View source for Antifungal

{{Short description|Pharmaceutical fungicide or fungistatic used to treat and prevent mycosis}}
{{Distinguish|Antifungal protein}}
{{Use dmy dates|date=March 2023}}
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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 [[Cryptococcus (fungus)|cryptococcal]] [[meningitis]], and others. Such drugs are usually obtained by a doctor's [[Prescription drug|prescription]], but a few are available [[Over-the-counter drugs|over the counter]] (OTC). The evolution of [[Antimicrobial resistance|antifungal resistance]] is a growing threat to health globally.<ref name=":112">{{cite journal |last1=Fisher |first1=Matthew C. |last2=Alastruey-Izquierdo |first2=Ana |last3=Berman |first3=Judith |last4=Bicanic |first4=Tihana |last5=Bignell |first5=Elaine M. |last6=Bowyer |first6=Paul |last7=Bromley |first7=Michael |last8=Brüggemann |first8=Roger |last9=Garber |first9=Gary |last10=Cornely |first10=Oliver A. |last11=Gurr |first11=Sarah. J. |last12=Harrison |first12=Thomas S. |last13=Kuijper |first13=Ed |last14=Rhodes |first14=Johanna |last15=Sheppard |first15=Donald C. |date=29 March 2022 |title=Tackling the emerging threat of antifungal resistance to human health |journal=Nature Reviews Microbiology |language=en |volume=20 |issue=9 |pages=557–571 |doi=10.1038/s41579-022-00720-1 |pmid=35352028 |pmc=8962932 |issn=1740-1526}}</ref>

== Routes of administration ==

=== Ocular ===
Indicated when the fungal infection is located in the eye. There is currently only one ocular antifungal available: [[natamycin]]. However, various other antifungal agents could be compounded in this formulation.<ref>{{cite book |last=Mcgee |first=Karen |title=Naplex review guide |publisher=McGraw Hill Medical |year=2019 |isbn=978-1-260-13592-3 |edition=3rd |location=United states |pages= |chapter=Chapter 68 - Ocular pharmacology}}</ref>

=== Intrathecal ===
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]].<ref name=":03">{{cite journal |last1=Nau |first1=Roland |last2=Blei |first2=Claudia |last3=Eiffert |first3=Helmut |date=2020-06-17 |title=Intrathecal Antibacterial and Antifungal Therapies |journal=Clinical Microbiology Reviews |language=en |volume=33 |issue=3 |pages=e00190–19 |doi=10.1128/CMR.00190-19 |issn=0893-8512 |pmc=7194852 |pmid=32349999}}</ref>

=== Vaginal ===
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]].<ref>{{cite web |last=Sobel |first=Jack |title=Candida vulvovaginitis: Treatment |url=https://www.uptodate.com/login |website=UpToDate |access-date=21 May 2023 |archive-date=15 May 2023 |archive-url=https://web.archive.org/web/20230515184141/https://www.uptodate.com/login |url-status=live }}</ref>

=== Topical ===
{{Main articles|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]].<ref>{{cite journal |last1=Ward |first1=Harry |last2=Parkes |first2=Nicholas |last3=Smith |first3=Carolyn |last4=Kluzek |first4=Stefan |last5=Pearson |first5=Richard |date=April 2022 |title=Consensus for the Treatment of Tinea Pedis: A Systematic Review of Randomised Controlled Trials |journal=Journal of Fungi |language=en |volume=8 |issue=4 |page=351 |doi=10.3390/jof8040351 |issn=2309-608X |pmc=9027577 |pmid=35448582 |doi-access=free }}</ref>

=== Oral ===
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]].<ref name=":13">{{cite book |last=Carver |first=Peggy |title=Pharmacotherapy: a pathophysiological approach |edition=11th}}</ref>

=== Intravenous ===
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.<ref name=":13" />

==Classes==
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.<ref>{{cite journal |last1=Hoenigl |first1=Martin |last2=Sprute |first2=Rosanne |last3=Egger |first3=Matthias |last4=Arastehfar |first4=Amir |last5=Cornely |first5=Oliver A. |last6=Krause |first6=Robert |last7=Lass-Flörl |first7=Cornelia |last8=Prattes |first8=Juergen |last9=Spec |first9=Andrej |last10=Thompson |first10=George R. |last11=Wiederhold |first11=Nathan |last12=Jenks |first12=Jeffrey D. |date=9 October 2021 |title=The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin |journal=Drugs |language=en |volume=81 |issue=15 |pages=1703–1729 |doi=10.1007/s40265-021-01611-0 |issn=0012-6667 |pmc=8501344 |pmid=34626339}}</ref>

===Polyenes===
{{Main|Polyene antimycotic}}

A [[polyene]] is a molecule with multiple [[Conjugated system|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 antimycotic]]s bind with [[sterol]]s 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<sup>+</sup>, Na<sup>+</sup>, H<sup>+</sup>, and Cl<sup>−</sup>) and small organic molecules leak, which is regarded as one of the primary ways a cell dies.<ref name=baginski>{{cite journal | vauthors = Baginski M, Czub J | title = Amphotericin B and its new derivatives - mode of action | journal = Current Drug Metabolism | volume = 10 | issue = 5 | pages = 459–69 | date = June 2009 | pmid = 19689243 | doi = 10.2174/138920009788898019 }}</ref> 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|date=July 2022}}
* [[Amphotericin B]]
* [[Candicidin]]
* [[Filipin]] – 35 carbons, binds to cholesterol (toxic)
* [[Hamycin]]
* [[Natamycin]] – 33 carbons, binds well to ergosterol
* [[Nystatin]]
* [[Rimocidin]]

===Azoles===
[[Azole]] antifungals inhibit the conversion of [[lanosterol]] to [[ergosterol]] by inhibiting [[lanosterol 14α-demethylase]].<ref name=sheehan>{{cite journal | vauthors = Sheehan DJ, Hitchcock CA, Sibley CM | title = Current and emerging azole antifungal agents | journal = Clinical Microbiology Reviews | volume = 12 | issue = 1 | pages = 40–79 | date = January 1999 | pmid = 9880474 | pmc = 88906 | doi=10.1128/cmr.12.1.40}}</ref> These compounds have a five-membered ring containing two or three nitrogen atoms.<ref name=":0">{{Citation |last1=Dixon |first1=Dennis M. |title=Antifungal Agents |date=1996 |url=https://www.ncbi.nlm.nih.gov/books/NBK8263/ |work=Medical Microbiology |editor-last=Baron |editor-first=Samuel |access-date=2022-12-02 |edition=4th |place=Galveston (TX) |publisher=University of Texas Medical Branch at Galveston |isbn=978-0-9631172-1-2 |pmid=21413319 |last2=Walsh |first2=Thomas J. |archive-date=12 July 2023 |archive-url=https://web.archive.org/web/20230712182914/https://www.ncbi.nlm.nih.gov/books/NBK8263/ |url-status=live }}</ref> The imidazole antifungals contain a 1,3-diazole ([[imidazole]]) ring (two nitrogen atoms), whereas the triazole antifungals have a ring with three nitrogen atoms.<ref>{{cite web |last=PubChem |title=Imidazole |url=https://pubchem.ncbi.nlm.nih.gov/compound/795 |access-date=2022-12-02 |website=pubchem.ncbi.nlm.nih.gov |language=en |archive-date=10 May 2023 |archive-url=https://web.archive.org/web/20230510184350/https://pubchem.ncbi.nlm.nih.gov/compound/795 |url-status=live }}</ref><ref name=":0" />

====Imidazoles====
{{Div col|colwidth=18vw|gap=2vw}}
* [[Bifonazole]]
* [[Butoconazole]]
* [[Clotrimazole]]
* [[Econazole]]
* [[Fenticonazole]]
* [[Isoconazole]]
* [[Ketoconazole]]
* [[Luliconazole]]
* [[Miconazole]]
* [[Omoconazole]]
* [[Oxiconazole]]
* [[Sertaconazole]]
* [[Sulconazole]]
* [[Tioconazole]]
{{Div col end}}
====Triazoles====
{{Div col|colwidth=18vw|gap=2vw}}
* [[Albaconazole]]
*[[Cyproconazole]]
* [[Efinaconazole]]
* [[Epoxiconazole]]
* [[Fluconazole]]
* [[Isavuconazole]]
* [[Itraconazole]]
* [[Posaconazole]]
* [[Propiconazole]]
* [[Ravuconazole]]
* [[Terconazole]]
* [[Voriconazole]]
{{Div col end}}
====Thiazoles====
{{Div col|colwidth=18vw|gap=2vw}}
* [[Abafungin]]
{{Div col end}}

===Allylamines===
[[Allylamine]]s<ref>{{cite journal | vauthors = Ameen M | title = Epidemiology of superficial fungal infections | journal = Clinics in Dermatology | volume = 28 | issue = 2 | pages = 197–201 | date = March 2010 | pmid = 20347663 | doi = 10.1016/j.clindermatol.2009.12.005 | publisher = Elsevier Inc. }}</ref> inhibit [[squalene epoxidase]], another enzyme required for [[ergosterol]] synthesis. Examples include [[butenafine]], [[naftifine]], and [[terbinafine]].<ref>{{cite web|title = As Fungal Infections Expand, so Does Market {{!}} GEN Magazine Articles {{!}} GEN|url = http://www.genengnews.com/gen-articles/as-fungal-infections-expand-so-does-market/4003/|website = GEN|date = 15 February 2012|access-date = 17 October 2015|archive-date = 6 September 2015|archive-url = https://web.archive.org/web/20150906133147/http://www.genengnews.com/gen-articles/as-fungal-infections-expand-so-does-market/4003/|url-status = live}}</ref><ref>{{cite web|title = Research and Markets: Global Antifungal Therapeutics (Polyenes, Azoles, Echinocandins, Allylamines) Market:Trends and Opportunities (2014-2019) {{!}} Business Wire|url = http://www.businesswire.com/news/home/20140828005518/en/Research-Markets-Global-Antifungal-Therapeutics-Polyenes-Azoles|website = www.businesswire.com|date = 28 August 2014|access-date = 17 October 2015|archive-date = 4 March 2016|archive-url = https://web.archive.org/web/20160304115226/http://www.businesswire.com/news/home/20140828005518/en/Research-Markets-Global-Antifungal-Therapeutics-Polyenes-Azoles|url-status = live}}</ref><ref>{{cite web|title = Tinea Cruris|url = http://nurse-practitioners-and-physician-assistants.advanceweb.com/Web-Extras/NADNP/Tinea-Cruris.aspx|website = nurse-practitioners-and-physician-assistants.advanceweb.com|access-date = 17 October 2015|archive-url = https://web.archive.org/web/20170901233832/http://nurse-practitioners-and-physician-assistants.advanceweb.com/Web-Extras/NADNP/Tinea-Cruris.aspx|archive-date = 1 September 2017}}</ref>

===Echinocandins===
[[Echinocandin]]s inhibit the creation of [[glucan]] in the fungal [[cell wall]] by [[Enzyme inhibitor|inhibiting]] [[1,3-Beta-glucan synthase]]:
* [[Anidulafungin]]
* [[Caspofungin]]
* [[Micafungin]]

Echinocandins are administered intravenously, particularly for the treatment of resistant ''[[Candida (fungus)|Candida]]'' species.<ref>{{cite web|url=http://www.can-r.com/mediaResources/Echinocandins.pdf|title=Echinocandins for the treatment of systemic fungal infection &#124; Canadian Antimicrobial Resistance Alliance (CARA)|access-date=9 May 2015|archive-date=9 October 2021|archive-url=https://web.archive.org/web/20211009144842/http://www.can-r.com/mediaResources/Echinocandins.pdf|url-status=live}}</ref><ref>{{cite journal | vauthors = Cappelletty D, Eiselstein-McKitrick K | title = The echinocandins | journal = Pharmacotherapy | volume = 27 | issue = 3 | pages = 369–88 | date = March 2007 | pmid = 17316149 | doi = 10.1592/phco.27.3.369 | s2cid = 32016049 }}</ref>

===Triterpenoids===
* [[Ibrexafungerp]]

===Others===
* [[Acrisorcin]]
* [[Amorolfine]] – a morpholine derivative used topically in dermatophytosis<ref>{{cite journal|last=Polak|first=Annemarie|date=1983|title=Antifungal activity in vitro of Ro 14-4767/002, a phenylpropyl-morpholine|journal=Medical Mycology|volume=21|issue=3|pages=205–213|doi=10.1080/00362178385380321|pmid=6635894|issn=1369-3786}}</ref>
* [[Aurone]]s – possess antifungal properties<ref>{{cite journal | vauthors = Sutton CL, Taylor ZE, Farone MB, Handy ST | title = Antifungal activity of substituted aurones | journal = Bioorganic & Medicinal Chemistry Letters | volume = 27 | issue = 4 | pages = 901–903 | date = February 2017 | pmid = 28094180 | doi = 10.1016/j.bmcl.2017.01.012 }}</ref>
* [[Benzoic acid]] – has antifungal properties, such as in [[Whitfield's ointment]], [[Friar's Balsam]], and [[Balsam of Peru]]<ref>{{cite book|last1=Wilson|first1=Gisvold|last2=Block|first2=Beale|title=Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry|year=2004|publisher=Lippincott Williams & Wilkins|location=Philadelphia, Pa.|url=https://books.google.com/books?id=CIpWhgWV5q0C&q=%22benzoic+acid%22+antifungal+tinea&pg=RA1-PA234|isbn=0-7817-3481-9|access-date=8 November 2020|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114112907/https://books.google.com/books?id=CIpWhgWV5q0C&q=%22benzoic+acid%22+antifungal+tinea&pg=RA1-PA234|url-status=live}}</ref>
* [[Carbol fuchsin]] (Castellani's paint)
* [[Ciclopirox]] (ciclopirox olamine) – a hydroxypyridone antifungal that interferes with active membrane transport, cell membrane integrity, and fungal respiratory processes. It is most useful against [[tinea versicolour]].<ref>{{cite web |url= http://faculty.swosu.edu/scott.long/phcl/antifung.htm |title=Anti-Fungals |archive-url= https://web.archive.org/web/20080617102546/http://faculty.swosu.edu/scott.long/phcl/antifung.htm |archive-date= 17 June 2008 |last = Long|first = Scott F.|publisher = Southwestern Oklahoma State University}}</ref>
* [[Clioquinol]]
* [[Coal tar]]
* [[Copper(II) sulfate]]<ref>{{cite journal | vauthors = Borkow G | title = Using Copper to Improve the Well-Being of the Skin | journal = Current Chemical Biology | volume = 8 | issue = 2 | pages = 89–102 | date = August 2014 | pmid = 26361585 | pmc = 4556990 | doi = 10.2174/2212796809666150227223857 }}</ref>
* [[Crystal violet]] – a [[triarylmethane dye]]. It has antibacterial, antifungal, and [[anthelmintic]] properties and was formerly important as a [[topical]] antiseptic.<ref name=docampo>{{cite journal | vauthors = Docampo R, Moreno SN | title = The metabolism and mode of action of gentian violet | journal = Drug Metabolism Reviews | volume = 22 | issue = 2–3 | pages = 161–78 | year = 1990 | pmid = 2272286 | doi = 10.3109/03602539009041083 }}</ref>
* [[Chlorhexidine]] is a topical antibacterial and antifungal. It is commonly used in hospitals as an antiseptic. It is much more strongly antibacterial than antifungal, requiring at least a 10 times higher concentration to kill yeast compared to gram negative bacteria<ref>{{cite book |date=2007-08-10 |editor-last=Leikin |editor-first=Jerrold B. |editor2-last=Paloucek |editor2-first=Frank P. |title=Poisoning and Toxicology Handbook |publisher=CRC Press |doi=10.3109/9781420044805|isbn=978-0-429-19564-8 }}</ref>
* [[Chlorophetanol]]
* [[Diiodohydroxyquinoline]] (Iodoquinol)
* [[Flucytosine]] (5-fluorocytosine) – an [[antimetabolite]] pyrimidine analog<ref>{{cite journal | vauthors = Vermes A, Guchelaar HJ, Dankert J | title = Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions | journal = The Journal of Antimicrobial Chemotherapy | volume = 46 | issue = 2 | pages = 171–9 | date = August 2000 | pmid = 10933638 | doi = 10.1093/jac/46.2.171 | doi-access = free}}</ref>
* [[Fumagillin]]
* [[Griseofulvin]] – binds to [[microtubule]]s and inhibits [[mitosis]]<ref>{{cite journal |last1=Olson |first1=Jazmine M. |last2=Troxell |first2=Todd |title=Griseofulvin |url=https://www.ncbi.nlm.nih.gov/books/NBK537323/ |website= StatPearls |publisher=StatPearls Publishing |access-date=22 June 2021 |date=2021|pmid=30726008 }}</ref>
* [[Haloprogin]] – discontinued due to the emergence of antifungals with fewer side effects<ref>{{cite web |title=Haloprogin |work=DrugBank |publisher=University of Alberta |date=6 November 2006 |url=http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD01011.txt |access-date=17 February 2007 |archive-date=1 January 2007 |archive-url=https://web.archive.org/web/20070101044441/http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD01011.txt |url-status=live }}</ref>
* [[Miltefosine]] works by damaging fungal cell membranes <ref name="BrilhanteCaetano2015">{{cite journal | vauthors = Brilhante RS, Caetano EP, Lima RA, Castelo Branco DS, Serpa R, Oliveira JS, Monteiro AJ, Rocha MF, Cordeiro RA, Sidrim JJ | title = In vitro antifungal activity of miltefosine and levamisole: their impact on ergosterol biosynthesis and cell permeability of dimorphic fungi | journal = Journal of Applied Microbiology | volume = 119 | issue = 4 | pages = 962–9 | date = October 2015 | pmid = 26178247 | doi = 10.1111/jam.12891 | s2cid = 206011501 | doi-access = free }}</ref>
* [[Nikkomycin]] – blocks formation of chitin present in the cell wall of fungus.
* [[Orotomide]] (F901318) – pyrimidine synthesis inhibitor<ref name=oliver>{{cite journal | vauthors = Oliver JD, Sibley GE, Beckmann N, Dobb KS, Slater MJ, McEntee L, du Pré S, Livermore J, Bromley MJ, Wiederhold NP, Hope WW, Kennedy AJ, Law D, Birch M | title = F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 113 | issue = 45 | pages = 12809–12814 | date = November 2016 | pmid = 27791100 | pmc = 5111691 | doi = 10.1073/pnas.1608304113 | bibcode = 2016PNAS..11312809O | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hope WW, McEntee L, Livermore J, Whalley S, Johnson A, Farrington N, Kolamunnage-Dona R, Schwartz J, Kennedy A, Law D, Birch M, Rex JH | title = Aspergillus fumigatus: New Opportunities for Treatment of Multidrug-Resistant Fungal Disease | journal = mBio | volume = 8 | issue = 4 | pages = e01157-17 | date = August 2017 | pmid = 28830945 | pmc = 5565967 | doi = 10.1128/mBio.01157-17 }}</ref>
* [[Piroctone olamine]]
* [[Pentanenitrile]]
* [[Potassium iodide]] – preferred treatment for lymphocutaneous [[sporotrichosis]] and subcutaneous [[zygomycosis]] ([[basidiobolomycosis]]). The mode of action is obscure.<ref>{{cite book | chapter=Systemic Therapy | title=[[Rook's Textbook of Dermatology]] | edition=8th | volume=4 | year=2010 | page=74.48}}</ref>
* [[Potassium permanganate (medical use)|Potassium permanganate]] - for use only on thicker, more insensitive skin such as the soles of the feet.
* [[Selenium disulfide]]
* [[Sodium thiosulfate]]
* [[Sulfur]]
* [[Tolnaftate]] – a thiocarbamate antifungal, which inhibits fungal squalene epoxidase (similar mechanism to allylamines like terbinafine){{medical citation needed|date=April 2014}}
* [[Triacetin]] – hydrolysed to acetic acid by fungal [[esterase]]s<ref>{{cite book | chapter = Dermatotherapeutic Agents | title=[[Ullmann's Encyclopedia of Industrial Chemistry]] | edition=7th | year=2007 | doi= 10.1002/14356007.a08_301.pub2| last1=Gendimenico | first1=Gerard J. | isbn=978-3-527-30673-2 }}</ref>
* [[Undecylenic acid]] – an [[unsaturated fatty acid]] derived from natural [[castor oil]]; fungistatic, antibacterial, antiviral, and inhibits ''Candida morphogenesis''{{Citation needed|date=February 2012}}
* [[Zinc pyrithione]]

==Side effects==
Incidents of liver injury or failure among modern antifungal medicines are very low to non-existent. However, some can cause allergic reactions in people.<ref name="pmid27927037">{{cite journal | vauthors = Kyriakidis I, Tragiannidis A, Munchen S, Groll AH | title = Clinical hepatotoxicity associated with antifungal agents | journal = Expert Opinion on Drug Safety | volume = 16 | issue = 2 | pages = 149–165 | date = February 2017 | pmid = 27927037 | doi = 10.1080/14740338.2017.1270264 | s2cid = 43198078 }}</ref>

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.<ref name=doctorfungus/> Azole antifungals are also both substrates and inhibitors of the [[cytochrome P450]] family [[CYP3A4]],<ref name=doctorfungus>{{cite web |url=http://www.doctorfungus.org/thedrugs/antif_interaction.htm |work=doctorfungus |title=Antifungal Drug Interactions |archive-url=https://web.archive.org/web/20100619113816/http://www.doctorfungus.org/thedrugs/antif_interaction.htm |archive-date=19 June 2010 |first=Russell E. |last=Lewis |access-date=23 January 2010 }}</ref> causing increased concentration when administering, for example, [[calcium channel blockers]], [[immunosuppressants]], [[chemotherapeutic drugs]], [[benzodiazepines]], [[tricyclic antidepressants]], [[macrolide]]s and [[Selective serotonin reuptake inhibitor|SSRIs]].<ref>{{cite journal |last=Research |first=Center for Drug Evaluation and |date=2022-08-24 |title=Drug Development and Drug Interactions {{!}} Table of Substrates, Inhibitors and Inducers |url=https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers |journal=FDA |language=en |access-date=17 April 2023 |archive-date=4 November 2020 |archive-url=https://web.archive.org/web/20201104173036/https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers |url-status=live }}</ref>

Before oral antifungal therapies are used to treat [[nail disease]], a confirmation of the fungal infection should be made.<ref name="AADfive">{{cite web |author1=American Academy of Dermatology |author1-link=American Academy of Dermatology |date=February 2013 |title=Five Things Physicians and Patients Should Question |publisher=[[American Academy of Dermatology]] |work=[[Choosing Wisely]]: an initiative of the [[ABIM Foundation]] |url=http://www.choosingwisely.org/doctor-patient-lists/american-academy-of-dermatology/ |access-date=5 December 2013 |archive-date=1 December 2013 |archive-url=https://web.archive.org/web/20131201171621/http://www.choosingwisely.org/doctor-patient-lists/american-academy-of-dermatology/ |url-status=live }}, which cites
* {{cite journal | vauthors = Roberts DT, Taylor WD, Boyle J | title = Guidelines for treatment of onychomycosis | journal = The British Journal of Dermatology | volume = 148 | issue = 3 | pages = 402–10 | date = March 2003 | pmid = 12653730 | doi = 10.1046/j.1365-2133.2003.05242.x | author4 = British Association of Dermatologists | s2cid = 33750748 }}
* {{cite journal | vauthors = Mehregan DR, Gee SL | title = The cost effectiveness of testing for onychomycosis versus empiric treatment of onychodystrophies with oral antifungal agents | journal = Cutis | volume = 64 | issue = 6 | pages = 407–10 | date = December 1999 | pmid = 10626104 }}</ref> Approximately half of suspected cases of fungal infection in nails have a non-fungal cause.<ref name="AADfive"/> The side effects of oral treatment are significant and people without an infection should not take these drugs.<ref name="AADfive"/>

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.<ref>{{Citation |last1=Herrick |first1=Elizabeth J. |title=Antifungal Ergosterol Synthesis Inhibitors |date=2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK551581/#:~:text=The%20general%20mechanism%20of%20action,in%20cell%20lysis%20and%20death. |access-date=2024-08-26 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31869062 |last2=Patel |first2=Preeti |last3=Hashmi |first3=Muhammad F.}}</ref>

== Resistance ==
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.<ref name=":112"/>

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.<ref name=":112"/>

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.<ref name=":112"/><ref>{{Cite journal |last1=Manyi-Loh |first1=Christy |last2=Mamphweli |first2=Sampson |last3=Meyer |first3=Edson |last4=Okoh |first4=Anthony |date=2018-03-30 |title=Antibiotic Use in Agriculture and Its Consequential Resistance in Environmental Sources: Potential Public Health Implications |journal=Molecules |volume=23 |issue=4 |page=795 |doi=10.3390/molecules23040795 |doi-access=free |issn=1420-3049 |pmc=6017557 |pmid=29601469}}</ref><ref>{{cite journal |last1=Verweij |first1=Paul E. |last2=Arendrup |first2=Maiken C. |last3=Alastruey-Izquierdo |first3=Ana |last4=Gold |first4=Jeremy A.W. |last5=Lockhart |first5=Shawn R. |last6=Chiller |first6=Tom |last7=White |first7=P.Lewis |date=20 October 2022 |title=Dual use of antifungals in medicine and agriculture: How do we help prevent resistance developing in human pathogens? |journal=Drug Resistance Updates |language=en |volume=65 |article-number=100885 |doi=10.1016/j.drup.2022.100885|pmid=36283187 |s2cid=253052170 |doi-access=free |pmc=10693676 }}</ref>

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.<ref name="WHO">{{cite book |url=https://www.who.int/publications/i/item/9789240060241 |title=WHO fungal priority pathogens list to guide research, development and public health action |date=25 October 2022 |isbn=978-92-4-006024-1 |language=En |format=PDF |access-date=27 October 2022 |archive-url=https://web.archive.org/web/20221026235331/https://www.who.int/publications/i/item/9789240060241 |archive-date=26 October 2022 |url-status=live |publisher=World Health Organization | vauthors = Organization WH }}</ref>

==References==
{{Reflist}}

==External links==
* [http://www.fungalguide.ca/treatments/antifungal_drugs.html Antifungal Drugs] – Detailed information on antifungals from the Fungal Guide written by R. Thomas and K. Barber
* {{cite web | url = https://www.canesten.com.ph/canesten-cream | publisher = Bayer Philippines | work = Clotrimazole (Canesten) | title = Clotrimazole }}

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