SOME CONTEMPORARY VIEWS ON NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
Abstract
Background. Non-steroidal anti-inflammatory drugs (NSAID) are important for the treatment of inflammation and pain. In equal doses these drugs provide more or less equal effects. As a result of the prostaglandin inhibition they cause gastrointestinal adverse effects, disturbances of kidney function and blood coagulation. Clinically significant are their gastrointestinal adverse effects, manifested as perforations, ulcerations and hemorrhages. Non-steroidal anti-inflammatory drugs differ in their potency of inhibition of two cyclooxygenase isoforms. Their adverse effects are primarily due to the inhibition of constitutive cyclooxygenase 1. Consequently, the treatment of choice is a less harmful nonsteroidal anti-inflammatory drug, which is a less potent inhibitor of cyclooxygenase 1. The newer drugs of the class of coxibs have a less potent effect on the gastrointestinal prostaglandins, so they cause fewer gastrointestinal adverse effects, however they inhibit the constitutive cyclooxygenase 2 in the kidneys. In this way they reduce prostaglandin synthesis and blood flow in the kidneys. Contraindications for their use are similar to those characteristic of conventional nonsteroidal anti-inflammatory drugs, especially heart and kidney failure, gastrointestinal ulcerations and bleeding, and inflammatory bowel disease. An additional new indication has been established for these drugs – treatment of familial adenomatous polyposis.
Conclusions. The conventional nonsteroidal anti-inflammatory agents are relatively safe drugs when used in lower doses and for the shortest possible time. Safe use of these drugs is based on correct intake, careful selection of patients and protection of patients who present with risk factors for gastrointestinal adverse effects.
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References
Douthwaite AH, Lintott GAM. Gastroscopic observation of effect of aspirin and certain other substances on stomach. Lancet 1938; 2: 1222–5.
Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for the aspirin-like drugs. Nature 1971; 231: 232–5.
Wolfe MM, Lichenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999; 340: 1888–99.
Brooks P, Emery P, Evans JF et al. Interpreting the clinical significance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2. Rheumatology 1999; 38: 779–88.
McKenna F. COX-2: Separating myth from reality. Scand J Rheumatol 1999; 28; Suppl 109: 19–29.
Vane JR, Botting RM. Mechanism of action of nonsteroidal anti-inflammatory drugs. Am J Med 1998; 104: 2S–8S.
Wolfe MM, Sol AH. The physiology of gastric acid secretion. N Engl J Med 1998; 319: 1707–15.
Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ 2000; 321: 1183–7.
Weil J, Colin-Jones D, Langman M, Lawson D, Logan R, Murphy M. Prophylactic aspirin and risk of peptic ulcer bleeding. BMJ 1995; 310: 827–30.
Cryer B, Feldman M. Effects of very low dose daily, long-term aspirin therapy on gastric, duodenal, and rectal prostaglandin levels and on mucosal injury in healthy humans. Gastroenterology 1999; 117: 17–25.
Burgess MI, Densem CG, Brooks NH, Levy RD, Lee HS. The real cost of aspirin. Postgrad Med J 2000; 76: 734–5.
Markovič S. Škodljivi učinki nesteroidnih protivnetnih zdravil na prebavila. In: Mrevlje F, Možina H, Kocijančič A. 42. Tavčarjevi dnevi. Zbornik predavanj. Ljubljana: Littera picta d.o.o, 2000: 20–7.
Phisician’s desk reference. 54th edition. Montvale, NJ: Medical Economics Company 2000: 1913–3.
Malfertheiner P, Labenz J. Does Helicobacter pylori status affect nonsteroidal anti-inflammatory drug associated gastroduodenal pathology? Am J Med 1998; 104: 35S–40S.
Santolaria S, Lanas A, Benito R, Pérez-Aisa MA, Montoro M, Sainz R. Helicobacter pylori infection is a protective factor for bleeding gastric ulcer but not for bleeding duodenal ulcers in NSAID users. Aliment Pharmacol Ther 1999; 13: 1511–8.
Hawkey CJ. Personal review: Helicobacter pylori, NSAIDs and cognitive dissonance. Aliment Pharmacol Ther 1999; 13: 695–702.
Chan FKL, Sung JJY, Suen R et al. Does eradication of Helicobacter pylori impair healing of nonsteroidal anti-inflammatory drug associated bleeding peptic ulcers? A prospective randomized study. Aliment Pharmacol Ther 1998; 12: 1201–5.
Hawkey CJ. Is Helicobacter pylori eradication useful in patients taking NSAIDs? Eu J Gastroenterol Hepatol 1999; 11: Suppl 2: S47–50.
Gotzche PC. Extracts from clinical evidence. Non-steroidal anti-inflammatory drugs. BMJ 2000; 320: 1058–61.
Hernandez-Diaz S, Garcia Rodriguez LA. Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal bleeding/perforation. An overview of epidemiologic studies published in the 1990s. Arch Int Med 2000; 160: 2093–9.
Garcia Rodriguez LA. Variability in risk of gastrointestinal complications with different nonsteroidal anti-inflammatory drugs. Am J Med 1998; 104: 30S–40S.
Whelton A. Renal effects of over-the counter analgesics. J Clin Pharmacol 1995; 35: 454–63.
Page J, Henry D. Consumption of NSAIDs and the development of congestive heart failure in elderly patients. An underrecognized public health problem. Arch Intern Med 2000; 160: 777–84
Feenstra J, Grobbee DE, Mosterd A, Stricker BHC. Adverse cardiovascular effects of NSAIDs in patients with congestive hearth failure. Drug Safety 1997: 17: 166–80.
Leeuw PW. Nonsteroidal anti-inflammatory drugs and hypertension. The risk in perspective. Drugs 1996; 51: 179–87.
Vane JR, Warner TD. Nomenclature for COX-2 inhibitors. Lancet 2000; 356: 1373–4.
Tegeder I, Lötsch J, Krebs S et al. Comparison of inhibitory effects of meloxicam and diclofenac on human tromboksane biosynthesis after single doses and at steady state. Clin Pharmacol Ther 1999; 65: 533–44.
De Meijer A, Vollaard H, de Metz M et al. Meloxicam, 15 mg/day, spares platelet function in healthy volunteers. Clin Pharmacol Ther 1999; 66: 425–30.
Van Hecken A, Schwartz JI, Depré M et al. Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol 2000; 40: 1109–20.
Distel M, Mueller C, Bluhmki E, Friess J. Safety of meloxicam: a global analysis of clinical trials. Br J Rheum 1996; 35: Suppl 1: 68–77.
Fenn GC, Morant SV, Shield MJ. Gastrointestinal complications and meloxicam. Br J Rheum 1997; 36: 1234–4.
Hawkey C, Kahan A, Steinbrück K et al. Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. Br J Rheumatol 1998; 37; 9: 937–45.
Jones AK. Re: Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients (C. Hawkey et al., Br J Rheumatol 1998; 37: 937–45). Rheumatology (Oxford) 1999; 38: 793–3.
Anon. Meloxicam (Mobic) for arthritis. The Medical Letter 2000; 42; 1079: 47–8.
Jackson LM, Hawkey CJ. COX-2 selective nonsteroidal anti-inflammatory drugs. Do they really offer any advantages? Drugs 2000; 59: 1207–16.
Rofecoxib. In: Non-steroidal anti-inflammatory drugs. British national formulary 40, sept. 2000; 452–62.
Langman MJ, Jensen DM, Watson DJ et al. Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA 1999; 282: 1929–33.
Cryer B, Peterson WL. COX-1 sparing NSAIDs. Is the enthusiasm justified? JAMA 1999; 282; 20: 1961–63.
Farber MS, Milad AJ, Zaran FK, Farmer RL, Ragatzki PA. Evaluation of nonsteroidal anti-inflammatory drug use in a health system: identification of opportunities for medication use improvement. ASHP, Annual meeting; 2000; 57; P-80.
Anon. Drugs for rheumatoid arthritis. The Medical Letter 2000; 42: 57–64.
Noble SL, King DS, Olutade JI. Cyclooxygenase-2 enzyme inhibitors: place in therapy. Am Fam Physician 2000; 61: 3669–76.
Lipsky PE, Brooks P, Crofford L et al. Unresolved issues in the role of cyclooxygenase-2 in normal physiologic processe and disease. Arch Intern Med 2000; 160: 913–20.
Wallace JL. Selective COX-2 inhibitors: is the water becoming muddy? TIPS 1999; 20: 4–5.
Hawkey CJ. COX-2 inhibitors. Lancet 1999; 353: 307–14.
Simon LS. Are biologic and clinical effects of the COX-2 specific inhibitors an advance compared with the traditional NSAIDs? Curr Opin Rheumatol 2000; 12: 163–70.
Emery P. COX-1, COX-2: so what? Scand J Rheumatol 1999; 28: 6–9.
Hinz B, Brune K. Spezifische Zyklooxygenase-2-Inhibitoren. Anaesthesist 2000; 49: 964–71.
Brater CD. Effects of nonsteroidal anti-inflammatory drugs on renal function: focus on cyclooxygenase-2-selective inhibition. Am J Med 1999; 107: 65S–71S.
In large head to head COX-2 inhibitor safety study, Vioxx® associated with significant increases in blood pressure and edema vs. Celebrex®. Press release. 22nd junij 2000. http://www.pharmacia.com/News/Archive.asp
Swan S, Rudy DW, Lasseter KC et al. Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving low-salt diet. Ann Int Med 2000; 133: 1–9.
Perazella MA, Eras J. Are selective COX-2 inhibitors nephrotoxic? Am J Kidney Dis 2000; 35: 937–40.
Anon. Celecoxib linked with acute renal failure. Reactions 2000; 822: 2–2.
Anon. Questions raised about rofecoxib’s cardiovascular profile. Reactions 2000; 802: 3–3.
Bombardier C, Laine L, Reicin A et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Eng J Med 2000; 343: 1520–8.
Crofford LJ, Oates JC, McCune WJ et al. Trombosis in patients with connective tissue diseases treated with specific cyclooxygenase 2 inhibitors. A report of four cases. Arthritis Rheum 2000; 43: 1891–6.
Eleven deaths among UK Vioxx users. Reuters Medical News, 8th September 2000. http://www.medscape.com/reuters/prof/2000/09/09.08/2000090rglt007.htlm
Anon. Updates from the UK CSM and MCA. Reactions 2000; 822: 4–4.
Vane J. Aspirin and other anti-inflammatory drugs. Thorax 2000; 55: Suppl 2: S3–S9.
Reddy SB, Chinthalapally VR. Colon cancer. A role for cyclo-oxygenase-2 specific nonsteroidal anti-inflammatory drugs. Drugs & Aging 2000; 16: 329–34.
Jones MK, Wang H, Peskar BM et al. Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: Insights into mechanism and implications for cancer growth and ulcer healing. Nature Med 1999; 5: 1418–23.
Henney JE. Celecoxib indicated for FAP. From the Food and Drug Administration. JAMA 2000; 283; 9–9.
McGeer P. Cyclo-oxygenase-2 inhibitors. Rationale and therapeutic potential for Alzheimer’s disease. Drugs & Aging 2000; 17: 1–11.
Sainali SM, Ingram DM, Talwaker S. Results of a double blind, placebocontrolled study of celecoxib in the treatment of Alzheimer’s disease (abstract). 6th International Stockholm-Springfeld symposium of advances in Alzheimer therapy; 2000, Apr 5–8; Stockholm.
American college of rheumatology subcommittee on osteoarthritis guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum 2000; 43; 9: 1905–15.
Schnitzer TJ. Non-NSAID therapeutic options for management of chronic pain. Am J Med 1998; 105: 45S–52S.
Cicero TJ, Adams EH, Geller A et al. A postmarketing surveillance program to monitor tramadol hydrochloride abuse in United States. Drug Alc Dep 1999; 57: 7–22.
Schnitzer TJ, Kamin M, Olson WH. Tramadol allows reduction of naproxen dose among patients with naproxen-responsive osteoarthritis pain. Arthritis Rheum 1999; 42: 1370–7.
Watson DJ, Harper SE, Zhao PL, Quan H, Bolognese JA, Simon TJ. Gastrointestinal tolerability of the selective cyclooxygenase-2 inhibitor rofecoxib compared with nonselective COX-1 and COX-2 inhibitors in osteoarthritis. Arch Intern Med 2000; 160: 2998–3003.
Silverstein FE, Faich G, Goldstein JL et al. Gastrointestinal toxicity with celecoxib vs. nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis. The CLASS study: a randomizes controlled trial. JAMA 2000; 284: 1247–55.
Anon. Role of proton pump inhibitors in the prevention of NSAID-induced ulcers now emerging. Drugs & Therapy Perspectives 2000; 16; 12: 6–9.
Brown GJE, Yeomans ND. Prevention of the gastrointestinal adverse effects of nonsteroidal anti-inflammatory drugs. Drugs Safety 1999; 21: 503–12.
Hawkey CJ, Karrasch JA, Szczepański L et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1998; 338: 727–34.
Yeomans ND, Tulassay Z, Juhász L et al. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1998; 338: 719–26.
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