13 Antifungal, Antimalarial, and Antiprotazoal Agents

Fungal Infections Fungi may enter body through skin, mucous membranes, and respiratory tract. Healthy individuals are usually resistant to most fungal infections, or mycoses.

Fungal Infections Use of broad-spectrum antimicrobials, immunosuppressive drugs for cancer and organ transplantation, and HIV place more patients at risk for mycoses.

Common Mycoses Candidiasis (also moniliasis or thrush) Yeast infection in the mouth caused by Candida albicans

Courtesy of Charles J. Kirkpatrick, M.D., President, Innovative Therapeutics, Inc. Figure 13-1 Oral Candida albicans. Courtesy of Charles J. Kirkpatrick, M.D. President, Innovative, Therapeutics, Inc.

Superinfections Usually occur in anal and genital areas or in the vagina or mouth Normally, the vaginal bacteria Doderlein bacillus controls overgrowth of fungi. Penicillin therapy may destroy these bacteria, allowing fungi to multiply rapidly.

Superinfections Ask all patients if they have a history of allergies, such as hay fever, rashes or asthma, or have had unusual reactions to any drugs taken orally or by injection.

Thrush in Infants Causes difficulty in breastfeeding and chronic diaper rash May infect the mother’s nipples, causing drying or cracking

Antifungals: Mechanism of Action Most antifungal drugs interfere with synthesis of ergosterol, a chemical in fungal cell membranes. Cause change in permeability of fungal cell membrane, slowing growth or destroying fungal organism

Antifungal Drugs Three categories of antifungal drugs: Drugs for systemic mycoses Oral drugs for mucocutaneous infections Topical drugs for mucocutaneous infections

Table 13-1 Antifungal Agents

Table 13-1 (continued) Antifungal Agents

Systemic Antifungals Amphotericin B (Amphocin) Flucytosine (Ancobon) Ketoconazole (Nizoral) Griseofulvin (Fulvicin, Grifulvin V)

Amphotericin B (Amphocin) Has widest spectrum of antifungal activity of any systemic antifungal drug IV: treats systemic fungal diseases Topical: treats superficial moniliasis infections Nasal spray: for prophylaxis of aspergillosis in immunocompromised patients Oral: treats oral candidiasis

Amphotericin B: Adverse Effects Common: chills and fever, nausea and vomiting, diarrhea, abdominal cramps, dyspepsia, headache, vertigo, thrombophlebitis, anemia, skin rashes Serious: renal damage, blood dyscrasias, loss of hearing, cardiac arrest

Amphotericin B: Contraindications Use cautiously in patients with impaired renal function Interacts with antineoplastics, cardiac glycosides, corticosteroids, nephrotoxic drugs (including antibiotics and pentamidine), thiazides, and flucytosine (Ancobon) Should not be used with leukocyte transfusions

Amphotericin B: Patient Information Teach patients to report loss of hearing, dizziness, cloudy or pink urine, or greatly increased urination. Advise patients that treatment of cutaneous infections, such as nail infections, usually requires several months of therapy.

Amphotericin B and Kidney Damage Amphotericin B (Amphocin) is nephrotoxic (damages kidneys). Elderly patients who have renal impairment should be tested for creatinine clearance.

Interactions Between Gossypol and Amphotericin B The herb gossypol, which is derived from cottonseed oil, is sometimes used to treat endometriosis in women. Use of gossypol with amphotericin B increases the risk of nephrotoxicity.

Flucytosine (Ancobon) Drug of choice to treat chromomycosis Second choice to treat systemic candidiasis May be combined with amphotericin B for first-choice treatment of aspergillosis or cryptococcosis (a fungal disease of the lungs), especially in patients with meningitis

Flucytosine: Adverse Effects Common: nausea, vomiting, diarrhea, skin rashes Serious: bone marrow suppression, manifest by anemia, leukopenia, thrombocytopenia Infrequent: sedation, confusion, headache, hallucinations, vertigo

Flucytosine: Contraindications Use with extreme caution in patients with impaired hepatic or renal function or bone marrow suppression. Interacts with amphotericin B, causing synergistic effects and enhancing toxicity

Flucytosine: Patient Teaching Teach patients to report fever, sore mouth or throat, and unusual bleeding or bruising. Advise patients that duration of therapy is 4 to 6 weeks. Warn women to avoid breastfeeding.

Ketoconazole (Nizoral) Drug of choice for treatment of blastomycosis, coccidioidosis, and histoplasmosis. Alternative drug for candidiasis

Ketoconazole: Adverse Effects Common: nausea and vomiting, diarrhea, pruritus (severe itching), abdominal cramps, headache, photophobia, fever, impotence

Ketoconazole: Contraindications Use cautiously in patients with a history of liver disease, alcoholism, or HIV infection. Safety during pregnancy and lactation and in children younger than 2 years not established.

Ketoconazole: Contraindications Interacts with cimetidine (Tagamet) and rifampin (Rifadin) Decreases biosynthesis of androgens and estrogens

Ketoconazole: Patient Teaching Advise patients to promptly report signs and symptoms of hepatotoxicity. Tell patients to avoid over-the-counter (OTC) drugs for gastric distress (such as Rolaids, Tums, and Alka-Seltzer). Tell patients to take drug as directed.

Griseofulvin (Fulvicin, Grifulvin V) Fungistatic, but not fungicidal (having a killing action on fungi). Highly effective in management of dermatophyte infections of skin, hair, and nails.

Griseofulvin: Adverse Effects Common: hypersensitivity, skin rashes, pruritus, serum sickness, severe headache, insomnia, fatigue, mental confusion, psychotic symptoms, vertigo, heartburn, nausea, vomiting, diarrhea, flatulence, dry mouth, unpleasant taste sensations Serious: nephrotoxicity and hepatotoxicity

Griseofulvin: Contraindications Do not use in patients with porphyria (a group of diseases affecting heme, the oxygen-binding portion of hemoglobin) or liver disease. Safe use during pregnancy, lactation, or in children younger than 2 years not established

Griseofulvin: Contraindications Interacts with alcohol, barbiturates, oral anticoagulants, estrogen May decrease efficacy of oral contraceptives

Griseofulvin: Patient Teaching Teach patients to avoid exposure to intense natural or artificial sunlight. Advise patients to take drug as prescribed. Warn women to avoid breastfeeding.

Malarial Infections A serious disease caused by a protozoan, a single-celled highly mobile microorganism Plasmodium protozoans, which cause malaria, are transmitted to humans by mosquitos. Malaria can become a long-term condition and can kill affected persons because of its severity.

Table 13-2 Antimalarial Drugs

Antimalarial Agents: Mechanism of Action Interrupt different points of cycle of parasite (an organism that lives on or in another and from which it draws its nourishment)

Antimalarial Drugs Chloroquine (Aralen) Primaquine (Primaquine) Quinine (Quinamm) Hydroxychloroquine (Plaquenil)

Chloroquine (Aralen) Drug of choice for oral treatment of all malaria except that caused by resistant P. falciparum

Chloroquine: Adverse Effects Common: pigmentation of skin and nail beds, pruritus, fatigue Serious: toxic psychosis, ototoxicity, retinopathy, corneal opacities

Chloroquine: Contraindications Patients with liver disease, hypersensitivity to 4-aminoquinolines, psoriasis, porphyria, renal disease Should not be used in children or in pregnant or lactating women Certain antacids and laxatives decrease chloroquine absorption.

Chloroquine: Patient Teaching Tell patients to promptly report visual or hearing disturbances, muscle weakness, loss of balance, fever, sore mouth or throat, unexplained fatigue, easy bruising, or bleeding. Advise patients to wear dark glasses in sunlight.

Chloroquine: Patient Teaching Warn patients against driving or other potentially hazardous activities. Urine may be rusty yellow or brown.

Primaquine (Primaquine) Used for radical cure of relapsing vivax or ovale malaria

Primaquine: Adverse Effects Recommended doses are generally well tolerated. Infrequent: nausea, vomiting, abdominal cramps, headache Serious (but rare): leukopenia, agranulocytosis, cardiac arrhythmias

Primaquine: Contraindications Avoid use in patients with rheumatoid arthritis and lupus erythematosus, and in pregnant patients.

Primaquine: Patient Teaching Instruct patients to examine urine and report darkening or red tinge or a decrease in urine volume. Advise patients to report chills, fever, pain in the diaphragm, and cyanosis. Warn women to avoid breastfeeding.

Quinine (Quinamm) First-line therapy for falciparum malaria, especially severe disease Not used in chemoprophylaxis because of its toxicity

Quinine: Adverse Effects Common: visual and hearing disturbances, fever, headache, flushing, syncope (fainting), vomiting, diarrhea, abdominal pain Serious: cardiovascular collapse

Quinine: Contraindications Avoid in patients with visual or auditory problems. Use cautiously in patients with underlying cardiac abnormalities. Reduce dosage in patients with renal insufficiency. Interactions: Aluminum-containing antacids may block absorption; quinine can raise warfarin and digoxin levels

Quinine: Patient Teaching Advise patients to report faintness. Instruct patients to eat a balanced diet with no excesses in fruit juices or milk. Warn patients to avoid OTC drugs and to take as directed.

Hydroxychloroquine (Plaquenil) Suppresses malaria attacks caused by P. vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum Used adjunctively with primaquine (Primaquine) for eradication of P. vivax and P. malariae Commonly prescribed for treatment of rheumatoid arthritis and lupus erythematosus

Hydroxychloroquine: Adverse Effects Common: nausea, vomiting, anorexia, diarrhea, abdominal cramps, weight loss, fatigue, vertigo, headache, anxiety, retinopathy, blurred vision, mood changes Serious (but rare): aplastic anemia, agranulocytosis, thrombocytopenia, alopecia, retinopathy

Hydroxychloroquine: Contraindications Visual field changes, psoriasis, porphyria Safe use for juvenile arthritis or in lactating women not established. Use cautiously in patients with liver disease, alcoholism, and impaired renal function.

Hydroxychloroquine: Contraindications Interactions: Aluminum-and magnesium-containing antacids and laxatives decrease absorption

Hydroxychloroquine: Patient Teaching Instruct patients about adverse effects and related symptoms. Advise patients to take as directed. Instruct patients to keep this drug out of reach of children and to avoid breastfeeding.

Antimalarial Drugs in Children Children who will travel to countries that require antimalarial vaccinations should be vaccinated 4 to 6 weeks prior to leaving. Dosages for children and infants must be specially prepared and guidelines followed exactly. Overdosage can be fatal.

Protozoal Infections Entamoeba histolytica and Giardia lamblia cause dysentery (an inflammatory disease of the lower intestinal tract) in humans. Trichomonas vaginalis (T. vaginalis) causes a sexually transmitted disease called trichomoniasis. G. lamblia causes giardiasis.

Centers for Disease Control and Prevention (CDC) Figure 13-2 Vaginal discharge with microorganisms due to trichomoniasis.

Antiprotozoal Agents Metronidazole (Flagyl) Iodoquinol (Yodoxin) Tetracyclines Paromomycin (Humatin) Combination therapy can eliminate parasites from all sites

Table 13-3 Antiprotozoal Agents

Metronidazole (Flagyl) Used to treat liver abscess, intestinal amebiasis, trichomoniasis, anaerobic infections, vaginosis, diarrhea, colitis, and pelvic inflammatory disease (PID) For prevention of postoperative infection following colorectal surgery

Metronidazole: Adverse Effects Common: nausea, vomiting, anorexia, abdominal cramps, metallic or bitter taste, skin rashes, pruritus, flushing, fever, vertigo, headache, confusion, depression, restlessness, insomnia Sometimes: dark-colored urine

Metronidazole: Contraindications Avoid in patients with diseases of the central nervous system. Withhold during pregnancy in most cases. Interactions: cimetidine, disulfiram, lithium, oral anticoagulants, phenobarbital, alcohol, phenytoin

Metronidazole: Patient Teaching Instruct patients to take as directed. Advise patients to refrain from intercourse during therapy for trichomoniasis unless a condom is used to prevent reinfection. Advise patients to have sexual partners treated concurrently.

Iodoquinol (Diquinol, Yodoxin) Anti-amebicide, anti-infective, antiprotozoal agent Works in intestinal lumen Enters cells of protozoa, affecting DNA, inhibiting synthesis, and causing cell death

Iodoquinol: Adverse Effects Common: diarrhea, nausea, vomiting, abdominal pain, anorexia, headache, rash, pruritus, blurred vision, optic atrophy, permanent loss of vision, thyroid hypertrophy

Iodoquinol: Contraindications Avoid in patients with hypersensitivity to any iodine-containing preparations or foods, and those with hepatic or renal damage. Safe use during pregnancy or lactation is not established.

Iodoquinol: Patient Teaching Instruct patients to report skin rash, chills, fever, weakness, or fatigue. Advise patients to take as directed. Explain to patients that their stools need to be examined at 1, 3, and 6 months after termination of treatment.