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, itraconazole, fluconazole, fosfluconazole, voriconazole, posaconazole, and isavuconazole. Examples of non-azole systemic antifungals include griseofulvin 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 antimycotics bind with sterols in the fungal cell membrane, principally ergosterol. This changes the transition temperature of the cell membrane, thereby placing the membrane in a less fluid, more crystalline state. As a result, the cell's contents including monovalent ions, small organic molecules leak and this 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.
Ciclopirox – – is a hydroxypyridone antifungal that interferes with active membrane transport, cell membrane integrity, and fungal respiratory processes. It is most useful against tinea versicolour.
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 of any medicine. For example, the azole antifungals such as ketoconazole or itraconazole can be both substrates and inhibitors of the P-glycoprotein, which excretes toxins and drugs into the intestines. Azole antifungals also are both substrates and inhibitors of the cytochrome P450 family CYP3A4, 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. 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.
