PHARMACODYNAMICS OF CALCIUM BLOCKERS IN ASTHMA

细胞内钙调节的改变可能是最后的共同点 哮喘的发病机制。 然而，钙的作用 这种疾病中的通道阻滞剂尚未确定。 本研究提出 以逻辑和系统的方式研究潜在的疗效， 这组药物在控制慢性 哮喘，并评估乙酰胆碱诱导的 支气管收缩，以选择临床有效的成员， 给药类别、途径、剂量和频率。 在第一阶段， 三组10名慢性哮喘患者将接受7次治疗， 分开的日子，安慰剂和分级剂量的吸入维拉帕米， 吸入地尔硫卓或口服地尔硫卓;每组一种药物。 支气管 在每次检查之前和之后， 次给药结束 心电图、血压和是否存在主观主诉 将定期监测副作用，以确定每种药物的安全性。 次给药结束 每隔一段时间采集血样以测量维拉帕米， 地尔硫卓和代谢物血清浓度。 每种药物的剂量， 产生最大的阻断作用，无毒性，将用于阶段 二. 在这个阶段，吸入维拉帕米，口服和吸入的效果 地尔硫卓和安慰剂阻断支气管收缩反应 将在双盲随机交叉试验中测定乙酰甲胆碱 方法对40例慢性哮喘患者进行问卷调查。 连续四天 将进行乙酰甲胆碱激发，测量血清浓度， 在给药后12小时内以2小时间隔评估毒性。 次给药结束 响应时间曲线下面积将用于确定 相对强度和持续时间。 第三阶段，40 患者将用安慰剂治疗三个月， II期研究中的两种活性药物方案被判定为效果最差， 最有效的，以随机双盲交叉的方式。 剂量 和给药频率将与阶段中使用的相同 二. 哮喘症状的频率、不良反应、呼气峰 流速，以及吸入β受体激动剂和其他药物的需求 对于急性症状，患者将在日记中记录两次 日报 此外，患者将每隔两周接受一次随访， 评估，肺功能测定，标准运动负荷试验，血清 测量和合规性检查。

Altered regulation of intracellular calcium is probably the final common pathway for the pathogenesis of asthma. However, the role of calcium channel blockers in this disease has not been defined. This study proposes to investigate, in a logical and systematic manner, the potential efficacy and safety of this group of drugs in controlling the symptoms of chronic asthma, and to evaluate the usefulness of methacholine-induced bronchoconstriction for selecting a clinically effective member of this class, route, dose and frequency of administration. In the first phase, three groups of ten patients with chronic asthma will receive, on seven separate days, placebo and graded doses of either inhaled verapamil, inhaled diltiazem or oral diltiazem;one drug per group. A bronchial provocation test with methacholine will be performed before and after each dose. ECG, blood pressure and the presence of subjective complaints of side effects will be monitored at intervals to determine the safety of each dose. Blood samples will be obtained at intervals to measure verapamil, diltiazem and metabolite serum concentrations. The dose of each drug that produces maximum blocking effect without toxicity will be used for Phase II. In this phase, the effect of inhaled verapamil, oral and inhaled diltiazem and placebo in blocking the bronchoconstrictor response to methacholine will be determined in a double-blind randomized cross-over manner in 40 patients with chronic asthma. On four separate days serial methacholine challenges will be performed, serum concentrations measured, and toxicity assessed at 2 hour intervals for a 12 hour period after the dose. The area under the response-time curve will be used to determine the relative intensity and durationof each regimen. In the third phase, 40 patients will be treated for three one month periods with placebo and the two active drug regimens in Phase II that were judged least effective and most effective, in a randomized double-blind cross-over manner. The dose and frequency of administration will be the same as those used in Phase II. The frequency of asthmatic symptoms, adverse effects, peak expiratory flow rate, and the need for inhaled beta agonists and additional medicatons for acute symptoms will be recorded by the patinets in a diary twice daily. In addition, patients will be seen at two week intervals for evaluation, spirometry, a standardized exercise stress test, serum level measurements, and compliance check.