van Rijnsoever E W, Kwee-Zuiderwijk W J, Feenstra J
Pharmacy Apotheek Leusden, The Netherlands.
Arch Intern Med. 1998 Oct 12;158(18):2063-5. doi: 10.1001/archinte.158.18.2063.
Angioedema is a well-known adverse effect of angiotensin-converting enzyme inhibitors. The bradykinin accumulation as a result of the decreased degradation of bradykinin is thought to be the causal mechanism. Angiotensin II antagonists seem to have no effect on the degradation of bradykinin. Therefore, it was expected that angioedema would not occur during treatment with losartan potassium, the first orally active angiotensin II antagonist.
We reviewed the 13 case reports of angioedema associated with the use of losartan reported to Lareb (Netherlands Pharmacovigilance Foundation, Den Bosch) and to the Drug Safety Unit of the Inspectorate for Health Care, Ryswyh, in the Netherlands since the introduction of losartan in 1995 until May 1997.
In all 13 cases, a diagnosis of angioedema attributed to the use of losartan seems to be very plausible. In 7 cases the diagnosis could not be confirmed by a physician because the symptoms had already been resolved, but the signs and symptoms clearly indicated angioedema. The adverse reactions occurred within 24 hours to 16 months after the initiation of losartan therapy. Three patients had previously experienced angioedema during treatment with an angiotensin-converting enzyme inhibitor. Eleven of the patients involved were women and 2 were men.
Our observations strongly suggest that the onset of angioedema was associated with the use of losartan. Physicians and pharmacists should be aware of this potentially life-threatening complication. It may be advisable not to prescribe angiotensin II antagonists to patients with a history of angioedema (of whatever origin).
血管性水肿是血管紧张素转换酶抑制剂众所周知的不良反应。缓激肽降解减少导致的缓激肽蓄积被认为是其致病机制。血管紧张素II拮抗剂似乎对缓激肽的降解没有影响。因此，预计在使用首个口服活性血管紧张素II拮抗剂氯沙坦钾治疗期间不会发生血管性水肿。
我们回顾了自1995年氯沙坦上市至1997年5月期间，向荷兰药品警戒基金会（位于登博斯）和荷兰里斯维赫医疗保健检查局药品安全部门报告的13例与氯沙坦使用相关的血管性水肿病例报告。
在所有13例病例中，因使用氯沙坦导致血管性水肿的诊断似乎非常合理。7例病例因症状已缓解，医生无法确诊，但体征和症状明确提示血管性水肿。不良反应发生在氯沙坦治疗开始后的24小时至16个月内。3例患者此前在使用血管紧张素转换酶抑制剂治疗期间曾发生血管性水肿。涉及的患者中11例为女性，2例为男性。
我们的观察结果强烈提示血管性水肿的发生与氯沙坦的使用有关。医生和药剂师应意识到这种潜在的危及生命的并发症。对于有血管性水肿病史（无论何种原因）的患者，可能不宜开具血管紧张素II拮抗剂。
