Abstract
In recent years, two new approaches have emerged for reducing the gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs); namely, selective inhibitors of cyclooxygenase (COX)-2 and nitric oxide-releasing NSAIDs (NO-NSAIDs). A large number of studies have been published which provide convincing data supporting the claims for gastrointestinal (GI)-sparing properties of these two classes of drugs [1–9]. In the case of the selective COX-2 inhibitors, the reduced GI toxicity is attributable to the sparing of GI prostaglandin (PG) synthesis, which is largely derived via COX-1. In the case of NO-NSAIDs, it is the slow release of nitric oxide (NO) that accounts for the reduced GI toxicity, most likely by maintaining gastrointestinal blood flow and inhibiting the activation of leukocytes within the GI microcirculation [5,6,10].
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Keywords
- Gastric Damage
- Gastric Ulcer Healing
- Gastrointestinal Blood Flow
- Accelerate Ulcer Healing
- Ulcerogenic Property
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References
Boyce S, Chan CC, Gordon R, et al. L-745,337: a selective inhibitor of cyclooxygenase-2 elicits antinociception but not gastric ulceration in rats. Neuropharmacology 1994; 33: 1609–11.
Masferrer IL, Zweifel BS, Manning PT, et al. Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc Natl Acad Sci USA 1994; 91: 3228–32.
Seibert, K., Zhang, Y., Leahy, K., et al. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci USA 1994; 91: 12013–17.
Chan CC, Boyce S, Brideau C, et al. Pharmacology of a selective cyclooxygenase-2 inhibitor, L-745,337: a novel nonsteroidal anti-inflammatory agent with an ulcerogenic sparing effect in rat and nonhuman primate stomach. J Pharmacol Exp Ther 1995; 274: 1531–37.
Wallace JL, Reuter B, Cicala C, McKnight W, Grisham MB, Cirino G. Novel NSAID derivatives with markedly reduced ulcerogenic properties. Gastroenterology 1994; 107: 173–79.
Wallace JL, Reuter B, Cicala C, McKnight W, Grisham MB, Cirino G. A diclofenac derivative without ulcerogenic properties. Eur J Pharmacol 1994; 257: 249–55.
Reuter BK, Cirino G, Wallace JL. Markedly reduced intestinal toxicity of a diclofenac derivative. Life Sci 1994;55:PL1–PL8.
Wallace JL, McKnight W, Del Soldato P, Baydoun AR, Cirino G. Anti-thrombotic effects of a nitric oxide-generating, gastric-sparing aspirin derivative. J Clin Invest 1995; 96: 27 1118.
Davies NM, Roseth AG, Appleyard CB, et al. NO-naproxen vs. naproxen: ulcerogenic, analgesic and anti-inflammatory effects. Aliment Pharmacol Ther 1997; 11: 69–79.
Wallace, JL, Elliott SN, Del Soldato P, McKnight W, Sannicolo F, Cirino G. Gastrointestinal sparing anti-inflammatory drugs: the development of nitric oxide-relasing NSAIDs Drug Develop Res 1997; 42: 144–49.
Mizuno H., Sakamoto C, Matsuda K, et al. Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice. Gastroenterology 1997; 112: 387–97.
Schmassmann A, Peskar BM, Stettler C,et al. Effects of inhibition of prostaglandin endoperoxide synthase-2 in chronic gastro-intestinal ulcer models in rats. Br J Pharmacol 1998; 123: 795–804.
Takeuchi K, Suzuki K, Yamamoto H, Araki H, Mizoguchi h, Ukawa H. Cyclooxygenase2 selective and nitric oxide-releasing nonsteroidal anti-inflammatory drugs and gastric mucosal responses. J Physiol Pharmacol 1998; 49: 501–13.
Reuter BK, Asfaha S, Buret A, Sharkey KA, Wallace JL. Exacerbation of inflammation-associated colonic injury in rat through inhibition of cyclooxygenase-2. J Clin Invest 1996; 98: 2076–85.
Elliott SN, McKnight W, Cirino G, Wallace JL. A nitric oxide-releasing nonsteroidal anti-inflammatory drug accelerates gastric ulcer healing in the rat. Gastroenterology 1995; 109: 524–30.
Wallace JL, McKnight W, Wilson TL, Del Soldato P, Cirino G. Reduction of shock-induced gastric damage by a nitric oxide-releasing aspirin derivative: role of neutrophils. Am J Physiol 1997; 273: G1246 - G51.
Maricic N, Ehrlich K, Gretzer B, Schuligoi R, Respondek M, Peskar BM. Selective cyclooxygenase-2 inhibitors aggravate ischaemia-reperfusion injury in the rat stomach. Br J Pharmacol 1999; 128: 1659–66.
Fujihara CK, Malheiros DMAC, Donato IL, Poli A, deNucci G, ZatzR. Nitroflurbiprofen, a new nonsteroidal anti-inflammatory, ameliorates structural injury in the remnant kidney. Am J Physiol 1998; 274: F573 - F79.
Goldblatt H, Haas E, Klick RL, Lewis LV. The effect of main artery occlusion of one kidney on blood pressure of dogs. Proc Natl Acad Sci USA 1976; 73: 1722–24.
Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med 1999; 106: 13S - 24S.
McAdam BF, Catella-Lawson F, Mardini IA, Kapoor S, Lawson JA, FitzGerald GA. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci USA 1999; 96: 27277.
Catella-Lawson F, McAdam B, Morrison BW, et al Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids. J Pharmacol Exp Ther 1999; 289: 735–41.
MuscarĂ¢ MN, Vergnolle N, Lovren F, Triggle DR, Elliott SN, Asfaha Wallace JL. Selective cyclooxygenase-2 inhibition with celecoxib elevates blood pressure and promotes leukocyte adherence. Br J Pharmacol 2000: 129: 1423–1430.
Wallace JL, Chapman K, McKnight W. Limited anti-inflammatory efficacy of cyclooxygenase-2 inhibition in carrageenan-airpouch inflammation. Br J Pharmacol 1999; 126: 1200–1204.
Wallace JL, McKnight W, Reuter BK, Wallace JL. NSAID-induced gastric damage in the rat: requirement for inhibition of both cyclooxygenase-1 and -2. Gastroenterology, 2000; in press.
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MuscarĂ¡, M.N., McKnight, W., Dicay, M., Wallace, J.L. (2001). GI and Cardiovascular Profiles of New NSAIDs: Selective COX-2 Inhibitors and NO-NSAIDs. In: Samuelsson, B., Paoletti, R., Folco, G.C., Granström, E., Nicosia, S. (eds) Advances in Prostaglandin and Leukotriene Research. Medical Science Symposia Series, vol 16. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9721-0_32
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DOI: https://doi.org/10.1007/978-94-015-9721-0_32
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