Antifungal drugs.

Introduction:

A pharmaceutical fungicide or fungistatic called an antifungal medicine, also referred to as an antimycotic medication, is used to treat and prevent mycosis, including athlete's foot, ringworm, candidiasis (thrush), and dangerous systemic infections such cryptococcal meningitis. Fungi can be found throughout the world in all kinds of environments. Most fungi don’t cause disease in people. However, some species can infect humans and cause illness. Antifungal drugs are medications that are used to treat fungal infections. While most fungal infections affect areas such as the skin and nails, some can lead to more serious and potentially life threatening conditions like meningitis or pneumonia.

There are several types of antifungal drugs available to fight fungal infections.

How They Operate:

Generally speaking, antifungal drugs can work in two ways: by directly killing fungal cells or by preventing fungal cells from growing and thriving. Antifungal drugs target structures or functions that are necessary in fungal cells but not in human cells, so they can fight a fungal infection without damaging your body’s cells. Two structures that are commonly targeted are the fungal cell membrane and the fungal cell wall. Both of these structures surround and protect the fungal cell. When either one becomes compromised, the fungal cell can burst open and die.

Types of antifungal drugs:

Antifungal drugs are very diverse. They can be given orally, as a topical treatment, or via IV. How an antifungal drug is given depends on factors like the specific drug, the type of infection you have, and the severity of your infection. Antifungal drugs are classified by their chemical structure as well how they work. Below, we’ll discuss the different types of antifungal drugs and give some examples of the types of infections they treat. Antifungals come in two varieties:

 Local

 Systemic

Depending on the illness being treated, topical or vaginal administration of local antifungals is typical. Oral or intravenous administration is used for systemic antifungals. Only a small number of the azole antifungals used in clinical settings are administered systemically. Itraconazole, fluconazole, fosfluconazole, posaconazole, and isavuconazole are a few of them. The non-azole systemic antifungals griseofulvin and terbinafine are two examples.

Antifungal drugs:

Ergosterol, a special sterol found in fungal cell membranes, replaces the cholesterol present in human cell membranes. A medicine known as an antifungal agent selectively removes fungal pathogens from a host with little harm to the host.

Fig.1 Mode of action of antifungal drugs.

Different Classes of antifungal drugs:

Azoles:

Some of the most widely used antifungals are azoles. They disrupt an enzyme necessary for the formation of the fungal cell membrane. The result is an unstable cell membrane that may eventually leak and cause cell death.

Azole antifungals fall into two categories: imidazoles and triazoles.

Examples of the disorders they treat:

 Blastomycosis, histoplasmosis, ketoconazol-induced skin and hair infections, Candida infections of the skin and mucosal membranes

 Clotrimazole: infections of the skin and mucous membranes

 Miconazole: infections of the skin and mucous membranes

The following are some instances of triazoles and the ailments they treat:

Candida infections, such as invasive, systemic, and mucosal infections, can be treated with fluconazole.

 Itraconazole: mucosal Candida infections, aspergillosis, blastomycosis, histoplasmosis, coccidioidomycosis (off-label), and onychomycosis

 Posaconazole: invasive, mucosal, and off-label treatment for aspergillosis and yeast infections.

 Voriconazole: invasive or mucosal aspergillosis Infections with Fusarium species, Candida, and isavuconazole for aspergillosis and mucormycosis

Mode of action:

The mechanism of action of azoles is blocking the synthesis of ergosterol, the primary sterol in the fungal cell membrane. The depletion of ergosterol alters the fluidity of the cell membrane and alters the action of the membrane-associated enzymes. This results in inhibition of replication and inhibition of the transformation of candidal yeast forms into hyphae, which is the invasive and pathogenic form of the parasite.

Fig. 2 Mode of Action of Azoles

 The sterol components of the fungal membrane are synthesised by the azole antifungal medications, however this process is inhibited.

 Azoles primarily act as fungistatics.

 They block the demethylation of lanosterol to ergosterol, the primary sterol of fungal membranes, by inhibiting C-14 -demethylase, a cytochrome P450 [CYP450] enzyme; this disruption of membrane function and structure then prevents the proliferation of fungal cells.

 Imidazoles and triazoles are the two main categories for azoles.

The imidazoles group includes Clotrimazole, Econazole, Miconazole, and Ketoconazole, whereas the triazoles group includes Fluconazole, Itraconazole, Posaconazole, and Voriconazole.

The loss of cytoplasmic components has effects comparable to those of the polyenes, and the imidazoles and triazoles rapidly impair the integrity of the fungal membrane.

They hinder the formation of ergosterol, which results in a series of irregularities in the membrane.