Introduction – Anti-Fungals
- Drugs (all systemic unless otherwise noted)
- amphotericin B
- nystatin
- topical formulation only
- terbinafine
- topical or systemic
- echinocandins
- anidulafungin
- caspofungin
- micafungin
- azoles
- topical formulations (too toxic for systemic use)
- clotrimazole
- miconazole
- econazole
- systemic
- itraconazole
- fluconazole
- isavuconazole
- ketoconazole (can also be topical)
- voriconazole
- topical formulations (too toxic for systemic use)
- griseofulvin
- flucytosine
- selenium sulfide
- topical formulation only
- Clinical use
- fungal infections
Anti-Fungal Medications | |||
Drug | Mechanism of Action | Adverse Effects of Systemic Treatment | Indications |
Amphotericin B |
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Nystatin |
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Terbinafine |
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Echinocandins |
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Griseofulvin |
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Flucytosine |
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Selenium sulfide |
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Different Classes
Anti-fungal medications work by targeting different parts of the fungal cell, such as the cell membrane, cell wall, or DNA synthesis, to inhibit their growth and/or kill the fungi. There are several different classes of anti-fungal medications, including:
- Azoles: Azoles inhibit the synthesis of ergosterol, a key component of the fungal cell membrane. This disrupts the integrity of the membrane, leading to cell death. Azoles are commonly used to treat infections caused by yeasts, such as Candida, as well as dermatophytes and some molds.
- Polyenes: Polyenes bind to ergosterol in the fungal cell membrane, causing membrane damage and ultimately cell death. Polyenes are typically used to treat systemic fungal infections, such as cryptococcal meningitis and invasive aspergillosis.
- Echinocandins: Echinocandins inhibit the synthesis of beta-glucan, a component of the fungal cell wall. This weakens the cell wall, leading to osmotic instability and ultimately cell death. Echinocandins are typically used to treat invasive candidiasis and invasive aspergillosis.
- Allylamines and azoles: Allylamines and azoles inhibit the synthesis of ergosterol and interfere with the synthesis of fungal cell membranes. These drugs are commonly used to treat fungal infections of the skin and nails, such as athlete’s foot and onychomycosis.
| Anti-Fungal Medications | |||
| Drug | Mechanism of Action | Adverse Effects of Systemic Treatment | Indications |
| Amphotericin B | 1. Binds to ergosterol in the membrane that is unique to fungi, forming membrane pores through which electrolytes and other cell content leak 2. Can be fungistatic or fungicidal | 1. Fevers, chills, and flu-like reaction Fevers, chills, and flu-like reaction 2. Renal toxicity – hydrate – supplement potassium and magnesium 3. Arrhythmias 4. Anemia 5. IV phlebitis | Systemic mycoses 1. Cryptococcus 2. Blastomyces 3. Coccidioides 4. Histoplasma 5. Candida 6. Mucor |
| Nystatin | 1. Binds to ergosterol 2. Can be fungistatic or fungicidal | 1. Topical formulation only – adverse effects are too toxic for systemic use | 1. Oral candidiasis 2. Topical yeast – infection – diaper rash -vaginal – candidiasis – intertrigo |
| Terbinafine | 1. Inhibits squalene epoxidase, an enzyme in fungi that is key in lanosterol synthesis 2. Fungicidal | 1.Gastrointestinal upset 2. Liver toxicity (rarely, can cause fulminant liver failure requiring liver transplant) 3. Taste disturbance | 1. Widespread dermatophyte infections 2. Onychomycosis |
| Echinocandins | 1. Disrupts cell wall synthesis by inhibiting beta-glucan synthesis 2. Can be fungistatic or fungicidal | 1. Gastrointestinal upset 2. Flushing – mediated by histamine | 1. Aspergillosis 2. Candida |
| Azoles | 1. Inhibits 14-alpha-demethylase, which is key in ergosterol synthesis in fungi 2. Fungistatic | 1. Anti-androgen effects via inhibiting testosterone synthesis – gynecomastia (in particular, ketoconazole) 2. Inhibits cytochrome P450 | 1. Local mycoses 2. Mild systemic mycoses 3. Specific indications – fluconazole * chronic suppression of Cryptococcus in immunosuppressed patients – itraconazole * Blastomyces * Coccidioides * Histoplasma – voriconazole * Aspergillus * Candida – isavuconazole *Aspergillus *Mucor |
| Griseofulvin | 1. Disrupts mitosis via microtubule dysfunction 2. Especially targets keratin-containing tissues such as nails 3. Fungistatic | 1. Teratogenic 2. Disulfiram-like reaction 3. Neurologic symptoms – confusion – headaches | 1. Superficial infections 2. Dermatophytes – inhibits growth |
| Flucytosine | 1. Converted by fungal enzyme cytosine deaminase to 5-fluorouracil, which then inhibits nucleic acid synthesis 2. Can be fungistatic or fungicidal | 1. Bone marrow suppression | 1. Systemic mycoses – Cryptococcus |
| Selenium sulfide | 1. Disrupts mitosis, resulting in decreased turnover of epidermal cells and decreased flaking 2. Also has mild antibacterial and antifungal activity | 1 | 1. Seborrheic dermatitis 2. Pityriasis versicolor |
Studies
- Clinical trials: Clinical trials are studies that test the safety and effectiveness of new anti-fungal medications in humans. These studies involve recruiting participants who have fungal infections and randomly assigning them to receive either the new medication or a placebo. The outcomes of the study are then compared between the two groups to determine if the medication is effective.
- Resistance studies: Fungal resistance to anti-fungal medications is a growing concern, particularly in patients with weakened immune systems. Resistance studies investigate the mechanisms by which fungi become resistant to anti-fungal medications and identify new targets for drug development.
- Pharmacokinetic studies: Pharmacokinetic studies investigate how anti-fungal medications are absorbed, distributed, metabolized, and eliminated by the body. These studies can help to determine the optimal dose and duration of treatment for different types of fungal infections.
- Drug-drug interaction studies: Anti-fungal medications can interact with other medications, leading to adverse effects or reduced effectiveness. Drug-drug interaction studies investigate how anti-fungal medications interact with other commonly used medications and identify potential drug interactions.
- Mechanism of action studies: Mechanism of action studies investigate how anti-fungal medications work at the cellular and molecular level. These studies can help to identify new drug targets and improve the design of existing anti-fungal medications.
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