Antifungals Flashcards
1
Q
Amphotericin B
A
*Cell membrane target- polyene – oral is topical in GI lumen, topical for superficial infections, parenteral for systemic (slow IV)
Selective toxicity (we have cholesterol)
- Binds to ergosterol and forms pores (alter membrane permeability – leak intracellular Na, K, H), cause cell death
- Local irritation, GI irritation, IV immediate (fever, chills, spasms, vomiting, headache – offset by slowing infusion) and slower (nephrotoxicity but reversible, anemia)
- Broadest spectrum – drug of choice for treating most life threatning systemic fungal infections (Candida, Apergillus, Cryptococcus) – usually fungicidal
2
Q
Nystatin
A
- Cell membrane target – polyene – too toxic to be used parenterally – not metabolized or well absorbed so use topically
- Binds to ergosterol and forms pores (alter membrane permeability – leak intracellular Na, K, H), cause cell death
- Bitter and very unpleasant taste but mild effects
- Narrower spectrum than Amphotericin – candida infections of mucosa, skin, intestinal tract, vagina – drug of choice for oral cavity (thrus, denture stomatitis)
3
Q
Clotrimazole
A
- Cell membrane target – imidazole (less selective toxicity so greater unwanted drug interactions)
- Inhibition of ergosterol synthesis by blocking fungal CYP enzyme activity (lanosterol 14-a-demethylase), impair fungi cell membrane synthesis)
- Hepatitis, minor GI upset
- Oral/topical for local distribution (more palatable alternative to nystatin for thrush) – drug of choice for oropharyngela candidiasis in AIDS
4
Q
Ketoconazole
A
- Cell membrane target – imidazole (less selective toxicity so greater unwanted drug interactions)
- Inhibition of ergosterol synthesis by blocking fungal CYP enzyme activity (lanosterol 14-a-demethylase), impair fungi cell membrane synthesis)
- Inhibits mammal CYPs the most – inhibit adrenal and gonadal steroids (sterility), enhance other drugs toxicity, symptomatic hepatitis
- Rarely used
5
Q
Miconazole
A
- Cell membrane target – imidazole (less selective toxicity so greater unwanted drug interactions)
- Inhibition of ergosterol synthesis by blocking fungal CYP enzyme activity (lanosterol 14-a-demethylase), impair fungi cell membrane synthesis)
- Thrombophlebitis after IV administration, hepatitis
- Topical (cutaneous candidiasis) – jock itch, ringworm, athlete’s foot, vaginal infections, oral thrush
6
Q
Fluconazole
A
- Cell membrane target – triazole (more selective for fungal CYPs) – better CNS penetration (only azole that does this) – oral and IV
- Inhibition of ergosterol synthesis by blocking fungal CYP enzyme activity (lanosterol 14-a-demethylase), impair fungi cell membrane synthesis)
- Most common systemic antifungal – 1st line for invasive infections by Candida (except C. krusei), refractory mucocutaneous candidiasis, Cryptococcal meningitis, prophylaxis immunocompromised
7
Q
Itraconazole
A
- Cell membrane target – triazole – oral (well absorbed) and IV – long ½ life, high tissue concentration
- Inhibition of ergosterol synthesis by blocking fungal CYP enzyme activity (lanosterol 14-a-demethylase), impair fungi cell membrane synthesis)
- Broader spectrum than fluconazole – dimorphic fungi (Histoplasma, Blastomyces, Coccidioides) and molds (Aspergillus) – treat Aspergillus infections and some fluconazole resistant Candida
8
Q
Posaconazole
A
- Cell membrane target – triazole – god oral bioavailability
- Inhibition of ergosterol synthesis by blocking fungal CYP enzyme activity (lanosterol 14-a-demethylase), impair fungi cell membrane synthesis)
- Skin rash, elevated hepatic enzmyes, no evidence of visual effects
- Only azole with activity against zygomycoses (Rhizopus, Mucor) – prophylaxis of invasive fungal infections in BMT with GVHD, hematologic malignancy and prolonged neutropenia
9
Q
Voriconazole
A
- Cell membrane target – triazole (good oral bioavailability and IV)
- Inhibition of ergosterol synthesis by blocking fungal CYP enzyme activity (lanosterol 14-a-demethylase), impair fungi cell membrane synthesis)
- Low toxicity – dose related transient visual side effects, skin rash, elevated hepatic enzymes
Many drug interactions – inhibits CYP3A4
*Broader spectrum than fluconazole – dimorphic fungi (Histoplasma, Blastomyces, Coccidioides) and molds (Aspergillus) –invasive mold infections in immunocompromised (aspergillosis – fungicidal)
10
Q
Efinaconazole
A
- Cell membrane target - triazole
- Inhibition of ergosterol synthesis by blocking fungal CYP enzyme activity (lanosterol 14-a-demethylase), impair fungi cell membrane synthesis)
- Minimal side effects – redness, itching
No drug interactions
*Topical treatment of onychomycosis (nail infection)
11
Q
Terbinafine
A
- Allylamine – topical or oral (accumulates in skin, nails, fatty tissues)
- Inhibits ergosterol synthesis by blocking activity of squalene epoxidase
- Fungicidal – effective against dermatophytes – mainstay for skin/nail infections, unusual/refractor mold infections
12
Q
Anidulafungin
Caspofungin
Micafungin
A
- Cell wall target – echinocandin – given by IV
- Glucan synthesis inhibitor – weaken fungal cell wall, osmotic shock and lysis (fungicidal)
- Relatively safe
- Primarily Aspergillus, azole-resistant Candida
13
Q
Flucytosine
A
- DNA synthesis antimetabolite – oral – selective toxicity (human cells don’t covert it)
- Enzyme cytosine deaminase converts it to 5-FU in fungal cells – blocks fungal DNA synthesis and reduces protein synthesis
- GI intolerance, depresses bone marrow, anemia, leukopenia, thrombocytopenia
- Systemic fungal infections (candida and Cryptococcus) – fungistatic (don’t use alone) – combo with amphotericin B (meningitis – good CNS penetration)
14
Q
Griseofulvin
A
- Mitotic spindle target
- Interacts with polymerized microtubules to block fungal mitosis
- Alters pharmacologic effectiveness of drugs, don’t use in pregnancy or men conceiving
- Fungistatic – oral administration for systemic treatment of dermatophytosis
