大环内酯类抗菌药物和钙通道阻滞剂联合使用有导致血压过低的风险

The Risk of Hypotension Following Co-prescription of Macrolide Antibiotics and Calcium channel Blockers

目的：大环内酯类抗菌药物如克拉霉素、红霉素，可通过抑制细胞色素P450同工酶3A4而增强钙通道阻滞剂的药理作用。本文拟对大环内酯类抗菌药物与钙通道阻滞剂联合用药致低血压发生的风险进行评估。方法：该研究纳入了1994年4月1日到2009年3月31日间入院应用钙通道阻滞剂治疗的66岁以上的老年患者。这些患者中包括那些因低血压或休克而送往医院救治的患者。评估采用配对的分析方法，对患者用药情况进行对照研究。结果：在7100个接受钙通道阻滞剂治疗后因低血压住院的病人中．有176个病人给予了大环内酯类抗菌药物。红霉素与低血压发生率关系最为紧密（OR值为58．95％Cl为23～150），其次是克拉霉素（OR值为37．95％CI为23～61）。阿奇霉素与低血压的发生率无直接关系（OR值为1.5，95％CI为0.8～2.8）。该研究在对病人只接受了二氢吡啶钙通道阻滞剂治疗的分层分析中也发现了类似的结果。结论：在接受钙通道阻滞剂治疗的老年病患中．红霉素或克拉霉素的使用导致患者发生低血压及休克的风险增加。所以当使用钙通道阻滞剂的病人须联用大环内酯类抗菌药物治疗时．建议应优先考虑阿奇霉素。

Objective： The macrolide antibiotics clarithromycin and erythromycin may potentiate calcium-channel blockers by inhibiting cytochrome P450 isoenzyme 3A4. We explored the risk of hypotension following the simultaneous use of calcium-channel blockers and macrolide antibiotics. Method： We conducted a study involving people aged 66 years and older who had been prescribed a calcium-channel blocker between Apr. 1, 1994, and Mar. 31, 2009. Of these patients, we included those who had been admitted to hospital for the treatment of hypotension or shock. Pair-matched analytic approach was used to contrast each patient＇ s exposure to drugs. Result： Of the 7100 patients admitted to hospital because of hypotension while receiving a calcium-channel blocker, 176 had been prescribed a macrolide antibiotic. Erythromycin was most strongly associated with hypotension （OR 5.8, 95%CI 2.3- 15.0）, followed by clarithromycin （OR3.7, 95% CI 2.3- 6.1）. Azithromycin was not associated with an increased risk of hypotension （OR1.5, 95 % CI 0.8 -2.8）. We found similar results in a stratified analysis of patients who received only dihydropyridine calcium-channel blockers. Conclusion： In older patients receiving a calcium- channel blocker, use of erythromycin or clarithromycin was associated with an increased risk of hypotension or shock requiring admission to hospital. Preferential use of azithromycin should be considered when a macrolide antibiotic is required for patients already,receiving a calcium-channel blocker.