McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 1 1  Antifungal agents

F ungal infections in humans range from conditions such as the annoying “athlete’s foot” to potentially fatal systemic infections. An infection caused by a fungus is called a mycosis . Fungi differ from bacteria in that the fungus has a rigid cell wall that is made up of chitin and various polysaccharides and a cell membrane that contains ergosterol . The composition of the protective layers of the fungal cell makes the organism resistant to antibiotics. Conversely, because of their cellular makeup, bacteria are resistant to antifungal drugs. The incidence of fungal infections has increased with the rising number of immunocompromised indi- viduals—people with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC), those taking immunosuppressant drugs, those who have undergone transplantation surgery or cancer treatment and members of the increasingly large elderly popula- tion, whose body is no longer able to protect itself from the many fungi that are found throughout the environ- ment (Box 11.1). For example, Candida , a fungus that is normally found on mucous membranes, can cause yeast infections or “thrush” in the gastrointestinal (GI) tract and yeast infections or “vaginitis” in the vagina.

SYSTEMIC ANTIFUNGALS The drugs used to treat systemic fungal infections (Table 11.1) can be toxic to the host and are not used indiscriminately. It is important to get a culture of the fungus causing the infection to ensure that the right drug is being used so that the person is not put at addi- tional risk from the toxic adverse effects associated with these drugs. A zole antifungals The azoles are a large group of antifungals used to treat systemic and topical fungal infections (Table 11.1). The azoles include fluconazole ( Canesoral , Diflucan, Dizole ), itraconazole ( Sporanox ), ketoconazole ( Nizoral ), posa- conazole ( Noxafil ), terbinafine ( Lamisil , Tamsil ) and voriconazole ( Vfend ). Although azoles are considered less toxic than some other antifungal agents, such as amphotericin B, they may also be less effective in very severe and progressive infections. Therapeutic actions and indications These drugs bind to sterols and can cause cell death (a fungicidal effect) or interfere with cell replication (a fungistatic effect), depending on the type of fungus being affected and the concentration of the drug. (See Figure 11.1.) risk to the fetus or neonate. Women of childbearing age should be advised to use barrier contraceptives if any of these drugs are used. A severe fungal infection may threaten the life of the mother and/or fetus; in these situations, the potential risk of treatment should be carefully explained. Topical agents should not be used over open or draining areas, which would increase the risk of systemic absorption. OLDER ADULTS Older people may be more susceptible to the adverse effects associated with these drugs and should be monitored closely. People with hepatic dysfunction are at increased risk for worsening hepatic problems and toxic effects of many of these drugs (ketoconazole, itraconazole, griseofulvin). If hepatic dysfunction is expected (extreme age, alcohol abuse, use of other hepatotoxic drugs), the dose may need to be lowered and the person monitored more frequently. Other agents are associated with renal toxicity (flucytosine, fluconazole, griseofulvin) and should be used cautiously in the presence of renal impairment. People at risk for renal toxicity should be monitored carefully.

Drug therapy across the lifespan

BOX 11.1

Antifungal agents CHILDREN

Children are very sensitive to the effects of most antifungal drugs and more severe reactions can be expected when these drugs are used in children. Many of these drugs do not have proven safety and efficacy in children and extreme caution should be exercised when using them. Fluconazole, ketoconazole, terbinafine and griseofulvin have established paediatric doses and would be drugs of choice if appropriate for a particular infection. Topical agents should not be used over open or draining areas that would increase the risk of systemic absorption and toxicity. Occlusive dressings, including tight nappies, should be avoided over the affected areas. ADULTS These drugs can be very toxic to the body, and their use should be reserved for situations in which the causative organism has been identified. Over-the-counter topical preparations are widely used, and people should be cautioned to follow the instructions and to report continued problems to their healthcare provider. PREGNANCY AND BREASTFEEDING Pregnant and breastfeeding women should not use these drugs unless the benefit clearly outweighs the potential