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Are systemic levels of non steroidal anti inflammatory drugs relevant to acute upper gastrointestinal haemorrhage?

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Summary

It is uncertain as to the extent which gastrointestinal (GI) haemorrhage related to NSAIDs is due to a local, topical effect or to an action related to systemic absorption. We hypothesised that, should systemic drug concentrations be of importance, plasma levels of NSAIDs might be higher in patients who had developed GI haemorrhage, from controls who had not.

Ten patients with GI haemorrhage, who had ingested piroxicam (and no other NSAID), within the preceding 64 h, at the same dosage and on no new medication for the past 14 days, had blood taken at presentation for measurement of piroxicam concentrations. Plasma piroxicam concentrations were measured in 19 community dwelling controls, matched for age ±8 years, gender, daily piroxicam dosage, and time from last dose as their respective index case. All had been taking piroxicam for at least 3 months, and none had experienced GI adverse effects. Median plasma piroxicam concentrations in patients at 8.27 μg/l, was higher than in controls at 5.06 μg/l.

These results suggest that a systemic component, at least with piroxicam, may play a significant (though not necessarily exclusive) role in causing major gastrointestinal haemorrhage.

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References

  1. Hawkey CJ (1990) Non-steroidal anti-inflammatory drugs and peptic ulcers. BMJ 300: 278–284

    Google Scholar 

  2. Rainsford KD (1989) Mechanism of gastrointestinal toxicity of non-steroidal anti-inflammatory drugs. Scand J Gastroenterol Suppl 163: 9–16

    Google Scholar 

  3. Laporte J-R, Carne X, Vidal X, Moreno V, Juan J (1991) Upper gastrointestinal bleeding in relation to previous use of analgesics and non-steroidal anti-inflammatory drugs. Lancet I: 85–89

    Google Scholar 

  4. Twomey TM, Bartolucci SR, Hobbs DC (1980) Analysis of piroxicam in plasma by high performance liquid chromatography. J Chromatogr 183: 104–108

    Google Scholar 

  5. Darragh A, Gordon AJ, O'Byrne H, Hobbs D, Casey E (1985) Single-dose and steady state pharmacokinetics of piroxicam in elderly vs young adults. Eur J Clin Pharmacol 28: 305–309

    Google Scholar 

  6. Hobbs DC, Gordon AJ (1985) Focus on piroxicam. Royal Society of Medicine International Congress & Symposium Series 67: 91–94

    Google Scholar 

  7. Thorsen WB, Wester D, Tanaka Y, Morrissey JF (1968) Aspirin injury to the gastric mucos: gastric-camera observations of the effect of pH. Arch Intern Med 121: 499–506

    Google Scholar 

  8. Lanza FL, Rack MF, Wagner GS, Balm TK (1985) Reduction in gastric mucosal haemorrhage and ulceration with chronic high-level dosing of enteric-coated aspirin granules two and four times a day. Dig Dis Sci 30: 509–512

    Google Scholar 

  9. Hawthorne AB, Mahida YR, Cole AT, Hawkey CJ (1991) Aspirin-induced gastric mucosal damage: prevention by enteric coating and relation to prostaglandin synthesis. Br J Clin Pharmac 32: 77–83

    Google Scholar 

  10. Ryan JR, Riley WA, Vargs R, Offen WW, Gruber CM (1987) Enteric coating of fenprofen calcium reduces gastrointestinal microbleeding. Clin Pharmacol Ther 42: 28–32

    Google Scholar 

  11. Prichard PJ, Poniatowska TJ, Willars JE, Ravenscroft AT, Hawkey CJ (1988) Effect in man of aspirin, standard indomethacin and sustained release indomethacin preparations on gastric bleeding. Br J Clin Pharmac 26: 167–172

    Google Scholar 

  12. Gizzi G, Villani V, Brandi G, Paganelli GM, DiFebo G, Biasco G (1990) Ano-rectal lesions in patients taking suppositories containing non-steroidal anti-inflammatory drugs (NSAID). Endoscopy 22: 146–148

    Google Scholar 

  13. Uribe A, Johansson C, Slezak P, Rubid C (1986) Ulceration of the colon associated with naproxen and acetyl salicylic acid treatment. Gastrointest Endoc 32: 242–244

    Google Scholar 

  14. Rampton DS (1987) Non-steroidal anti-inflammatory drugs and the lower gastrointestinal tract — Review. Scant J Gastroenterol 22: 1–4

    Google Scholar 

  15. Carson J, Notis WM, Orris ES (1990) Colonic ulceration and bleeding during diclofenac therapy. N Eng J Med 323: 135

    Google Scholar 

  16. Langman MJS, Morgan L, Worral A (1985) Use of anti-inflammatory drugs by patients admitted with small or large bowerl perforation and haemorrhage. BMJ 290: 347–349

    Google Scholar 

  17. Baroni L, Grossi E, Trombetta N (1983) Multicentre investigation into use of injectable diclofenac in painful conditions: analysis of clinical findings on 1873 patients. Clinica Terapeutica 106: 447–456

    Google Scholar 

  18. Serratrice G (1982) Study of diclofenac injectable on the basis of 10 167 cases: role of the general practitioners in the evaluation. Tribune Med 46: 43–48

    Google Scholar 

  19. Bugat R, Thompson MR, Aures D, Grossman MI (1976) Gastric mucosal lesions produced by intravenous infusion of aspirin in cats. Gastroenterology 71: 754–759

    Google Scholar 

  20. Ligumsky M, Sestieri M, Karmeli F, Zimmerman J, Okon E, Rachmilewitz D (1990) Rectal administration of non steroidal antiinflammatory drugs: effect on rat gastric ulcerogenicity and prostaglandin EZ synthesis. Gastroenterology 98: 1245–1249

    Google Scholar 

  21. Graham DY (1989) Prevention of gastrointestinal injury induced by chronic non steroidal anti-inflammatory drug therapy. Gastroenterology 96: 675–681

    Google Scholar 

  22. McIntosh JH, Byth K, Piper DW (1985) Environmental factors in aetiology of chronic gastric ulcer: a case control study of exposure variables before the first symptoms. Gut 16: 789–798

    Google Scholar 

  23. Zeidler H (1991) Epidemiology of NSAID induced gastropathy. J Rheumatol 18: 2–5

    Google Scholar 

  24. Carson JL, Strom BL (1988) The gastrointestinal side effects of the non-steroidal anti-inflammatory drugs. J Clin Pharmacol 28: 554–559

    Google Scholar 

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Wynne, H.A., Rawlins, M.D. Are systemic levels of non steroidal anti inflammatory drugs relevant to acute upper gastrointestinal haemorrhage?. Eur J Clin Pharmacol 44, 309–313 (1993). https://doi.org/10.1007/BF00316464

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  • DOI: https://doi.org/10.1007/BF00316464

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