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19 Cards in this Set
- Front
- Back
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Reasons that fungal infections are hard to treat
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1.) Fungi are eukaryotic so hard to target
2.) Slow growth 3.) Infection often poorly vascularized 4.) Patients may be immunocompromised |
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Polyene drugs
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Bind to ergosterol in fungal cell membrane and altered permeability
Fungicidal High incidence of toxicity |
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Azole drugs
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Interfere w/ synthesis of membrane ergosterol leading to altered permeability
Inhibit Cytochrome p450 so many drug-drug interactions *Teratogenic Cardiac effects w/ many drugs |
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Echinocandin drugs
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inhibit synthesis of glucan, which causes disruption of the cell wall
fungicidal EchinoCANdin CAN be used w/ Cytochrome p450 metabolized drugs. CAN cause histamine RXN. Used for severe CANdidiasis (and Aspergillus) No Cytochrome p450 interactions so limited drug interactions Limited toxicity b/c no cell wall in humans Drawback is that it's IV only |
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Allylamines
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Interferes w/ the synthesis of lanosterola, which is a precursor of ergosterol
Works by inhibiting squalene epoxidase Fungistatic Added benefit that it causes squalene buildup, which is toxic to fungi (fungicidal) |
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Terbinafine (Lamisil)
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Allylamine drug (inhibits squalene epoxidase)
Used to treat tinea capitis, onychomycosis AKA tinea unguium, etc. Reaches high conc. in stratum corneum, hair, and nails, AND stays there for a long time Headache and GI side effects Potential hepatic toxicity so must monitor hepatic function increases clearance of cyclosporine Rifampin = increased clearance by 100% ("amp up clearance") Cimetidine = decreased clearance |
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Itraconazole
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Broad spectrum triazole (azole drug) - fungistatic
Oral capsule w/ food, or solution without food Good distribution, but NOT IN THE CSF Teratogen Inhibits clearance of multiple drugs (All Azole drugs have drug-drug interactions due to Cytochrome p450 interactions) Can increase QT interval *DOC for systemic fungal infections |
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Fluconazole
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Azole drug - interferes w/ ergosterol synthesis
Used for systemic fungal infections Fungistatic triazole Has a potential for resistance Oral and IV Good distribution w/ HIGH CSF levels GI side effects Also increased QT interval and many drug interactions like other Azoles Used for Candidiasis, dermatophycosis, and cryptococcosis (treats this form of meningitis b/c gets into CNS well) |
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Griseofulvin
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Used to treat Dermatophytic fungal infections
Inhibits fungal cell mitosis and nuclear acid synthesis Oral and distribution aided by fatty foods "Greasy foods helps absorption of Griseofulvin" Must accumulate in keratinzed tissue so need long treatment time Headaches and hypersensitivity RXNs since it's a product of Penicillin Highly teratogenic & carcigenic Only used when other agents fail |
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Treatments of Superficial Candidiasis
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Cutaneous = Clotrimazole
Systemic = Fluconazole or Itraconazole Cutaneous (diaper rash) - clotrimazole for topical azole treatment, fluconazole or itraconazole for systemic infections and immunocompromised Vulvovaginal canididasis - topical azoles such as butoconazole or clortrimazole. Systemic treatment w/ fluconazole and itraconazole Thrush - clotrimazole lozenges, nystatin Esophageal - systemic treatment required. oral fluconazole or IV fluconazole |
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Nystatin
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Polyene macrolide - binds to membrane ergosterol
Not absorbed from GI tract and too toxic for systemic use Used to treat Candida of skin, vagina, mouth, and lower GI tract |
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Broad Spectrum Topical Antifungal Drugs for Superficial Candidiasis and Dermatophytic infections
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Clotrimazole (Lotrimin), Mycelex (candidiasis & tinea), Terbinafine (tinea), and Miconazole (Tinea and candidiasis)
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Echinocandins / Micafungin
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Newest class - used to treat Deep fungal diseases
IV only Inhibits synthesis of Beta glucan component of the fungal cell well Redistribution and slow metabolism Well tolerated, but can get histamine-mediated reactions Teratogen Levels increased by cyclosporine and decreased by rifampin Most Commonly used for severe Candida infections. Also used for Aspergillosis and prophylaxis against Candida in stem cell transplant patients |
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Itraconazole
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Azole drug - interferes w/ ergosterol synthesis
Used for systemic fungal infections DOC for histoplasmosis, blastomycosis, paracoccidioidomycosis, and sporotrichosis Oral |
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Voriconazole
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Azole drug - interferes w/ ergosterol synthesis
Used for systemic fungal infections Deep fungal infection drug Triazole drug Oral or IV, good distribution Reversible visual disturbances, photosensitivity, and liver problems Like all Azoles, many drug interactions **Used for Invasive aspergillosis |
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Posaconazole
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Extremely potent & has the broadest spectrum
"Like a Pos! (Boss)" - extremely potent Oral Azole drug Absorption is greatly increased w/ a high fat meal and also increased by decreasing the pH Fecal elimination Many drug interactions like with other Azoles Used for Prevention of Candida and Aspergillus in severely immunocompromised |
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Amphotericin B
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*Broad spectrum, fungicidal polyene antibiotic
Binds to ergosterol in the fungal cell membrane and forms a pore that leaks out macromolecules / ions that kills the cell IV Liposomal formulation (expensive, but better) and deoxycholate form (more side effects) Wide distribution, but NO CSF DISTRIBUTION 90% protein bound, but liposmal preparation prevents host from binding Very toxic - renal toxicity (lower in liposomal preps), infusion reactions (fevers / chills & can pre-treat w/ antihistamines and anti-inflammatory), hypokalemia Antineoplastic agents and cyclosporine enhance potential for renal toxicity Used in combination w/ flucytosine for synergism Used for treatment of *rapidly progressing or severe mycoses such as aspergillosis, blastomycosis, and systemic candidiasis OK to use in pregnant women |
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Treatment of Pneumocystis jiroveci formerly P (PCP)
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1.) Trimethoprim-sulfamethoxazole (Bactrim) is DOC
2.) Pentamidine - 2nd choice (use w/ sulfa allergies) aerosol administration Can cause cough, hypotenstion, hypoglycemia 3.) Atovaquone - interferes w/ mitochondrial electron transfer, which inhibits nucleic acid and ATP synthesis |
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2 classes of anti-fungals that affect ergosterol
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Fungi have ergosterol instead of sterol - can be targeted
1.) Polyenes (amphotericine, nystatin) 2.) Azoles (Imidazoles and triazoles) |
