Sunday, July 24, 2011

A Short Note On Anti-Fungal Drugs Used In Dentistry

Antifungal Drugs
          Polyene antibiotics:  Amphotericin B, nystatin
          Antimetabolites:  5-Fluorocytosine
                Imidazoles: Ketoconazole, miconazole (topical)
                Trizoles: Itraconazole, Fluconazole  
          Topical antifungal agents: imidazoles, polyenes and others.

Adverse Effects
          Acute: Infusion-related
        Chills, fever, dyspnea, nausea, vomiting, bronchospasm, hypotension, convulsions
                azotemia, impaired concentration, impaired urinary acidification, K & Mg wasting with hypokalemia and hypomagnesemia

        Normochromic, normocytic anemia (↓ erythropoietin)

   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.

(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

          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
          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).


  1. Systemic anti-fungal medicine work best when the amount of medicine in the body is kept constant. This means that the medicine has to be taken regularly. Try to take the medicine at the same time every day, and do not miss any doses. While taking this medicine, visit the physician as often as the physician recommends.

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