质子泵抑制药加重非甾体抗炎药所致小肠损伤及其防治措施的文献综述
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摘要
质子泵抑制药(PPIs)可有效治疗胃和十二指肠的损伤出血,但对非甾体抗炎药(NSAIDs)所致小肠损伤效果不佳,甚至加重损伤的程度。PPIs通过改变肠道菌群和增加胆汁酸的细胞毒性等机制加重NSAIDs药物引起的小肠损伤,联合用药前应充分评估患者的获益及风险,治疗时需兼顾上下消化道,可选用具消化道黏膜保护功能的特殊组胺H_2受体拮抗药如拉呋替丁;尽可能选用对消化道影响较小的NSAIDs药物如选择性COX-2抑制药;补充肠道益生菌,纠正肠道微生态;使用消化道黏膜保护药物;必要时使用肠道的局部抗菌药。考虑到COX-2抑制药和PPIs的心血管风险,对于患有心脑血管疾病和存在心脑血管疾病风险的患者,应慎用此两类药物。
PPIs may effectively treat upper gastrointestinal injuries, however, it is not effective for small intestinal injuries caused by NSAIDs, and even aggravate the degree of the injuries. Its enteropathy mechanisms are related to altering intestinal flora and increasing cytotoxicity of bile acids. Patients should be fully evaluated for their benefits and risks before combination therapy, the unreasonable use of PPIs should be reduce or stop. The upper and lower digestive tract should be considered together when selecting drugs. Lafutidine, a special histamine H_2 receptor with digestive tract mucosal protection effect, can be used as an alternative medicine of PPIs. NSAIDs with less impact on the digestive tract, such as selective COX-2 inhibitors, can be used as much as possible, Supplementing intestinal probiotics can correct intestinal microecology. Digestive mucosal protective agent and intestinal antibiotics can be used when necessary. Considering the cardiovascular risk of COX-2 inhibitors and PPIs. These two drugs should be used with caution in patients with cardiovascular and cerebrovascular diseases and risk.
PPIs may effectively treat upper gastrointestinal injuries, however, it is not effective for small intestinal injuries caused by NSAIDs, and even aggravate the degree of the injuries. Its enteropathy mechanisms are related to altering intestinal flora and increasing cytotoxicity of bile acids. Patients should be fully evaluated for their benefits and risks before combination therapy, the unreasonable use of PPIs should be reduce or stop. The upper and lower digestive tract should be considered together when selecting drugs. Lafutidine, a special histamine H_2 receptor with digestive tract mucosal protection effect, can be used as an alternative medicine of PPIs. NSAIDs with less impact on the digestive tract, such as selective COX-2 inhibitors, can be used as much as possible, Supplementing intestinal probiotics can correct intestinal microecology. Digestive mucosal protective agent and intestinal antibiotics can be used when necessary. Considering the cardiovascular risk of COX-2 inhibitors and PPIs. These two drugs should be used with caution in patients with cardiovascular and cerebrovascular diseases and risk.
引文
1 Casado Arroyo R,Polo-Tomas M,Roncalés MP,et al.Lower GI bleeding is more common than upper among patients on dual antiplatelet therapy:long-term follow-up of a cohort of patients commonly using PPI co-therapy[J].Heart,2012,98(9):718-723
2 Washio E,Esaki M,Maehata Y,et al.Proton pump inhibitors increase incidence of nonsteroidal anti-inflammatory drug-induced small bowel injury:a randomized,placebo-controlled trial[J].Clin Gastroenterol Hepatol,2016,14(6):809-815
3 Maiden L,Thjodleifsson B,Theodors A,et al.A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy[J].Gastroenterology,2005,128(5):1172-1178
4 Goldstein JL,Eisen GM,Lewis B,et al.Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole,as assessed by video capsule endoscopy[J].Aliment Pharmacol Ther,2007,25(10):1211-1122
5 Goldstein JL,Eisen GM,Lewis B,et al.Video capsule endoscopy to prospectively assess small bowel injury with celecoxib,naproxen plus omeprazole,and placebo[J].Clin Gastroenterol Hepatol,2005,3(2):133-141
6 Kuramoto T,Umegaki E,Nouda S,et al.Preventive effect of irsogladine or omeprazole on non-steroidal anti-inflammatory drug-induced esophagitis,peptic ulcers,and small intestinal lesions in humans,a prospective randomized controlled study[J].BMC Gastroenterol,2013,13:85
7 Wallace JL,Syer S,Denou E,et al.Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis[J].Gastroenterology,2011,141(4):1314-1322
8 Satoh H,Amagase K,Takeuchi K.Exacerbation of nonsteroidal anti-inflammatory drug-induced small intestinal lesions by antisecretory drugs in rats:the role of intestinal motility[J].J Pharmacol Exp Ther,2012,343(2):270-277
9 Blackler RW,De Palma G,Manko A,et al.Deciphering the pathogenesis of NSAID enteropathy using proton pump inhibitors and a hydrogen sulfide-releasing NSAID[J].Am J Physiol Gastrointest Liver Physiol,2015,308(12):G994-1003
10 任牡丹,马文慧,卢桂芳,等.胶囊内镜下非甾体抗炎药相关小肠损伤的特点[J].西安交通大学学报(医学版),2018,39(5):715-718
11 罗佳,王惠吉,郝瑞瑞.非甾体抗炎药所致肠道损伤[J].中国药物警戒,2011,8(5):302-305
12 Endo H,Sakai E,Taniguchi L,et al.Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users:data from a prospective multicenter capsule endoscopy registry[J].Gastrointest Endosc,2014,80(5):826-834
13 Endo H,Hosono K,Inamori M,et al.Incidence of small bowel injury induced by low-dose aspirin:a crossover study using capsule endoscopy in healthy volunteers[J].Digestion,2009,79(1):44-51
14 Smecuol E,Pinto Sanchez MI,Suarez A,et al.Low-dose aspirin affects the small bowel mucosa:results of a pilot study with a multidimensional assessment[J].Clin Gastroenterol Hepatol,2009,7(5):524-529
15 Maiden L,Thjodleifsson B,Theodors A,et al.A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy[J].Gastroenterology,2005,128(5):1172-1178
16 Tachecí I,Bradna P,Douda T,et al.Small intestinal injury in NSAID users suffering from rheumatoid arthritis or osteoarthritis[J].Rheumatol Int,2016,36(11):1557-1561
17 薄陆敏,廖专,徐灿,等.1000例OMOM胶囊内镜检查患者的回顾性分析研究[J].中华消化内镜杂志,2014,31(2):102-105
18 薄陆敏,杨俊驰,廖专,等.胶囊内镜对非甾体类抗炎药致小肠黏膜损伤的诊断价值研究[J].中华消化内镜杂志,2015,32(1):6-9
19 何旭东,姜红梅,王文峰,等.NSAIDs致下消化道损伤的研究[J].临床消化杂志,2011,23(5):305-307
20 Scheiman JM.NSAID-induced gastrointestinal injury:a focused update for clinicians[J].J Clin Gastroenterol,2016,50(1):5-10
21 Graham DY.Efficient identification and evaluation of effective Helicobacter pylori therapies[J].Clin Gastroenterol Hepatol,2009,7(2):145-148
22 Park SC,Chun HJ,Kang CD,et al.Prevention and management of non-steroidal anti-inflammatory drugs-induced small intestinal injury[J].World J Gastroenterol,2011,17(42):4647-4653
23 Watanabe T,Takeuchi T,Handa O,et al.A multicenter,randomized,double-blind,placebo-controlled trial of high-dose rebamipide treatment for low-dose aspirin-induced moderate-to-severe small intestinal damage[J].PLoS One,2015,10(4):e0122330
24 Tachecí I,Bradna P,Douda T,et al.NSAID-induced enteropathy in rheumatoid arthritis patients with chronic occult gastrointestinal bleeding:a prospective capsule endoscopy study[J].Gastroenterol Res Pract,2013,2013:268382
25 Hayashi Y,Yamamoto H,Taguchi H,et al.Nonsteroidal anti-inflammatory drug-induced small-bowel lesions identified by double-balloon endoscopy:endoscopic features of the lesions and endoscopic treatments for diaphragm disease[J].J Gastroenterol,2009,44(Suppl 19):57-63
26 Fujimori S,Takahashi Y,Gudis K,et al.Rebamipide has the potential to reduce the intensity of NSAID-induced small intestinal injury:a double-blind,randomized,controlled trial evaluated by capsule endoscopy[J].J Gastroenterol,2011,46(1):57-64
27 唐雯,张大宽,陈东风,等.非甾体消炎药物致小肠黏膜损伤的研究进展[J].医学综述,2013,19(17):3117-3119
28 Edogawa S,Takeuchi T,Kojima Y,et al.Current topics of strategy of NSAID-induced small intestinal lesions[J].Digestion,2015,92(2):99-107
29 张字澄,张平,连滨静,等.非甾体抗炎药引起小肠黏膜损伤机制及其治疗的研究进展[J].胃肠病学,2013,18(8):497-499
30 Gwee KA,Goh V,Lima G,et al.Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs:risks versus benefits[J].J Pain Res,2018,11:361-374
31 Marlicz W,Loniewski I,Grimes DS,et al.Nonsteroidal anti-inflammatory drugs,proton pump inhibitors,and gastrointestinal injury:contrasting interactions in the stomach and small intestine[J].Mayo Clin Proc,2014,89(12):1699-1709
32 朱兰平,赵经文,陈鑫等.PPIs使用与NSAIDs相关小肠损伤:如何平衡风险和获益[J].世界华人消化杂志,2018,26(22):1334-1339
33 Daniell HW.NSAID-PPI enteropathy in humans[J].Gastroenterology,2012,142(4):e20-e21
34 金玉,曾繁典,谭诗云,等.具抑酸和消化道黏膜保护作用的H2受体拮抗药拉呋替丁[J].医药导报,2014,33(7):891-894
35 金晶,谭诗云,张家明,等.质子泵抑制药的心血管风险及其机制概述[J].药物流行病学杂志,2018,27(11):759-764
36 Kurokawa S,Katsuki S,Fujita T,et al.A randomized,doubleblinded,placebo-controlled,multicenter trial,healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury[J].J Gastroenterol,2014,49(2):239-244
37 Mizukami K,Murakami K,Abe T,et al.Aspirin-induced small bowel injuries and the preventive effect of rebamipide[J].World J Gastroenterol,2011 ,17(46):5117-5122
38 Yamada S,Naito Y,Takagi T,et al.Rebamipide ameliorates indomethacin-induced small intestinal injury in rats via the inhibition of matrix metalloproteinases activity[J].J Gastroenterol Hepatol,2012,27(12):1816-1824
39 石柳,夏忠胜,赖宇,等.瑞巴派特对阿司匹林诱导的小鼠小肠上皮屏障损伤的修复[J].中国病理生理杂志,2017,33(9):1669-1675
40 杨成,崔梅花,梁君,等.瑞巴派特对阿司匹林损伤大鼠小肠黏膜通透性的保护作用[J].胃肠病学和肝病学杂志,2017 ,26(11):1258-1262
41 Endo H,Higurashi T,Hosono K,et al.Efficacy of Lactobacillus casei treatment on small bowel injury in chronic low-dose aspirin users:a pilot randomized controlled study[J].J Gastroenterol,2011,46(7):894-905
42 Montalto M,Gallo A,Curigliano V,et al.Clinical trial:the effects of a probiotic mixture on non-steroidal anti-inflammatory drug enteropathy-a randomized,double-blind,cross-over,placebo- controlled study[J].Aliment Pharmacol Ther,2010,32(2):209-214
43 Suzuki T,Masui A,Nakamura J,et al.Yogurt containing lactobacillus gasseri mitigates aspirin-induced small bowel injuries:a prospective,randomized,double-blind,placebocontrolled trial[J].Digestion,2017,95(1):49-54
44 Jarupongprapa S,Ussavasodhi P,Katchamart W.Comparison of gastrointestinal adverse effects between cyclooxygenase-2 inhibitors and non-selective,non-steroidal anti- inflammatory drugs plus proton pump inhibitors:a systematic review and meta-analysis[J].J Gastroenterol,2013,48(7):830-838
45 Mamdani M,Rochon PA,Juurlink DN,et al.Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs[J].BMJ,2002,325(7365):624
46 Bombardier C,Laine L,Reicin A,et al.Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis.VIGOR Study Group[J].N Engl J Med,2000 ,343(21):1520-1528
47 Calanni F,Renzulli C,Barbanti M,et al.Rifaximin:beyond the traditional anti- biotic activity [J].J Antibiot(Tokyo),2014,67(9):667-670
48 刘响,曹海龙,姜葵,等.利福昔明防治肠道疾病的作用机制及疗效的研究进展[J].国际消化病杂志,2016,36:277-279
49 Fornai M,Antonioli L,Pellegrini C,et al.Small bowel protection against NSAID-injury in rats:Effect of rifaximin,a poorly absorbed,GI targeted,antibiotic[J].Pharmacol Res,2016,104:186-196
50 Scarpignato C,Dolak W,Lanas A,et al.Rifaximin reduces the number and severity of intestinal lesions associated with use of nonsteroidal anti-inflammatory drugs in humans[J].Gastroenterology,2017,152(5):980-982
2 Washio E,Esaki M,Maehata Y,et al.Proton pump inhibitors increase incidence of nonsteroidal anti-inflammatory drug-induced small bowel injury:a randomized,placebo-controlled trial[J].Clin Gastroenterol Hepatol,2016,14(6):809-815
3 Maiden L,Thjodleifsson B,Theodors A,et al.A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy[J].Gastroenterology,2005,128(5):1172-1178
4 Goldstein JL,Eisen GM,Lewis B,et al.Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole,as assessed by video capsule endoscopy[J].Aliment Pharmacol Ther,2007,25(10):1211-1122
5 Goldstein JL,Eisen GM,Lewis B,et al.Video capsule endoscopy to prospectively assess small bowel injury with celecoxib,naproxen plus omeprazole,and placebo[J].Clin Gastroenterol Hepatol,2005,3(2):133-141
6 Kuramoto T,Umegaki E,Nouda S,et al.Preventive effect of irsogladine or omeprazole on non-steroidal anti-inflammatory drug-induced esophagitis,peptic ulcers,and small intestinal lesions in humans,a prospective randomized controlled study[J].BMC Gastroenterol,2013,13:85
7 Wallace JL,Syer S,Denou E,et al.Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis[J].Gastroenterology,2011,141(4):1314-1322
8 Satoh H,Amagase K,Takeuchi K.Exacerbation of nonsteroidal anti-inflammatory drug-induced small intestinal lesions by antisecretory drugs in rats:the role of intestinal motility[J].J Pharmacol Exp Ther,2012,343(2):270-277
9 Blackler RW,De Palma G,Manko A,et al.Deciphering the pathogenesis of NSAID enteropathy using proton pump inhibitors and a hydrogen sulfide-releasing NSAID[J].Am J Physiol Gastrointest Liver Physiol,2015,308(12):G994-1003
10 任牡丹,马文慧,卢桂芳,等.胶囊内镜下非甾体抗炎药相关小肠损伤的特点[J].西安交通大学学报(医学版),2018,39(5):715-718
11 罗佳,王惠吉,郝瑞瑞.非甾体抗炎药所致肠道损伤[J].中国药物警戒,2011,8(5):302-305
12 Endo H,Sakai E,Taniguchi L,et al.Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users:data from a prospective multicenter capsule endoscopy registry[J].Gastrointest Endosc,2014,80(5):826-834
13 Endo H,Hosono K,Inamori M,et al.Incidence of small bowel injury induced by low-dose aspirin:a crossover study using capsule endoscopy in healthy volunteers[J].Digestion,2009,79(1):44-51
14 Smecuol E,Pinto Sanchez MI,Suarez A,et al.Low-dose aspirin affects the small bowel mucosa:results of a pilot study with a multidimensional assessment[J].Clin Gastroenterol Hepatol,2009,7(5):524-529
15 Maiden L,Thjodleifsson B,Theodors A,et al.A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy[J].Gastroenterology,2005,128(5):1172-1178
16 Tachecí I,Bradna P,Douda T,et al.Small intestinal injury in NSAID users suffering from rheumatoid arthritis or osteoarthritis[J].Rheumatol Int,2016,36(11):1557-1561
17 薄陆敏,廖专,徐灿,等.1000例OMOM胶囊内镜检查患者的回顾性分析研究[J].中华消化内镜杂志,2014,31(2):102-105
18 薄陆敏,杨俊驰,廖专,等.胶囊内镜对非甾体类抗炎药致小肠黏膜损伤的诊断价值研究[J].中华消化内镜杂志,2015,32(1):6-9
19 何旭东,姜红梅,王文峰,等.NSAIDs致下消化道损伤的研究[J].临床消化杂志,2011,23(5):305-307
20 Scheiman JM.NSAID-induced gastrointestinal injury:a focused update for clinicians[J].J Clin Gastroenterol,2016,50(1):5-10
21 Graham DY.Efficient identification and evaluation of effective Helicobacter pylori therapies[J].Clin Gastroenterol Hepatol,2009,7(2):145-148
22 Park SC,Chun HJ,Kang CD,et al.Prevention and management of non-steroidal anti-inflammatory drugs-induced small intestinal injury[J].World J Gastroenterol,2011,17(42):4647-4653
23 Watanabe T,Takeuchi T,Handa O,et al.A multicenter,randomized,double-blind,placebo-controlled trial of high-dose rebamipide treatment for low-dose aspirin-induced moderate-to-severe small intestinal damage[J].PLoS One,2015,10(4):e0122330
24 Tachecí I,Bradna P,Douda T,et al.NSAID-induced enteropathy in rheumatoid arthritis patients with chronic occult gastrointestinal bleeding:a prospective capsule endoscopy study[J].Gastroenterol Res Pract,2013,2013:268382
25 Hayashi Y,Yamamoto H,Taguchi H,et al.Nonsteroidal anti-inflammatory drug-induced small-bowel lesions identified by double-balloon endoscopy:endoscopic features of the lesions and endoscopic treatments for diaphragm disease[J].J Gastroenterol,2009,44(Suppl 19):57-63
26 Fujimori S,Takahashi Y,Gudis K,et al.Rebamipide has the potential to reduce the intensity of NSAID-induced small intestinal injury:a double-blind,randomized,controlled trial evaluated by capsule endoscopy[J].J Gastroenterol,2011,46(1):57-64
27 唐雯,张大宽,陈东风,等.非甾体消炎药物致小肠黏膜损伤的研究进展[J].医学综述,2013,19(17):3117-3119
28 Edogawa S,Takeuchi T,Kojima Y,et al.Current topics of strategy of NSAID-induced small intestinal lesions[J].Digestion,2015,92(2):99-107
29 张字澄,张平,连滨静,等.非甾体抗炎药引起小肠黏膜损伤机制及其治疗的研究进展[J].胃肠病学,2013,18(8):497-499
30 Gwee KA,Goh V,Lima G,et al.Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs:risks versus benefits[J].J Pain Res,2018,11:361-374
31 Marlicz W,Loniewski I,Grimes DS,et al.Nonsteroidal anti-inflammatory drugs,proton pump inhibitors,and gastrointestinal injury:contrasting interactions in the stomach and small intestine[J].Mayo Clin Proc,2014,89(12):1699-1709
32 朱兰平,赵经文,陈鑫等.PPIs使用与NSAIDs相关小肠损伤:如何平衡风险和获益[J].世界华人消化杂志,2018,26(22):1334-1339
33 Daniell HW.NSAID-PPI enteropathy in humans[J].Gastroenterology,2012,142(4):e20-e21
34 金玉,曾繁典,谭诗云,等.具抑酸和消化道黏膜保护作用的H2受体拮抗药拉呋替丁[J].医药导报,2014,33(7):891-894
35 金晶,谭诗云,张家明,等.质子泵抑制药的心血管风险及其机制概述[J].药物流行病学杂志,2018,27(11):759-764
36 Kurokawa S,Katsuki S,Fujita T,et al.A randomized,doubleblinded,placebo-controlled,multicenter trial,healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury[J].J Gastroenterol,2014,49(2):239-244
37 Mizukami K,Murakami K,Abe T,et al.Aspirin-induced small bowel injuries and the preventive effect of rebamipide[J].World J Gastroenterol,2011 ,17(46):5117-5122
38 Yamada S,Naito Y,Takagi T,et al.Rebamipide ameliorates indomethacin-induced small intestinal injury in rats via the inhibition of matrix metalloproteinases activity[J].J Gastroenterol Hepatol,2012,27(12):1816-1824
39 石柳,夏忠胜,赖宇,等.瑞巴派特对阿司匹林诱导的小鼠小肠上皮屏障损伤的修复[J].中国病理生理杂志,2017,33(9):1669-1675
40 杨成,崔梅花,梁君,等.瑞巴派特对阿司匹林损伤大鼠小肠黏膜通透性的保护作用[J].胃肠病学和肝病学杂志,2017 ,26(11):1258-1262
41 Endo H,Higurashi T,Hosono K,et al.Efficacy of Lactobacillus casei treatment on small bowel injury in chronic low-dose aspirin users:a pilot randomized controlled study[J].J Gastroenterol,2011,46(7):894-905
42 Montalto M,Gallo A,Curigliano V,et al.Clinical trial:the effects of a probiotic mixture on non-steroidal anti-inflammatory drug enteropathy-a randomized,double-blind,cross-over,placebo- controlled study[J].Aliment Pharmacol Ther,2010,32(2):209-214
43 Suzuki T,Masui A,Nakamura J,et al.Yogurt containing lactobacillus gasseri mitigates aspirin-induced small bowel injuries:a prospective,randomized,double-blind,placebocontrolled trial[J].Digestion,2017,95(1):49-54
44 Jarupongprapa S,Ussavasodhi P,Katchamart W.Comparison of gastrointestinal adverse effects between cyclooxygenase-2 inhibitors and non-selective,non-steroidal anti- inflammatory drugs plus proton pump inhibitors:a systematic review and meta-analysis[J].J Gastroenterol,2013,48(7):830-838
45 Mamdani M,Rochon PA,Juurlink DN,et al.Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs[J].BMJ,2002,325(7365):624
46 Bombardier C,Laine L,Reicin A,et al.Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis.VIGOR Study Group[J].N Engl J Med,2000 ,343(21):1520-1528
47 Calanni F,Renzulli C,Barbanti M,et al.Rifaximin:beyond the traditional anti- biotic activity [J].J Antibiot(Tokyo),2014,67(9):667-670
48 刘响,曹海龙,姜葵,等.利福昔明防治肠道疾病的作用机制及疗效的研究进展[J].国际消化病杂志,2016,36:277-279
49 Fornai M,Antonioli L,Pellegrini C,et al.Small bowel protection against NSAID-injury in rats:Effect of rifaximin,a poorly absorbed,GI targeted,antibiotic[J].Pharmacol Res,2016,104:186-196
50 Scarpignato C,Dolak W,Lanas A,et al.Rifaximin reduces the number and severity of intestinal lesions associated with use of nonsteroidal anti-inflammatory drugs in humans[J].Gastroenterology,2017,152(5):980-982