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Antifungal Drugs Contraindications Precautions And Intrerations

Fungal infections range from superficial skin infections to life-threatening systemic infections. Systemic fungal infections are serious infections that occur when fungi gain entrance into the interior of the body.
A fungus is a colorless plant that lacks chlorophyll.
Fungi that cause disease in humans may be yeastlike or moldlike; the resulting infections are called mycotic
infections or fungal infections.Mycotic (fungal) infections may be one of two types:
1. Superficial mycotic infections
2. Deep (systemic) mycotic infections
The superficial mycotic infections occur on the surface of, or just below, the skin or nails. Superficial infections include tinea pedis (athlete’s foot), tinea cruris (jock itch), tinea corporis (ringworm), onychomycosis (nailfungus), and yeast infections, such as those caused by Candida albicans.
Yeast infections or those caused by C. albicans affect women in the vulvovaginal area and can be difficult
to control. Women who are at increased risk for vulvovaginal yeast infections arethose who have diabetes, are pregnant, or are taking oral contraceptives, antibiotics, or corticosteroids. Deep mycotic infections develop inside the body, such as in the lungs. Treatment for deep mycotic infections is often difficult and prolonged.
ACTIONS
Antifungal drugs may be fungicidal (able to destroy fungi) or fungistatic (able to slow or retard the multiplication of fungi). Amphotericin B (Fungizone IV),miconazole (Monistat), nystatin (Mycostatin), and ketoconazole (Nizoral) are thought to have an effect on the cell membrane of the fungus, resulting in a fungicidal or fungistatic effect. The fungicidal or fungistatic effect of these drugs appears to be related to their concentration in body tissues. Fluconazole (Diflucan) has fungistatic activity that appears to result from the depletion of sterols (a group of substances related to fats) in the fungus cells. Griseofulvin (Grisactin) exerts its effect by being deposited in keratin precursor cells, which are then gradually lost (due to the constant shedding of top skin cells), and replaced by new , noninfected cells.The mode of action of flucytosine (Ancobon) is not clearly understood. Clotrimazole (Lotrimin, Mycelex) binds with phospholipids in the fungal cell membrane,increasing permeability of the cell and resulting in loss of intracellular components.

USES
Antifungal drugs are used to treat superficial and deep fun-gal infections. The antifungal drugs specifically discussed in this chapter are: amphotericin B (Fungizone), flucona-zole (Diflucan), flucytosine (Ancobon), griseofulvin (Grisactin), ketoconazole (Nizoral), and miconazole (Monistat).
Miconazole is an antifungal drug used to treat vulvo-vaginal “yeast” infections and is representative of all of the vaginal antifungal agents.Fungal infections of the skin or mucous membranes may be treated with topical or vaginal preparations.

ADVERSE REACTIONS
When topical antifungal drugs, such as clotrimazole, are applied to the skin or mucous mem-branes, few adverse reactions are seen. On occasion, a local reaction, such as irritation or burning, may occur with topical use. The vulvovaginal antifungal drugs may cause local irritation, redness, stinging, or abdominal
pain. Few adverse reactions are seen with the use of the vulvovaginal antifungal drugs.

Amphotericin B
Amphotericin B is the most effective drug available forthe treatment of most systemic fungal infections.Administration often results in serious reactions,including fever, shaking, chills, headache, malaise, anorexia, joint and muscle pain, abnormal renal func-tion, nausea, vomiting, and anemia. This drug is given
parenterally, usually for a period of several months.Its use is reserved for serious and potentially life-threatening fungal infections. Some of these adverse reactions may be lessened by use of aspirin, antihistamines, or antiemetics.

Fluconazole
Administration may result in nausea, vomiting,headache, diarrhea, abdominal pain, and skin rash.Abnormal liver function tests may be seen and may require follow-up tests to determine if liver function has been affected.
Flucytosine
Administration may result in nausea, vomiting, diar-rhea, rash, anemia, leukopenia, and thrombocytopenia.Signs of renal impairment include elevated blood urea nitrogen (BUN) and
serum creatinine levels. Periodic renal function tests are usually performed during therapy.

Griseofulvin
Administration may result in a hypersensitivity-type reaction that includes rash and urticaria. Nausea, vomit-ing, oral thrush, diarrhea, and headache also may be seen.
Itraconazole
The most common adverse reactions are nausea, vomit-ing, and diarrhea. On occasion, severe hypokalemia (low potassium level) has occurred in patients receiving 600 mg or more of the drug on a daily basis. Hepatotoxicity is a possibility with itraconazole administration.

Ketoconazole

This drug is usually well tolerated, but nausea, vomit-ing, headache, dizziness, abdominal pain, and pruritus may be seen. Most adverse reactions are mild and transient. On rare occasions, hepatic toxicity may be seen,and use of the drug must be discontinued immediately.Periodic hepatic function tests are recommended to monitor for hepatic toxicity.
Miconazole
Administration of miconazole for a vulvovaginal fungal infection may cause irritation, sensitization, or vulvo- vaginal burning. Skin irritation may result in redness, itching, burning, or skin fissures. Other adverse reac-tions with miconazole include cramping, nausea, and headache. Adverse reactions associated with topical use are usually not severe.

CONTRAINDICATIONS, PRECAUTIONS,
AND INTERACTIONS


Amphotericin B

Amphotericin B is contraindicated in patients with a his-tory of allergy to the drug and during lactation. It is used cautiously in patients with renal dysfunction, electrolyte imbalances, and in combination with antineoplastic drugs (because it can cause severe bone marrow sup-pression). This drug is a Pregnancy Category B drug and is used during pregnancy only when the situation is life threatening. When given with the corticosteroids, severe hypokalemia may occur. There may be an increased risk of digitalis toxicity if digoxin is administered con-currently with amphotericin B. Administration with nephrotoxic drugs (eg,aminoglycosides or cyclosporine)may increase the risk of nephrotoxicity in patients also taking amphotericin B. Amphotericin B decreases the effects of miconazole. Amphotericin B is given only under close supervision in the hospital setting.
Fluconazole

Fluconazole is contraindicated in patients with known hypersensitivity to the drug. The drug is used cautiously in patients with renal impairment and during pregnancy (Category C) and lactation. The drug is given during pregnancy only if the benefit of the drug clearly outweighs any possible risk to the infant. When fluconazole is administered with oral hypoglycemics, there is an increased effect of the oral hypoglycemics.Fluconazole may decrease the metabolism of phenytoin and warfarin.

Flucytosine

Flucytosine is contraindicated in patients with known hypersensitivity to the drug. Flucytosine is used autiously in patients with bone marrow depression and with extreme caution in those with renal impairment.
The drug is also used cautiously during pregnancy (Category C) and lactation. When flucytosine and
amphotericin B are administered concurrently, the risk of flucytosine toxicity is increased.

Griseofulvin

Griseofulvin is contraindicated in patients with known hypersensitivity to the drug and in those with severe liver disease. This drug is used cautiously during pregnancy (Category C) and lactation. It is impor-tant to use caution when administering concurrently with penicillin because there is a possibility of crosssensitivity. When griseofulvin is administered with warfarin, the anticoagulant effect may be decreased.When administered with the barbiturates the effect of griseofulvin may be decreased. A decrease in the effects of oral contraceptives may occur with griseo-fulvin therapy, causing breakthrough bleeding, preg-nancy, or amenorrhea. Blood salicylate concentrations may be decreased when the salicylates are adminis tered with griseofulvin.


Itraconazole

Itraconazole is contraindicated in patients with a known hypersensitivity to the drug. The drug is used cautiously in patients with hepatitis, those with human immunodeficiency virus, impaired liver function, and in pregnant women (Pregnancy Category C). In patients with hypochlorhydria, the absorption of itraconazole
is decreased. Multiple drug interactions occur with itraconazole. Itraconazole elevates blood concentrations of digoxin and cyclosporine. Phenytoin decreases blood levels of itraconazole and alters the metabolism of phenytoin. Histamine antagonists, isoniazid, and rifampin decrease plasma levels of itraconazole. There is
an increased anticoagulant effect when warfarin is administered concurrently with itraconazole.

Ketoconazole
Ketoconazole is contraindicated in patients with known hypersensitivity to the drug. Ketoconazole is used cau-tiously in patients with hepatic impairment, those who are pregnant (Category C), and during lactation. The absorption of ketoconazole is impaired when the drug is taken with histamine antagonists and antacids.
Ketoconazole enhances the anticoagulant effect of warfarin and causes an additive hepatotoxicity when given with other hepatotoxic drugs and alcohol.
Administration of ketoconazole with rifampin or isoni-azid may decrease the blood levels of ketoconazole.

Miconazole
Miconazole is contraindicated in patients with known hypersensitivity to the drug. The drug is given cau-tiously in cases of chronic or recurrent candidiasis.With recurrent or chronic candidiasis the patient may have underlying diabetes. Recurrent or chronic candidi-asis requires an evaluation for diabetes. The drug is
used cautiously during pregnancy (Category C). If used during pregnancy, a vaginal applicator may be con-traindicated. Manual insertion of the vaginal tablets may be preferred. Because small amounts of these drugs may be absorbed from the vagina, the drug is used dur-ing the first trimester only when essential.
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Ditulis oleh: Shahzad Khan - Wednesday, 21 April 2010