Advances in drug-induced gastrointestinal bleeding and its pathological mechanism

XU Han; ZHANG Yuanyuan; KOU Junping

doi:10.11665/j.issn.1000-5048.20190604

Journal of China Pharmaceutical University > 2019 > 50(6): 659-665. > DOI: 10.11665/j.issn.1000-5048.20190604

XU Han, ZHANG Yuanyuan, KOU Junping. Advances in drug-induced gastrointestinal bleeding and its pathological mechanism[J]. Journal of China Pharmaceutical University, 2019, 50(6): 659-665. DOI: 10.11665/j.issn.1000-5048.20190604

Citation:

PDF (1839 KB)

Advances in drug-induced gastrointestinal bleeding and its pathological mechanism

More Information

Graphical Abstract

Abstract

Abstract

Drug-induced gastrointestinal bleeding is caused by drugs acting on the gastrointestinal tract, which damages the gastrointestinal mucosa causing erosion and ulceration. Many drugs can cause gastrointestinal bleeding including non-steroidal anti-inflammatory drugs, antithrombotic drugs, chemotherapy drugs, and antibacterial drugs, drugs induced gastrointestinal bleeding by destroying gastrointestinal mucosal barrier, inhibiting of angiogenesis, destroying coagulation mechanism and there are still few prevention methods. This study focused on the clinical research and mechanism of drugs. The research in recent 5 years were reviewed to illustrate drug-induced gastrointestinal bleeding, so as to illustrate the characteristic actions of drug and provide some references and clues for the prevention of drug-induced gastrointestinal bleeding.
- gastrointestinal bleeding,
- mechanism,
- signaling pathway,
- advances

FullText(HTML)

References (58)

References

[1]	Aoki T,Hirata Y,Yamada A,et al.Initial management for acute lower gastrointestinal bleeding[J].World J Gastroenterol,2019,25(1):69-84.
[2]	Ur-Rahman A,Guan J,Khalid S,et al.Both full Glasgow-blatchford score and modified Glasgow-blatchford score predict the need for intervention and mortality in patients with acute lower gastrointestinal bleeding[J].Dig Dis Sci,2018,63(11):3020-3025.
[3]	Sengupta N,Cifu AS.Management of patients with acute lower gastrointestinal tract bleeding[J].JAMA,2018,320(1):86-87.
[4]	Yuan JQ,Tsoi KK,Yang M,et al.Systematic review with network meta-analysis:comparative effectiveness and safety of strategies for preventing NSAID-associated gastrointestinal toxicity[J].Aliment Pharmacol Ther,2016,43(12):1262-1275.
[5]	Chi TY,Zhu HM,Zhang M.Risk factors associated with nonsteroidal anti-inflammatory drugs(NSAIDs)-induced gastrointestinal bleeding resulting on people over 60 years old in Beijing[J].Medicine(Baltimore),2018,97(18):e0665.
[6]	Park J,Jeon SR,Kim JO,et al.Rebleeding rate and risk factors in nonsteroidal anti-inflammatory drug-induced enteropathy[J].J Dig Dis,2018,19(5):279-287.
[7]	Chen WC,Lin KH,Huang YT,et al.The risk of lower gastrointestinal bleeding in low-dose aspirin users[J].Aliment Pharmacol Ther,2017,45(12):1542-1550.
[8]	García Rodríguez LA,Martín-Pérez M,Hennekens CH,et al.Bleeding risk with long-term low-dose aspirin:a systematic review of observational studies[J].PLoS One,2016,11(8):e0160046.
[9]	Sostres C, Carrera-Lasfuentes P, Lanas A. Non-steroidal anti-inflammatory drug related upper gastrointestinal bleeding:types of drug use and patient profiles in real clinical practice[J].Curr Med Res Opin,2017,33(10):1815-1820.
[10]	Chan FK,Leung Ki EL,Wong GL,et al.Risks of bleeding recurrence and cardiovascular events with continued aspirin use after lower gastrointestinal hemorrhage[J].Gastroenterology,2016,151(2):271-277.
[11]	Figueiras A,Estany-Gestal A,Aguirre C,et al.CYP2C9 variants as a risk modifier of NSAID-related gastrointestinal bleeding:a case-control study[J].Pharmacogenet Genomics,2016,26(2):66-73.
[12]	Mo C,Sun G,Lu ML,et al.Proton pump inhibitors in prevention of low-dose aspirin-associated upper gastrointestinal injuries[J].World J Gastroenterol,2015,21(17):5382-5392.
[13]	Lué A,Lanas A.Protons pump inhibitor treatment and lower gastrointestinal bleeding:balancing risks and benefits[J].World J Gastroenterol,2016,22(48):10477-10481.
[14]	Colucci R,Pellegrini C,Fornai M,et al.Pathophysiology of NSAID-associated intestinal lesions in the rat:luminal bacteria and mucosal inflammation as targets for prevention[J].Front Pharmacol,2018,9:1340.
[15]	Yokoe S,Nakagawa T,Kojima Y,et al.Indomethacin-induced intestinal epithelial cell damage is mediated by pVHL activation through the degradation of collagen I and HIF-1α[J].Biochem Biophys Res Commun,2015,468(4):671-676.
[16]	Lichtenberger LM,Bhattarai D,Phan TM,et al.Suppression of contractile activity in the small intestine by indomethacin and omeprazole[J].Am J Physiol Gastrointest Liver Physiol,2015,308(9):G785-G793.
[17]	Mayo SA,Song YK,Cruz MR,et al.Indomethacin injury to the rat small intestine is dependent upon biliary secretion and is associated with overgrowth of enterococci[J].Physiol Rep,2016,4(6):e12725.
[18]	Amagase K,Nakamura E,Kato S,et al.Glutamate as a potential protective drug in the gastrointestinal mucosa[J].Yakugaku Zasshi,2015,135(6):779-782.
[19]	Lai Y,Zhong W,Yu T,et al.Rebamipide promotes the regeneration of aspirin-induced small-intestine mucosal injury through accumulation of β-catenin[J].PLoS One,2015,10(7):e0132031.
[20]	Majeed A,Wallvik N,Eriksson J,et al.Optimal timing of vitamin K antagonist resumption after upper gastrointestinal bleeding.A risk modelling analysis[J].Thromb Haemost,2017,117(3):491-499.
[21]	Verdecchia P,Vedovati MC,Conti S,et al.Long-term outcome in patients with non-valvular atrial fibrillation on dabigatran:a prospective cohort study[J].Expert Opin Drug Saf,2018,17(11):1063-1069.
[22]	Bartlett JW,Renner E,Mouland E,et al.Clinical safety outcomes in patients with nonvalvular atrial fibrillation on rivaroxaban and diltiazem[J].Ann Pharmacother,2019,53(1):21-27.
[23]	Gieling EM,van den Ham HA,van Onzenoort H,et al.Risk of major bleeding and stroke associated with the use of vitamin K antagonists,nonvitamin K antagonist oral anticoagulants and aspirin in patients with atrial fibrillation:a cohort study[J].Br J Clin Pharmacol,2017,83(8):1844-1859.
[24]	Sherid M,Sulaiman S,Samo S,et al.Risk of gastrointestinal bleeding with rivaroxaban:a comparative study with warfarin[J].Gastroenterol Res Pract,2016,2016:9589036.
[25]	Go AS,Singer DE,Toh S,et al.Outcomes of dabigatran and warfarin for atrial fibrillation in contemporary practice:a retrospective cohort study[J].Ann Intern Med,2017,167(12):845-854.
[26]	Graham DJ,Reichman ME,Wernecke M,et al.Cardiovascular,bleeding,and mortality risks in elderly medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation[J].Circulation,2015,131(2):157-164.
[27]	Mirkov I,Popov AA,Demenesku J,et al.Intestinal toxicity of oral warfarin intake in rats[J].Food Chem Toxicol,2016,94:11-18.
[28]	Fahmy AI, Mekkawy MA, Abou-Ali A. Evaluation of adverse events involving bleeding associated with oral P2Y12 inhibitors use in the food and drug administration adverse event reporting system[J].Int J Clin Pharmacol Ther,2019,57(4):175-181.
[29]	Yang C,Qian J,Tang X,et al.Meta-analysis on the efficacy and adverse events of aspirin plus clopidogrel versus aspirin-monotherapy in patients with ischemic stroke or transient ischemic attack[J].Chin J Epidemiol(中华流行病学杂志),2015,36(12):1430-1435.
[30]	Nishtala PS,Jamieson HA,Hanger HC,et al.Examining the risks of major bleeding events in older people using antithrombotics[J].Cardiovasc Drugs Ther,2019,33(3):323-329.
[31]	Patel P,Nigam N,Sengupta N.Lower gastrointestinal bleeding in patients with coronary artery disease on antithrombotics and subsequent mortality risk[J].J Gastroenterol Hepatol,2018,33(6):1185-1191.
[32]	Oakland K,Desborough MJ,Murphy MF,et al.Rebleeding and mortality after lower gastrointestinal bleeding in patients taking antiplatelets or anticoagulants[J].Clin Gastroenterol Hepatol,2019,17(7):1276-1284.
[33]	Lucotti S,Cerutti C,Soyer M,et al.Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/thromboxane A2[J].J Clin Invest,2019,129(5):1845-1862.
[34]	Luo JC,Peng YL,Chen TS,et al.Clopidogrel inhibits angiogenesis of gastric ulcer healing via downregulation of vascular endothelial growth factor receptor 2[J].J Formos Med Assoc(台湾医学会杂志),2016,115(9):764-772.
[35]	Li JJ,Wu XY,Chen JL,et al.Antiplatelet drug ticagrelor delays gastric ulcer healing in rats[J].Exp Ther Med,2017,14(4):3774-3779.
[36]	Chisti MM,Khachani A,Brahmanday GR,et al.Dasatinib-induced haemorrhagic colitis in chronic myeloid leukaemia(CML)in blast crisis[J].BMJ Case Rep,2013,2013:2013200610.
[37]	Kreutzman A,Colom-Fernández B,Jiménez AM,et al.Dasatinib reversibly disrupts endothelial vascular integrity by increasing non-muscle myosin II contractility in a ROCK-dependent manner[J].Clin Cancer Res,2017,23(21):6697-6707.
[38]	Wang ML,Blum KA,Martin P,et al.Long-term follow-up of MCL patients treated with single-agent ibrutinib:updated safety and efficacy results[J].Blood,2015,126(6):739-745.
[39]	Zhu XQ,Tian XL,Yu CY,et al.Increased risk of hemorrhage in metastatic colorectal cancer patients treated with bevacizumab:an updated meta-analysis of 12 randomized controlled trials[J].Medicine(Baltimore),2016,95(34):e4232.
[40]	Kroschinsky F,Stölzel F,von Bonin S,et al.New drugs,new toxicities:severe side effects of modern targeted and immunotherapy of cancer and their management[J].Crit Care,2017,21(1):89.
[41]	Gonzales P,Klusewitz S,Marowske J,et al.Everolimus implicated in case of severe gastrointestinal hemorrhage[J].Case Rep Oncol Med,2017,2017:3657812.
[42]	Assi H,Abdel-Samad N.Severe gastrointestinal hemorrhage during targeted therapy for advanced breast carcinoma[J].Curr Oncol,2014,21(5):e732-e735.
[43]	Tsuchihashi K,Shimokawa H,Takayoshi K,et al.Regorafenib-induced retinal and gastrointestinal hemorrhage in a metastatic colorectal cancer patient with liver dysfunction:a case report[J].Medicine(Baltimore),2017,96(42):e8285.
[44]	Burcu B,Kanter M,Orhon ZN,et al.Protective effects of vitamin E on methotrexate-induced jejunal mucosal damage in rats[J].Anal Quant Cytopathol Histpathol,2016,38(2):87-94.
[45]	Frank M,Hennenberg EM,Eyking A,et al.TLR signaling modulates side effects of anticancer therapy in the small intestine[J].J Immunol,2015,194(4):1983-1995.
[46]	Gao J,Gao J,Qian L,et al.Activation of p38-MAPK by CXCL4/CXCR3 axis contributes to p53-dependent intestinal apoptosis initiated by 5-fluorouracil[J].Cancer Biol Ther,2014,15(8):982-991.
[47]	Araújo RS,Silveira ALM,de Sales E Souza éL,et al.Intestinal toxicity evaluation of long-circulating and pH-sensitive liposomes loaded with cisplatin[J] Eur J Pharm Sci,2017,106:142-151.
[48]	Cai ZY,Yang W,He YY,et al.Cefoperazone/sulbactam-induced abdominal wall hematoma and upper gastrointestinal bleeding:a case report and review of the literature[J].Drug Saf-Case Rep,2016,3(1):2.
[49]	Katukuri GR,Maddala RN,Ramamoorthi K,et al.Cefoperazone induced gastrointestinal bleeding[J].J Clin Diagn Res,2016,10(8):OD10-OD11.
[50]	Wan Q, Cheng RY, Guo JW, et al. Effect of ceftriaxone on the intestinal epithelium and Microbiota in neonatal mice[J].Chin J Contemp Pediatr(中国当代儿科杂志),2018,20(4):318-325.
[51]	Fotouhie A,Desai H,Parsa NA,et al.Gastrointestinal bleeding secondary to trimethoprim sulfamethoxazole-induced vitamin K deficiency[J].BMJ Case Rep,2016,2016:2016214437.
[52]	Hsu SC,Chang SS,Lee MG,et al.Risk of gastrointestinal perforation in patients taking oral fluoroquinolone therapy:an analysis of nationally representative cohort[J].PLoS One,2017,12(9):e0183813.
[53]	Yuet WC, Derasari D, Sivoravong J, et al. Selective serotonin reuptake inhibitor use and risk of gastrointestinal and intracranial bleeding[J].J Am Osteopath Assoc,2019,119(2):102-111.
[54]	Patel H,Gaduputi V,Sakam S,et al.Serotonin reuptake inhibitors and post-gastrostomy bleeding:reevaluating the link[J].Ther Clin Risk Manag,2015,11:1283-1289.
[55]	Narum S,Westergren T,Klemp M.Corticosteroids and risk of gastrointestinal bleeding:a systematic review and meta-analysis[J].BMJ Open,2014,4(5):e004587.
[56]	Tomizawa M,Shinozaki F,Hasegawa R,et al.Immunosuppressive agents are associated with peptic ulcer bleeding[J].Exp Ther Med,2017,13(5):1927-1931.
[57]	Jerebtsova M, Das JR, Tang PT, et al. Angiopoietin-1 prevents severe bleeding complications induced by heparin-like drugs and fibroblast growth factor-2 in mice[J].Am J Physiol Heart Circ Physiol,2015,309(8):H1314-H1325.
[58]	Qasim M,Rahman H,Ahmed R,et al.Mycophenolic acid mediated disruption of the intestinal epithelial tight junctions[J].Exp Cell Res,2014,322(2):277-289.

[1]	LI Yue, XU Kai, YANG Rui, YANG Huiying. Application of ultra-high performance convergence chromatography-tandem quadrupole time-of-flight mass spectrometry in the analysis of Span composition[J]. Journal of China Pharmaceutical University, 2024, 55(6): 742-749. DOI: 10.11665/j.issn.1000-5048.2024010502
[2]	LI Yan, JIA Huanhuan, HUANG Qing, YUAN Yaozuo, CHEN Minhui, ZHANG Jinlin. Impurity spectra of lansoprazole enteric-coated preparations by high performance liquid chromatography-high resolution orbital trap mass spectrometry[J]. Journal of China Pharmaceutical University, 2023, 54(5): 577-585. DOI: 10.11665/j.issn.1000-5048.2023042601
[3]	HU Zhaoliang, ZOU Wenyu, SONG Min, HANG Taijun, LU Yuting. Correlation between in-vivo mercury exposure from Cinnabaris and memory disorders in juvenile rat[J]. Journal of China Pharmaceutical University, 2023, 54(4): 483-489. DOI: 10.11665/j.issn.1000-5048.2023042603
[4]	YU Lili, CHU Tingting, HOU Chenzhi, WANG Youmei, DI Bin. Quantitative determination of 10 illicit drugs in wastewater by liquid-liquid extraction-ultra performance liquid chromatography-tandem mass spectrometry[J]. Journal of China Pharmaceutical University, 2021, 52(6): 707-712. DOI: 10.11665/j.issn.1000-5048.20210608
[5]	XIE Feng, LI Zhan-bin, TAN Hong, WANG Yan-jiao. Determination of chromium in capsule shells by ultrasonic wave promoting dissolution-graphite furnace atomic absorption spectrometry[J]. Journal of China Pharmaceutical University, 2012, 43(3): 281-282.
[6]	SHEN Wei-yang, ZHONG Shao-peng, CHEN Jian-qiu. Interaction between silicotungstic acid,silicon tungsten-cobalt heteropoly acid and bovine serum albumin by fluorescence spectrometry[J]. Journal of China Pharmaceutical University, 2011, 42(2): 131-135.
[7]	Determination of Arsenic in Chinese Herbal Extract by Flow Injection-Hydride Generation-Atomic Absorption Spectrometry[J]. Journal of China Pharmaceutical University, 2003, (4): 48-50.
[8]	Determination of Trace Arsenic in Spirulina plaensis Tablets by Flow Injection Hydride Generation Atomic Fluorescence Spectrometry[J]. Journal of China Pharmaceutical University, 1998, (6): 473-474.
[9]	Determination of Arsenic in Chinese Traditional Patent Drug XINLINGWAN by Zeeman Graphite Furnace Atomic Absorption Spectrometry[J]. Journal of China Pharmaceutical University, 1995, (2): 94-96.
[10]	Determination of 11 Metal Elements in Chinese Traditional Medicine by Use of Atomic Absorption Spectrophotometry[J]. Journal of China Pharmaceutical University, 1991, (1): 33-35.

Cited By

Get Citation

PDF

XML

Article views (432) PDF downloads (926)

Turn off MathJax

Article Contents

Abstract

References

Advances in drug-induced gastrointestinal bleeding and its pathological mechanism

Abstract

References

Related Articles

Catalog

Advances in drug-induced gastrointestinal bleeding and its pathological mechanism

Abstract

References

Related Articles

Catalog

Export File

Citation

Format

Content