関: antifungal、antifungal agent、antifungal drug、antifungals、antimycotic、antimycotic agent

WordNet

any agent that destroys or prevents the growth of fungi (同)antifungal_agent, fungicide, antimycotic, antimycotic_agent

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/04/25 20:57:31」(JST)

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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.

1 Adverse effects
2 Classes
- 2.1 Polyene antifungals
- 2.2 Imidazole, triazole, and thiazole antifungals
  - 2.2.1 Imidazoles
  - 2.2.2 Triazoles
  - 2.2.3 Thiazoles
- 2.3 Allylamines
- 2.4 Echinocandins
- 2.5 Others
- 2.6 Alternatives
3 Mechanism of action
4 Antidandruff shampoos
5 See also
6 References
7 External links

Adverse effects

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.^[1] Azole antifungals also are both substrates and inhibitors of the cytochrome P450 family CYP3A4,^[1] causing increased concentration when administering, for example, calcium channel blockers, immunosuppressants, chemotherapeutic drugs, benzodiazepines, tricyclic antidepressants, macrolides and SSRIs.

Classes

Polyene antifungals

Main article: Polyene antimycotic

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.^[2] 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.^[3]

Imidazoles

Canesten (clotrimazole) antifungal cream

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.^[4]

Others

Benzoic acid – has antifugal properties, but must be combined with a keratolytic agent such as in Whitfield's ointment^[5]
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. ^[6]
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 ^[7]
Polygodial ^[8]^[9] – 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 morphogenesis^{[citation needed]}
Crystal violet – a triarylmethane dye, it has antibacterial, antifungal, and anthelmintic properties and was formerly important as a topical antiseptic.^[10]

Alternatives

Research conducted in 1996 indicated the following substances or essential oils had antifungal properties:^[11]

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 <0.1ug per ml. In contrast, Caprylic Acid (a mixture of calcium and magnesium salts, a natural anti-fungal fatty acid), is 0.5ug.
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 antifungal compound polygodial.^[8]
Turnip
Chives
Radish

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.^[12]^[13]^[14]

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.

Antidandruff shampoos

Nizoral (ketoconazole) 2% shampoo

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
Ketoconazole^[15]	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.^[16]
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	Octopirox^[17] and Nivea Complete Control^[18]	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 pyrithione^[19]	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.
Tar^[20]	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 oil^[21]	Dr. Bronner's Castile Soap	It is used topically as an ingredient in creams, ointments, lotions, soaps, and shampoos. In addition to antifungal properties, tea tree oil has antiseptic, antibacterial, and antiviral actions. It is also effective against mites (such as scabies), and lice (such as head lice).

References

^ ^a ^b doctorfungus > Antifungal Drug Interactions Content Director: Russell E. Lewis, Pharm.D. Retrieved on Jan 23, 2010
^ [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.
^ "antifung". Archived from the original on 17 June 2008. Retrieved 2008-07-09.
^ accessdate = 2007-02-17 "Haloprogin". DrugBank. University of Alberta. November 6, 2006.
^ ^a ^b 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.
^ 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.
^ Ketoconazole Shampoo: Effect of Long-Term Use in Androgenic Alopecia
^ 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. PMID 16149717.
^ NIVEA
^ 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.

External links

Antifungal Drugs – Detailed information on antifungals from the Fungal Guide written by Drs. R. Thomas and K. Barber

UpToDate Contents

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1. カンジダ性外陰膣炎 candida vulvovaginitis
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English Journal

Selective determination of antimycotic drugs in environmental water samples by mixed-mode solid-phase extraction and liquid chromatography quadrupole time-of-flight mass spectrometry.

Casado J1, Rodríguez I2, Ramil M1, Cela R1.Author information 1Departamento de Química Analítica, Nutrición y Bromatología, Instituto de Investigación y Análisis Alimentario (IIAA), Universidad de Santiago de Compostela, Santiago de Compostela 15782, Spain.2Departamento de Química Analítica, Nutrición y Bromatología, Instituto de Investigación y Análisis Alimentario (IIAA), Universidad de Santiago de Compostela, Santiago de Compostela 15782, Spain. Electronic address: isaac.rodriguez@usc.es.AbstractThe suitability of mixed-mode (reversed-phase and cationic exchange) solid-phase extraction (SPE) for the selective concentration of basic antimycotic drugs (belonging to triazole, imidazole and allylamine chemical classes) in environmental water samples has been demonstrated for first time. The use of a sequential elution protocol, allowing the removal of neutral and acidic interferences before analytes extraction, led to a significant reduction of matrix effects, during electrospray ionization (ESI), in comparison with results reported for reversed-phase sorbents. In combination with liquid chromatography (LC) quadrupole time-of-flight (QTOF) mass spectrometry (MS) determination, the developed method attained limits of quantification (LOQs) comprised between 2 and 15ngL(-1). After internal surrogate correction, accurate results (in most cases, recoveries ranged between 75 and 117%) were obtained for spiked aliquots of raw and treated wastewater, as well as river water, using quantification against calibration standard solutions in methanol (2% in NH3). Accurate, scan MS/MS spectra allowed the unambiguous identification of target compounds in environmental samples; furthermore, the information contained in MS spectra was used for the screening of additional antimycotics in the processed samples. Fluconazole, ketoconazole, miconazole and clotrimazole were measured in wastewater samples at concentrations up to 200ngL(-1). The screening capabilities of the LC-QTOF-MS system permitted to identify the systematic presence of climbazole in the processed samples.
Journal of chromatography. A.J Chromatogr A.2014 Apr 25;1339:42-9. doi: 10.1016/j.chroma.2014.02.087. Epub 2014 Mar 12.
The suitability of mixed-mode (reversed-phase and cationic exchange) solid-phase extraction (SPE) for the selective concentration of basic antimycotic drugs (belonging to triazole, imidazole and allylamine chemical classes) in environmental water samples has been demonstrated for first time. The use
PMID 24657048

The in vitro effects of new D186 dendrimer on virulence factors of Candida albicans.

Staniszewska M1, Bondaryk M1, Zielińska P2, Urbańczyk-Lipkowska Z2.Author information 1National Institute of Public Health-National Institute of Hygiene, Warsaw, Poland.2Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland.AbstractThe emergence of drug-resistant Candida albicans strains necessitates identifying new antimycotics along with studying their modes of action. The influence of a new rationally designed dendrimer D186 containing N,N-dioctyl tail and four tryptophane residues on inhibition of planktonic cells, aspartic protease SAP5 expression and adhesion to epithelial cells was investigated. In vitro anti-Candida activities were determined against wild types, Δsap mutants and morphogenesis mutants: Δefg1, Δcph1 and Δcph1/Δefg1. MICs of D186 determined with M27-A3 protocol were in the range 2-16 μg ml-1. Adherence assay of C. albicans to Caco-2 was performed in 24-well plate. Group I (MIC=8 μg ml-1, inhibition=82.05-100%) was the most frequent followed by Group II (MIC=4 μg ml-1, inhibition=99.64-100%) and Group III (MIC=2 μg ml-1, inhibition=96.47-96.98%). SAP5 expression was analyzed using RT-PCR; relative quantification was normalized against ACT1 in cells after 18-h growth on Caco-2 cell line. D186 exhibited more potent inhibition activity (statistically significant P0.05) against Δsap10 and Δsap9/Δsap10 (MIC=2 μg ml-1) than the remaining strains tested. Pretreating cells with D186 significantly inhibited adhesion of all Candida strains compared with their non-treated counterparts (P0.05). D186 affected SAP5 expression of all strains suggesting that this gene is controlled by environmental conditions. A hypothesis can be formulated that the hydrophobicity of D186 and presence of four Trp residues favors its accumulation in the membrane causing membrane disruption, especially facilitated in mutants perturbed in the cell wall compositions. The D186 mode of action was attributed to reduced virulence in terms of adhesiveness and pathogenic potential related to SAP5 expression and morphogenesis.The Journal of Antibiotics advance online publication, 2 April 2014; doi:10.1038/ja.2014.25.
The Journal of antibiotics.J Antibiot (Tokyo).2014 Apr 2. doi: 10.1038/ja.2014.25. [Epub ahead of print]
The emergence of drug-resistant Candida albicans strains necessitates identifying new antimycotics along with studying their modes of action. The influence of a new rationally designed dendrimer D186 containing N,N-dioctyl tail and four tryptophane residues on inhibition of planktonic cells, asparti
PMID 24690909

Synergy against fungal pathogens: working together is better than working alone.

Musiol R, Mrozek-Wilczkiewicz A, Polanski J1.Author information 1Institute of Chemistry, University of Silesia, Szkolna 9, 40-007 Katowice, Poland. robert.musiol@us.edu.pl.AbstractOpportunistic fungi are the most important pathogens in modern world. They are responsible for severe infections in majority of immunocompromised patients. These microorganisms are commonly present in our environment which is natural reservoir of new, resistant species. For this reason mycoses are mainly chronic or long-lasting diseases. Our arsenal of antifungal drugs is growing but still insufficient for emerging resistant pathogens. An alternative for novel chemical entity drugs is the multidrug approach. This exploiting the drugs being currently on market applying simultaneously for better efficacy or to eradicate resistance. Synergy is the term that describes the phenomenon of increased potency of two or more drugs administered in combination. In the last decades it gains more interest and numbers of synergy claimed reports is growing exponentially. However these have rather low impact on clinical trials or practical use of antimycotics. In present review we wish to discuss current status of synergy between antifungal drugs. Both theoretical point of view and practical applicability in clinical terms are covered. There are serious differences between the assumptions, methods and interpretations of the results and sometimes even obvious mistakes in the procedure that was applied or in the outcomes discussed. On the other hands the specificity of fungal infections introduce dozens of factors affecting the observed results. Shift form in vitro studies to clinical trials reveals further difficulties. Hopefully multi-drug approach seems to be effective even if no strong synergy is displayed.
Current medicinal chemistry.Curr Med Chem.2014 Mar;21(7):870-93.
Opportunistic fungi are the most important pathogens in modern world. They are responsible for severe infections in majority of immunocompromised patients. These microorganisms are commonly present in our environment which is natural reservoir of new, resistant species. For this reason mycoses are m
PMID 24350847

Japanese Journal

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Anzawa Kazushi,Mochizuki Takashi,Nishibu Akiko [他]
Japanese Journal of Infectious Diseases 64(6), 458-462, 2011-11
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医原性接触皮膚炎の3例

清原英司,片山一朗
Journal of environmental dermatology and cutaneous allergology = / the Japanese Society for Dermatoallergology and Contact Dermatitis 5(4), 395-399, 2011-07-31
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