Friedel H A, Buckley M M
Adis Drug Information Services, Auckland, New Zealand.
Drugs. 1991 Jan;41(1):81-103. doi: 10.2165/00003495-199141010-00008.
Torasemide (torsemide) is a high-ceiling loop diuretic which acts on the thick ascending limb of the loop of Henle to promote rapid and marked excretion of water, sodium and chloride. Like furosemide (frusemide), its major site of action is from the luminal side of the cell. Torasemide is at least twice as potent as furosemide on a weight-for-weight basis, produces equivalent diuresis and natriuresis at lower urinary concentrations and has a longer duration of action, allowing once-daily administration without the paradoxical antidiuresis seen with furosemide. Torasemide also appears to promote excretion of potassium and calcium to a lesser extent than furosemide. In trials of up to 48 weeks' duration in patients with mild to moderate essential hypertension, torasemide, administered as a single daily dose, has been shown to achieve adequate blood pressure control reaching steady-state within 8 to 12 weeks. Those patients not responding initially have generally responded to a doubling of the dose. Comparative trials of up to 6 months show torasemide is as effective as indapamide, hydrochlorothiazide or a combination of triamterene/hydrochlorothiazide in maintaining control of blood pressure. Torasemide has also been used successfully to treat oedematous states associated with chronic congestive heart failure, renal disease and hepatic cirrhosis. In short term trials control of blood pressure, bodyweight and residual oedema has been sustained. Torasemide appears to be a useful alternative to furosemide in these patients, providing potent and long-lasting diuresis while being relatively potassium and calcium sparing. In clinical trials to date torasemide has been well tolerated with adverse effects of a mild, transient nature reported by only small numbers of patients. Changes in biochemical parameters have been common, including decreases in plasma sodium and potassium levels and increases in plasma creatinine and uric acid levels. These changes are typical of loop diuretics. No changes were clinically significant nor were clinically relevant changes noted in glucose metabolism, cholesterol or triglyceride levels or in haematological values. Thus, torasemide is an interesting new loop diuretic with potential use in the treatment of mild to moderate essential hypertension and of oedematous states in which diuretic therapy is warranted. Preliminary studies suggest it to be as efficacious as other diuretics in common use and to have some advantage over furosemide in duration of action and in effects on potassium and calcium. However, further long term trials in larger groups of patients are needed to delineate the place of torasemide in therapy fully, both as a single agent and in combination with other currently accepted drug regimens.
托拉塞米是一种高效能袢利尿剂，作用于髓袢升支粗段，促进水、钠和氯的快速、显著排泄。与呋塞米一样，其主要作用部位在细胞腔面。按重量计算，托拉塞米的效力至少是呋塞米的两倍，在较低尿液浓度下产生等量的利尿和利钠作用，且作用持续时间更长，允许每日一次给药，不会出现呋塞米所见的反常抗利尿现象。托拉塞米促进钾和钙排泄的程度似乎也比呋塞米小。在轻度至中度原发性高血压患者中进行的长达48周的试验表明，托拉塞米每日单次给药，在8至12周内可达到稳态，实现充分的血压控制。最初无反应的患者通常对剂量加倍有反应。长达6个月的对比试验表明，托拉塞米在维持血压控制方面与吲达帕胺、氢氯噻嗪或氨苯蝶啶/氢氯噻嗪组合一样有效。托拉塞米还成功用于治疗与慢性充血性心力衰竭、肾病和肝硬化相关的水肿状态。在短期试验中，血压、体重和残余水肿得到持续控制。在这些患者中，托拉塞米似乎是呋塞米的一种有用替代药物，能提供强效且持久的利尿作用，同时相对较少排钾和钙。在迄今为止的临床试验中，托拉塞米耐受性良好，只有少数患者报告有轻度、短暂的不良反应。生化参数变化很常见，包括血浆钠和钾水平降低，血浆肌酐和尿酸水平升高。这些变化是袢利尿剂的典型表现。在葡萄糖代谢、胆固醇或甘油三酯水平或血液学指标方面，未发现具有临床意义的变化，也未观察到与临床相关的变化。因此，托拉塞米是一种有趣的新型袢利尿剂，在治疗轻度至中度原发性高血压以及有必要进行利尿治疗的水肿状态方面具有潜在用途。初步研究表明，它与其他常用利尿剂一样有效，在作用持续时间以及对钾和钙的影响方面比呋塞米有一些优势。然而，需要在更大规模的患者群体中进行进一步的长期试验，以全面确定托拉塞米在治疗中的地位，包括作为单一药物以及与其他目前公认的药物方案联合使用时的地位。
