COMMON ANTI FUNGAL DRUGS

[drmithila]

Antifungal agents
Class Summary
These agents are used to treat oral candidiasis in association with hairy tongue.

Clotrimazole (Mycelex)

Broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal cells. Reevaluate diagnosis if no clinical improvement after 2 wk. Effective in the treatment of oral candidiasis; however, it has some drawbacks. Has high sugar content and peppermint flavor to mask the bitter taste of clotrimazole. High sugar content makes it relatively contraindicated in persons with diabetes. Dosing regimen occasionally results in poor patient compliance; nevertheless, it is an effective medication to treat oral candidiasis and is especially efficacious in treating candidal infections on the dorsal surface of the tongue.

Nystatin (Mycostatin)

Fungicidal and fungistatic antibiotic obtained from Streptomyces noursei. Effective against various yeasts and yeastlike fungi. Changes permeability of fungal cell membrane after binding to cell membrane sterols, causing cellular contents to leak. Treatment should continue until 48 h after disappearance of symptoms. Drug is not significantly absorbed from GI tract.

Effective to treat oral candidiasis; however, it has some drawbacks. Has high sugar content and licorice flavor to mask the bitter taste of nystatin. High sugar content makes it relatively contraindicated in persons with diabetes. Some patients have an aversion to licorice flavoring. Dosing regimen occasionally results in poor patient compliance; nevertheless, it is an effective medication to treat oral candidiasis and is especially efficacious in treating candidal infections on the dorsal surface of the tongue.

Ketoconazole (Nizoral)

Fungistatic activity. Imidazole broad-spectrum antifungal agent. Inhibits synthesis of ergosterol, causing cellular components to leak and resulting in fungal cell death. Effective in treating oral candidiasis, especially when patients do not comply with multidosing topical therapies or are unable to tolerate sugar-containing troches and pastilles. Take with food.
Fluconazole (Diflucan)

Fungistatic activity. Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. Effective in treating oral candidiasis, especially when patients do not comply with multidosing topical therapies or are unable to tolerate sugar-containing troches and pastilles. Normally prescribed in situations where other topical or systemic medications have not been successful. Especially useful in treating oral candidiasis in patients who are immunosuppressed.

        

[drsushant]

A fluorinated pyrimidine
• Converted to 5 fluorouracil by a deaminase then to 5-fdUMP, which inhibits thymidylate synthase and DNA synthesis
• Selective toxicity to fungal cells (no deaminase in mammalian cells)
• Resistance is common. Do not use alone, but in combination with AmB cryptococcal meningitis
• Bone marrow toxicity – pancytopenia -reversible

The Azoles
Imidazoles and Triazoles
• Triazoles newer with fewer side effects
• Impair synthesis of ergosterol; inhibit sterol 14 α-demethylase (of cyt. P450). Acumulation of precursors which inhibit growth.
• Mammalian cells can incorporate already formed cholesterol; fungi have to synthesize
• Adverse effects due to inhibition of mammalian steroid synthesis
• Drug interactions due to inbibition of cyt. P450 enzymes.

Ketoconazole
(older, more toxic, replaced by itraconazole, but less costly)
• Absorption variable (better in acidic medium)
• Poor concentration in CSF
• Metabolized by Cyt. P450 enzymes
• Adverse effects:
– Nausea, anorexia, vomiting
– Endocrine: menstrual abnormalities, gynecomastia, azoospermia, decreased libido and potency
– Hypertension and fluid retention
– Hepatitis (rare-fatal)
– Drug Interactions (inhibition of cyt. P450)
• Therapeutic Use: coccidiomycosis, histoplasmosis if not severely ill or immunocompromized. Oral, esophageal, mucocutaneous candidiasis

Triazoles
Itraconazole
• Varied absorption. Metabolized by cyt P450
• Has less endocrine effects but occur at high doses
• Less hepatitis
• Histoplasmosis and blastomycosis
• Many drug interactions (due to inhibition of cyt P4503A4) Fluconazole
• Completely absorbed and better tolerated
• Renal excretion
• Less endocrine effects
• Penetrates well into CSF
• Cryptococcal, coccidial meningitis. Candidiasis.
• Drug Interactions
• Other Antifungal Agents
Griseofulvin
• Binds to microtubules/ disrupts mitosis
• Deposits in keratin layers
• Dermatophytes actively concentrate it
• Infections of skin, hair, nails; Prolonged therapy.
• Toxicity: headache, neuro & hepatotoxicity, photo-sensitivity, carcinogenic.
Topical Antifungals
• For stratum corneum, mucosa, cornea by dermatophytes & Candida.
• Not for subcutaneous, nail or hair infections.
• Many azoles; Tolnaftate; nystatin (Candida only); naftifine; terbinafine; Whitfield’s ointment (Benzoic+Salicylic Acid).

 

        

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