Antifungal medication

An antifungal medication is a medication used to treat fungal infections such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription or purchased over-the-counter.

Adverse effects
Apart from side effects like liver damage or affecting estrogen levels, many anti-fungal medicines  can cause allergic reactions in people. For example, the azole group of drugs is known to have caused anaphylaxis.

There are also many drug interactions. Patients must read in detail the enclosed data sheet(s) of the medicine. For example, the azole antifungals such as ketoconazole or itraconazole can be both substrates and inhibitors of the P-glycoprotein, which (among other functions) excretes toxins and drugs into the intestines. Azole antifungals also are both substrates and inhibitors of the cytochrome P450 family CYP3A4, causing increased concentration when administering, for example, calcium channel blockers, immunosuppressants, chemotherapeutic drugs, benzodiazepines, tricyclic antidepressants, macrolides and SSRIs.

Polyene antifungals
A polyene is a molecule with multiple conjugated double bonds. A polyene antifungal is a macrocyclic polyene with a heavily hydroxylated region on the ring opposite the conjugated system. This makes polyene antifungals amphiphilic. The polyene antimycotics bind with sterols in the fungal cell membrane, principally ergosterol. This changes the transition temperature (Tg) of the cell membrane, thereby placing the membrane in a less fluid, more crystalline state. As a result, the cell's contents including monovalent ions (K+, Na+, H+, and Cl-), small organic molecules leak and this is regarded one of the primary ways cell dies. Animal cells contain cholesterol instead of ergosterol and so they are much less susceptible. However, at therapeutic doses, some amphotericin B may bind to animal membrane cholesterol, increasing the risk of human toxicity. Amphotericin B is nephrotoxic when given intravenously. As a polyene's hydrophobic chain is shortened, its sterol binding activity is increased. Therefore, further reduction of the hydrophobic chain may result in it binding to cholesterol, making it toxic to animals.
 * Amphotericin B
 * Candicidin
 * Filipin – 35 carbons, binds to cholesterol (toxic)
 * Hamycin
 * Natamycin – 33 carbons, binds well to ergosterol
 * Nystatin
 * Rimocidin

Imidazole, triazole, and thiazole antifungals
Azole antifungal drugs inhibit the enzyme lanosterol 14 α-demethylase; the enzyme necessary to convert lanosterol to ergosterol. Depletion of ergosterol in fungal membrane disrupts the structure and many functions of fungal membrane leading to inhibition of fungal growth.

Imidazoles



 * Bifonazole
 * Butoconazole
 * Clotrimazole
 * Econazole
 * Fenticonazole
 * Isoconazole
 * Ketoconazole
 * Miconazole
 * Omoconazole
 * Oxiconazole
 * Sertaconazole
 * Sulconazole
 * Tioconazole

Triazoles

 * Albaconazole
 * Fluconazole
 * Isavuconazole
 * Itraconazole
 * Posaconazole
 * Ravuconazole
 * Terconazole
 * Voriconazole

Thiazoles

 * Abafungin

Allylamines
Allylamines inhibit squalene epoxidase, another enzyme required for ergosterol synthesis:
 * Amorolfin
 * Butenafine
 * Naftifine
 * Terbinafine

Echinocandins
Echinocandins may be used for systemic fungal infections in immunocompromised patients, they inhibit the synthesis of glucan in the cell wall via the enzyme 1,3-β glucan synthase:


 * Anidulafungin
 * Caspofungin
 * Micafungin

Echinocandins are poorly absorbed when administered orally. When administered by injection they will reach most tissues and organs with concentrations sufficient to treat localized and systemic fungal infections.

Others

 * Benzoic acid – has antifugal properties but must be combined with a keratolytic agent such as in Whitfield's Ointment
 * Ciclopirox – (ciclopirox olamine) – a hydroxypyridone antifungal. Interferes with active membrane transport, cell membrane integrity, and fungal respiratory processes. Most useful against Tinea versicolour
 * Flucytosine or 5-fluorocytosine – an antimetabolite pyrimidine analog
 * Griseofulvin – binds to polymerized microtubules and inhibits fungal mitosis
 * Haloprogin – discontinued due to the emergence of more modern antifungals with fewer side effects
 * Polygodial – strong and fast-acting in-vitroantifungal activity against Candida albicans.
 * Tolnaftate – a thiocarbamate antifungal, which inhibits fungal squalene epoxidase (similar mechanism to allylamines like terbinafine)
 * Undecylenic acid – an unsaturated fatty acid derived from natural castor oil; fungistatic, anti-bacterial, anti-viral, and inhibits Candida morphogenesis.
 * Crystal violet – a triarylmethane dye. Crystal violet has antibacterial, antifungal, and anthelmintic properties and was formerly important as a topical antiseptic.

Alternatives
Research conducted in 1996 indicated that the following substances or essential oils had anti-fungal properties:


 * Allicin – created from crushing garlic
 * Citronella oil – obtained from the leaves and stems of different species of Cymbopogon (Lemon grass)
 * Coconut oil – medium chain triglycerides in the oil have antifungal activities
 * Iodine – Lugol's iodine
 * lemon myrtle
 * Neem Seed Oil
 * Olive leaf
 * Orange oil
 * palmarosa oil
 * patchouli
 * Selenium – in dietary supplements or natural food sources, particularly Brazil nuts
 * Tea tree oil – ISO 4730 ("Oil of Melaleuca, Terpinen-4-ol type")
 * Zinc – in dietary supplements or natural food sources, including pumpkin seeds and chickpeas

Horopito (Pseudowintera colorata) leaf contains the anti-fungal compound polygodial.

Israeli researchers at Tel Aviv University's Department of Plant Sciences published a study in 2009 indicating that carnivorous plants like the Venus flytrap contain compounds that may be useful in providing a new class of anti-fungal drugs for use in humans, for fungal infections that are resistant to current anti-fungal drugs.

Mechanism of action
Antifungals work by exploiting differences between mammalian and fungal cells to kill the fungal organism without dangerous effects on the host. Unlike bacteria, both fungi and humans are eukaryotes. Thus fungal and human cells are similar at the molecular level. This makes it more difficult to find or design drugs that target fungi without affecting human cells. As a consequence, many antifungal drugs cause side-effects. Some of these side-effects can be life-threatening if the drugs are not used properly.

Anti-dandruff shampoos


Antifungal agents (such as ketoconazole) are often found in anti-dandruff shampoos. The antifungal drugs inhibit the yeast Malassezia globosa which encourages seborrhoeic dermatitis and tinea versicolor.