arrhythmias
- anemia
- IV phlebitis
- hydration decreases nephrotoxicity
- liposomal amphotericin decreases toxicity
4
Q
Nystatin
mechanism
A
- same as amphotericin B
- topical form
- too toxic for systemic use
5
Q
Nystatin
clinical use
A
- “swish & swallow” for oral candidiasis (thrush)
- topical for diaper rash or vaginal candidiasis
6
Q
Azoles
A
- fluconazole
- ketoconazole
- clotrimazole
- miconazole
- itraconazole
- voriconazole
7
Q
Azoles
mechanism
A
- inhibit fungal sterol (ergosterol) synthesis
- inhibit CYP450 enzyme that converts lanosterol to ergosterol
8
Q
Azoles
clinical use
A
- local & less serious systemic mycoses
- fluconazole - chronic suppression of cryptococcal meningitis in AIDS patients & candidal infections of all types
- itraconazole - Blastomyces, Coccidioides, Histoplasma
- clotrimazole & miconazole - topical fungal infections
9
Q
Azoles
toxicity
A
- testosterone synthesis inhibition
- gynecomastia (ketoconazole)
- liver dysfunction
- inhibits CYP450
10
Q
Flucytosine
mechanism
A
- inhibits DNA & RNA biosynthesis
- conversion to 5-FU by cytosine deaminase
11
Q
Flucytosine
clinical use
toxicity
A
- systemic fungal infections
- combination w/ amphotericin B
- bone marrow suppression
12
Q
Echinocandins
A
- caspofungin
- micafungin
- anidulafungin
13
Q
Echinocandins
mechanism
A
inhibits cell wall synthesis
inhibits synthesis of ß-glucan
14
Q
Echinocandins
clinical use
toxicity
A
- invasive aspergillosis, Candida
- GI upset, flushing (histamine release)
15
Q
Terbinafine
mechanism
A
inhibits the fungal enzyme squalene epoxidase
16
Q
Terbinafine
clinical use
toxicity
A
- dermatophytoses
- GI upset, headaches, hepatotoxicity, taste disturbance
17
Q
Griseofulvin
mechanism
A
- interferes w/ MT function
- disrupts mitosis
- deposits in keratin-containing tissues (nails)
18
Q
Griseofulvin
clinical use
A
- oral treatment of superficial infections
- inhibits growth of dermatophytes
- tinea, ringworm
19
Q
Griseofulvin
toxicity
A
- teratogenic
- carcinogenic
- confusion
- headaches
- increased P450 & warfarin metabolism
20
Q
Antiprotozoan therapy
- Toxoplasmosis
- Trypanosoma brucei
- T. cruzi
- Leishmaniasis
A
- Toxoplasmosis
- pyrimethamine
- Trypanosoma brucei
- suramin
- melarsoprol
- T. cruzi
- nifurtimox
- Leishmaniasis
- sodium stibogluconate
21
Q
Chloroquine
mechanism
A
- blocks detoxification of heme into hemozoin
- heme accumulates & is toxic to plasmodia
22
Q
Chloroquine
clinical use
A
- **treatment of plasmodial species other than P. falciparum **
- resistance due to membrane pump (decreases intracellular conc of drug)
- treat P. falciparum w/ artemether/lumefantrine or atovaquone/proguanil
- life threatening malaria: quinidine
23
Q
Chloroquine
toxicity
A
- retinopathy
- pruritis (esp dark skinned individuals)
24
Q
antihelminthic therapy
A
- mebendazole, pyrantel pamoate, ivermectin, diethylcarbamazine, praziquantel (immobilize helminths)
- flukes (schistosoma): praziquantal
