An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide
used to treat and prevent mycosis
such as athlete's foot
(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 OTC (over-the-counter
Types of anti fungal
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 antifungal
s, only a handful are used systemically.
These include ketoconazole
, and isavuconazole
Examples of non-azole systemic antifungals include griseofulvin
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
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+
, and Cl−
) and small organic molecules leak, which is regarded one of the primary ways a cell dies.
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
– 35 carbons, binds to cholesterol (toxic)
– 33 carbons, binds well to ergosterol
Azoles inhibit conversion of lanosterol
by inhibition of lanosterol 14α-demethylase
s inhibit squalene epoxidase
, another enzyme required for ergosterol
synthesis. Examples include amorolfin
, and terbinafine
s 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
- have been shown to possess antifungal properties
* Benzoic acid
– has antifungal properties, such as in Whitfield's ointment
, Friar's Balsam
, and Balsam of Peru
– (ciclopirox olamine) – is a hydroxypyridone antifungal that interferes with active membrane transport, cell membrane integrity, and fungal respiratory processes. It is most useful against tinea versicolour
or 5-fluorocytosine – an antimetabolite
– binds to polymer
s and inhibits fungal mitosis
– discontinued due to the emergence of more modern antifungals with fewer side effects
– 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''
- hydrolysed to acetic acid by fungal esterase
* Crystal violet
– a triarylmethane dye
, it has antibacterial, antifungal, and anthelmintic
properties and was formerly important as a topical
* Castellani's paint
(F901318) - pyrimidine synthesis inhibitor.
disrupts fungal cell membrane dynamics by interacting with ergosterol
* Potassium iodide
is the preferred treatment for lymphocutaneous sporotrichosis
and subcutaneous zygomycosis
). The mode of action is obscure.
blocks formation of chitin present in the cell wall of fungus.
* Coal tar
* Copper(II) sulfate
* Selenium disulfide
* Sodium thiosulfate
* Piroctone olamine
* Zinc pyrithione
Apart from side effects like altered estrogen
levels and liver
damage, 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 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 family CYP3A4,] [doctorfungus > Antifungal Drug Interactions] causing increased concentration when administering, for example, calcium channel blockers, immunosuppressants, chemotherapeutic drugs, benzodiazepines, tricyclic antidepressants, macrolides and SSRIs.
Before oral antifungal therapies are used to treat nail disease, a confirmation of the fungal infection should be made.
Content Director: Russell E. Lewis, Pharm. D. Retrieved on Jan 23, 2010
[, 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.
– Detailed information on antifungals from the Fungal Guide written by R. Thomas and K. Barber