Antifungals | Antimicrobials | Pharmacology

Antifungals

Antifungals are divided into the following classes:

Azoles: These include imidazoles (clotrimazole, ketoconazole, miconazole) and triazoles (fluconazole, itraconazole, terconazole, voriconazole). They inhibit ergosterol synthesis (a key component of the fungal cell membrane) by inhibiting the cytochrome P450 enzyme.

Adverse effects include GI upset, diarrhea, hepatotoxicity, and rash. Ketoconazole may have anti-androgenic effects, including gynaecomastia, decreased libido, and decreased sperm count and motility.

Azoles also inhibit the hepatic cytochrome P450 system. Use caution when drugs such as cisapride, dasatinib, tamsulosin, warfarin, triazolam, alprazolam, phenytoin, sirolimus, etc. are used along with azoles.

Ketoconazole is used as a topical agent and orally to treat dermatophytes, Candida spp, Blastomyces dermatitidis, and Coccidiodes spp. Fluconazole, voriconazole, and itraconazole are used to treat invasive or systemic fungal infections such as Candida spp, Cryptococcus neoformans, Aspergillus spp., dematiaceous fungi, and Sporothrix schenckii (the last three: itraconazole and voriconazole only). Posaconazole is active against zygomycetes as well.
Polyenes: This class includes amphotericin B, nystatin, and natamycin. Polyenes bind to ergosterol in the fungal cell membrane and disrupt the membrane, leading to increased cellular permeability. Liposomal and carrier forms are available to reduce adverse effects.

Amphotericin B is used to treat systemic fungal infections such as Candida spp, Aspergillus spp, etc. Adverse effects include nephrotoxicity, hematologic toxicity, and infusion-related reactions such as fever, headache, and thrombophlebitis. Premedication with acetaminophen and heparin is used to prevent infusion-related adverse effects. Intravenous hydration with normal saline and correction of electrolyte imbalance help prevent nephrotoxicity.

Nystatin is given orally or topically.
Allylamines: This class includes terbinafine. It inhibits the enzyme squalene monooxygenase, which is involved in sterol synthesis. It is used to treat onychomycosis. It may cause hepatitis, elevated liver enzymes, and lymphopenia.
Echinocandins: This class includes caspofungin, micafungin, and anidulafungin. They inhibit the enzyme beta 1,3 D-glucan synthase, thereby blocking the synthesis of beta 1,3 D-glucan in the cell wall. This causes cell lysis.

They are used in the treatment of candidiasis, aspergillosis, etc. Anidulafungin can be safely used in the presence of hepatic or renal failure. C.neoformans is resistant to echinocandins because its cell wall lacks beta glucan.

They are well tolerated. Adverse effects include GI upset, infusion reactions, hypotension, and rash.
Flucytosine: This drug is converted to 5-fluorouracil (5-FU) by the enzyme cytosine deaminase inside fungal cells. 5-FU interrupts fungal DNA and protein synthesis. It is used as combination therapy and is active against Candida sp, Cryptococcus sp, Aspergillus sp, and dematiaceous fungi. Adverse effects include diarrhea, nausea, vomiting, myelosuppression, and hepatotoxicity.

Antifungals

Antifungals are divided into the following classes:

Azoles: These include imidazoles (clotrimazole, ketoconazole, miconazole) and triazoles (fluconazole, itraconazole, terconazole, voriconazole). They inhibit ergosterol synthesis (a key component of the fungal cell membrane) by inhibiting the cytochrome P450 enzyme.

Adverse effects include GI upset, diarrhea, hepatotoxicity, and rash. Ketoconazole may have anti-androgenic effects, including gynaecomastia, decreased libido, and decreased sperm count and motility.

Azoles also inhibit the hepatic cytochrome P450 system. Use caution when drugs such as cisapride, dasatinib, tamsulosin, warfarin, triazolam, alprazolam, phenytoin, sirolimus, etc. are used along with azoles.

Ketoconazole is used as a topical agent and orally to treat dermatophytes, Candida spp, Blastomyces dermatitidis, and Coccidiodes spp. Fluconazole, voriconazole, and itraconazole are used to treat invasive or systemic fungal infections such as Candida spp, Cryptococcus neoformans, Aspergillus spp., dematiaceous fungi, and Sporothrix schenckii (the last three: itraconazole and voriconazole only). Posaconazole is active against zygomycetes as well.
Polyenes: This class includes amphotericin B, nystatin, and natamycin. Polyenes bind to ergosterol in the fungal cell membrane and disrupt the membrane, leading to increased cellular permeability. Liposomal and carrier forms are available to reduce adverse effects.

Amphotericin B is used to treat systemic fungal infections such as Candida spp, Aspergillus spp, etc. Adverse effects include nephrotoxicity, hematologic toxicity, and infusion-related reactions such as fever, headache, and thrombophlebitis. Premedication with acetaminophen and heparin is used to prevent infusion-related adverse effects. Intravenous hydration with normal saline and correction of electrolyte imbalance help prevent nephrotoxicity.

Nystatin is given orally or topically.
Allylamines: This class includes terbinafine. It inhibits the enzyme squalene monooxygenase, which is involved in sterol synthesis. It is used to treat onychomycosis. It may cause hepatitis, elevated liver enzymes, and lymphopenia.
Echinocandins: This class includes caspofungin, micafungin, and anidulafungin. They inhibit the enzyme beta 1,3 D-glucan synthase, thereby blocking the synthesis of beta 1,3 D-glucan in the cell wall. This causes cell lysis.

They are used in the treatment of candidiasis, aspergillosis, etc. Anidulafungin can be safely used in the presence of hepatic or renal failure. C.neoformans is resistant to echinocandins because its cell wall lacks beta glucan.

They are well tolerated. Adverse effects include GI upset, infusion reactions, hypotension, and rash.
Flucytosine: This drug is converted to 5-fluorouracil (5-FU) by the enzyme cytosine deaminase inside fungal cells. 5-FU interrupts fungal DNA and protein synthesis. It is used as combination therapy and is active against Candida sp, Cryptococcus sp, Aspergillus sp, and dematiaceous fungi. Adverse effects include diarrhea, nausea, vomiting, myelosuppression, and hepatotoxicity.