Hemstreet Brian A
Department of Clinical Pharmacy, University of Colorado School of Pharmacy, Denver, Colorado 80262, USA.
Pharmacotherapy. 2004 Jan;24(1):94-104. doi: 10.1592/phco.24.1.94.34805.
Development of bleeding gastroesophageal varices is a serious consequence of portal hypertension secondary to cirrhosis. Nonselective beta-blockers have been used to reduce portal pressures and prevent primary and secondary bleeding episodes. However, up to two thirds of patients may not respond appropriately to these agents. Nonselective beta-blockers combined with vasodilatory drugs result in enhanced lowering of portal pressures by targeting several mechanisms involved in this process. Unfortunately, this practice is associated with increased adverse effects, such as hypotension, and minimal reductions in mortality. Carvedilol possesses both nonselective beta-antagonist and alpha1-receptor antagonist activity. Given its combined mechanism of action, carvedilol presents a potential option for lowering portal pressures. Its effects on lowering portal pressures and its role in therapy are undefined. Using MEDLINE (1966-2003) and International Pharmaceutical Abstracts (1970-2003), the English-language literature was searched to identify human studies assessing carvedilol's effects on lowering portal pressure. In general, carvedilol therapy was associated with mean reductions of 16-43% in portal pressure, assessed by the hepatic venous pressure gradient (HVPG) after single and multiple doses. Studies comparing carvedilol with propranolol revealed equal or enhanced efficacy in lowering HVPG. Large percentages of patients had significant HVPG reductions to levels that prevent variceal bleeding. Carvedilol also was associated with substantial symptomatic hypotension, especially in patients with ascites or Child-Pugh class B or C cirrhosis. Efficacy and adverse effects generally seem to be dose related. Carvedilol appears to be a potentially viable option for treating portal hypertension. Further multiple-dose trials comparing carvedilol with standard therapy are needed to assess the agent's long-term safety and effectiveness in preventing variceal bleeding.
出血性胃食管静脉曲张的发生是肝硬化继发门静脉高压的严重后果。非选择性β受体阻滞剂已被用于降低门静脉压力并预防初次和再次出血事件。然而，多达三分之二的患者可能对这些药物反应不佳。非选择性β受体阻滞剂与血管扩张药物联合使用，通过针对这一过程中涉及的多种机制，可增强门静脉压力的降低。不幸的是，这种做法会增加不良反应，如低血压，且死亡率降低幅度极小。卡维地洛兼具非选择性β受体拮抗和α1受体拮抗活性。鉴于其联合作用机制，卡维地洛是降低门静脉压力的一个潜在选择。其降低门静脉压力的效果及其在治疗中的作用尚不明确。利用MEDLINE（1966 - 2003年）和《国际药学文摘》（1970 - 2003年）检索英文文献，以确定评估卡维地洛降低门静脉压力效果的人体研究。一般来说，卡维地洛治疗后，通过肝静脉压力梯度（HVPG）评估，单次和多次给药后门静脉压力平均降低16% - 43%。将卡维地洛与普萘洛尔比较的研究显示，在降低HVPG方面疗效相同或更佳。很大比例的患者HVPG显著降低至预防静脉曲张出血的水平。卡维地洛还与明显的症状性低血压相关，尤其是在腹水患者或Child-Pugh B级或C级肝硬化患者中。疗效和不良反应通常似乎与剂量相关。卡维地洛似乎是治疗门静脉高压的一个潜在可行选择。需要进一步进行将卡维地洛与标准疗法比较的多剂量试验，以评估该药物在预防静脉曲张出血方面的长期安全性和有效性。
