Chapman George, Tanner Stephanie
Medicine for Older People - Community Assessment and Treatment Service, Buckinghamshire Healthcare NHS Trust, Aylesbury, UK
Medicine for Older People - Community Assessment and Treatment Service, Buckinghamshire Healthcare NHS Trust, Aylesbury, UK.
BMJ Case Rep. 2020 Feb 10;13(2):e231839. doi: 10.1136/bcr-2019-231839.
A 90-year-old woman is referred six months after a transient ischaemic attack (TIA) with asymptomatic cholestatic liver function test (LFT) derangement. Following the TIA, atorvastatin and clopidogrel therapy are initiated. This is added to pre-existent once daily nifedipine for hypertension. Nifedipine (a weak inhibitor of CYP3A4 and competing substrate) and clopidogrel (a competitive inhibitor of CYP3A4) may have affected the metabolism of atorvastatin, resulting in the elevation of serum alkaline phosphatase levels to over six times the upper limit of normal. More often, statin therapy elevates serum alanine aminotransferase levels. Drug-induced liver injury (DILI) was deemed 'probable' as judged by the Roussel Uclaf Causality Assessment Method score. Statin therapy remains overwhelmingly safe, with benefits outweighing risks in the vast majority. The UK recommended LFT monitoring regime facilitates early recognition of DILI. Case reports are examined where similar drug combinations resulted in severe morbidity and mortality.
一名90岁女性在短暂性脑缺血发作(TIA)六个月后前来就诊,伴有无症状性胆汁淤积性肝功能试验(LFT)紊乱。TIA发作后,开始使用阿托伐他汀和氯吡格雷治疗。这两种药物加用了之前每日服用一次的硝苯地平用于治疗高血压。硝苯地平(一种CYP3A4的弱抑制剂和竞争性底物)和氯吡格雷(一种CYP3A4的竞争性抑制剂)可能影响了阿托伐他汀的代谢,导致血清碱性磷酸酶水平升高至正常上限的六倍以上。更常见的是,他汀类药物治疗会使血清丙氨酸氨基转移酶水平升高。根据乌法因果关系评估法评分,药物性肝损伤(DILI)被判定为“很可能”。他汀类药物治疗总体上仍然非常安全,在绝大多数情况下益处大于风险。英国推荐的LFT监测方案有助于早期识别DILI。对一些病例报告进行了研究,其中类似的药物组合导致了严重的发病和死亡。