Antifungal

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

An antifungal medication, also known as an antimycotic medication, is a

over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.[1]

Routes of administration

Ocular

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

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

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

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

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

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

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

A

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

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

Triazoles

Thiazoles

Allylamines

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

Echinocandins

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

Others

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.[33]

There are also many

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 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.[citation needed]

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 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]

Unlike 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][37]

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.[38]

References

  1. ^
    PMID 35352028
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  4. ^ Sobel J. "Candida vulvovaginitis: Treatment". UpToDate. Archived from the original on 15 May 2023. Retrieved 21 May 2023.
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  6. ^ a b Carver P. Pharmacotherapy: a pathophysiological approach (11th ed.).
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  10. ^ 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. PMID 20347663
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  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. S2CID 32016049
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  20. 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.
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  26. . 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. S2CID 206011501
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  31. ^ "Systemic Therapy". Rook's Textbook of Dermatology. Vol. 4 (8th ed.). 2010. p. 74.48.
  32. .
  33. .
  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. ^ from the original on 1 December 2013. Retrieved 5 December 2013., which cites
  37. .
  38. ISBN 978-92-4-006024-1. Archived from the original on 26 October 2022. Retrieved 27 October 2022. {{cite book}}: |website= ignored (help
    )

External links

  • Antifungal Drugs – Detailed information on antifungals from the Fungal Guide written by R. Thomas and K. Barber
  • "Clotrimazole". Clotrimazole (Canesten). Bayer Philippines.