Block 3 material simplified (Antifungals) Flashcards
Amphotericin B
MOA:
Clinical use:
Adverse effects:
Resistance:
MOA: Systemic Antifungal
Binds ergosterol in fungi to form pores that leak electrolytes
“Tears holes through the fungi”
Clinical use:
Aspergillus
Blastomycosis
Cryptococcal meningitis
Coccidioides meningitis
Candida esophagitis
Histoplasmosis
Leishmaniasis
Mucormycosis
Adverse effects:
1) Shake & bake
2) Hypotension
3) Nephrotoxicity (K+ & Mg2+ loss)
4) Arrythmias
5) Anemia
6) IV phlebitis
(Give hydration!!!)
Resistance:
Reductions in ergosterol biosynthesis (Aspergillus terreus)
MOA: Systemic Antifungal
Binds ergosterol in fungi to form pores that leak electrolytes
“Tears holes through the fungi”
Clinical use:
Aspergillus
Blastomycosis
Cryptococcal meningitis
Coccidioides meningitis
Candida esophagitis
Histoplasmosis
Leishmaniasis
Mucormycosis
Adverse effects:
1) Shake & bake
2) Hypotension
3) Nephrotoxicity (K+ & Mg2+ loss)
4) Arrythmias
5) Anemia
6) IV phlebitis
(Give hydration!!!)
Resistance:
Reductions in ergosterol biosynthesis (Aspergillus terreus)
Amphotericin B
Nyastatin
MOA:
Clinical use:
MOA: Polyenes (Topical/oral antifungal)
Bind ergosterol in fungi to tear holes in the fungal cell membrane
Clinical use:
Swish & swallow for oral candidiasis
Topical for diaper rash
Adverse effects:
1) Skin irritation or hypersensitivity
MOA: Polyenes (Topical/oral antifungal)
Bind ergosterol in fungi to tear holes
Clinical use:
Swish & swallow for oral candidiasis
Topical for diaper rash
Adverse effects:
1) Skin irritation or hypersensitivity
Nyastatin
Flucytosine
MOA:
Clinical use:
Adverse effects:
Resistance:
MOA: Systemic Antifungal
Inhibits DNA/RNA synthesis by converting 5-fluorouracil via cytosine deaminase.
5FU is then converted to 5FUMP & incorporated into RNA or its turned into 5FdUMP to inhibit thymidylate synthase
Clinical use: Narrow spectrum fungistatic
1) Cryptococcus meningitis
(given with amphotericin B)
Adverse effects:
1) Myelosuppression (anemia, thrombocytopenia, & leukopenia)
2) Nephrotoxicity
3) Hepatotoxicity
4) N/V
Resistance:
Secondary resistance – used alone
Decreased UPRTase or cytosine deaminase
MOA: Systemic Antifungal
Inhibits DNA/RNA synthesis by converting 5-fluorouracil via cytosine deaminase.
5FU is then converted to 5FUMP & incorporated into RNA or its turned into 5FdUMP to inhibit thymidylate synthase
Clinical use: Narrow spectrum fungistatic
1) Cryptococcus meningitis
(given with amphotericin B)
Adverse effects:
1) Myelosuppression (anemia, thrombocytopenia, & leukopenia)
2) Nephrotoxicity
3) Hepatotoxicity
4) N/V
Resistance:
Secondary resistance – used alone
Decreased UPRTase or cytosine deaminase
Flucytosine
Azoles
MOA:
Clinical use:
Adverse effects:
Clotrimazole, Fluconazole, Isavuconazole, Ketoconazole, Miconazole, Voriconazole, & Itraconazole
MOA: Systemic & topical superficial antifungal
Inhibits ergosterol (sterol) synthesis by inhibiting CYP450 (14a-demethylase)
Clinical use:
1. All (Cryptococcal meningitis in HIV patients or candida infections)
- Itraconazole (Blastomyces, Coccidioides, Histoplasma, Sporothrix schenckii)
- Clotrimazole & Miconazole (Topical fungal infection)
- Voriconazole (Aspergillus & Candida)
- Isavuconazole (Aspergillus & Mucor)
- Ketoconazole (Non-CNS blastomycosis, coccidiomycosis, Oropharyngeal candidiasis)
- Fluconazole (Candidiasis)
Adverse effects:
1) Gynecomastia (Ketoconazole)
2) Liver dysfunction
Clotrimazole, Fluconazole, Isavuconazole, Ketoconazole, Miconazole, Voriconazole, & Itraconazole
MOA: Systemic & topical superficial antifungal
Inhibits ergosterol (sterol) synthesis by inhibiting CYP450 (14a-demethylase)
Clinical use:
1. All (Cryptococcal meningitis in HIV patients or candida infections)
- Itraconazole (Blastomyces, Coccidioides, Histoplasma, Sporothrix schenckii)
- Clotrimazole & Miconazole (Topical fungal infection)
- Voriconazole (Aspergillus & Candida)
- Isavuconazole (Aspergillus & Mucor)
- Ketoconazole (Non-CNS blastomycosis, coccidiomycosis, Oropharyngeal candidiasis)
- Fluconazole (Candidiasis)
Adverse effects:
1) Gynecomastia (Ketoconazole)
2) Liver dysfunction
Azoles
Terbinafine
MOA:
Clinical use:
Adverse effects:
MOA: Allylamines Antifungal
Inhibits fungal squalene oxidase
Clinical use:
Dermatophytes (tinea)
Onychomycosis (nail infections)
Ring worm (tinea capitis)
Adverse effects:
1) Metallic taste
2) Hepatotoxicity
3) Headache/Gi upset
MOA: Allylamines Antifungal
Inhibits fungal squalene oxidase
Clinical use:
Dermatophytes (tinea)
Onychomycosis (nail infections)
Ring worm (tinea capitis)
Adverse effects:
1) Metallic taste
2) Hepatotoxicity
3) Headache/Gi upset
Terbinafine
Fluconazole
MOA:
Effect
MOA:
Inhibits CYP2C9, CYP2C19 and CYP3A4
Effects:
Candida infection
MOA:
Inhibits CYP2C9, CYP2C19 and CYP3A4
Effects:
Candida infection
Fluconazole
Voriconazole
MOA:
Effect
MOA:
Inhibits CYP 2C9, CYP 3A4 ,CYP 2C19
Effects are↑ levels of:
Sirolimus, tacrolimus, cyclosporine, warfarin – lead to toxicity
Clinical uses:
1) Invasive aspergillosis
2) Esophageal candidiasis
3) Candedemia
Adverse effects:
1) Visual disturbances
2) Hepatotoxicity
3) Phototoxicity (SJS)
4) Confusion/hallucinations
5) Nephrotoxicity
MOA:
Inhibits CYP 2C9, CYP 3A4 ,CYP 2C19
Effects are↑ levels of:
Sirolimus, tacrolimus, cyclosporine, warfarin – lead to toxicity
Clinical uses:
1) Invasive aspergillosis
2) Esophageal candidiasis
3) Candedemia
Adverse effects:
1) Visual disturbances
2) Hepatotoxicity
3) Phototoxicity (SJS)
4) Confusion/hallucinations
5) Nephrotoxicity
Voriconazole
Itraconazole
MOA:
Effect
Clinical uses:
Adverse effects:
MOA:
Inhibits CYP 3A4
Effects are↑ levels of:
1) Cisapride, Astemizole, Terfinadine - severe cardiac arrythmias
2) Cyclosporine, Midazolam
Clinical uses:
1) Meningeal infections (H. capsulatum, C. immitis, P.brasiliensis)
2) Invasive aspergillosis (lungs)
3) Sublingual onychomycosis
4) AIDs associated histoplasmosis
5) Oropharyngeal/esophagitis candidiasis
Adverse effects:
1) Hepatotoxicity
2) Rash
3) Hypokalemia
4) N/V
5) Adrenal insufficiency, edema, & HTN (high doses)
MOA:
Inhibits CYP 3A4
Effects are↑ levels of:
1) Cisapride, Astemizole, Terfinadine - severe cardiac arrythmias
2) Cyclosporine, Midazolam
Clinical uses:
1) Meningeal infections (H. capsulatum, C. immitis, P.brasiliensis)
2) Invasive aspergillosis (lungs)
3) Sublingual onychomycosis
4) AIDs associated histoplasmosis
5) Oropharyngeal/esophagitis candidiasis
Adverse effects:
1) Hepatotoxicity
2) Rash
3) Hypokalemia
4) N/V
5) Adrenal insufficiency, edema, & HTN (high doses)
Itraconazole
Posaconazole
MOA:
Effect
Clinical uses:
Adverse effects:
MOA:
Inhibits CYP 3A4
Effects are↑ levels of:
1) Tacrolimus, cyclosporine, sirolimus, midazolam – increased toxicity
AVOID with drugs that prolong Qtc interval (methadone, haloperidol, pimozide, quinidine, risperidone, halofantrine)
CLinical uses:
Refractory oropharyngeal candidiasis
Aspergillosis
Mucormycosis
Adverse effects:
1) Gi upset & headache
2) Hepatotoxicity
MOA:
Inhibits CYP 3A4
Effects are↑ levels of:
1) Tacrolimus, cyclosporine, sirolimus, midazolam – increased toxicity
AVOID with drugs that prolong Qtc interval (methadone, haloperidol, pimozide, quinidine, risperidone, halofantrine)
CLinical uses:
Refractory oropharyngeal candidiasis
Aspergillosis
Mucormycosis
Adverse effects:
1) Gi upset & headache
2) Hepatotoxicity
Posaconazole
Echinocandins
MOA:
Clinical use:
Adverse effects:
Anidulafungin, Caspofungin, & Micafungin
MOA:
Inhibits B-glucan synthesis
Clinical use:
1) Invasive candidiasis (Caspo & Andidula)
2) Esophageal candidiasis
3) Invasive aspergillosis (Caspo)
Adverse effects:
Gi upset
Phlebitis
Flushing (histamine)
Hepatotoxicity
Anidulafungin, Caspofungin, & Micafungin
MOA:
Inhibits B-glucan synthesis
Clinical use:
1) Invasive candidiasis (Caspo & Andidula)
2) Esophageal candidiasis
3) Invasive aspergillosis (Caspo)
Adverse effects:
Gi upset
Phlebitis
Flushing (histamine)
Hepatotoxicity
Echinocandins
Griseofulvin
MOA:
Clinical use:
Adverse effects:
MOA:
Inhibits microtubule formation to disrupt mitosis (eat with a fatty meal)
Clinical use:
1) Dermatophytes (tinea & ring worm)
2) Onychomycoses (nail infection)
Adverse effects:
1) Peripheral neuritis, dizziness, headaches
2) Hepatotoxicity
3) Albuminuria
4) Disulfiram-like reaction
5) Induce CYP450 (reduce warfarin levels)
6) Photosensitivity rash
MOA:
Inhibits microtubule formation to disrupt mitosis (eat with a fatty meal)
Clinical use:
1) Dermatophytes (tinea & ring worm)
Adverse effects:
1) Peripheral neuritis, dizziness, headaches
2) Hepatotoxicity
3) Albuminuria
4) Disulfiram-like reaction
5) Induce CYP450 (reduce warfarin levels)
Griseofulvin
Topical antifungals:
Clomitrazole (clinical use)
Vaginal:
Dermatophyte infections
Cutaneous candidiasis
Topical antifungals:
Miconazole (clinical use)
Tinea infections
Vulvovaginitis
