antifungal drug
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What is an antifungal drug?
An antifungal drug is a substance that targets fungal pathogens, treating mycosis, or fungal infections. These drugs fall into major groups, including polyenes, azoles, and allyamines, categorized by their chemical structure and how they work.
Azoles, like imidazoles and triazoles, disrupt fungal membranes by blocking the synthesis of lipids, especially ergosterol. Some antifungals, such as terbinafine and miconazole, are available over the counter for conditions like athlete's foot, while others, like fluconazole, require prescriptions for severe infections. Ketoconazole also works by disrupting ergosterol synthesis, weakening the fungal cell membrane and causing cell death.
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What kinds of infections do antifungal drugs treat?
Antifungal drugs treat various fungal infections (mycoses) that invade tissues, causing superficial, subcutaneous, or systemic diseases.
Examples of fungal infections treated by these drugs:
* Superficial infections: Athlete’s foot, ringworm, and oral, skin, and vaginal infections
* Subcutaneous infections: Sporotrichosis
* Systemic infections: Candidiasis, cryptococcosis, histoplasmosis, blastomycosis, and paracoccidiosisSome commonly used antifungals include azoles, which have broad antifungal activity, and triazoles, which are effective against systemic or deep-seated fungal infections. Topical antifungals are typically used for superficial infections, while drugs like amphotericin B and flucytosine are used for subcutaneous and systemic mycoses.
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How do antifungal drugs work to fight fungi?
Antifungal drugs combat fungal infections (mycosis) by selectively targeting fungal pathogens. These drugs generally operate through distinct mechanisms based on their chemical structure.
Polyenes, like amphotericin B and nystatin, interact with ergosterol, a steroid in fungal membranes. This interaction leads to the formation of channels, causing the leakage of cytoplasmic components due to compromised membrane permeability. Azoles interfere with the synthesis of fungal lipids, especially ergosterol, by binding to fungal membranes. Disrupting ergosterol weakens the membrane, leading to cell death.
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What are some common types of antifungal drugs?
Antifungal drugs combat fungal pathogens that cause mycosis, or fungal infections. The major categories of antifungals, distinguished by their chemical structure and action mechanisms, include polyenes, azoles, and allylamines.
Polyenes like amphotericin B and nystatin interact with ergosterol in fungal membranes, causing the formation of channels, resulting in a loss of selective permeability in the membrane, and leakage of cytoplasmic components. Because of its toxicity, nystatin is restricted to topical use.
The azole group of antifungals includes imidazoles and triazoles. They block the synthesis of fungal lipids, especially ergosterol, by binding to fungal membranes. Azoles treat skin, oral, and vaginal infections.
Allylamines, such as terbinafine and naftifine, are effective against dermatophytes and act by inhibiting fungal ergosterol biosynthesis.
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What are possible side effects of antifungal drugs?
The use of antifungal drugs can cause side effects due to their mechanism of action. Polyenes, such as amphotericin B and nystatin, interact with ergosterol in fungal membranes, causing a loss of membrane-selective permeability and leakage of cytoplasmic components. Because cholesterol in human cell membranes is similar to ergosterol, these drugs can be toxic.
Amphotericin B may cause fever, chills, hypotension, nausea, and shortness of breath during administration. Kidney toxicity is common, but renal function usually improves after therapy. Lipid-based formulations may reduce toxicity. Nystatin is more toxic and is used orally or topically for treating infections of the skin and mucous membranes caused by Candida albicans. Antifungal drugs treat fungal infections by acting against fungal pathogens.
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How can fungi become resistant to antifungal drugs?
Fungi can develop resistance to antifungal drugs through several mechanisms. Spontaneous mutations in the fungus's DNA can lead to resistance, where the drug kills non-resistant microbes, leaving the mutants to thrive. Fungi can also prevent drugs from entering their cells or modify the drug, rendering it ineffective. Another method is altering the drug's target site within the fungus, so it no longer binds effectively. The use of antimicrobial agents can result in an alteration in the number and type of microorganisms normally found on the skin and mucosal surfaces.
Biofilms can also confer resistance to antibiotics. The overuse of antifungal drugs accelerates the evolution of resistant strains, complicating the treatment of fungal infections.
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antifungal drug, any substance that acts selectively against a fungal pathogen (disease-causing organism) in the treatment of fungal infection (mycosis). The major groups of antifungals are the polyenes, the azoles, and the allyamines; these groups are distinguished primarily by chemical structure and mechanism of action. Important drugs that do not fall within these groups but that are used in the treatment of fungal infections include griseofulvin and flucytosine.
The polyenes
Polyenes, such as amphotericin B and nystatin, are macrolide antibiotics made up of alternating conjugated double bonds. The polyene drugs work by interacting with ergosterol, a type of steroid that is found in fungal membranes; this binding causes channels to form in the fungal membrane, resulting in the loss of membrane-selective permeability and of cytoplasmic components. Because cholesterol found in human cell membranes is similar in structure to ergosterol, there is some toxicity associated with the use of these drugs. Amphotericin B is used primarily in the treatment of serious fungal diseases, such as cryptococcal meningitis, histoplasmosis, and blastomycosis. During administration an individual may experience fever, chills, hypotension (low blood pressure), nausea, and shortness of breath. Most patients who receive amphotericin B experience some degree of toxicity to the kidney, but renal function usually improves after completion of therapy. Lipid-based formulations of amphotericin B are thought to have reduced toxicity while retaining antifungal action. Nystatin is more toxic and is not used systemically. It is not absorbed from the gastrointestinal tract and is only used orally or topically for the treatment of infections of the skin and mucous membranes caused by Candida albicans.
The azoles
The azole antifungal agents, which are further divided into the imidazoles and triazoles, according to the number of nitrogen molecules in their organic ring structure, exert their effects by binding to fungal membranes and blocking the synthesis of fungal lipids, especially ergosterol. The azoles have broad antifungal activity and are active against fungi that infect the skin and mucous membranes and those that cause deep tissue infections. Clotrimazole, econazole, miconazole, and tioconazole are given topically and are used for treating oral, skin, and vaginal infections. Introduction of the triazoles (fluconazole and itraconazole) provided an alternative to amphotericin B in the treatment of endemic mycoses. The triazoles are active against most of the organisms that cause systemic or deep-seated fungal infections, such as cryptococcosis, candidiasis, histoplasmosis, blastomycosis, and paracoccidiosis.
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The allyamines
The allylamines (terbinafine and naftifine) are synthetic antifungal agents that are effective in the topical and oral treatment of dermatophytes (fungi that infect the skin and other integumentary structures). Like the azoles, the allylamines act through inhibition of fungal ergosterol biosynthesis. Oral terbinafine is used in the oral treatment of nail infections by dermatophytes.
Other antifungal drugs
Griseofulvin is given orally for the treatment of several superficial fungal infections of the skin (e.g., ringworm, athlete’s foot) and diseases of the hair and nails. Griseofulvin binds to keratin, thus depositing high levels in the skin. Griseofulvin affects the fungus by binding to microtubules, structures responsible for forming mitotic spindles during cell division and for processing cell wall components needed for growth.
Flucytosine (5-FC) is unique in that it becomes active only when converted to 5-fluorouracil (5-FU) by an enzyme, cytosine deaminase, found in fungi but not present in human cells. Flucytosine inhibits RNA and DNA synthesis. 5-FC is used primarily in the treatment of systemic cryptococcal and Candida infections and chronomycosis. Because drug resistance may emerge against 5-FC, the agent often is used in combination with other antifungals, particularly amphotericin B.