Antifungal

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Type Chemical Class Drug Trade name Mechanism of action P-kinetics Spectrum Clinical use Side effects / drug interactions
Ergosterol target: Agents that disrupt membrane integrity (Cell membrane target) Azoles Clotrimazole Mycelex, Gyne-Lotrimin, Canesten, Gynocanesten Inhibits synthesis of ergosterol (inhibits lanosterol 14α-demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol). topical dermatophytes and many strains of Candida Vulvovaginal candidiasis, Dermatophytic infections (tineas)
Econazole

Ecostatin, Pevaryl, Spectazole





Ketoconazole Nizoral topical, oral, does not cross BBB, hepatic metabolism

*Inhibition of mammalian CYP3A4 (Co-administration of this agent with drugs that are metabolized by Cyp3A4, will lead to higher blood level of such drugs)
*Inhibits also adrenal and gonadal hormone synthesis (inhibits the activity of several enzymes necessary for the conversion of cholesterol to steroid hormones such as testosterone and cortisol)
*Absorption is blocked by antacids and H2 antagonists due to lowering of gastric acidity
Miconazole Daktarin, Monistat topical, IV, It does not cross BBB candidal species and dermatophytes Vulvovaginal candidiasis, Dermatophytic infections (tineas), also oropharyngeal thrush
Sertaconazole Zalain, Ertaczo, Dermofix



Fluconazole Diflucan, Flucess, Fluconazol, Flucoric, Triflucan oral, IV, crosses BBB, excreted unchanged in urine
Meningitis caused by susceptible fungi and in AIDS patients with life threatening systemic fungal infections Inhibits CYP450, in particular CYP2C9, which leads to dangerous drug-drug interactions with drugs such as warfarin and phenytoin
Itraconazole Sporanox oral, IV, does NOT cross BBB, metabolized by CYP in liver


Posaconazole Noxafil, Posanol oral, IV, crosses BBB invasive aspergillosis and Candida Prophylaxis of invasive Aspergillus and Candida infections in immunocompromised patients
Oropharyngeal candidiasis refractory to itraconazole and/or fluconazole.
Co-administration with Sirolimus, pimozide, quinidine, atorvastatin, lovastatin, simvastatin, ergotamine, dihydroergotamine is contraindicated.
Voriconazole Vfend Oral, IV, hepatic metabolism same spectrum as Fluconazole, but is also active against Aspergillus infections where Fluconazole is ineffective Less toxic than ampho b and more effective in the treatment of invasive aspergillosis visual disturbances
Polyene antimycotics
Nystatin Micostatin, Mycostatin, Nilstat, Nistatina, Nystatin Binds to ergosterol and forms cytotoxic pores in cell membranes that allows the exit of essential ions and elements required for the fungus (amphipathic molecule). Binds more specifically to ergosterol found in yeast only but can bind to cholesterol in mammalian cells = toxicity
topical and oral (poorly absorbed, this is good) candida albicans Mucocutaneous candidal infections
Amphotericin B Abelcet, Ambisome (liposomal formulation), Fungilin, Fungizone IV and oral, does not cross BBB, metabolized in liver Broad: candida albicans, cryptococcus neoformans, aspergillus, histoplasma capsulatum, blastomyces dermatitidis Because of its toxic side effects and broad spectrum this drug is reserved for serious systemic mycotic infections and mycotic infections in immunocomprimised patients. Often used as the initial agent followed by an azole 1) immediate reactions via drug infusion hypersensitivity reactions (nausea, vomiting, chills, hypotension) --slow administration or premeditate.
2) Slower Toxicities: Nephrotoxicity, Hypokalemia, hypomagnesaemia and arrhythmias
Allylamines Amorolfine Loceryl, Locetar Inhibits squalene epoxidase, this results in deceased synthesis of ergosterol and accumulation of toxic squalene (fungicidal effect)
topical nail lacquer dermatophytes, candida, and nondermatophytic molds Onychomycosis (nail infection) rare
Naftifine Naftin, Exoderil topical Dermatophytes dermatophytoses (especially onychomycosis) Rare
Terbinafine Lamisil topical and oral Dermatophytes dermatophytoses (especially onychomycosis)
Cell wall target
Echinocandins
Anidulafungin Ecalta, Eraxis Inhibits synthesis of cell wall component b(1-3) glycan. This leads to cell wall weakening that favours the cell wall lysis and death of the fungi




Caspofungin Cancidas IV, liver metabolism Aspergillus salvage therapy (failed Ampho B therapy) for aspergillosis
Micafungin Mycamine



Pyrimidine analogues: Nucleic acid inhibitors
Flucytosine Ancobon, Ancotil
inhibits fungal DNA and RNA synthesis, must be converted by yeast enzymes into active metabolite (human cells are unable to do this)




 Mitotic inhibitors
Griseofulvin Grifulvin V, Gris-PEG, Fulvicin, Fulcin disrupts fungal microtubules prevents mitotic spindle function



Others
Ciclopirox Loprox, Penlac, Batrafen acts by chelation of polyvalent cations (Fe+3 or Al+3) resulting in the inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides (toxic metabolites) within the fungal cell