Cough is a normal physiologic reflex(生理反射) mediated by the 'cough center' of the brain. The function of this reflex is to clear airways of inhaled irritants, debris(碎屑), or secretions that have accumulated as a result of bacterial or viral infection. Cough may also occur in response to irritation of inflame respiratory epithelium(道上皮), as is commonly seen with some viral infections. Irritant-initiated cough often has little effect on clearance of secretions and is called 'nonproductive cough'(咳痰). APPROACHES TO TREATMENT Cough accompanies many different disorders. Suppressing a productive cough(千咳)can interfere with normal defense mechanisms and be potentially harmful. Suppression of nonproductive cough is safer but is not essential. Antitussive(镇咳的) use is justifiable in severe cases in which nonproductive cough is causing emesis, exhaustion, or significant loss of sleep. ANTITUSSIVE AGENTS Three antitussive agents are commonly used: Codeine. Codeine suppresses the cough reflex by acting directly on the medullary(延髓的) cough center of the brain. Its drying effect on the respiratory mucosa can increase the viscosity of bronchial secretions. Antitussive effects of codeine are dose dependent in adults, but complete cough suppression may not be possible at nontoxic doses. Although codeine is the standard against which other antitussive medications are compared, it may be less effective in children than in adults. The recommended dosage for children is 1mg/kg/day in four divided doses(maximum of 60 mg/day). Antitussive effects are greatest at one to two hours and persist for about four hours. Nausea, vomiting, constipation, and dizziness are the most common side effects. In over doses, toxicity consists primarily of respiratory depression and narcosis. Limited data suggest that single doses of more than 5 mg/kg may be lethal in children. Infants may be more sensitive to codeine' s effects and may have decreased ability to metabolize the drug, thus, use of codeine in children less than one year old should be discouraged. Dextromethorphan(美沙芬). Like codeine, dextromethorphan has antitussive activity but a very low addictive potential. In adults, the two drugs are considered equipotent. Dextromethorphan's antitussive effect can begin as early as 15 to 30 minutes after a dose is taken, and its duration of action is between three and six hours. Because the drug is metabolized through oxidative pathways, infants metabolize dextromethorphan slowly and are at greater risk of dose-dependent side effects, particularly if given multiple doses. Dextromethorphan and codeine both act at the same central nervous system(CNS)site. Although CNS depression can be seen with either agent, dextromethorphan has a wider margin of safety. Overdoses of up to 100 times the usual adult dose have not resulted in any fatalities. Treatment of overdose should include supportive measures and use of naloxone(纳洛酮), if respiratory depression occurs. Minor adverse effects (副作用) sometimes seen in nonintoxicated patients include nausea, dizziness, and slight drowsiness. Diphenhydramine(苯海拉明). The antihistamine diphenhydramine has weak anti tussive effects. These effects may often be incomplete, however, and cough suppression may not be achived without side effects. In addition to acting on medullary cough centers, diphenhydramine has peripheral anticholinergic(抗胆碱能的) effects that may contribute to its cough-suppressing action. The anticholinergic effects may also help to dry the respiratory tract and thicken secretions—undesirable effects in patients with productive cough. In adults, 25 to 50 mg of diphenhydramine has produced cough suppression equivalent to that of 15 mg of codeine. Similar data in children are not available. GUIDELINES FOR USE OF ANTITUSSIVES Remember that cough