Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-55f67697df-7l9ct Total loading time: 0 Render date: 2025-05-08T19:01:46.433Z Has data issue: false hasContentIssue false

13 - Antipyretic analgesics

from SECTION IV - PHARMACOLOGICAL TREATMENT

Published online by Cambridge University Press:  06 July 2010

By
BURKHARD HINZ  and
KAY BRUNE
Edited by
Eduardo D. Bruera  and
Russell K. Portenoy
BURKHARD HINZ
Affiliation:
University of Rostock
KAY BRUNE
Affiliation:
Friedrich-Alexander University, Erlangen
Eduardo D. Bruera
Affiliation:
University of Texas, Houston
Russell K. Portenoy
Affiliation:
Albert Einstein College of Medicine, New York
Get access

Summary

Introduction>

Antipyretic (or nonopioid) analgesics are a group of heterogenous substances including acidic (nonsteroidal anti-inflammatory drugs [NSAIDs]) and nonacidic (acetaminophen, pyrazolinones) drugs. Moreover, various selective cyclooxygenase-2 (COX-2) inhibitors with improved gastrointestinal tolerability compared with conventional NSAIDs have been established for symptomatic pain treatment in recent years. This chapter summarizes the pharmacology of all these drugs, with particular emphasis on their rational use based on their diverse pharmacokinetic characteristics and adverse drug reaction profiles. Moreover, the mechanisms underlying their antihyperalgesic action are extensively discussed.

Mode of action of antipyretic analgesics

Inhibition of cyclooxygenase enzymes

In 1971, Vane showed that the anti-inflammatory action of NSAIDs rests in their ability to inhibit the activity of the COX enzyme, which in turn results in a diminished synthesis of proinflammatory prostaglandins. This action is considered not the sole but a major factor of the mode of action of NSAIDs. The pathway leading to the generation of prostaglandins has been elucidated in detail. Within this process, the COX enzyme (also referred to as prostaglandin H synthase) catalyzes the first step of the synthesis of prostanoids by converting arachidonic acid into prostaglandin H2, which is the common substrate for specific prostaglandin synthases. The enzyme is bifunctional, with fatty-acid COX activity (catalyzing the conversion of arachidonic acid to prostaglandin G2) and prostaglandin hydroperoxidase activity (catalyzing the conversion of prostaglandin G2 to prostaglandin H2).

In the early 1990s, COX was demonstrated to exist as two distinct isoforms.

Type
Chapter
Information
Cancer Pain
Assessment and Management
 , pp. 255 - 271
Publisher: Cambridge University Press
Print publication year: 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Vane, JR. Inhibition of prostaglandin synthesis as a mechanism of action of aspirin-like drugs. Nat New Biol 231:232–5, 1971.CrossRefGoogle ScholarPubMed
Masferrer, JL, Zweifel, BS, Seibert, S, Needleman, P. Selective regulation of cellular cyclooxygenase by dexamethasone and endotoxin in mice. J Clin Invest 86:1375–9, 1990.CrossRefGoogle ScholarPubMed
Xie, W, Chipman, JG, Robertson, DL, et al. Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci U S A 88:2692–6, 1991.CrossRefGoogle ScholarPubMed
Onoe, Y, Miyaura, C, Kaminakayashiki, T, et al. IL-13 and IL-4 inhibit bone resorption by suppressing cyclooxygenase-2-dependent prostaglandin synthesis in osteoblasts. J Immunol 156:758–64, 1996.Google ScholarPubMed
Niiro, H, Otsuka, T, Izuhara, K, et al. Regulation by interleukin-10 and interleukin-4 of cyclooxygenase-2 expression in human neutrophils. Blood 89:1621–8, 1997.Google ScholarPubMed
Nantel, F, Denis, D, Gordon, R, et al. Distribution and regulation of cyclooxygenase-2 in carrageenan-induced inflammation. Br J Pharmacol 128:853–9, 1999.CrossRefGoogle ScholarPubMed
Hinz, B, Brune, K, Pahl, A. Cyclooxygenase-2 expression in lipopolysaccharide-stimulated human monocytes is modulated by cyclic AMP, prostaglandin E2 and nonsteroidal anti-inflammatory drugs. Biochem Biophys Res Commun 278:790–6, 2000.CrossRefGoogle ScholarPubMed
Hinz, B, Brune, K, Pahl, A. Prostaglandin E2 up-regulates cyclooxygenase-2 expression in lipopolysaccharide-stimulated RAW 264.7 macrophages. Biochem Biophys Res Commun 272:744–8, 2000.CrossRefGoogle Scholar
Hinz, B, Rösch, S, Ramer, R, et al. Latanoprost induces matrix metalloproteinase-1 expression in human non-pigmented ciliary epithelial cells through a cyclooxygenase-2-dependent mechanism. FASEB J 19:1929–31, 2005.CrossRefGoogle Scholar
Maldve, RE, Kim, Y, Muga, SJ, Fischer, SM. Prostaglandin E2 regulation of cyclooxygenase expression in keratinocytes is mediated via cyclic nucleotide-linked prostaglandin receptors. J Lipid Res 41:873–81, 2000.Google ScholarPubMed
Ramer, R, Weinzierl, U, Schwind, B, et al. Ceramide is involved in R(+)-methanandamide-induced cyclooxygenase-2 expression in human neuroglioma cells. Mol Pharmacol 64:1189–98, 2003.CrossRefGoogle Scholar
Hinz, B, Ramer, R, Eichele, K, et al. Upregulation of cyclooxygenase-2 expression is involved in R(+)-methanandamide-induced apoptotic death of human neuroglioma cells. Mol Pharmacol 66:1643–51, 2004.CrossRefGoogle Scholar
Patrignani, P, Panara, MR, Sciulli, MG, et al. Differential inhibition of human prostaglandin endoperoxide synthase-1 and -2 by nonsteroidal anti-inflammatory drugs. J Physiol Pharmacol 48:623–31, 1997.Google ScholarPubMed
Picado, C.Mechanisms of aspirin sensitivity. Curr Allergy Asthma Rep 6:198–202, 2006.CrossRefGoogle ScholarPubMed
Hinz, B, Brune, K. Cyclooxygenase-2 – ten years later. J Pharmacol Exp Ther 300:367–75, 2002.CrossRefGoogle Scholar
Brune, K.How aspirin might work: a pharmacokinetic approach. Agents Actions 4:230–2, 1974.CrossRefGoogle ScholarPubMed
Brune, K, Glatt, M, Graf, P. Mechanism of action of anti-inflammatory drugs. Gen Pharmacol 7:27–33, 1976.CrossRefGoogle ScholarPubMed
Brune, K, Rainsford, KD, Schweitzer, A. Biodistribution of mild analgesics. Br J Clin Pharmacol 10(Suppl 2):279–84, 1980.CrossRefGoogle ScholarPubMed
McCormack, K, Brune, K. Classical absorption therapy and the development of gastric mucosal damage associated with the non-steroidal anti-inflammatory drugs. Arch Toxicol 60:261–9, 1987.CrossRefGoogle Scholar
Price, AH, Fletcher, M. Mechanisms of NSAID-induced gastroenteropathy. Drugs 40(Suppl 5):1–11, 1990.CrossRefGoogle ScholarPubMed
Somasundaram, S, Rafi, S, Hayllar, J, et al. Mitochondrial damage: a possible mechanism of the “topical” phase of NSAID induced injury to the rat intestine. Gut 41:344–53, 1997.CrossRefGoogle ScholarPubMed
Wallace, JL.Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years. Gastroenterology 112:1000–16, 1997.CrossRefGoogle ScholarPubMed
Langenbach, R, Morham, SG, Tiano, HF, et al. Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Cell 83:483–92, 1995.CrossRefGoogle ScholarPubMed
Schaible, HG, Schmidt, RF. Time course of mechanosensitivity changes in articular afferents during a developing experimental arthritis. J Neurophysiol 60:2180–95, 1988.CrossRefGoogle ScholarPubMed
Neugebauer, V, Geisslinger, G, Rümenapp, P, et al. Antinociceptive effects of R(−)- and S(+)-flurbiprofen on rat spinal dorsal horn neurons rendered hyperexcitable by an acute knee joint inflammation. J Pharmacol Exp Ther 275:618–28, 1995.Google ScholarPubMed
Akopian, AN, Sivilotti, L, Wood, JN. A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature 379:257–62, 1996.CrossRefGoogle ScholarPubMed
England, S, Bevan, S, Docherty, RJ. PGE2 modulates the tetrodotoxin-resistant sodium current in neonatal rat dorsal root ganglion neurones via the cyclic AMP-protein kinase A cascade. J Physiol (Lond) 495:429–40, 1996.CrossRefGoogle ScholarPubMed
Gold, MS, Reichling, DB, Shuster, MJ, Levine, JD. Hyperalgesic agents increase a tetrodotoxin-resistant Na +current in nociceptors. Proc Natl Acad Sci U S A 93:1108–12, 1996.CrossRefGoogle ScholarPubMed
Benn, SC, Costigan, M, Tate, S, et al. Developmental expression of the TTX-resistant voltage-gated sodium channels Nav1.8 (SNS) and Nav1.9 (SNS2) in primary sensory neurons. J Neurosci 21:6077–85, 2001.CrossRefGoogle Scholar
Lopshire, JC, Nicol, GD. Activation and recovery of the PGE2-mediated sensitization of the capsaicin response in rat sensory neurons. J Neurophysiol 78:3154–64, 1997.CrossRefGoogle ScholarPubMed
Caterina, MJ, Leffler, A, Malmberg, AB, et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306–13, 2000.CrossRefGoogle ScholarPubMed
Davis, JB, Gray, J, Gunthorpe, MJ, et al. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405:183–7, 2000.CrossRefGoogle ScholarPubMed
Beiche, F, Scheuerer, S, Brune, K, et al. Upregulation of cyclooxygenase-2 mRNA in the rat spinal cord following peripheral inflammation. FEBS Lett 390:165–9, 1996.CrossRefGoogle ScholarPubMed
Smith, CJ, Zhang, Y, Koboldt, CM, et al. Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc Natl Acad Sci U S A 95:13313–18, 1998.CrossRefGoogle ScholarPubMed
Samad, TA, Moore, KA, Sapirstein, A, et al. Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 410:471–5, 2001.CrossRefGoogle ScholarPubMed
Baba, H, Kohno, T, Moore, KA, Woolf, CJ. Direct activation of rat spinal dorsal horn neurons by prostaglandin E2. J Neurosci 21:1750–6, 2001.CrossRefGoogle ScholarPubMed
Ahmadi, S, Lippross, S, Neuhuber, WL, Zeilhofer, HU. PGE2 selectively blocks inhibitory glycinergic neurotransmission onto rat superficial dorsal horn neurons. Nat Neurosci 5:34–40, 2002.CrossRefGoogle ScholarPubMed
Harvey, RJ, Depner, UB, Wassle, H, et al. GlyR α3: an essential target for spinal PGE2-mediated inflammatory pain sensitization. Science 304:884–7, 2004.CrossRefGoogle ScholarPubMed
Reinold, H, Ahmadi, S, Depner, UB, et al. Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype. J Clin Invest 115:673–9, 2005.CrossRefGoogle ScholarPubMed
Ferrer-Brechner, T, Ganz, P. Combination therapy with ibuprofen and methadone for chronic cancer pain. Am J Med 77(Suppl 1A):78–83, 1984.CrossRefGoogle ScholarPubMed
Minotti, V, Patoia, L, Roila, F, et al. Double-blind evaluation of analgesic efficacy of orally administered diclofenac, nefopam, and acetylsalicylic acid (ASA) plus codeine in chronic cancer pain. Pain 36:177–83, 1989.CrossRefGoogle ScholarPubMed
Carlson, RW, Borrison, RA, Sher, HB, et al. A multiinstitutional evaluation of the analgesic efficacy and safety of ketorolac tromethamine, acetaminophen plus codeine, and placebo in cancer pain. Pharmacotherapy 10:211–16, 1990.Google ScholarPubMed
Ventafridda, V, Conno, F, Panerai, AE, et al., Non-steroidal anti-inflammatory drugs as the first step in cancer pain therapy: double-blind, within-patient study comparing nine drugs. J Int Med Res 18:21–9, 1990.CrossRefGoogle ScholarPubMed
Björkman, R, Ullman, A, Hedner, J. Morphine-sparing effect of diclofenac in cancer pain. Eur J Clin Pharmacol 44:1–5, 1993.CrossRefGoogle ScholarPubMed
Dellemijn, PL, Verbiest, HB, Vliet, JJ, et al. Medical therapy of malignant nerve pain. A randomised double-blind explanatory trial with naproxen versus slow-release morphine. Eur J Cancer 30A:1244–50, 1994.CrossRefGoogle ScholarPubMed
Bonica, JJ. Cancer pain. In: Bonica, JJ, ed. The management of pain. Philadelphia: Lea & Febiger, 1990, pp 400–60.Google Scholar
Portenoy, RK. Cancer pain management. Semin Oncol 20(Suppl 1):19–35, 1993.Google ScholarPubMed
Winter, CA, Risley, EA, Nuss, GW. Carrageenin-induced edema in hind paw of the rat as an assay for anti-inflammatory drugs. Proc Soc Exp Biol Med 111:544–52, 1962.CrossRefGoogle Scholar
Brune, K, Lanz, R. Pharmacokinetics of non-steroidal anti-inflammatory drugs. In: Bonta, IL, Bray, MA, Parnham, MJ, eds. The pharmacology of inflammation, vol. 5, Handbook of inflammation. Amsterdam: Elsevier Science, 1985, pp 413–49.Google Scholar
Hinz, B, Dorn, CP, Shen, TY, Brune, K. Anti-inflammatory–antirheumatic drugs. In: McGuire, JL, ed. Pharmaceuticals – classes, therapeutic agents, areas of application, vol 4. Weinheim: Wiley-VCH, 2000, pp 1671–711.Google Scholar
Geisslinger, G, Menzel, S, Wissel, K, Brune, K. Single dose pharmacokinetics of different formulations of ibuprofen and aspirin. Drug Invest 5:238–42, 1993.CrossRefGoogle Scholar
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 randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. J Am Med Assoc 284:1247–55, 2000.CrossRefGoogle ScholarPubMed
Rudy, AC, Knight, PM, Brater, DC, Hall, SD. Stereoselective metabolism of ibuprofen in humans: administration of R-, S- and racemic ibuprofen. J Pharmacol Exp Ther 259:1133–9, 1991.Google ScholarPubMed
Hinz, B, Rau, T, Auge, D, et al. Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther 74:222–35, 2003.CrossRefGoogle ScholarPubMed
Henry, D, Lim, LL, Garcia Rodriguez, , et al. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. Br Med J 312:1563–6, 1996.CrossRefGoogle ScholarPubMed
Hinz, B, Chevts, J, Renner, B, et al. Bioavailability of diclofenac potassium at low doses. Br J Clin Pharmacol 59:80–84, 2005.CrossRefGoogle ScholarPubMed
Kimmey, MB. Cardioprotective effects and gastrointestinal risks of aspirin: maintaining the delicate balance. Am J Med 117(Suppl 5A):72S–78S, 2004.Google ScholarPubMed
Schnitzer, TJ, Burmester, GR, Mysler, E, et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet 364:665–74, 2004.CrossRefGoogle ScholarPubMed
Catella-Lawson, F, Reilly, MP, Kapoor, SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med 345:1809–17, 2001.CrossRefGoogle ScholarPubMed
Capone, ML, Sciulli, MG, Tacconelli, S, et al. Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects. J Am Coll Cardiol 45:1295–301, 2005.CrossRefGoogle ScholarPubMed
MacDonald, TM, Wei, L. Effect of ibuprofen on cardioprotective effect of aspirin. Lancet 361:573–4, 2003.CrossRefGoogle ScholarPubMed
,U.S. Food and Drug Administration. FDA science paper: concomitant use of ibuprofen and aspirin: potential for attenuation of the anti-platelet effect of aspirin. 9/8/2006. Available at: http://www.fda.gov/cder/drug/infopage/ibuprofen/default.htm.
Bridger, S, Henderson, K, Glucksman, E, et al. Deaths from low dose paracetamol poisoning. BMJ 316:1724–5, 1998.CrossRefGoogle ScholarPubMed
Seeff, LB, Cuccherini, BA, Zimmerman, HJ, et al. Paracetamol hepatotoxicity in alcoholics. Ann Intern Med 104:399–404, 1986.CrossRefGoogle ScholarPubMed
Schnitzer, TJ. Update of ACR guidelines for osteoarthritis: role of the coxibs. J Pain Symptom Manage 23(Suppl 4):S24–30, 2002.CrossRefGoogle ScholarPubMed
Brandt, K.Paracetamol in the treatment of osteoarthritis pain. Drugs 63 Spec No 2:23–41, 2003.CrossRefGoogle ScholarPubMed
Botting, RM. Mechanism of action of acetaminophen: is there a cyclooxygenase 3?Clin Infect Dis 31(Suppl 5):S202–10, 2000.CrossRefGoogle Scholar
Flower, RJ, Vane, JR. Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-acetamidophenol). Nature 240:410–11, 1972.CrossRefGoogle Scholar
Lanz, R, Polster, P, Brune, K. Antipyretic analgesics inhibit prostaglandin release from astrocytes and macrophages similarly. Eur J Pharmacol 130:105–9, 1986.CrossRefGoogle ScholarPubMed
Swierkosz, TA, Jordan, L, McBride, M, et al. Actions of paracetamol on cyclooxygenases in tissue and cell homogenates of mouse and rabbit. Med Sci Monit 8:BR496–503, 2002.Google ScholarPubMed
Warner, TD, Vojnovic, I, Giuliano, F, et al. Cyclooxygenases 1, 2, and 3 and the production of prostaglandin I2: investigating the activities of acetaminophen and cyclooxygenase-2-selective inhibitors in rat tissues. J Pharmacol Exp Ther 310:642–7, 2004.CrossRefGoogle ScholarPubMed
Graham, GG, Scott, KF. Mechanism of action of paracetamol. Am J Ther 12:46–55, 2005.CrossRefGoogle ScholarPubMed
Chandrasekharan, NV, Dai, H, Roos, KL, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci U S A 99:13926–31, 2002.CrossRefGoogle ScholarPubMed
Kis, B, Snipes, JA, Busija, DW. Acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts, fictions, and uncertainties. J Pharmacol Exp Ther 315:1–7, 2005.CrossRefGoogle ScholarPubMed
Boutaud, O, Aronoff, DM, Richardson, JH, et al. Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H2 synthases. Proc Natl Acad Sci U S A 99:7130–5, 2002.CrossRefGoogle Scholar
Boardman, PL, Hart, FD. Clinical measurement of the anti-inflammatory effects of salicylates in rheumatoid arthritis. BMJ 4:264–8, 1967.CrossRefGoogle ScholarPubMed
Ring, EF, Collins, AJ, Bacon, PA, Cosh, JA. Quantitation of thermography in arthritis using multi-isothermal analysis. II. Effect of nonsteroidal anti-inflammatory therapy on the thermographic index. Ann Rheum Dis 33:353–6, 1974.CrossRefGoogle ScholarPubMed
Skjelbred, P, Lokken, P. Paracetamol versus placebo: effects on post-operative course. Eur J Clin Pharmacol 15:27–33, 1979.CrossRefGoogle ScholarPubMed
Bjornsson, GA, Haanaes, HR, Skoglund, . A randomized, double-blind crossover trial of paracetamol 1000 mg four times daily vs ibuprofen 600 mg: effect on swelling and other postoperative events after third molar surgery. Br J Clin Pharmacol 55:405–12, 2003.Google ScholarPubMed
Ferreira, SH, Lorenzetti, BB, Correa, FM. Blockade of central and peripheral generation of prostaglandins explains the antialgic effect of aspirin like drugs. Pol J Pharmacol Pharm 30:133–40, 1978.Google ScholarPubMed
Honore, P, Buritova, J, Besson, JM. Aspirin and acetaminophen reduced both Fos expression in rat lumbar spinal cord and inflammatory signs produced by carrageenin inflammation. Pain 63:365–75, 1995.CrossRefGoogle ScholarPubMed
Garcia Rodriguez, , Hernandez-Diaz, S. Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs. Epidemiology 12:570–6, 2001.CrossRefGoogle Scholar
Mielke, CH Jr. Comparative effects of aspirin and acetaminophen on hemostasis. Arch Intern Med 141:305–10, 1981.CrossRefGoogle ScholarPubMed
Jenkins, C, Costello, J, Hodge, L. Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice. BMJ 328:434, 2004.CrossRefGoogle ScholarPubMed
Hinz, B, Cheremina, O, Brune, K. Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. FASEB J 22:383–90, 2008.CrossRefGoogle ScholarPubMed
Forman, JP, Stampfer, MJ, Curhan, GC. Non-narcotic analgesic dose and risk of incident hypertension in US women. Hypertension 46:500–7, 2005.CrossRefGoogle ScholarPubMed
Chan, AT, Manson, JE, Albert, CM, et al. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation 113:1578–87, 2006.CrossRefGoogle ScholarPubMed
Rodriguez, M, Barutell, C, Rull, M, et al. Efficacy and tolerance of oral dipyrone versus oral morphine for cancer pain. Eur J Cancer 30A:584–7, 1994.CrossRefGoogle ScholarPubMed
Kaufman, DW, Kelly, JP, Levy, M, Shapiro, S. The drug etiology of agranulocytosis an aplastic anemia. In: Monographs in epidemiology and biostatistics 18. New York: Oxford University Press, 1991.Google Scholar
Risks of agranulocytosis and aplastic anemia: a first report of their relation to drug use with special reference to analgesics. The International Agranulocytosis and Aplastic Anemia Study. JAMA 256:1749–57, 1986.CrossRef
Ibanez, L, Vidal, X, Ballarin, E, Laporte, JR. Agranulocytosis associated with dipyrone (metamizol). Eur J Clin Pharmacol 60:821–9, 2005.CrossRefGoogle Scholar
Andrade, SE, Martinez, C, Walker, AM. Comparative safety evaluation of non-narcotic analgesics. J Clin Epidemiol 51:1357–65, 1998.CrossRefGoogle ScholarPubMed
Hackenthal, E.Paracetamol and metamizol in the treatment of chronic pain syndromes. Schmerz 11:269–75, 1997.CrossRefGoogle ScholarPubMed
Brune, K, Alpermann, H. Non-acidic pyrazoles: inhibition of prostaglandin production, carrageenan oedema and yeast fever. Agents Actions 13:360–3, 1983.CrossRefGoogle ScholarPubMed
Tatsuo, MA, Carvalho, WM, Silva, CV, et al. Analgesic and antiinflammatory effects of dipyrone in rat adjuvant arthritis model. Inflammation 18:399–405, 1994.CrossRefGoogle ScholarPubMed
Hinz, B, Cheremina, O, Bachmakov, J, et al. Dipyrone elicits substantial inhibition of peripheral cyclooxygenases in humans: new insights into the pharmacology of an old analgesic. FASEB J 21:2343–51, 2007.CrossRefGoogle ScholarPubMed
Laporte, JR, Carne, X. Blood dyscrasias and the relative safety of non-narcotic analgesics. Lancet 1:809, 1987.CrossRefGoogle ScholarPubMed
Laporte, JR, Carne, X, Vidal, X, et al. Upper gastrointestinal bleeding in relation to previous use of analgesics and non-steroidal anti-inflammatory drugs. Catalan Countries Study on Upper Gastrointestinal Bleeding. Lancet 337:85–9, 1991.CrossRefGoogle ScholarPubMed
Brune, K, Hinz, B. Selective cyclooxygenase-2 inhibitors: similarities and differences. Scand J Rheumatol 33(Suppl 1):1–6, 2004.CrossRefGoogle ScholarPubMed
Werner, U, Werner, D, Pahl, A, et al. Investigation of the pharmacokinetics of celecoxib by liquid chromatography-mass spectrometry. Biomed Chromatogr 16:56–60, 2002.CrossRefGoogle ScholarPubMed
Werner, U, Werner, D, Rau, T, et al. Celecoxib inhibits metabolism of cytochrome P450 2D6 substrate metoprolol in humans. Clin Pharmacol Ther 74:130–7, 2003.CrossRefGoogle ScholarPubMed
Hinz, B, Dormann, H, Brune, K. More pronounced inhibition of cyclooxygenase-2, increase of blood pressure and decrease of heart rate by treatment with diclofenac compared with celecoxib and rofecoxib. Arthritis Rheum 54:282–91, 2006.CrossRefGoogle Scholar
Rodrigues, AD, Halpin, RA, Geer, , et al. Absorption, metabolism, and excretion of etoricoxib, a potent and selective cyclooxygenase-2 inhibitor, in healthy male volunteers. Drug Metab Dispos 31:224–32, 2003.CrossRefGoogle ScholarPubMed
Scott, G, Rordorf, C, Reynolds, C, et al. Pharmacokinetics of lumiracoxib in plasma and synovial fluid. Clin Pharmacokinet 43:467–78, 2004.CrossRefGoogle ScholarPubMed
,Australian Government, Department of Health and Ageing, Therapeutic Goods Administration. Urgent advice regarding management of patients taking lumiracoxib (Prexige) [safety alert, 13 August 2007]. Available at: http://www.tga.gov.au/alerts/prexige.htm.
Hinz, B, Renner, B, Cheremina, O, et al. Lumiracoxib inhibits cyclo-oxygenase-2 completely at the 50 mg dose: is liver toxicity avoidable by adequate dosing?Ann Rheum Dis 68:289–91, 2009.CrossRefGoogle ScholarPubMed
Esser, R, Berry, C, Du, Z, et al. Preclinical pharmacology of lumiracoxib: a novel selective inhibitor of cyclooxygenase-2. Br J Pharmacol 144:538–50, 2005.CrossRefGoogle ScholarPubMed
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. N Engl J Med 343:1520–8, 2000.CrossRefGoogle ScholarPubMed
Dahlen, B, Szczeklik, A, Murray, JJ, Celecoxib in Aspirin-Intolerant Asthma Study Group. Celecoxib in patients with asthma and aspirin intolerance. The Celecoxib in Aspirin-Intolerant Asthma Study Group. N Engl J Med 344:142, 2001.Google Scholar
Stevenson, DD, Simon, RA. Lack of cross-reactivity between rofecoxib and aspirin in aspirin-sensitive patients with asthma. J Allergy Clin Immunol 108:47–51, 2001.CrossRefGoogle ScholarPubMed
Szczeklik, A, Nizankowska, E, Bochenek, G, et al. Safety of a specific COX2 inhibitor in aspirin-induced asthma. Clin Exp Allergy 31:219–25, 2001.CrossRefGoogle ScholarPubMed
Woessner, KM, Simon, RA, Stevenson, DD. The safety of celecoxib in patients with aspirin-sensitive asthma. Arthritis Rheum 46:2201–6, 2002.CrossRefGoogle ScholarPubMed
Bresalier, RS, Sander, RS, Quan, H, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352:1092–102, 2005.CrossRefGoogle Scholar
Solomon, SD, McMurray, JJ, Pfeffer, MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 352:1071–80, 2005.CrossRefGoogle Scholar
Nussmeier, NA, Whelton, AA, Brown, MT, et al. Complications of the COX2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 352:1081–91, 2005.CrossRefGoogle ScholarPubMed
U.S. Food and Drug Administration. FDA announces series of changes to the class of marketed non-steroidal anti-inflammatory drugs (NSAIDs) [news release]. Available at: http://www.fda.gov/bbs/topics/news/2005/NEW01171.html.
,European Medicines Agency. European medicines agency concludes action on COX2 inhibitors [public statement]. London: EMEA, 27 June 2005.Google Scholar
,European Medicines Agency. European Medicines Agency update on non-selective NSAIDs [press release]. London: EMEA, 17 October 2005.Google Scholar
Kearney, PM, Baigent, C, Godwin, J, et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ 332:1302–8, 2006.CrossRefGoogle ScholarPubMed
Hippisley-Cox, J, Coupland, C. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ 330:1366, 2005.CrossRefGoogle ScholarPubMed
Singh, G, et al. Both selective COX2 inhibitors and non-selective NSAIDs increase the risk of acute myocardial infarction in patients with arthritis: selectivity is with the patient, not with the drug class. Presented at Annual European Congress of Rheumatology. Vienna, Austria, June 8–11, 2005 (abstract OP0091).Google Scholar
Cannon, CP, Curtis, SP, FitzGerald, GA, et al. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet 368:1771–81, 2006.CrossRefGoogle ScholarPubMed
McAdam, BF, Catella-Lawson, F, Mardini, JA, et al. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX2. Proc Natl Acad Sci U S A 96:272–7, 1999.CrossRefGoogle Scholar
Catella-Lawson, F, McAdam, BF, Morrison, BW, et al. Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids. J Pharmacol Exp Ther 289:735–41, 1999.Google ScholarPubMed
Schwartz, JI, Vandormael, K, Malice, MP, et al. Comparison of rofecoxib, celecoxib, and naproxen on renal function in elderly subjects receiving a normal-salt diet. Clin Pharmacol Ther 72:50–61, 2002.CrossRefGoogle ScholarPubMed
Whelton, A, Maurath, CJ, Verburg, KM, Geis, GS. Renal safety and tolerability of celecoxib, a novel cyclooxygenase-2 inhibitor. Am J Ther 7:159–75, 2000.CrossRefGoogle ScholarPubMed
Singh, G, Miller, JD, Huse, DM, et al. Consequences of increased systolic blood pressure in patients with osteoarthritis and rheumatoid arthritis. J Rheumatol 30:714–19, 2003.Google ScholarPubMed
Reilly, IA, FitzGerald, GA. Inhibition of thromboxane formation in vivo and ex vivo: implications for therapy with platelet inhibitory drugs. Blood 69:180–6, 1987.Google ScholarPubMed
Capone, ML, Tacconelli, S, Sciulli, MG, et al. Clinical pharmacology of platelet, monocyte, and vascular cyclooxygenase inhibition by naproxen and low-dose aspirin in healthy subjects. Circulation 109:1468–71, 2004.CrossRefGoogle ScholarPubMed
Jakobsson, PJ, Thoren, S, Morgenstern, R, Samuelsson, B. Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potent novel drug target. Proc Natl Acad Sci U S A 96:7220–5, 1999.CrossRefGoogle Scholar
Zeilhofer, HU, Brune, K. Analgesic strategies beyond the inhibition of cyclooxygenases. Trends Pharmacol Sci 27(Suppl 9):467–74, 2006.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×