Antifungal Drugs Classification and Mechanisms

5-FU inhibits the synthesis of nucleic acids (DNA and RNA) in fungi, disrupting their growth.

Human cells are less efficient at converting flucytosine to 5-FU, making it less toxic to humans than fungi.

Azole antifungals target a specific enzyme in fungal cell membranes, disrupting ergosterol synthesis which weakens the cell membrane.

Imidazole and Triazole are two groups of azole antifungal drugs, each with a different number of nitrogen atoms in their chemical structure.

The absorption of azoles from the stomach can be affected by food and gastric acid, but fluconazole can penetrate the brain.

Drugs that target and kill fungi, primarily by interfering with their cell walls, membranes, or metabolic processes.

Fungi are eukaryotic organisms, meaning their cells have a nucleus and other complex internal structures. This makes it more challenging to develop antifungal drugs that specifically target fungal cells without harming human cells.

A rigid outer layer that surrounds fungal cells, composed of chitin and polysaccharides.

A molecule found in fungal cell membranes, which plays a crucial role in their structure and function.

A class of antifungal drugs that disrupt fungal cell membranes by binding to ergosterol, altering permeability, and leading to cell death.

A common example of a polyene antifungal drug used systemically to treat serious fungal infections.

A major side effect of Amphotericin B, characterized by chills, fever, and other symptoms.

A class of antifungal drugs that inhibit the synthesis of ergosterol, a key component of fungal cell membranes.

A common example of an Azole antifungal drug used to treat a variety of fungal infections, including Candida infections.

A class of antifungal drugs that inhibit the synthesis of ergosterol and lanosterol, both important molecules in fungal cell membranes.

A common example of an Allylamines antifungal drug used to treat dermatophyte infections, such as athlete's foot.

A class of antifungal drugs that inhibit the synthesis of fungal cell walls, interfering with their structural integrity.

A common example of an Echinocandins antifungal drug used to treat serious fungal infections, particularly Candida infections.

An antifungal drug that is structurally similar to pyrimidine bases, which are essential components of DNA and RNA.

A prodrug, meaning it needs to be converted into its active form inside the fungal cell to exert its antifungal effects.

Ketoconazole is the only imidazole antifungal that is used systemically, while the other three imidazoles are only used topically.

Triazole antifungals are now mostly replacing ketoconazole for systemic fungal infections.

The most common adverse effect of azole antifungals is hepatotoxicity, which can manifest as elevated serum transaminase levels.

Ketoconazole has antiandrogenic effects, leading to gynecomastia (breast enlargement) and impotence in males.

Ketoconazole's absorption is favored by an acidic environment.

Ketoconazole's half-life is approximately 8 to 10 hours.

Ketoconazole is effective against a wide range of fungi, including yeasts and molds.

Oral ketoconazole is effective for dermatophytosis, mucosal candidiasis, and some systemic mycoses. However, its poor absorption limits its use for severe infections.

Fluconazole is a water-soluble triazole antifungal drug with excellent absorption, wider activity than ketoconazole, and effectiveness against Candida albicans and Cryptococcus neoformans. It is a valuable treatment option for fungal infections but has limitations due to resistance developed by some Candida species.

Fluconazole exhibits intrinsic resistance against certain Candida species like C. krusei, which is always resistant, and C. glabrata, which shows moderate resistance. This resistance is not acquired but inherent to these species.

Acquired fluconazole resistance can occur due to extended use in immunocompromised patients, leading to the selection of resistant species or mutations. This can involve changes in fungal genes or an upregulation of efflux pumps.

Itraconazole, another triazole, is a newer oral antifungal with broader spectrum activity including molds and Aspergillus. It has a varied absorption pattern and is known for its effectiveness in immunocompromised patients.

Voriconazole, a second-generation triazole, boasts high oral bioavailability and penetration into the cerebrospinal fluid. It is highly effective for treating invasive aspergillosis and other fungal infections.

Posaconazole, the newest triazole, exhibits structural similarity to itraconazole with a broad spectrum of activity including various Candida species, Aspergillus, Cryptococcus neoformans, and Zygomycetes. It is often used as salvage therapy for immunocompromised patients.

Topical azoles, like clotrimazole and miconazole, are used to treat vulvovaginal candidiasis, oral thrush, and dermatophytic infections. They have minimal absorption and rare adverse effects.

Terbinafine, a member of the allylamines, is orally and topically effective against Candida and dermatophytes. Its unique mechanism of action targets squalene epoxidase, disrupting ergosterol synthesis.

Echinocandins are a class of antifungal drugs that inhibit the synthesis of β-1,3-D glucan, a crucial component of fungal cell walls. This leads to cell wall disruption and fungal death effectively treating Candida and Aspergillus infections.

Griseofulvin is a drug that inhibits fungal mitosis by binding to microtubules and preventing spindle formation. It is effective against dermatophyte infections of hair and nails, requiring long-term therapy.

Dermatophytes are a group of fungi that cause skin infections like Tinea corporis (ringworm), Tinea pedis (athlete's foot), and Tinea cruris (jock itch). These infections are often treated with topical antifungals or oral medications.

Candida albicans is a yeast species that is commonly found in the human body. While usually harmless, under specific conditions, it can cause infections like oral thrush, vaginal candidiasis, and more severe systemic infections.

Aspergillus is a genus of mold that can cause various infections, ranging from superficial skin infections to life-threatening invasive aspergillosis. Antifungal drugs are crucial for treating these infections.

Cryptococcus neoformans is a yeast that commonly causes infections in immunocompromised individuals. It can affect the lungs, brain, and other organs.

Zygomycetes are a diverse group of fungi that can cause serious infections in immunocompromised individuals. These infections can be challenging to treat and often require aggressive antifungal therapy.