An antifungal medication, also known as an antimycotic medication, is a
pharmaceutical
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...
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 yes obtained by a doctor's
prescription, but a few are available
over the counter (OTC).
Types of antifungal
There are two types of antifungals: local and systemic. Local antifungals are usually administered topically or vaginally, depending on the condition being treated. Systemic antifungals are administered orally or intravenously.
Of the clinically employed azole antifungals, only a handful are used systemically.
These include
ketoconazole
Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous ca ...
,
itraconazole,
fluconazole
Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prev ...
,
fosfluconazole
Fosfluconazole () is a water-soluble phosphate prodrug of fluconazole — a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections.
The phosphate ester bond is hydrolyzed by the action of a p ...
,
voriconazole
Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by ' ...
,
posaconazole
Posaconazole, sold under the brand name Noxafil among others, is a triazole antifungal medication.
It was approved for medical use in the United States in September 2006, and is available as a generic medication.
Medical uses
Posaconazole is u ...
, and
isavuconazole.
Examples of non-azole systemic antifungals include
griseofulvin
Griseofulvin is an antifungal medication used to treat a number of types of dermatophytoses (ringworm). This includes fungal infections of the nails and scalp, as well as the skin when antifungal creams have not worked. It is taken by mouth.
C ...
and
terbinafine.
Classes
Polyenes
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 antimycotic Polyene antimycotics, sometimes referred to as polyene antibiotics, are a class of antimicrobial polyene compounds that target fungi. These polyene antimycotics are typically obtained from some species of ''Streptomyces'' bacteria. Previously, ...
s bind with
sterols in the fungal
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
, 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.
Animal cells contain
cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell memb ...
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
Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis ...
*
Candicidin
Candicidin is an antifungal compound obtained from ''Streptomyces griseus''. It is active against some fungi including ''Candida albicans''. Candicidin is administered intravaginally in the treatment of vulvovaginal candidiasis.
This bioactive c ...
*
Filipin – 35 carbons, binds to cholesterol (toxic)
*
Hamycin
Hamycin is a pair polyene antimycotic organic compounds described in India. It is a heptaene antifungal compound rather similar in chemical structure to amphotericin B except that it has an additional aromatic group bonded to the molecule. When ...
*
Natamycin – 33 carbons, binds well to ergosterol
*
Nystatin
*
Rimocidin
Azoles
Azole antifungals inhibit conversion of
lanosterol to
ergosterol by inhibition of
lanosterol 14α-demethylase
Lanosterol 14α-demethylase (CYP51A1) is the animal version of a cytochrome P450 enzyme that is involved in the conversion of lanosterol to 4,4-dimethylcholesta-8(9),14,24-trien-3β-ol. The cytochrome P450 isoenzymes are a conserved group of ...
.
These compounds have a five-membered ring containing two or three nitrogen atoms. The imidazole antifungals contain a 1,3-diazole (imidazole) ring (two nitrogen atoms), whereas the triazole antifungals have a ring with three nitrogen atoms.
Imidazoles
*
Bifonazole
*
Butoconazole
Butoconazole (trade names Gynazole-1, Mycelex-3) is an imidazole antifungal used in gynecology. It is administered as a vaginal cream.Butoconazole
Synthesis
Reaction of epichlorohydrin
Epichlorohydrin (abbreviated ECH) is an organochlorine ...
*
Clotrimazole
Clotrimazole, sold under the brand name Lotrimin, among others, is an antifungal medication. It is used to treat vaginal yeast infections, oral thrush, diaper rash, tinea versicolor, and types of ringworm including athlete's foot and jock ...
*
Econazole
Econazole is an antifungal medication of the imidazole class.
It was patented in 1968, and approved for medical use in 1974.
Medical uses
Econazole is used as a cream to treat skin infections such as athlete's foot, tinea, pityriasis versicol ...
*
Fenticonazole
*
Isoconazole
Isoconazole is an azole antifungal drug and could inhibit gram positive bacteria. For foot and vaginal infections, isoconazole has a similar effectiveness to clotrimazole. Isoconazole nitrate may be used in combination with corticosteroid difluco ...
*
Ketoconazole
Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous ca ...
*
Luliconazole
*
Miconazole
*
Omoconazole
*
Oxiconazole
*
Sertaconazole
*
Sulconazole
*
Tioconazole
Tioconazole is an antifungal medication of the imidazole class used to treat infections caused by a fungus or yeast. It is marketed under the brand names Trosyd and Gyno-Trosyd (Pfizer, now Johnson & Johnson). Tioconazole ointments serve to treat ...
Triazoles
*
Albaconazole
Albaconazole (development code UR-9825) is an experimental triazole
A triazole is a heterocyclic compound featuring a five-membered ring of two carbon atoms and three nitrogen atoms with molecular formula C2H3N3. Triazoles exhibit substantial ...
*
Efinaconazole
*
Epoxiconazole
*
Fluconazole
Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prev ...
*
Isavuconazole
*
Itraconazole
*
Posaconazole
Posaconazole, sold under the brand name Noxafil among others, is a triazole antifungal medication.
It was approved for medical use in the United States in September 2006, and is available as a generic medication.
Medical uses
Posaconazole is u ...
*
Propiconazole
*
Ravuconazole
Ravuconazole (codenamed BMS-207147 and ER-30346) is a potent triazole antifungal, the development of which was discontinued in 2007. The drug has shown to have a similar spectrum of activity to voriconazole, with an increased half-life. However, ...
*
Terconazole
Terconazole is an antifungal drug used to treat vaginal yeast infection. It comes as a lotion or a suppository and disrupts the biosynthesis of fats in a yeast cell. It has a relatively broad spectrum compared to azole compounds but not triazole ...
*
Voriconazole
Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by ' ...
Thiazoles
*
Abafungin
Abafungin (INN) is a broad-spectrum antifungal agent with a novel mechanism of action for the treatment of dermatomycoses.
Abasol is a topical cream formulation of abafungin by York Pharma.
History
Abafungin was first synthesized at Bayer AG ...
Allylamines
Allylamines inhibit
squalene epoxidase, another enzyme required for
ergosterol synthesis. Examples include
butenafine
Butenafine, sold under the brand names Lotrimin Ultra, Mentax, and Butop (India), is a synthetic benzylamine antifungal. It is structurally related to synthetic allylamine antifungals such as terbinafine.
Medical uses
Butenafine is indicated ...
,
naftifine, and
terbinafine.
Echinocandins
Echinocandins inhibit the creation of
glucan in the fungal
cell wall
A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mec ...
by
inhibiting 1,3-Beta-glucan synthase:
*
Anidulafungin
Anidulafungin (INN) (trade names Eraxis, Ecalta) is a semisynthetic echinocandin used as an antifungal drug. It was previously known as LY303366. It may also have application in treating invasive ''Aspergillus'' infection when used in combinatio ...
*
Caspofungin
Caspofungin (INN) (brand name Cancidas) is a lipopeptide antifungal drug from Merck & Co., Inc. discovered by James Balkovec, Regina Black and Frances A. Bouffard. It is a member of a new class of antifungals termed the echinocandins. It work ...
*
Micafungin
Echinocandins are administered intravenously, particularly for the treatment of resistant ''
Candida'' species.
Triterpenoids
*
Ibrexafungerp
Others
*
Acrisorcin
*
Amorolfine
Amorolfine (or amorolfin), is a morpholine antifungal drug that inhibits Δ14-sterol reductase and cholestenol Δ-isomerase, which depletes ergosterol and causes ignosterol to accumulate in the fungal cytoplasmic cell membranes. Marketed as Cur ...
– a morpholine derivative used topically in dermatophytosis
*
Aurones – possess antifungal properties
*
Benzoic acid
Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoin ...
– has antifungal properties, such as in
Whitfield's ointment Whitfield's ointment is an acidic ointment used for the topical treatment of dermatophytosis, such as athlete's foot. It can have a slight burning effect that goes away after a few minutes. It is named after Arthur Whitfield (1868–1947), a Britis ...
,
Friar's Balsam, and
Balsam of Peru
*
Carbol fuchsin (Castellani's paint)
*
Ciclopirox
Ciclopirox (sometimes known by the abbreviation CPX) is a synthetic antifungal agent for topical dermatologic treatment of superficial mycoses. It is most useful against tinea versicolor. It is sold under many brand names worldwide.Drugs.coInte ...
(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
Tinea versicolor (also pityriasis versicolor) is a condition characterized by a skin eruption on the trunk and proximal extremities. The majority of tinea versicolor is caused by the fungus ''Malassezia globosa'', although ''Malassezia furfur'' is ...
.
*
Clioquinol
*
Coal tar
Coal tar is a thick dark liquid which is a by-product of the production of coke and coal gas from coal. It is a type of creosote. It has both medical and industrial uses. Medicinally it is a topical medication applied to skin to treat pso ...
*
Copper(II) sulfate
Copper(II) sulfate, also known as copper sulphate, is an inorganic compound with the chemical formula . It forms hydrates , where ''n'' can range from 1 to 7. The pentahydrate (''n'' = 5), a bright blue crystal, is the most commonly encountered h ...
*
Crystal violet
Crystal violet or gentian violet, also known as methyl violet 10B or hexamethyl pararosaniline chloride, is a triarylmethane dye used as a histological stain and in Gram's method of classifying bacteria. Crystal violet has antibacterial, antif ...
– a
triarylmethane dye. It has antibacterial, antifungal, and
anthelmintic properties and was formerly important as a
topical
A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
antiseptic.
*
Chlorophetanol
Chlorophetanol is an antifungal
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), seriou ...
*
Diiodohydroxyquinoline
The quinoline derivative diiodohydroxyquinoline (INN), or iodoquinol (USAN), can be used in the treatment of amoebiasis.
It is poorly absorbed from the gastrointestinal tract and is used as a luminal amebicide. It acts by chelation of ferrous io ...
(Iodoquinol)
*
Flucytosine
Flucytosine, also known as 5-fluorocytosine (5-FC), is an antifungal medication. It is specifically used, together with amphotericin B, for serious ''Candida'' infections and cryptococcosis. It may be used by itself or with other antifungals for ...
(5-fluorocytosine) – an
antimetabolite pyrimidine analog
*
Fumagillin
Fumagillin is a complex biomolecule and used as an antimicrobial agent. It was isolated in 1949 from the microbial organism ''Aspergillus fumigatus''.
Uses
In animals
It was originally used against microsporidian parasites '' Nosema apis'' infect ...
*
Griseofulvin
Griseofulvin is an antifungal medication used to treat a number of types of dermatophytoses (ringworm). This includes fungal infections of the nails and scalp, as well as the skin when antifungal creams have not worked. It is taken by mouth.
C ...
– binds to
microtubules and inhibits
mitosis
*
Haloprogin – discontinued due to the emergence of antifungals with fewer side effects
*
Miltefosine
Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as ''Naegleria fowleri'' and ''Balamuthia mandrillaris''. This includes the three forms of le ...
– disrupts fungal cell membrane dynamics by interacting with
ergosterol
*
Nikkomycin – blocks formation of chitin present in the cell wall of fungus.
*
Orotomide
Orotomides are a class of experimental antifungals. They were discovered in 2015 by British scientists at the pharmaceutical company F2G Ltd. while searching for a new drug for ''Aspergillus'' infection. The discovery was formally announced at the ...
(F901318) – pyrimidine synthesis inhibitor
*
Piroctone olamine
*
Pentanenitrile
*
Potassium iodide – preferred treatment for lymphocutaneous
sporotrichosis
Sporotrichosis, also known as rose handler's disease, is a fungal infection that affects skin, lungs, bone and joint, and can be widespread. It presents with firm painless nodules that later ulcerate. It can be localized or widespread. The disea ...
and subcutaneous
zygomycosis (
basidiobolomycosis). The mode of action is obscure.
*
Potassium permanganate - for use only on thicker, more insensitive skin such as the soles of the feet.
*
Selenium disulfide
*
Sodium thiosulfate
Sodium thiosulfate (sodium thiosulphate) is an inorganic compound with the formula . Typically it is available as the white or colorless pentahydrate, . The solid is an efflorescent (loses water readily) crystalline substance that dissolves well ...
*
Sulfur
Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formul ...
*
Tolnaftate – a thiocarbamate antifungal, which inhibits fungal squalene epoxidase (similar mechanism to allylamines like terbinafine)
*
Triacetin – hydrolysed to acetic acid by fungal
esterases
*
Undecylenic acid
Undecylenic acid is an organic compound with the formula CH2=CH(CH2)8CO2H. It is an unsaturated fatty acid. It is a colorless oil. Undecylenic acid is mainly used for the production of Nylon-11 and in the treatment of fungal infections of the s ...
– an
unsaturated fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...
derived from natural
castor oil; fungistatic, antibacterial, antiviral, and inhibits ''Candida morphogenesis''
*
Zinc pyrithione
Side effects
Apart from side effects like altered
estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
levels and
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
damage, many antifungal medicines can cause allergic reactions in people.
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.
[ Azole antifungals also are both substrates and inhibitors of the ]cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
family CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules ( xenobiotics), such as toxins or drugs, so that they can be removed from ...
,[doctorfungus > Antifungal Drug Interactions]
Content Director: Russell E. Lewis, Pharm. D. Retrieved on Jan 23, 2010 causing increased concentration when administering, for example, calcium channel blockers, immunosuppressants
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system.
Classification
Immunosuppressive drugs can be classified in ...
, chemotherapeutic drugs, benzodiazepines, tricyclic antidepressants, macrolides and SSRIs
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
SSRIs increase the extracellu ...
.
Before oral antifungal therapies are used to treat nail disease
A nail disease or onychosis is a disease or deformity of the nail. Although the nail is a structure produced by the skin and is a skin appendage, nail diseases have a distinct classification as they have their own signs and symptoms which may re ...
, a confirmation of the fungal infection should be made.[, which cites
*
* ] Approximately half of suspected cases of fungal infection in nails have a non-fungal cause. The side effects of oral treatment are significant and people without an infection should not take these drugs.
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.
See also
* Fungicide
* Antimicrobial
* Etest
References
External links
Antifungal Drugs
– Detailed information on antifungals from the Fungal Guide written by R. Thomas and K. Barber
*
{{DEFAULTSORT:Antifungal Drug
Anti-infective agents
.