Drugs used to treat infections caused by fungi

Systemic Topical

Very large and diverse group of microorganismsBroken down into yeasts and molds

Fungal infections also known as mycoses

Some fungi are part of the normal flora of the skin, mouth, intestines, vagina

Reproduce by budding Can be used for

BakingAlcoholic beverages

Multicellular

Characterized by long, branching filaments called hyphae

Four general types Cutaneous Subcutaneous Superficial Systemic*

*Can be life threatening

*Usually occur in immunocompromised host

Candida albicans Due to antibiotic therapy, antineoplastics,

or immunosuppressants (corticosteroids) May result in overgrowth and systemic infections Growth in the mouth is called thrush or oral

candidiasis Common in newborn infants and

immunocompromised patients

Vaginal candidiasis “Yeast infection” Pregnancy, women with diabetes mellitus, women

taking oral contraceptives

Systemic amphotericin B, caspofungin, fluconazole,

ketoconazole, others

Topical Examples: clotrimazole, miconazole, nystatin

Major groups based on their mechanisms of action

Polyenes: amphotericin B and nystatin Imidazoles: ketoconazole (Nizoral) Triazoles: fluconazole (Diflucan), itraconazole

(Sporanox) Echinocandins: caspofungin (Cancidas), micafungin Listed individually, not by mechanism of action:

griseofulvin, flucytosine

Polyenes: amphotericin B and nystatin

Bind to sterols in cell membrane lining

Result: fungal cell death

Do not bind to human cell membranes or kill human cells

Use: Serious systemic fungal infections Administered: IV, PO, topical

Flucytosine (Ancobon)

Also known as 5-fluorocytosine (antimetabolite)

Taken up by fungal cells and interferes with DNA synthesis

Result: fungal cell death

Use: Systemic mycoses due to Candida species or Cryptococcus neoformans – administered orally

Imidazoles and triazoles:

Ketoconazole (Nizoral), fluconazole (Diflucan)

Inhibit fungal cell cytochrome P-450 enzymes, resulting in cell membrane leaking

Lead to altered cell membrane

Result: fungal cell death

Use: Ketoconazol (Nizoral): (po/topical): candidiasis, histoplasmosis, coccidoidomycosis; cutaneous candidiasis; tinea infections

Use: fluconazole (Diflucan): (po/IV): systemic, oral, esophageal or vaginal candidiasis; prevention of candidiasis after bone marrow transplant; cryptococcal meningitis.

griseofulvin

Disrupts cell division

Result: inhibited fungal mitosis (reproduction)

Use: (po) Dermatophytosis (skin, hair, nails)

Echinocandins: capsofungin (Cancidas)

Prevent the synthesis of glucans, which are essential components of fungal cell walls

Causes fungal cell death

Use: (IV) Invasive aspergillosis, Candidiasis

Systemic and topical fungal infections

Drug of choice for the treatment of many severe systemic fungal infections is amphotericin B

Choice of drug depends on type and location of infection

Fever / Headache Malaise Hypotension Muscle and joint pain Lowered potassium and magnesium levels Main concerns:

*Renal toxicity*Neurotoxicity: seizures and paresthesias

Many other adverse effects

Chills Dysrhythmias Nausea Anorexia

Fluconazole (Diflucan)

Nausea, vomiting, diarrhea, stomach pain, increased liver function studies

Flucytosine (Ancobon)

Nausea, vomiting, anorexia, headache, dizziness, others

griseofulvin

Rash, urticaria, headache, nausea, vomiting, anorexia, others

Liver failure

Renal failure

Porphyria: genetic disorder-erythrocyte formation/liver dysfunction (griseofulvin)

Many antifungal drugs are metabolized by the cytochrome P-450 enzyme system

Co administration of two drugs that are metabolized by this system may result in competition for these enzymes, and thus higher levels of one of the drugs

Before beginning therapy, assess for hypersensitivity, contraindications, and conditions that require cautious use

Obtain baseline VS, CBC, liver and renal function studies, and EKG

Assess for other medications used (prescribed and OTC) in order to avoid drug interactions

Follow manufacturer’s directions reconstitution and administration

Monitor VS of patients receiving IV infusions every 15 to 30 minutes

During IV infusions, monitor I&O to identify adverse effects

amphotericin B

To reduce the severity of the infusion-related reactions, pretreatment with an antipyretic (acetaminophen), antihistamines, antiemetics, and corticosteroid may be given

Use IV infusion pumps and the most distal veins possible

Some oral forms should be given with meals to decrease GI upset; others require an empty stomach—be sure to check

Nystatin given as an oral lozenge should be slowly and completely dissolved in the mouth (not chewed or swallowed whole)

Nystatin suspension should be swished thoroughly in the mouth as long as possible before swallowing

Monitor for therapeutic effectsEasing of the symptoms of infection Improved energy levelsNormal vital signs, including temperature

Monitor carefully for adverse effects