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48 Cards in this Set
- Front
- Back
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What are some systemic fungal infections?
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Blastomycosis, histoplasmosis, coccidioidomycosis, sporotrichosis
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What are the only drugs we have to treat systemic fungal infections?
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AMB, flucytosin, imidazole compounds (keo, fluco, itra)
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What is the only polyene available as an IV?
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AMB
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Amphotericin PAFE
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Candida albacans and Cryptococcus
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FluconazolePAFE
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Candida albicans (only in the presence of human serum)
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Nystatins PAFE
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Candida spp
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AMB half life
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initial phase : 24 hours,
second phase : approx. 15 days |
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What is the major toxic reaction of polyenes ?
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toxicity to the glomerlus; renal toxicity
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What is the target for drugs affective against EMT fungal organisms?
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fungal squalene epoxidase; allylamines
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What toxicities can occur if levels of Flucytosine rise above 100 mcg/ml?
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a. Bone marrow suppression (fatal SE) 5FU
b. Liver toxicity (reversible) |
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What does amorolfine target?
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Delta14 reductase and Delta8,delta7-isomerase (EMT)
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What are the levels of susceptibility/resistance of Fluconazole?
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a. Susceptible if: <= 8mcg/ml
b. Resistance if: >= 64 mcg/ml c. 16-32 mcg/mL: use increased doses |
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What is the MIC for Itraconazole?
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MIC >= 1 mcg/ml
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What antifungal has better activity in the presence of human serum?
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Fluconazole
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How does food affect Ketoconazole, Fluconazole and Itraconazole absorption?
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a. Fluconazole: don’t have to worry about acid or food
b. Itraconazole: Increased absorption if food is present c. Ketoconazole: decreases absorption if food is present |
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Ketoconazole, Itraconazole and Fluconazole metabolism:
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Ketoconazole and Itraconazole undergo extensive metabolism by us; no metabolites have appreciable activity
Fluconazole has minimal metabolism |
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Azole drug interactions:
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Potent P450 inhibitors
(F = I =V =P< K) |
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Voriconazole (Vfend) and spectrum of activity?
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i. Candida (mostly fungistatic)
ii. Aspirgillia (fungicidal) iii. Blaso, histo, coccidiodes (fungicidal) |
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Indications for Voriconazole:
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a. Invasive aspergillosus
b. Fusarium and scedosporium in patients intolerant to other therapy (Amphotericin B DOC) c. Esophageal candidiasis d. Candidemia, invasive candidiasis |
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What are the SE of Voriconazole?
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a. Liver toxicity: s transaminsae abnormalities
b. Visual distirbances (10-20% transient) photosensitivity c. Rash d. LOTS of DI |
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What is unique about posaconazole (noxafil)
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a. Very long half life: 25 hrs
b. Very potent: most potent of disussed agents so far c. May bind at different 14alpha demethylase site than other ‘azoles |
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What are AE of posaconazole?
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a. Hypotension
b. Fatigue, headache, somnolence, dizziness c. **Confusion (because more CNS penetration) d. NVD, GI pain (more so than the other agents) e. Rashes f. Musculoskeletal pain g. Fever |
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What drugs are used to treat dermophytic infections?
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a. Either with topical agents or:
b. One of three oral agents: Ketoconazole, griseofulvin, or terbinafine |
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What are uses of Griseofulvin?
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orally for EMT fungi
orally for Onychomycosis(Tinea unguium) **won’t convey resistance with other fungus. **Concentrates in nail beds. Does not work topically |
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What are SE of griseofulvin?
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Fatigue, nausea, vomiting, long term use can cause blood abnormalities
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What are CI of griseofulvin?
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Kids, pregnancy, lactation
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What is the MOA of griseofulvin?
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Disrupt mycotic spindle structure, inhibiting mitosis
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What is Butenafine (metax) used for and MOA?
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a. Only used topically for EMT
b. Cream BID in tinea P, Cr, Co c. MOA: Inhibitis squalene epoxidation |
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What is Amorolfine used for, and MOA?
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a. Only as a nail lacquer for mild onychomycosis
b. MOA: inhibitor of delta14 reductase and delta 7-8 isomerase |
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What does Thiocarbamate (tolnaftate) treat?
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Topical for EMT treatment
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Terbinafine-lamisil indication
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Topical for EMT treatment
(Terbinafine also available PO as Naftifine) |
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What does Haloprogin treat?
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Topical for EMT treatment
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What does Undecyclenic acid treat?
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Topical for EMT treatment (Zn salt)
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What does Clioquinol treat?
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Topical for EMT treatment
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What are the Allylamines and other non-azole egosterol biosynthesis inhibitors?
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Amorolfine
Butenafine Naftifine Terbinafine |
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What drugs are the Anti-Metabolites?
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Flucytosine
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What are the ORAL Azoles?
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Fluconazole
Itraconazole Ketoconazole Posaconazole Voriconazole |
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What are the IV Azoles?
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Fluconazole
Itraconazole Voriconazole |
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What are the Glucan synthesis inhibitors and what is their route of administration?
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Capsofungin
Micafungin Anidulafungin (all of therse are IV) |
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What are ALL of the ORAL antifungals?
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Griseofulvin
ABOS Fluconazole Itraconazole Ketoconazole Posaconazole Voriconazole Flucystosine Terbenifine |
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What are the IV drugs?
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Flucytosine
Fluconazole Itraconazole Voriconazole Capsofungin Micafungin Anidulafungin AMB |
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Azole MOA
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Inhibit synthesis of ergosterol, the principle sterol in fungal cell membrane, through inhibition of lanosterol 14alpha demthylase (a cytochrome P450
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Polyene MOA
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create small holes in fungal membrane and it leaks out important cations
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Amphotericin B SE
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fever, chills, N, HA;cardiotoxicity if rapid infusion; toxicity to the glomerlus; renal toxicit (elevated BUN), hypokalemia, normochromic normyocytic anemia, inhibits EPO, leukopenia
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Flucytosine SE
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Extreme toxicity; used only in combo with AMP and life-threatening infections such a fungal meningitis. Known carcinogen and teratogen;
Bone marrow suppression (fatal SE) 5FU; Liver toxicity (reversible) |
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What SE are common to mos of the azoles?
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Liver toxicity, GIT rxs, ND, itching, rash, somnolence
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DOC for coccidiodal meningitis
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Fluconazole
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DOC for most cases of mild to moderate histoplasmoss, blastomycosis, and sporotrichosis
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Itraconazole
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