Adverse Reactions to Drugs Used in Respiratory Medicine
Although the pharmacologic treatment of respiratory diseases such as asthma, allergies, and infections can be accomplished effectively with a variety of commercially available drugs, all of these therapies carry the potential for bothersome or severe adverse reactions. Numerous scientific posters presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, San Francisco, CA, provided details of the types of adverse events that can be associated with drugs used to treat a variety of respiratory diseases. For example:
Antibiotic Reactions in Children
An evaluation of 86 children followed for 5 years has helped determine the incidence of adverse events to antibiotics. These events typically manifested as skin rashes. All of these children had been treated for an upper respiratory tract infection; by age 3, 80% of the children had experienced an adverse event to an antibiotic. Of these, 85% had erythema and 15% had urticaria. The most commonly used drugs were amoxicillin, Ceclor, Pediazole, and Suprax. The infection itself may have caused the event in some of the children. The investigators found that many adverse events in children might be avoided by using dye-free antibiotics.
Gender Differences in Adverse Drug Reactions
Several studies have suggested that adverse drug reactions occur more frequently in women than men. One study of 2,367 Canadian patients designed to confirm these earlier findings indicated that the most frequent event reported over a 10-year period, rash, was reported by 19.8% of men and 19.9% of women. The next most common events were allergic or immunologic reactions and gastrointestinal disorders. Seven percent of the men and 8% of the women (p less than 0.05) experienced a severe adverse event. The three most common classes of drugs implicated for adverse events in both genders were systemic antibiotics, antiepileptic agents, and analgesics. Fifty percent of the women compared to 33% of the men reported having an adverse event in response to more than one medication (p less than 0.0005). These results supported previous findings that women are more likely than men to experience an adverse event in response to drug therapy.
Trimethoprim/Sulfamethoxazole (TMP/SMX)
Widely used for pediatric and respiratory infections in patients with HIV, TMP/SMX has been associated with a high incidence of adverse events. These may be decreased if patients are desensitized to the drug. One protocol for desensitizing adult patients is as follows: initial dose 0.04 mg TMP/0.2 mg SMX, doubled every 12 hours on the first two days and every 24 hours on the following days, until the therapeutic doses of 160 TMP/800 mg SMX are reached. In this way the full dose may be reached in 8 days.
Antihistamines in Children
Several reports have associated the use of terfenadine and astemizole with cardiac side effects, when they are given in high doses or when they are used in combination with ketoconazole or a macrolide antibiotic. One study assessed the cardiotoxic potential of these two drugs, along with that of loratadine and cetirizine, in 80 children (aged 5 to 12 years) with perennial allergic rhinitis and sinusitis. Patients received these drugs for 2 weeks then continued to receive the drugs concomitantly with erythromycin (50 mg/kg/day) for another 2 weeks. Terfenadine plus erythromycin significantly prolonged the QT interval of the ECG, but the QTc was not affected. These findings suggest that these four antihistamines are not likely to produce adverse cardiac events in children. However, prudent care dictates that terfenadine and other antihistamines not be used in conjunction with erythromycin if previous experience has shown that the combination has the potential for cardiac events.
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