In this essay we will discuss about the drugs used for the treatment of fungal infections.
1. Amphotericin B:
Amphotericin B is fungicidal and is the most important drug for severely ill patients with systemic fungal infections, namely systemic candidiasis, cryptococcal meningitis and histoplasmosis. Amphotericin is not absorbed orally and is given only by IV infusion. It is highly protein bound and penetrates poorly into body fluids. The drug is excreted very slowly in the urine and has a plasma half-life of 24 hours.
Amphotericin B is now available enclosed in liposomes, which makes it easier to use and is less toxic. It is also used in lozenges that are given four times daily in, the treatment of oral candidiasis. The major adverse effect of amphotericin B including the lipid form is nephrotoxicity. Common infusion-related effects (fever/ chills, nausea, headache and myalgias) can be prevented by premedication with antihistamine and glucocorticoid.
Flucytosine is fungicidal against Candida albicans and Cryptococcus. It is given orally and is excreted by kidneys. Flucytosine is used in combination with amphotricin B in the treatment of cryptococcal meningitis and systemic candidiasis. Adverse effects include dose related bone-marrow suppression and bloody diarrhea. It should be used cautiously in patients with impaired renal and hepatic function.
Azoles are fungistatic agents that inhibit ergosterol synthesis. Itraconazole is a broad-spectrum antifungal triazole that is effective in systemic candidiasis, histoplasmosis, blastomycosis and dermatophyte infections.
Orally, it is well absorbed and requires adequate gastric acidity for absorption and, therefore, should be taken with food to ensure maximum absorption. In serious cases, it is given by IV route.
It is equally and sometimes more effective than toxic antifungal amphotericin and flucytosine drugs. It should not be used in patients with liver disease, severe heart failure and renal impairment.
Fluconazole is the drug of choice for systemic candidiasis and cryptococcal meningitis. It can be given by oral as well as IV route. Its absorption is not dependent on gastric acid.
Single dose therapy is effective for vaginal candidiasis and for oropharyngeal infections. Serious side effects, particularly liver damage, have been reported.
Ketoconazole is useful for treating systemic fungal infections candidiasis, histoplasmosis, blastomycosis and chromomycosis, but is rarely used because of its side effects. It is given orally and its absorption is dependent on gastric acidity. The most important side effect is jaundice, others being nausea, drowsiness and rarely adrenal suppression.
Voriconazole is a new triazole antifungal with broad-spectrum activity against a wide rang of pathogenic fungi. Unlike, other azoles, it is active against all clinically important species of Aspergillus. It is even superior to the conventional amphotericin B therapy of invasive aspergillosis.
Voriconazole has the advantage of easy transition from IV to oral therapy, because of its excellent oral bioavailability.
Voriconaole may cause transient visual disturbances and its IV formulation may cause accumulation of toxic vehicle in renal impairment.
Clotrimazole and miconazole are only indicated for the treatment of superficial fungal infections. Clotrimazole vaginal pessaries, one inserted at night as a single dose is highly effective in the treatment of vaginal candidiasis. Miconazole gel is used for oral candidiasis in children.
Clotrimazole and miconazole ointments (1-2%) are applied to the skin for ringworm infections (dermatophytoses).
4. Caspofungin Acetate:
Capsofungin acetate is a fungicidal drug against most Aspergillus and Candida species, including azole-resistant Candida strains. It is not effective against Cryptococcus, Histoplasma or Mucor (Mucor is a genus of fungus found on decaying organic matter). It is not absorbed from GI tract and has to be given by IV route. It is metabolised by the liver, but does not involve cytochrome P-450 system significantly.
Caspofungin is effective in patients who do not respond to amphotericin B or itraconazole. It is better tolerated than amphotericin B for the treatment of infections caused by Candida species. Caspofungin is well tolerated. Fever, rash, nausea and phlebitis at the injection site are infrequent side effects. In liver diseases, the doses should be reduced.
Terbinafine is given orally and is the drug of choice for fungal nail and ringworm infections. It is not used for systemic infections. Side effects include GIT upset and rashes. Serious skin reactions and rarely liver toxicity have also been reported.
Griseofulvin is given orally for the ringworm infections of skin and scalp where local treatment is inadequate. It is a slow-acting drug and requires several weeks of therapy. It is not used for systemic infections. Side effects are infrequent except gastrointestinal upsets. It enhances the action of alcohol.
Nystatin is very poorly absorbed after oral administration and is mainly used to treat Candida infection of the intestinal tract, oral infection and vaginal candidiasis. It is not much used nowadays as it takes long to work.