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联合使用β受体激动剂/利尿剂治疗的低钾血症及心电图后遗症。常规剂量螺内酯有保护作用,但氨苯蝶啶无此作用。

Hypokalemic and ECG sequelae of combined beta-agonist/diuretic therapy. Protection by conventional doses of spironolactone but not triamterene.

作者信息

Lipworth B J, McDevitt D G, Struthers A D

机构信息

Department of Clinical Pharmacology, Ninewells Hospital, Dundee, Scotland.

出版信息

Chest. 1990 Oct;98(4):811-5. doi: 10.1378/chest.98.4.811.

Abstract

Salbutamol (Albuterol) and diuretics are commonly prescribed together in patients with airflow obstruction and are associated with electrocardiographic effects. We have now investigated whether the use of potassium-sparing drugs might prevent the ECG sequelae of such combined therapy. Ten healthy subjects received seven days of randomized treatments with: placebo, bendrofluazide (5 mg), bendrofluazide plus triamterene 50 mg (conventional dose), or triamterene 200 mg (high dose), and bendrofluazide plus spironolactone (100 mg). Potassium and ECG responses to inhaled salbutamol, 2 mg, were measured after each treatment period. The T-wave flattening in response to bendrofluazide and salbutamol (0.24[CI, 0.19 to 0.29]mV) was attenuated by the addition of triamterene, 200 mg (0.33[CI, 0.28 to 0.37]mV; p less than 0.05) and spironolactone 100 mg (0.42[CI, 0.37 to 0.47]mV; p less than 0.01), but not by triamterene 50 mg (0.25[CI, 0.20 to 0.30]mV). Spironolactone and high dose triamterene also diminished the frequency of U waves and ST depression. The ECG effects mirrored hypokalemic responses which were also blunted by high dose (p less than 0.01) but not low dose triamterene, as well as by spironolactone (p less than 0.001). Thus, the use of high dose triamterene and spironolactone protected against the hypokalemic and ECG sequelae of combined beta-agonist/diuretic therapy, whereas a conventional dose of triamterene had no effect. These findings may be important in the prevention of a potentially dangerous interaction in susceptible patients taking this combination of drugs.

摘要

沙丁胺醇(舒喘灵)和利尿剂常用于气流阻塞患者,二者联用会产生心电图效应。我们现研究保钾药物的使用是否能预防此类联合治疗的心电图后遗症。10名健康受试者接受为期7天的随机治疗,治疗方案如下:安慰剂、苄氟噻嗪(5毫克)、苄氟噻嗪加氨苯蝶啶50毫克(常规剂量)、氨苯蝶啶200毫克(高剂量),以及苄氟噻嗪加螺内酯(100毫克)。在每个治疗期后,测量吸入2毫克沙丁胺醇后的血钾及心电图反应。苄氟噻嗪和沙丁胺醇联用导致的T波低平(0.24[可信区间,0.19至0.29]毫伏),在加用200毫克氨苯蝶啶后有所减轻(0.33[可信区间,0.28至0.37]毫伏;p小于0.05),加用100毫克螺内酯后也减轻(0.42[可信区间,0.37至0.47]毫伏;p小于0.01),但加用50毫克氨苯蝶啶后无变化(0.25[可信区间,0.20至0.30]毫伏)。螺内酯和高剂量氨苯蝶啶还减少了U波出现频率及ST段压低。心电图效应反映了低钾血症反应,高剂量氨苯蝶啶(p小于0.01)及螺内酯(p小于0.001)也可减轻低钾血症反应,而低剂量氨苯蝶啶则无此作用。因此,高剂量氨苯蝶啶和螺内酯可预防β受体激动剂/利尿剂联合治疗导致的低钾血症及心电图后遗症,而常规剂量氨苯蝶啶则无效。这些发现对于预防服用此类药物组合的易感患者中可能存在的危险相互作用或许具有重要意义。

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