Anti-fungal Drugs

Pharmacology (Dr. Biag) Antifungals 22-23 January 2008

MYCOTIC INFECTIONS Four General Types Cutaneous Subcutaneous Can be superficial but may not be in the skin Superficial Systemic* *Can be life threatening *usually occur in immunocompromised Candida Albicans Due to antibiotic therapy, antineoplastics, or immunosuppresants (steroids) May result in overgrowth & systemic infections Opportunistic organism, may multiply in number because of the decline in the normal flora In the mouth: Oral candidiasis or thrush New born infants & immunocompromised patients have increased frequency of oral thrush Vaginal Cadidiasis “yeast infections” Pregnancy, DM, OCP May occur to both male and females (urethritis and balanitis) Antiviral Agents Broken Down into 4 major grps based on their chem’l structures (1) Polyenes: amphoterincin B , nystatin (2) Flucytosine (3) Imidazoles: ketoconazole, miconazole, clotrimazole, fluconazole (4) Griseofulvin Polyenes: Amphotericin B & Nystatin Binds to sterols in cell membrane lining Allowing K+ & Mg2+ to leak out, altering fungal cell metabolism Result: fungal cell death Uses: IV: fatal systemic mycotic infections Aspergillus fumigatum – growth is concentric with radiation – misdiagnosed as TB (SSX: chronic productive cough, low to moderate fever, immunocompromised patient, hemoptysis) Blastomycosis – ulcers, when scraped (+) yeasts Coccidiomycosis, paracoccidiodomycosis – San Joaquin fever dw (accdg to Fars) Crytococcosis – (CT scan of brain) lesion at basal ganglia, occipital lobe, L. temporal lobe; & meningitis

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Histoplasma capsulatum – may present as pulmo lesion Sporotrichosis – cutaneous erythematous nodules & papules Side Effects: Amphothericin B “Shake & Bake” Fever Chills Headache Anemia Malaise Nausea Hypotension Tachycardia Ms & jt pain Anaphylaxis K+ & Mg++ *renal toxicity monitor BUN and creatinine *neurotoxicity: seizures & paresthesias Flucytosine aka 5-fluorocytosine  5 – fluorouracil (antimetabolite) Taken up by fungal cells & interferes with DNA synthesis Result: fungal cell death Alone or in combination with amphotericin B for serious systemic infections caused by susceptible strains of Cryptococcus & candida species Side Effects: Nausea, vomiting, anorexia Confusion, hallucination, headache, sedation Agranulocytosis (dec WBC) Elevated BUN & creatinine Elevated transaminases Ketoconazole & Fluconazole Interferes with synthesis of ergosterol Increase in cell permeability & ultimately inhibition of fungal cell growth Side Effects (Ketoconazole) Rash (if topical), anaphylaxis N & V, liver cirrhosis Gynecomastia, uterine bleeding, loss of impotence, oligospermia, hair loss Acute hypoaldosteronism, renal hypofunction

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Side Effects (Fluconazole) Headache Nausea and vomiting Abdominal pain Diarrhea Increase AST in Px w/ cryptococcal meningitis & AIDS rash Miconazole inhibit uptake of components essential for cell reproduction & growth as well as cell wall structures, thus promoting cell death of fungi Side Effects: Vulvovaginal burning when used as ointment, cream and vaginal suppository Itching

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Pharmacology – Antifungals by Dra Biag

Irritation Maceration Allergic contact dermatitis

Clotrimazole Canesten: ointment, vaginal suppository Altering fungal cell membrane permeability Permeating loss of P cmpds, K & other essential intracellular constituents w/ consequent loss of ability to replicate Side Effects: Abnormal liver function tests Stinging, erythema, edema Cystitis, urethritis Vaginal soreness during intercourse Griseofulvin Disrupts cell division Result: inhibited fungal mitosis (reproduction) Deposits in keratin precursor cells & has special affinity for diseased tissue. It is tightly bound to new keratin of skin, hair, & nails, w/c becomes highly resistant to fungal invasion Side Effects: Rash, urticaria Headache Nausea/Vomiting & anorexia Leukopenia Nephrotoxicity Hepatotoxicity Overgrowth of nonsusceptible organisms (Candida)

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