Antifungal drugs

    Cards (143)

    • An antifungal drug is a medication used to treat fungal infections such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis etc.
    • Antifungals work by exploiting differences between mammalian and fungal cells to kill the fungal organism without dangerous effects on the host.
    • Unlike bacteria, both fungi and humans are eukaryotes, making it more difficult to find or design drugs that target fungi without affecting human cells.
    • Many antifungal drugs cause side-effects, some of which can be life-threatening if the drugs are not used properly.
    • Apart from side-effects like liver-damage or effects on estrogen levels, many medicines can cause allergic reactions in people.
    • The azole group of drugs is known to cause anaphylaxis.
    • Skin reactions: Rash, pruritus, and photosensitivity have all been noticed.
    • Scleritis: The recommended daily dose is 50 to 150 mg/kg of bodyweight orally, divided in four equal doses every six hours.
    • If problems exist to swallow a complete single dose, the dose may be given in several partial amounts over 15 minutes.
    • The dose for intravenous infusions is 50 mg/kg infused over 20 to 40 minutes every six hours.
    • Anaphylaxis: Sometimes cases of anaphylaxis consisting of diffuse erythema, pruritus, conjunctival injection, fever, abdominal pain, edema, hypotension and bronchospastic reactions are observed.
    • The duration of treatment depends on the clinical situation, but generally does not exceed seven days.
    • Azole antifungals are both substrates and inhibitors of the P-glycoprotein, which excretes toxins and drugs into the intestines.
    • Azole antifungals are both substrates and inhibitors the cytochrome P450 family CYP3A4, causing increased concentration when administering, for example, calcium channel blockers, immunosuppressants, chemotherapeutic drugs, benzodiazepines, tricyclic antidepressants, macrolides and SSRIs.
    • Polyene antifungals bind with sterols in the fungal cell membrane, principally ergosterol.
    • Animal cells contain cholesterol instead of ergosterol and so they are much less susceptible to polyene antifungals.
    • As a polyene's hydrophobic chain is shortened, its sterol binding activity is increased.
    • Further reduction of the hydrophobic chain may result in it binding to cholesterol, making it toxic to animals.
    • Examples of polyene antifungals include Nystatin, Amphotericin B, Candicin, Natamycin, Rimocidin, and Filipin.
    • Azole antifungals inhibit the enzyme cytochrome P450 CYP51 and 14α-demethylase, the enzyme necessary to convert lanosterol to ergosterol.
    • Depletion of ergosterol in fungal membrane disrupts the structure and many functions of fungal membrane leading to inhibition of fungal growth.
    • Examples of imidazoles include Miconazole, Ketoconazole, Clotrimazole, Econazole, Bifonazole, and Isoconazole.
    • Adverse drug reactions associated with fluconazole therapy include skin rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhea, and/or elevated liver enzymes.
    • Fluconazole can increase the risk of cardiac arrhythmia if used concurrently with other drugs that prolong the QT interval.
    • The elimination half-life of fluconazole follows zero order kinetics and only 10% of elimination is due to metabolism, the remainder is excreted in urine and sweat.
    • Like other imidazole- and triazole-class antifungals, fluconazole inhibits the fungal cytochrome P450 enzyme 14α-demethylase, preventing the conversion of lanosterol to ergosterol, an essential component of the fungal cytoplasmic membrane.
    • Fluconazole is almost completely absorbed within two hours and bioavailability is not significantly affected by the absence of stomach acid.
    • Concentrations measured in the urine, tears and skin are approximately 10 times the plasma concentration, while saliva, sputum and vaginal fluid concentrations are approximately equal to the plasma concentration.
    • Fluconazole is active against the following micro-organisms: Blastomyces dermatitidis, Candida spp (except C krusei and C glabrata), Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum, Epidermophyton spp, Microsporum spp, Trichophyton spp.
    • The standard dose range of fluconazole is between 100 mg and 400 mg per day.
    • Fluconazole is primarily fungistatic.
    • Fluconazole is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections.
    • Fluconazole is an inhibitor of the human cytochrome P450 system, particularly the isozymes CYP2C9 and CYP3A4, and can decrease the metabolism and increase the concentration of any drug metabolised by these enzymes.
    • Fluconazole is in the FDA pregnancy risk category C.
    • Fluconazole is indicated for the treatment and prophylaxis of fungal infections where other antifungals have failed or are not tolerated, including Candidiasis, Tinea corporis, tinea cruris or tinea pedis, Onychomycosis, Cryptococcal meningitis, and can be used first-line for Coccidioidomycosis, Cryptococcosis, Histoplasmosis, and Prophylaxis of candidiasis in immunocompromised people.
    • Examples of triazoles include Fluconazole, Itraconazole, Isavuconazole, Ravuconazole, Posaconazole, Voriconazole, and Terconazole.
    • In order to decrease the likelihood and severity of the symptoms, initial doses of Amphotericin B should be low and increased slowly.
    • Ketoconazole is a synthetic antifungal drug used to prevent and treat skin fungal infections, inhibiting the growth of dermatophytes and yeast species such as Candida albicans, especially in HIV/AIDS immune compromised patients.
    • Azole antifungals, Imidazoles, Miconazole, and Ketoconazole are used to treat fungal infections.
    • The symptoms of this reaction sometimes subside with later applications of the drug and may be due to histamine liberation.