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给药药物和化学物质的结肠毒性。

Colonic toxicity of administered drugs and chemicals.

作者信息

Cappell Mitchell S

机构信息

Division of Gastroenterology, St. Barnabas Hospital, Bronx, New York 10457-2594, USA.

出版信息

Am J Gastroenterol. 2004 Jun;99(6):1175-90. doi: 10.1111/j.1572-0241.2004.30192.x.

Abstract

Although uncommon, medication-induced colonotoxicity is important to recognize because medication cessation generally leads to prompt clinical improvement, while medication continuation results in disease exacerbation. This review categorizes the association between medications and colonotoxicity as "well-established" or "probable," according to the following criteria: total number of reported cases, number of different research groups reporting an association, experimental and pharmacologic evidence of an association, and validity of an association in each reported case. Cocaine, ergotamine, estrogen, sodium polystyrene, alosetron, amphetamines, pseudoephedrine, and vasopressin are associated with colonic ischemia. The mechanisms include vasospasm, thrombogenesis, and shunting of blood from mesenteric vessels. Narcotics, phenothiazines, vincristine, atropine, nifedipine, and tricyclic antidepressants are associated with colonic pseudo-obstruction. The mechanisms include antagonizing prokinetic neurotransmitters, stimulating antikinetic neurotransmitters, promoting dysmotility, relaxing smooth muscle, and injuring enteric neurons. Numerous antibiotics are associated with pseudomembranous colitis; ampicillin is associated with hemorrhagic colitis; chemotherapy is associated with neutropenic colitis; and deferoxamine is associated with Yersinia enterocolitis. Mechanisms of these toxicities include altering normal bowel flora, weakening immunologic defenses, promoting microorganism virulence, and mucosal injury. Gold compounds, nonsteroidal antiinflammatory drugs, alpha-methyldopa, salicylates, and sulfasalazine are associated with an inflammatory or cytotoxic colitis. The mechanisms include direct mucosal cytotoxicity, antimetabolite effects, or drug allergy. Nonsteroidal antiinflammatory drugs, cyclo 3 fort, flutamide, lansoprazole, and ticlopidine are associated with lymphocytic colitis. The mechanisms include immunologic activation or attenuated immunologic defenses. Chronic cathartic use leads to colonic hypomotility and abdominal distention. Intrarectally administered corrosive compounds can produce a toxic colitis.

摘要

尽管药物性结肠毒性并不常见,但认识到这一点很重要,因为停药通常会使临床症状迅速改善,而继续用药则会导致病情加重。本综述根据以下标准将药物与结肠毒性之间的关联分为“已明确”或“可能”:报告病例总数、报告关联的不同研究小组数量、关联的实验和药理学证据以及每个报告病例中关联的有效性。可卡因、麦角胺、雌激素、聚苯乙烯磺酸钠、阿洛司琼、苯丙胺、伪麻黄碱和加压素与结肠缺血有关。其机制包括血管痉挛、血栓形成以及肠系膜血管血液分流。麻醉剂、吩噻嗪类、长春新碱、阿托品、硝苯地平和三环类抗抑郁药与结肠假性梗阻有关。其机制包括拮抗促动力神经递质、刺激抗动力神经递质、促进运动障碍、使平滑肌松弛以及损伤肠神经元。许多抗生素与伪膜性结肠炎有关;氨苄西林与出血性结肠炎有关;化疗与中性粒细胞减少性结肠炎有关;去铁胺与耶尔森菌性小肠结肠炎有关。这些毒性的机制包括改变正常肠道菌群、削弱免疫防御、促进微生物毒力以及黏膜损伤。金化合物、非甾体抗炎药、α-甲基多巴、水杨酸盐和柳氮磺胺吡啶与炎症性或细胞毒性结肠炎有关。其机制包括直接黏膜细胞毒性、抗代谢物作用或药物过敏。非甾体抗炎药、环丙沙星、氟他胺、兰索拉唑和噻氯匹定与淋巴细胞性结肠炎有关。其机制包括免疫激活或免疫防御减弱。长期使用泻药会导致结肠运动减弱和腹胀。经直肠给予腐蚀性化合物可导致中毒性结肠炎。

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