Sica Domenic A
Expert Opin Pharmacother. 2009 Sep;10(13):2037-9. doi: 10.1517/14656560903158956.
Diuretic therapy remains a mainstay of hypertension treatment, either given as monotherapy or used in combination with other antihypertensive compounds. Several issues have complicated the issue of diuretic use with that of class effect being the one that has proven most difficult. Hydrochlorothiazide is a commonly used thiazide diuretic; whereas chlorthalidone is a structurally similar compound, quite dissimilar pharmacokinetically with a much longer half-life for effect and a wider volume of distribution with heavy partitioning in red blood cells. These pharmacokinetic features afford chlorthalidone a unique advantage in its capacity to act as an effective diuretic and blood-pressure-lowering agent, as well as a compound that improves cardiovascular outcomes in the patient with hypertension. Chlorthalidone has been used sparingly in clinical practice in large measure because it is not readily available in many fixed-dose combination products. Fixed-dose combinations containing chlorthalidone and an angiotensin-receptor blocker are now in development. It remains to be determined how well these two therapies will reduce blood pressure in the general population while keeping compound-specific side effects to a minimum.
利尿剂治疗仍然是高血压治疗的主要手段，可作为单一疗法使用，也可与其他抗高血压药物联合使用。有几个问题使利尿剂的使用问题变得复杂，其中类效应问题已被证明是最棘手的。氢氯噻嗪是一种常用的噻嗪类利尿剂；而氯噻酮是一种结构相似的化合物，其药代动力学有很大不同，作用半衰期长得多，分布容积更广，在红细胞中大量蓄积。这些药代动力学特性赋予氯噻酮独特优势，使其能够作为有效的利尿剂和降压药，也是一种能改善高血压患者心血管结局的化合物。氯噻酮在临床实践中使用较少，很大程度上是因为它在许多固定剂量复方制剂中不易获得。目前正在研发含氯噻酮和血管紧张素受体阻滞剂的固定剂量复方制剂。这两种疗法在普通人群中降低血压的效果如何，同时将特定化合物的副作用降至最低，仍有待确定。
