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28 Cards in this Set
- Front
- Back
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fungal infxs
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-classified as superficial (skin, hair and nails) or deep
-yeast/yeast-like or filamentous (mold) -candida, cryptococcus neoforms, malassezia furfur |
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systemic dimorphic yeasts (endemic mycoses)
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-exist in 2 forms
-histoplasma (soil) -blastomyces -coccidiodes -generally do not cause problems unless immunocomp |
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filamentous fungi (pathogenic)
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-aspergillus
-mucor and rhizopus--> severe -dermatophytes (tineas) -causes invasive disease in people who are immunocomp |
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antifungals 3 main MOA
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1. Alter cell membrane permeability
-Azoles, allylamines, polyenes, glucan synthesis inhibitor 2. Block nucleic acid synthesis -pyrimidine analog 3. Disrupt microtubule function -griseofulvin |
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azole class of antifungals MOA
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Reduce ergosterol (major sterol that makes up the cell membrane in fungal organisms) synthesis by inhibition of fungal cytochrome P450
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azole class of antifungal
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1. Imidazoles: Ketoconazole, miconazole (topical), clotrimazole (topical) (not as selective)
2. Triazoles: itraconazole and fluconazole, voriconazole and posiconazole (selective toxicity) |
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general pharm of azoles
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-most require acidic pH for absorption
-DI are common due to inhibition of P450 system so must check -triazoles are more selective for fungal enymes so less AE and ?DI -most common AE: GI, increased LFTs |
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azoles clinical use:
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-broad include candida infxs, cryptococcus (meningitis), dermatophytes, endemic mycoses, possibly aspergillus
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Fluconazole
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-IV/po
-only azole that can penetrate CNS!! -used for candida infxs and cryptococcal meningitis -150mg stat dose for vulvovaginitis |
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Ketoconazole
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-po, topical
-uses: mucocutaneous candidiases, seborrhea, tinea versicolor, tinea skin infections -less selective for fungal CYP P450 so AE and DI -hepatotoxicity (monitor LFTs) -GI side effects ARE COMMON -endocrine effects such as hypokalemia, gynecomastia, dec libido, abnomalities in menstrual cycle (b/c not as selective) |
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Itraconazole
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-IV/po
-most potent with widest spectrum!! -clinical: onychomycosis, tx of endemic histoplasmosis and blastomycosis -watch DI esp. quinidine, statins, certain macrolides -AE: GI, edema, and hepatotoxicity so monitor LFTs, may have endocrine effects in high doses -usually has to be used for long time |
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Voriconazole (Vfend)
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-IV and po for invasive aspergillosis
-candidemia and esophageal candidiases (2nd line) -AE: well-tol with occasional elevated LFTs, rash and visual disturbances (changes in color vision, sharper or blurred vision) -DI common -category D |
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Posiconazole
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-oral, newest azole
-for immunocomp pts with aspergillus and candida prophylaxis for severe IC pts -AE: N/V and liver damage (watch Qt interval) -DI |
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Topical azoles
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-numerous OTC and Rx preps for candidiases, tinea infxs
-clotrimazole, miconazole OTC agent for vulvovaginal candidiases, tinea infxs -clotrimazole troches for oral candidiases (thrush) -Ketoconazole cream, shampoo for tinea skin infxs and seborrhea |
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Caspofungin acetate- glucan inhibitor
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-MOA: inhibits beta 1,3 D-glucan in fungal cell wall
-IV for refractory invasive aspergillosis infxs -AE: allergic rxns with fever, flushing, GI effects -infusion vein inflammation (phelbitis) |
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Anidulafungin (Eraxis)
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-IV, glucan inhibitor
-usese: severe esophagela candidiases (2nd line to fluconazole), candidemia and other deep candida infxs -AE: diarrhea, hypokalemia and elevated ALT |
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Micafungin
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-glucan inhibitor, IV
-for candida prophlaxis in pts undergoing stem cell transplant -2nd for esophageal candidiases |
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Polyene antibiotics
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1. Amphotericin B- broadest spectrum antifungal-drug of choice for life-threatening fungal infxs
2. Nystatin (mostly used for topical application)-candida only -very toxic! |
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Amphotericin B
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-MOA: binds to ergosterol in fungal cell membrane and alteres permeability --> forms pores, causes leakage of intracell components
-capable of producing oxidative damage -IV only, 4 preps, standard and 3 lipid based forms (developed to provide less toxicity and more selectivity)- liposomal amphotericin B (more $$ and less toxic) -for severe fungal infxs -Tox: ampho "terrible" infusion related; fever, chills, muscle spasms, HA, hypotension; renal damage (dose-limiting); normocytic anemia -pts needs to be well hydrated and infused slowly |
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Nystatin
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-MOA: binds to ergosterol and forms holes in fingal cell membrane
-uses: oral candidiases, cutaneous candidiases (mycostatin); intestinal candidiases (mycostatin tablets) -category C -AE: GI, diarrhea, oral irritation |
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Allyalmines
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-terbinafine and naftidine (topical, good for tinea)
- Terbinafine (Lamisil) is po and topical therapy -uses: po therapy for onychomycosis, topical for tinea skin infxs -MOA: inhibits fungal sequalene epoxidase -category B -AE: baseline LFTs, GI, rash, liver problems |
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Pyrimidine analog- Flucytosine
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-MOA: converted by fungal enzyme into pyrimidine analogs
-IV, crosses BBB, narrow spectrum -uses: combo therapy with amphotericin B for cryptococcal meningitis (synergistic, allows amphotericin B to cross BBB) -AE: bone marrow toxicity, elevated LFTs |
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Penicillin derivative- Griseofulvin
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-MOA: not really known; may interfere with microtubules and seems to bind to keratin and makes keratin resistant to fungal infxs
-MAIN USE: tx of tinea capitis (4-6 wks) and sometime onychomycosis -pharm: give with fatty meals, milk for better absorption, use microsize or ultamicrosize preps -AE: allergic syndrome, skin rash |
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Overview of therapy
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1. Onychomycosis (po)
-Terbinafine or intraconazole po 6-12 wks 2. Tinea capitus (systemic tx) -Griseofulvin or Terbinafine or intraconazole 3. Skin infxs with dermatophytes (tinea) -Topical azole therapy of terbinafine |
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overview of therapy cont
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4. Cutaneous candidiases
-nystatin cream 5. Vulvovaginal candidiases -miconazole, clotimazole, terconazole supp, cream; fluconazole 6. Oropharyngeal and esophageal -topical nystatin or clotrimazole or systemic azole for esophageal candidiasis |
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systemic fungal infxs
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1. Blastomycosis: intraconazole long term therapy for severe infxs --> Amphoteracin B
2. Histoplasmosis: long term intraconazole or ketoconazole; severe --> IV amphotericin 3. Coccidioidomycosis: azoles for mild to mod disease; amphotericin B for severe 4. Cryptococcal meningitis: fluconazole long term, amphotericin B for severe |
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severe systemic infections
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1. Candidemia (widespread blood infx) with hematogenous spread: fluconazole IV or amphotericin B; new azoles and glucan inhibitors
2. Aspergillosis: Voriconazole or caspofungin acetate |
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Zygomycetes- Mucomycosis
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-Tx: Lipid AmphB and surgical debridement
-more common in severely immunocomp pts and causes infxs in sinuses, can invade into brain |
