毒理性
静脉注射高剂量四环素可以诱发脂肪肝疾病，可能导致严重的肝功能不全、急性肝衰竭甚至死亡。这种综合症在孕妇中更为常见，尤其是在妊娠晚期或产后早期。然而，也有报道称非孕妇、男性和儿童因静脉注射四环素而导致急性脂肪肝。损伤的特点是在治疗3到10天后出现虚弱、发热、疲劳、恶心和腹痛。实验室检查显示血清转氨酶和碱性磷酸酶水平轻度到中度升高，伴有轻度黄疸，但存在高氨血症和凝血病。胰腺炎、肾功能不全和乳酸酸中毒也很常见，尽管并非总是特别寻找。如果及时停止四环素治疗，这种综合症可能是可逆的，但通常识别较晚，即使停止用药也可能进展为多器官衰竭和死亡。高剂量的静脉注射多西环素和米诺环素也会引起这种综合症，但非常罕见。目前，由于四环素不再以注射形式提供，且更安全、更好耐受、更有效的广谱抗生素的出现，这种综合症很少见。
口服四环素与急性肝损伤的罕见病例有关，但与四环素使用相比，其他正在服用的药物的关联并不总是非常明确。尽管使用频繁，口服四环素仍然是导致肝损伤的非常罕见的原因。相比之下，多西环素和米诺环素引起的肝病病例已有很好的描述。急性脂肪肝的罕见病例被归因于口服四环素，尤其是在给孕妇高剂量使用时。目前，四环素在孕妇中被认为是禁忌的，特别是在妊娠晚期。
可能性评分：A[HD]（已知的临床明显肝损伤的常见原因，但通常是在静脉注射高剂量时）。
High doses of intravenous tetracycline can induce fatty liver disease and may result in severe hepatic dysfunction, acute liver failure and death. This syndrome is more common among pregnant women, largely during the last trimester or early postpartum period. However, instances of acute fatty liver attributed to intravenous tetracycline have been reported in nonpregnant women and in men and even in children. The injury is characterized by onset of weakness, fever, fatigue, nausea and abdominal pain after 3 to 10 days of therapy. Laboratory tests show minimal-to-moderate elevations in serum aminotransferase and alkaline phosphatase levels with mild jaundice, but presence of hyperammonemia and coagulopathy. Pancreatitis, renal dysfunction and lactic acidosis are also common, although not always specifically sought. The syndrome may be reversible if tetracycline is stopped promptly, but it is usually recognized late and can progress to multiorgan failure and death despite stopping the agent. This syndrome also occurs with high doses of intravenous doxycycline and minocycline, but quite rarely. This syndrome is rarely seen currently as tetracycline is no longer available in parenteral form and the use of intravenous tetracyclines has been superseded by availability of safer, better tolerated and more effective broad spectrum antibiotics.
Oral tetracycline has been associated with rare instances of acute liver injury, but the association with tetracycline use as opposed to other agents being taken has not always been very well shown. Despite frequency of its use, oral tetracycline remains a very rare cause of liver injury. In contrast, cases of doxycycline and minocycline induced liver disease are well described. Rare instances of acute fatty liver have been attributed to oral tetracycline, particularly when given to pregnant women in high doses. Currently, tetracycline is considered contraindicated in pregnant women, particularly during the last trimester.
Likelihood score: A[HD] (well known cause of clinically apparent liver injury but usually when given in high doses intravenously).
来源:LiverTox
