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Antifungal

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Not to be confused with Antifungal protein.

Antifungal
Drug class
Canesten (clotrimazole) antifungal cream
Synonymsantimycotic medication
Legal status
In Wikidata

An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis 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, but a few are available over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.[1]

Routes of administration

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Ocular

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Indicated when the fungal infection is located in the eye. There is currently only one ocular antifungal available. This is Natamycin. However, various other antifungal agents could be compounded in this formulation.[2]

Intrathecal

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Used occasionally when there's an infection of the central nervous system and other systemic options cannot reach the concentration required in that region for therapeutic benefit. Example(s): amphotericin B.[3]

Vaginal

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This may be used to treat some fungal infections of the vaginal region. An example of a condition they are sometimes used for is candida vulvovaginitis which is treated with intravaginal Clotrimazole[4]

Topical

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Main article: Topical antifungal drugs

This is sometimes indicated when there's a fungal infection on the skin. An example is tinea pedis; this is sometimes treated with topical terbinafine.[5]

Oral

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If the antifungal has good bioavailability, this is a common route to handle a fungal infection. An example is the use of ketoconazole to treat coccidioidomycosis.[6]

Intravenous

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Like the oral route, this will reach the bloodstream and distribute throughout the body. However, it is faster and a good option if the drug has poor bioavailability. An example of this is IV amphotericin B for the treatment of coccidioidomycosis.[6]

Classes

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The available classes of antifungal drugs are still limited but as of 2021 novel classes of antifungals are being developed and are undergoing various stages of clinical trials to assess performance.[7]

Polyenes

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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−) and small organic molecules leak, which is regarded as one of the primary ways a cell dies.[8] 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.[citation needed]

Azoles

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Azole antifungals inhibit the conversion of lanosterol to ergosterol by inhibiting lanosterol 14α-demethylase.[9] These compounds have a five-membered ring containing two or three nitrogen atoms.[10] The imidazole antifungals contain a 1,3-diazole (imidazole) ring (two nitrogen atoms), whereas the triazole antifungals have a ring with three nitrogen atoms.[11][10]

Imidazoles

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Triazoles

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Thiazoles

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Allylamines

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Allylamines[12] inhibit squalene epoxidase, another enzyme required for ergosterol synthesis. Examples include butenafine, naftifine, and terbinafine.[13][14][15]

Echinocandins

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Echinocandins inhibit the creation of glucan in the fungal cell wall by inhibiting 1,3-Beta-glucan synthase:

Echinocandins are administered intravenously, particularly for the treatment of resistant Candida species.[16][17]

Triterpenoids

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Others

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Side effects

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Incidents of liver injury or failure among modern antifungal medicines are very low to non-existent. However, some can cause allergic reactions in people.[33]

There are also many drug interactions. Patients must read in detail the enclosed data sheet(s) of any 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.[34] Azole antifungals are also both substrates and inhibitors of the cytochrome P450 family CYP3A4,[34] causing increased concentration when administering, for example, calcium channel blockers, immunosuppressants, chemotherapeutic drugs, benzodiazepines, tricyclic antidepressants, macrolides and SSRIs.[35]

Before oral antifungal therapies are used to treat nail disease, a confirmation of the fungal infection should be made.[36] Approximately half of suspected cases of fungal infection in nails have a non-fungal cause.[36] The side effects of oral treatment are significant and people without an infection should not take these drugs.[36]

Azoles are the group of antifungals which act on the cell membrane of fungi. They inhibit the enzyme 14-alpha-sterol demethylase, a microsomal CYP, which is required for the biosynthesis of ergosterol for the cytoplasmic membrane. This leads to the accumulation of 14-alpha-methylsterols resulting in impairment of function of certain membrane-bound enzymes and disruption of close packing of acyl chains of phospholipids, thus inhibiting growth of the fungi. Some azoles directly increase permeability of the fungal cell membrane.[37]

Resistance

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Antifungal resistance is a subset of antimicrobial resistance, that specifically applies to fungi that have become resistant to antifungals. Resistance to antifungals can arise naturally, for example by genetic mutation or through aneuploidy. Extended use of antifungals leads to the development of antifungal resistance through various mechanisms.[1]

Some fungi (e.g. Candida krusei and fluconazole) exhibit intrinsic resistance to certain antifungal drugs or classes, whereas some species develop antifungal resistance to external pressures. Antifungal resistance is a One Health concern, driven by multiple extrinsic factors, including extensive fungicidal use, overuse of clinical antifungals, environmental change and host factors.[1]

Like resistance to antibacterials, antifungal resistance can be driven by antifungal use in agriculture. Currently there is no regulation on the use of similar antifungal classes in agriculture and the clinic.[1][38][39]

The emergence of Candida auris as a potential human pathogen that sometimes exhibits multi-class antifungal drug resistance is concerning and has been associated with several outbreaks globally. The WHO has released a priority fungal pathogen list, including pathogens with antifungal resistance.[40]

References

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  1. ^ a b c d Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell EM, Bowyer P, et al. (29 March 2022). "Tackling the emerging threat of antifungal resistance to human health". Nature Reviews Microbiology. 20 (9): 557–571. doi:10.1038/s41579-022-00720-1. ISSN 1740-1526. PMC 8962932. PMID 35352028.
  2. ^ Mcgee K (2019). "Chapter 68 - Ocular pharmacology". Naplex review guide (3rd ed.). United states: McGraw Hill Medical. ISBN 978-1-260-13592-3.
  3. ^ Nau R, Blei C, Eiffert H (17 June 2020). "Intrathecal Antibacterial and Antifungal Therapies". Clinical Microbiology Reviews. 33 (3): e00190–19. doi:10.1128/CMR.00190-19. ISSN 0893-8512. PMC 7194852. PMID 32349999.
  4. ^ Sobel J. "Candida vulvovaginitis: Treatment". UpToDate. Archived from the original on 15 May 2023. Retrieved 21 May 2023.
  5. ^ Ward H, Parkes N, Smith C, Kluzek S, Pearson R (April 2022). "Consensus for the Treatment of Tinea Pedis: A Systematic Review of Randomised Controlled Trials". Journal of Fungi. 8 (4): 351. doi:10.3390/jof8040351. ISSN 2309-608X. PMC 9027577. PMID 35448582.
  6. ^ a b Carver P. Pharmacotherapy: a pathophysiological approach (11th ed.).
  7. ^ Hoenigl M, Sprute R, Egger M, Arastehfar A, Cornely OA, Krause R, et al. (9 October 2021). "The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin". Drugs. 81 (15): 1703–1729. doi:10.1007/s40265-021-01611-0. ISSN 0012-6667. PMC 8501344. PMID 34626339.
  8. ^ Baginski M, Czub J (June 2009). "Amphotericin B and its new derivatives - mode of action". Current Drug Metabolism. 10 (5): 459–69. doi:10.2174/138920009788898019. PMID 19689243.
  9. ^ Sheehan DJ, Hitchcock CA, Sibley CM (January 1999). "Current and emerging azole antifungal agents". Clinical Microbiology Reviews. 12 (1): 40–79. doi:10.1128/cmr.12.1.40. PMC 88906. PMID 9880474.
  10. ^ a b Dixon DM, Walsh TJ (1996), Baron S (ed.), "Antifungal Agents", Medical Microbiology (4th ed.), Galveston (TX): University of Texas Medical Branch at Galveston, ISBN 978-0-9631172-1-2, PMID 21413319, archived from the original on 12 July 2023, retrieved 2 December 2022
  11. ^ PubChem. "Imidazole". pubchem.ncbi.nlm.nih.gov. Archived from the original on 10 May 2023. Retrieved 2 December 2022.
  12. ^ Ameen M (March 2010). "Epidemiology of superficial fungal infections". Clinics in Dermatology. 28 (2). Elsevier Inc.: 197–201. doi:10.1016/j.clindermatol.2009.12.005. PMID 20347663.
  13. ^ "As Fungal Infections Expand, so Does Market | GEN Magazine Articles | GEN". GEN. 15 February 2012. Archived from the original on 6 September 2015. Retrieved 17 October 2015.
  14. ^ "Research and Markets: Global Antifungal Therapeutics (Polyenes, Azoles, Echinocandins, Allylamines) Market:Trends and Opportunities (2014-2019) | Business Wire". www.businesswire.com. 28 August 2014. Archived from the original on 4 March 2016. Retrieved 17 October 2015.
  15. ^ "Tinea Cruris". nurse-practitioners-and-physician-assistants.advanceweb.com. Archived from the original on 1 September 2017. Retrieved 17 October 2015.
  16. ^ "Echinocandins for the treatment of systemic fungal infection | Canadian Antimicrobial Resistance Alliance (CARA)" (PDF). Archived (PDF) from the original on 9 October 2021. Retrieved 9 May 2015.
  17. ^ Cappelletty D, Eiselstein-McKitrick K (March 2007). "The echinocandins". Pharmacotherapy. 27 (3): 369–88. doi:10.1592/phco.27.3.369. PMID 17316149. S2CID 32016049.
  18. ^ Polak A (1983). "Antifungal activity in vitro of Ro 14-4767/002, a phenylpropyl-morpholine". Medical Mycology. 21 (3): 205–213. doi:10.1080/00362178385380321. ISSN 1369-3786. PMID 6635894.
  19. ^ Sutton CL, Taylor ZE, Farone MB, Handy ST (February 2017). "Antifungal activity of substituted aurones". Bioorganic & Medicinal Chemistry Letters. 27 (4): 901–903. doi:10.1016/j.bmcl.2017.01.012. PMID 28094180.
  20. ^ Wilson G, Block B (2004). Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry. Philadelphia, Pa.: Lippincott Williams & Wilkins. ISBN 0-7817-3481-9. Archived from the original on 14 January 2023. Retrieved 8 November 2020.
  21. ^ Long SF. "Anti-Fungals". Southwestern Oklahoma State University. Archived from the original on 17 June 2008.
  22. ^ Borkow G (August 2014). "Using Copper to Improve the Well-Being of the Skin". Current Chemical Biology. 8 (2): 89–102. doi:10.2174/2212796809666150227223857. PMC 4556990. PMID 26361585.
  23. ^ Docampo R, Moreno SN (1990). "The metabolism and mode of action of gentian violet". Drug Metabolism Reviews. 22 (2–3): 161–78. doi:10.3109/03602539009041083. PMID 2272286.
  24. ^ Leikin JB, Paloucek FP, eds. (10 August 2007). Poisoning and Toxicology Handbook. CRC Press. doi:10.3109/9781420044805. ISBN 9780429195648.
  25. ^ Vermes A, Guchelaar HJ, Dankert J (August 2000). "Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions". The Journal of Antimicrobial Chemotherapy. 46 (2): 171–9. doi:10.1093/jac/46.2.171. PMID 10933638.
  26. ^ Olson JM, Troxell T (2021). "Griseofulvin". StatPearls. StatPearls Publishing. PMID 30726008. Retrieved 22 June 2021.
  27. ^ "Haloprogin". DrugBank. University of Alberta. 6 November 2006. Archived from the original on 1 January 2007. Retrieved 17 February 2007.
  28. ^ Brilhante RS, Caetano EP, Lima RA, Castelo Branco DS, Serpa R, Oliveira JS, et al. (October 2015). "In vitro antifungal activity of miltefosine and levamisole: their impact on ergosterol biosynthesis and cell permeability of dimorphic fungi". Journal of Applied Microbiology. 119 (4): 962–9. doi:10.1111/jam.12891. PMID 26178247. S2CID 206011501.
  29. ^ Oliver JD, Sibley GE, Beckmann N, Dobb KS, Slater MJ, McEntee L, et al. (November 2016). "F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase". Proceedings of the National Academy of Sciences of the United States of America. 113 (45): 12809–12814. Bibcode:2016PNAS..11312809O. doi:10.1073/pnas.1608304113. PMC 5111691. PMID 27791100.
  30. ^ Hope WW, McEntee L, Livermore J, Whalley S, Johnson A, Farrington N, et al. (August 2017). "Aspergillus fumigatus: New Opportunities for Treatment of Multidrug-Resistant Fungal Disease". mBio. 8 (4): e01157-17. doi:10.1128/mBio.01157-17. PMC 5565967. PMID 28830945.
  31. ^ "Systemic Therapy". Rook's Textbook of Dermatology. Vol. 4 (8th ed.). 2010. p. 74.48.
  32. ^ Gendimenico GJ (2007). "Dermatotherapeutic Agents". Ullmann's Encyclopedia of Industrial Chemistry (7th ed.). doi:10.1002/14356007.a08_301.pub2. ISBN 978-3527306732.
  33. ^ Kyriakidis I, Tragiannidis A, Munchen S, Groll AH (February 2017). "Clinical hepatotoxicity associated with antifungal agents". Expert Opinion on Drug Safety. 16 (2): 149–165. doi:10.1080/14740338.2017.1270264. PMID 27927037. S2CID 43198078.
  34. ^ a b Lewis RE. "Antifungal Drug Interactions". doctorfungus. Archived from the original on 19 June 2010. Retrieved 23 January 2010.
  35. ^ Research Cf (24 August 2022). "Drug Development and Drug Interactions | Table of Substrates, Inhibitors and Inducers". FDA. Archived from the original on 4 November 2020. Retrieved 17 April 2023.
  36. ^ a b c American Academy of Dermatology (February 2013). "Five Things Physicians and Patients Should Question". Choosing Wisely: an initiative of the ABIM Foundation. American Academy of Dermatology. Archived from the original on 1 December 2013. Retrieved 5 December 2013., which cites
    • Roberts DT, Taylor WD, Boyle J (March 2003). "Guidelines for treatment of onychomycosis". The British Journal of Dermatology. 148 (3): 402–10. doi:10.1046/j.1365-2133.2003.05242.x. PMID 12653730. S2CID 33750748.
    • Mehregan DR, Gee SL (December 1999). "The cost effectiveness of testing for onychomycosis versus empiric treatment of onychodystrophies with oral antifungal agents". Cutis. 64 (6): 407–10. PMID 10626104.
  37. ^ Herrick EJ, Patel P, Hashmi MF (2024), "Antifungal Ergosterol Synthesis Inhibitors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 31869062, retrieved 26 August 2024
  38. ^ Manyi-Loh C, Mamphweli S, Meyer E, Okoh A (30 March 2018). "Antibiotic Use in Agriculture and Its Consequential Resistance in Environmental Sources: Potential Public Health Implications". Molecules. 23 (4): 795. doi:10.3390/molecules23040795. ISSN 1420-3049. PMC 6017557. PMID 29601469.
  39. ^ Verweij PE, Arendrup MC, Alastruey-Izquierdo A, Gold JA, Lockhart SR, Chiller T, et al. (20 October 2022). "Dual use of antifungals in medicine and agriculture: How do we help prevent resistance developing in human pathogens?". Drug Resistance Updates. 65: 100885. doi:10.1016/j.drup.2022.100885. PMC 10693676. PMID 36283187. S2CID 253052170.
  40. ^ Organization WH (25 October 2022). WHO fungal priority pathogens list to guide research, development and public health action (PDF). World Health Organization. ISBN 978-92-4-006024-1. Archived from the original on 26 October 2022. Retrieved 27 October 2022.
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  • Antifungal Drugs – Detailed information on antifungals from the Fungal Guide written by R. Thomas and K. Barber
  • "Clotrimazole". Clotrimazole (Canesten). Bayer Philippines.
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