An antifungal medication is a pharmaceutical fungicide used to treat mycoses 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.
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. (In ordinary circumstances membrane sterols increase the packing of the phospholipid bilayer making the plasma membrane more dense.) 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.1 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
- Filipin – 35 carbons, binds to cholesterol (toxic)
- Natamycin – 33 carbons, binds well to ergosterol
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.2
Allylamines inhibit squalene epoxidase, another enzyme required for ergosterol synthesis:
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.3
- Benzoic acid – has antifugal properties, but must be combined with a keratolytic agent such as in Whitfield's ointment4
- Ciclopirox – (ciclopirox olamine) – is a hydroxypyridone antifungal which interferes with active membrane transport, cell membrane integrity, and fungal respiratory processes. It is most useful against tinea versicolour. 5
- 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 6
- Polygodial 78 – 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, antibacterial, antiviral, and inhibits Candida morphogenesiscitation needed
- Crystal violet – a triarylmethane dye, it has antibacterial, antifungal, and anthelmintic properties and was formerly important as a topical antiseptic.9
Research conducted in 1996 indicated the following substances or essential oils had antifungal properties:10
- Oregano – the most powerful anti-fungal of the essential oils, and possess significant activity against Candida albicans. The minimum inhibitory concentration against C. albicans has been found to be <0.1μg per ml. In contrast, caprylic acid (a mixture of calcium and magnesium salts, a natural anti-fungal fatty acid), is 0.5μg.
- 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
- 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 antifungal compound polygodial.7
Researchers at Tel Aviv University's Department of Plant Sciences published a study in 2009 indicating carnivorous plants, such as the Venus flytrap, contain compounds that may be useful in providing a new class of antifungal drugs for use in humans, for fungal infections that are resistant to current drugs.111213
Apart from side effects like liver damage or affecting estrogen levels, many antifungal 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.14 Azole antifungals also are both substrates and inhibitors of the cytochrome P450 family CYP3A4,14 causing increased concentration when administering, for example, calcium channel blockers, immunosuppressants, chemotherapeutic drugs, benzodiazepines, tricyclic antidepressants, macrolides and SSRIs.
Antifungals work by exploiting differences between mammalian and fungal cells to kill the fungal organism with fewer adverse effects to the host. Unlike bacteria, both fungi and humans are eukaryotes. Thus, fungal and human cells are similar at the biological level. This makes it more difficult to discover 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.
Antifungal agents (such as ketoconazole) are often found in antidandruff shampoos. The antifungal drugs inhibit the yeast Malassezia globosa which encourages seborrhoeic dermatitis and tinea versicolor.
|Agent||Trade names||Medical applications|
|Ketoconazole15||Nizoral, Fungoral and Sebizole||Preliminary findings, research and studies including the completion of a small controlled clinical trial have produced data suggesting ketoconazole shampoo is effective as a hair loss treatment in men with androgenic alopecia. Larger controlled clinical studies are still needed to evaluate the ideal dosage, formulation, and to determine the routine of treatment for this condition, thus ketoconazole shampoo is not FDA-approved for this indication.citation needed|
|Ciclopirox olamine||Loprox||The cream and lotion form of this agent is used to treat fungal infections of the skin. The lacquer form is used as part of a treatment plan to treat fungal infections of the nails. The shampoo form is used to treat and prevent dandruff or to treat seborrhoeic dermatitis.|
|Piroctone olamine||Octopirox16 and Nivea Complete Control17||Piroctone olamine is sometimes used as an antifungal agent, and it often used in dandruff shampoos in lieu of zinc. Piroctone olamine is said to be less toxic than other antidandruff agents, often bypassing some of the normal FDA warnings, but still must be used with care, and only externally.|
|Zinc pyrithione18||Head & Shoulders, Johnson and Johnson ZP-11, Clinic All Clear, Pantene Pro V and Sikkai Powder||An antifungal and antibacterial agent first reported in the 1930s, zinc pyrithione is best known for its use in the treatment of dandruff and seborrhoeic dermatitis. It also has antibacterial properties and is effective against many pathogens from the Streptococcus and Staphylococcus genera. Its other medical applications include treatments of psoriasis, eczema, ringworm, fungus, athletes foot, dry skin, atopic dermatitis, tinea, and vitiligo.|
|Selenium sulfide||Selsun Blue, Head & Shoulders and Vichy Dercos Anti-Dandruff Shampoo||Selenium sulfide is available as a 1% and 2.5% lotion and shampoo. In some countries, the higher-strength preparations require a doctor's prescription. The shampoo is used to treat dandruff and seborrhea of the scalp, and the lotion is used to treat tinea versicolor, a fungal infection of the skin.|
|Tar19||Neutrogena T-Gel||Is effective as a therapeutic treatment to control scalp itching and flaking symptomatic of scalp psoriasis, eczema, seborrhoeic dermatitis and dandruff.|
|Tea tree oil20||Dr. Bronner's Castile Soap||It is used topically as an ingredient in creams, ointments, lotions, soaps, and shampoos. 21|
- [Baginski M, Czub B. Amphotericin B and its new derivatives. Current Drug Metabolism. 2009 Jun;10(5) : 459-69]
- > Sheehan D., Hitchcock C, Sibley C. Current and Emerging Azole Antifungal Agents
- Echinocandins for the treatment of systemic fungal infection | Canadian Antimicrobial Resistance Alliance (CARA)
- Wilson, Gisvold, Block, Beale (2004). Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry. Philadelphia, Pa.: Lippincott Williams & Wilkins. ISBN 0-7817-3481-9.
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- accessdate = 2007-02-17 "Haloprogin". DrugBank. University of Alberta. November 6, 2006.
- McCallion R F, Cole A L J, Walker J R L, Blunt J W, Monro M H G. (1982) Antibiotic Substances from New Zealand Plants, Planta Medica, vol 44, pp134-138
- Lee S H, Lee J R, Lunde C S, Kubo I. (1999). In Vitro Antifungal Susceptibilities of Candida albicans and other Fungal Pathogens to Polygodial, a Sesquiterpene Dialdehyde, Planta Medica, vol 65, pp205-208
- Docampo, R.; Moreno, S.N. (1990), "The metabolism and mode of action of gentian violet", Drug Metab. Rev. 22 (2–3): 161–178, doi:10.3109/03602539009041083, PMID 2272286
- Pattnaik S, Subramanyam VR, Kole C (1996). "Antibacterial and antifungal activity of ten essential oils in vitro". Microbios 86 (349): 237–46. PMID 8893526.
- Eilenberg, Haviva; Smadar Pnini-Cohen, Yocheved Rahamim, Edward Sionov, Esther Segal, Shmuel Carmeli and Aviah Zilberstein (December 2009). "Induced production of antifungal naphthoquinones in the pitchers of the carnivorous plant Nepenthes khasiana". Journal of Experimental Botany (Oxford University Press) 61 (3): 911–922. doi:10.1093/jxb/erp359. PMC 2814117. PMID 20018905. Archived from the original on 12 April 2010. Retrieved 2010-04-22.
- "Carnivorous plants may save people". Israel 21c Innovation News Service. April 11, 2010. Archived from the original on 27 April 2010. Retrieved 2010-04-13.
- "From carnivorous plants to the medicine cabinet". physorg.com. February 18, 2010. Retrieved 2010-04-13.
- doctorfungus > Antifungal Drug Interactions Content Director: Russell E. Lewis, Pharm.D. Retrieved on Jan 23, 2010
- McGrath J, Murphy GM (1991). "The control of seborrhoeic dermatitis and dandruff by antipityrosporal drugs". Drugs 41 (2): 178–84. doi:10.2165/00003495-199141020-00003. PMID 1709848.
- Dubini F, Bellotti MG, Frangi A, Monti D, Saccomani L (2005). "In vitro antimycotic activity and nail permeation models of a piroctone olamine (octopirox) containing transungual water soluble technology". Arzneimittel-Forschung 55 (8): 478–83. doi:10.1055/s-0031-1296892. PMID 16149717.
- Warner RR, Schwartz JR, Boissy Y, Dawson TL (2001). "Dandruff has an altered stratum corneum ultrastructure that is improved with zinc pyrithione shampoo". J. Am. Acad. Dermatol. 45 (6): 897–903. doi:10.1067/mjd.2001.117849. PMID 11712036.
- Piérard-Franchimont C, Piérard GE, Vroome V, Lin GC, Appa Y (2000). "Comparative anti-dandruff efficacy between a tar and a non-tar shampoo". Dermatology (Basel) 200 (2): 181–4. doi:10.1159/000018362. PMID 10773717.
- Prensner R (2003). "Does 5% tea tree oil shampoo reduce dandruff?". The Journal of family practice 52 (4): 285–6. PMID 12681088.
- "Tea tree oil". Medline Plus, a service of the U.S. National Library of Medicine from the National Institutes of Health. 27 July 2012.
- Antifungal Drugs – Detailed information on antifungals from the Fungal Guide written by Drs. R. Thomas and K. Barber