Cyclooxygenase-2 selective inhibitors: Potential usage in dogs

Ignacio Lizárraga Madrigal; Héctor Sumano López; Fernanda Castillo Alcalá

2002, Number 3

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Vet Mex 2002; 33 (3)

Cyclooxygenase-2 selective inhibitors: Potential usage in dogs

Lizárraga MI, Sumano LH, Castillo AF

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Language: English/Spanish
References: 81
Page: 285-307
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ABSTRACT

Use of non-steroidal anti-inflammatory drugs (NSAIDs) in dogs is limited because of the adverse effects they produce. All NSAIDs inhibit, by different degrees, the cyclooxygenases (COX), enzymes that exist in at least two isoforms: COX-1 and COX-2. Inhibition of COX-1 is believed to be responsible for the adverse effects of NSAIDs, whereas inhibition of COX-2 is thought to be related to the therapeutic effects of this class of drugs. This theory, to some extent, seems to be true for humans suffering from osteoarthritis who receive COX-2 selective inhibitors. If this hypothesis also applies to dogs, COX-2 selective inhibitors should play an important role in canine therapeutics. This review highlights relevant physiopathologic aspects of COX-2 within the organism (e.g., gastrointestinal tract, kidneys, central nervous system), based on this information, the possible uses and adverse effects of selective COX-2 inhibitors (e.g., celecoxib, nimesulide, NS-398) in dogs are discussed. Clinical-pharmacological information on the use of selective COX-2 inhibitors (e.g., carprofen, celecoxib, nimesulide) specifically obtained from dogs is also presented.

REFERENCES

Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Ann Rev Pharmacol Toxicol 1998;38:97-120.
2. Sakamoto C. Roles of COX-1 and COX-2 in gastrointestinal pathophysiology. J Gastroenterol 1998;33:618-624.
3. Morham SG, Langenbach R, Loftin CD, Tiano HF, Vouloumanos N, Jennette JC, et al. Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell 1995;83:473-482.
4. Appleton I, Tomlinson A, Willoughby DA. Induction of cyclo-oxygenase and nitric oxide synthase in inflammation. Adv Pharmacol 1996;35:27-78.
5. Cryer B, Dubois A. The advent of highly selective inhibitors of cyclooxygenase - a review. Prostaglandins Lipid Mediat 1999;56:341-361.
6. Kirchner T, Argentieri DC, Barbone AG, Singer M, Steber M, Ansell J, et al. Evaluation of the antiinflammatory activity of a dual cyclooxygenase-2 selective/5-lipooxygenase inhibitor, RWJ 63556, in a canine model of inflammation. J Pharmacol Exp Ther 1997;282:1094-1101.
7. Langenbach R, Morham SG, Tiano HF, Loftin CD, Ghanayem BI, Chulada PC, et al. Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Cell 1995;83:483-492.
8. Mahler JF, Davis BJ, Morham SG, Langenbach R. Disruption of cyclooxygenase genes in mice. Toxicol Pathol 1996;24:717-719.
9. Shigeta J, Takahashi S, Okabe S. Role of cyclooxygenase-2 in the healing of gastric ulcers in rats. J Pharmacol Exp Ther 1998;286:1383-1390.
10. Tsukada K, Hasegawa T, Tsutsumi S, Kuwano H. Roles of cyclooxygenase-2 in tissue injury during hemorrhagic shock. Shock 2000;13:392-396.
11. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, van de Putte LBA, Lipsky PE. Cyclooxygenase in biology and disease. FASEB J 1998;12:1063-1073.
12. Venturini CM, Isakson P, Needleman P. Non-steroidal anti-inflammatory drug-induced renal failure: a brief review of the role of cyclo-oxygenase isoforms. Curr Opin Nephrol Hypertension 1998;7:79-82.
13. Khan KNM, Venturini CM, Bunch RT, Brassard JA, Koki AT, Morris DL, et al. Interspecies differences in renal localization of cyclooxygenase isoforms: implications in nonsteroidal antiinflammatory drug-related nephrotoxicity. Toxicol Pathol 1998;26:612-620.
14. Black SC, Brideau C, Cirino M, Belley M, Bosquet J, Chan C, Rodger IW. Differential effect of a selective cyclooxygenase-2 inhibitor versus indomethacin on renal blood flow in conscious volume-depleted dogs. J Cardiovasc Pharmacol 1998;32:686-694.
15. Catella-Lawson F, McAdam B, Morrison BW, Kapoor S, Kujubu D, Antes L, et al. Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids. J Pharmacol Exp Ther 1999;289:735-741.
16. Kaufmann WE, Andersson KI, Isakson PC, Worley PF. Cyclooxygenases and the central nervous system. Prostaglandins 1997;54:601-624.
17. Willingale HL, Gardiner NJ, McLymont N, Giblett S, Grubb BD. Prostanoids synthesized by cyclo-oxygenase isoforms in rat spinal cord and their contribution to the development of neuronal hyperexcitability. Br J Pharmacol 1997;122:1593-1604.
18. Minghetti L, Nicolini A, Polazzi E, Greco A, Perretti M, Parente L, Levi G. Down regulation of microglial cyclo-oxygenase-2 and inducible nitric oxide synthase expression by lipocortin 1. Br J Pharmacol 1999;126:1307-1314.
19. Cullen L, Kelly L, Connor SO, Fitzgerald DJ. Selective cyclooxygenase-2 inhibition by nimesulide in man. J Pharmacol Exp Ther 1998;287:578-582.
20. 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;96:272-277.
21. Mitchell JA, Warner TD. Cyclo-oxygenase-2: pharmacology, physiology, biochemistry and relevance to NSAID therapy. Br J Pharmacol 1999;128:1121-1132.
22. Ermert L, Ermert M, Althoff A, Merkle M, Grimminger F, Seeger W. Vasoregulatory prostanoid generation proceed via cyclooxygenase-2 in noninflammed rat lungs. J Pharmacol Exp Ther 1998;286:1309-1314.
23. Johnson SR, Knox AJ. Synthetic functions of airway smooth muscle in asthma. Trends Pharmacol Sci 1997;18:288-292.
24. Raisz LG. Potential impact of selective cyclooxygenase-2 inhibitors on bone metabolism in health and disease. Am J Med 2001;110 (Suppl3A):43S-45S.
25. Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, et al. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci USA 1994;91:12013-12017.
26. Smith CJ, Zhang Y, Koboldt CM, Muhammad J, Zweifel BS, Shaffer A, et al. Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc Natl Acad Sci USA 1998;95:13313-13318.
27. Zhang Y, Shaffer A, Portanova J, Seibert K, Isakson PC. Inhibition of cyclooxygenase-2 rapidly reverses inflammatory hyperalgesia and prostaglandin E2 production. J Pharmacol Exp Ther 1997;283:1069-1075.
28. Simon LS, Weaver AL, Graham DY, Kivitz AJ, Lipsky PE, Hubbard RC, et al. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis. J Am Med Assoc 1999;282:1921-1928.
29. Bensen WG, Fiechtner JJ, McMillen JI, Zhao WW, Yu SS, Woods EM, et al. Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial. Mayo Clin Proc 1999;74:1095-1105.
30. Emery P, Zeidler H, Kvien TK, Guslandi M, Naudin R, Stead H, et al. Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison. Lancet 1999;354:2106-2111.
31. Wallace JL, Chapman K, McKnight W. Limited anti-inflammatory efficacy of cyclo-oxygenase-2 inhibition in carrageenan-airpouch inflammation. Br J Pharmacol 1999;126:1200-1204.
32. Wallace JL. Selective COX-2 inhibitors: is the water becoming muddy? Trends Pharmacol Sci 1999;20:4-6.
33. Toutain PL, Cester CC, Haak T, Laroute V. A pharmacokinetic/pharmacodynamic approach vs. a dose titration for the determination of a dosage regimen: the case of nimesulide, a Cox-2 selective nonsteroidal anti-inflammatory drug in the dog. J Vet Pharmacol Ther 2001;24:43-55.
34. Ricketts AP, Lundy KM, Seibel SB. Evaluation of selective inhibition of canine cyclooxygenase 1 and 2 by carprofen and other nonsteroidal anti-inflammatory drugs. Am J Vet Res 1998;59:1441-1446.
35. Osuka K, Suzuki Y, Watanabe Y, Takayasu M, Yoshida J, Busija DW. Inducible cyclooxygenase expression in canine basilar artery after experimental subarachnoid hemorrhage. Stroke 1998;29:1219-1222.
36. Resnick DK, Graham SH, Dixon CE, Marion DW. Role of cyclooxygenase 2 in acute spinal cord injury. J Neurotrauma 2001;15:1005-1013.
37. Yamamoto T, Nozaki-Taguchi N. Analysis of the effects of cyclooxygenase (COX)-1 and COX-2 in spinal nociceptive transmission using indomethacin, a non-selective COX inhibitor, and NS-398, a COX-2 selective inhibitor. Brain Res 1996;739:104-110.
38. Ehrich EW, Dallob A, de Lepeleire I, van Hecken A, Riendeau D, Yuan W, et al. Characterization of rofecoxib as a cyclooxygenase-2 isoform inhibitor and demonstration of analgesia in the dental pain model. Clin Pharmacol Ther 1999;65:336-347.
39. Chan CC, Panneton M, Taylor AM, Therien M, Rodger IW. A selective inhibitor of cyclooxygenase-2 reverses endotoxin-induced pyretic responses in non-human primates. Eur J Pharmacol 1997;237:221-225.
40. Parrott RF, Vellucci SV. Comparison of the antipyretic actions of indomethacin and L-745,337, a selective cyclooxygenase-2 inhibitor, in endotoxin-treated prepubertal pigs. Gen Pharmacol 1998;30:65-69.
41. Johnston SA, Budsberg SC. Nonsteroidal anti-inflammatory drugs and corticosteroids for the management of canine osteoarthritis. Vet Clin North Am Small Anim Pract 1997;27:841-862.
42. Khan KNM, Knapp DW, Denicola DB, Harris RK. Expression of cyclooxygenase-2 in transitional cell carcinoma of the urinary bladder in dogs. Am J Vet Res 2000;61:478-481.
43. Chan TA, Morin PJ, Vogelstein B, Kinzler KW. Mechanisms underlying nonsteroidal antiinflammatory drug-mediated apoptosis. Proc Natl Acad Sci USA 1998;95:681-686.
44. Barnes PJ, Adcock IM. NF-kB: a pivotal role in asthma and a new target for therapy. Trends Pharmacol Sci 1997;18:46-50.
45. Rogers DF, Giembycz MA. Asthma therapy for the 21st century. Trends Pharmacol Sci 1998;19:160-164.
46. Moore JN, Barton MH. An update on endotoxaemia. Part 1: mechanisms and pathways. Equine Vet Educ 1998;10:300-306.
47. Leach M, Hamilton LC, Olbrich A, Wray GM, Thiemermann C. Effects of inhibitors of the activity of cyclo-oxygenase-2 on the hypotension and multiple organ dysfunction caused by endotoxin: a comparison with dexamethasone. Br J Pharmacol 1998;124:586-592.
48. Gust R, Kozlowski JK, Stephenson AH, Schuster DP. Role of cyclooxygenase-2 in oleic acid-induced acute lung injury. Am J Resp Crit Care Med 1999;160:1165-1170.
49. Frölich JC. A classification of NSAIDs according to the relative inhibition of cyclooxygenase isoenzymes. Trends Pharmacol Sci 1997;18:30-34.
50. Vasseur PB, Johnson AL, Budsberg SC, Lincoln JD, Toombs JP, et al. Randomized, controlled trial of the efficacy of carprofen, a nonsteroidal anti-inflammatory drug, in the treatment of osteoarthritis in dogs. J Am Vet Med Assoc 1995;206:807-811.
51. Welsh EM, Nolan AM, Reid J. Benefical effects of administering carprofen before surgery in dogs. Vet Rec 1997;141:251-253.
52. Lascelles BD, Butterworth SJ, Waterman AE. Postoperative analgesic and sedative effects of carprofen and pethidine in dogs. Vet Rec 1994;134:187-191.
53. Nolan A, Reid J. Comparison of the postoperative analgesic and sedative effects of carprofen and papaveretum in the dog. Vet Rec 1993;133:240-242.
54. Grisneaux E, Pibarot P, Dupuis J, Blais D. Comparison of ketoprofen and carprofen administered prior to orthopedic surgery for control of postoperative pain in dogs. J Am Vet Med Assoc 1999;215:1105-1110.
55. Ko JCH, Miyabiyashi T, Mandsager RE, Heaton-Jones TG, Mauragis DF. Renal effects of carprofen administered to healthy dogs anesthetized with propofol and isoflurane. J Am Vet Med Assoc 2000;217:346-349.
56. Priymenko N, Garnier F, Ferre JP, Delatour P, Toutain P. Enantioselectivity of the enterohepatic recycling of carprofen in the dog. Drug Metabol Disp 1998;26:170-176.
57. McKellar QA, Delatour P, Lees P. Stereospecific pharmacodynamics and pharmacokinetics of carprofen in the dog. J Vet Pharmacol Ther 1994;17:447-454.
58. Buritova J, Besson JM. Peripheral and/or central effects of racemic-, S(+)- and R(–)-flurbiprofen on inflammatory nociceptive processes: a c-Fos protein study in the rat spinal cord. Br J Pharmacol 1998;125:87-101.
59. Benton HP, Vasseur PB, Broderick-Villa GA, Koople M. Effects of carprofen on sulfated glycosaminoglycan metabolism, protein synthesis, and prostaglandin release by cultured osteoarthritic canine chondrocytes. Am J Vet Res 1997;58:286-292.
60. Reimer ME, Johnston SA, Leib MS, Duncan RB, Reimer DC, Marini M, Gimbert K. The gastroduodenal effects of buffered aspirin, carprofen, and etodolac in healthy dogs. J Vet Intern Med 1999;13:472-477.
61. McKellar QA, Pearson T, Bogan JA, Galbraith EA, Lees P, Ludwig B, Tiberghien MP. Pharmacokinetics, tolerance and serum thromboxane inhibition of carprofen in the dog. J Small Anim Pract 1990;31:443-448.
62. Mama K. New options for managing chronic pain in small animals. Vet Med 1999;94:352-356.
63. Sumano LH, De Vizcaya A, Brumbaugh GW. Tolerance and clinical evaluation of piroxicam in dogs. Canine Pract 1996;21:16-19.
64. MacPhail CM, Lappin MR, Meyer DJ, Smith SG, Webster CR, Armstrong PJ. Hepatocellular toxicosis associated with administration of carprofen in 21 dogs. J Am Vet Med Assoc 1998;212:1895-1901.
65. Toutain PL, Cester CC, Haak T, Metge S. Pharmacokinetic profile and in vitro selective cyclooxygenase-2 inhibition by nimesulide in the dog. J Vet Pharmacol Ther 2001;24:35-42.
66. Paulson SK, Kaprak TA, Gresk CJ, Fast DM, Baratta MT, Burton EG, et al. Plasma protein binding of celecoxib in mice, rat, rabbit, dog and human. Biopharm Drug Dispos 1999;20:293-299.
67. Findlay JW, Berge MA, Markos CS, Breau AP, Hribar JD, Yuan J. Comparison of celecoxib metabolism and excretion in mouse, rabbit, dog, Cynomolgus monkey and Rhesus monkey. Xenobiotica 2000;30:731-744.
68. Paulson SK, Vaughn MB, Jessen SM, Lawal Y, Gresk CJ, Yan B, et al. Pharmacokinetics of celecoxib after oral administration in dogs and humans: effect of food and site of absorption. J Pharmacol Exp Ther 2001;297:638-645.
69. Daun JM, Ball RW, Burger HR, Cannon JG. Aspirin-induced increases in soluble IL-1 receptor type II concentrations in vitro and in vivo. J Leukoc Biol 1999;65:863-866.
70. Peruzzi L, Gianoglio B, Porcellini G, Conti G, Amore A, Coppo R. Neonatal chronic kidney failure associated to cyclo-oxygenase inhibitors administered during pregnancy. Minerva Urol Nefrol 2001;53:113-116.
71. Peruzzi L, Gianoglio B, Porcellini MG, Coppo R. Neonatal end-stage renal failure associated with maternal ingestion of cyclo-oxygenase-type-2 selective inhibitor nimesulide as tocolytic. Lancet 1997;350:265-266.
72. Landau D, Shelef I, Polacheck H, Marks K, Holcberg G. Perinatal vasoconstrictive renal insufficiency associated with maternal nimesulide use. Am J Perinatol 1999;16:441-444.
73. Balasubramaniam J. Nimesulide and neonatal renal failure. Lancet 2000;355:575.
74. Figueras A, Estévez F, Laporte JR. New drugs, new adverse drug reactions, and bibliographic databases. Lancet 1999;353:1447.
75. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. J Am Med Assoc 2001;286:954-959.
76. Turull A, Queralt J. Selective cyclooxygenase-2 (COX-2) inhibitors reduce anti-Mycobacterium antibodies in adjuvant arthritic rats. Immunopharmacology 2000;46:71-77.
77. Takahashi Y, Roman C, Chemtob S, Tse MM, Lin E, Heymann MA, Clyman RI. Cyclooxygenase-2 inhibitors constrict the fetal lamb ductus arteriosus both in vitro and in vivo. Am J Physiol 2000;278:R1496-R1505.
78. Isaacs JP. Adverse effects of non-steroidal anti-inflammatory drugs in the dog and cat. Austr Vet Pract 1996;26:180-186.
79. Mathews KA. Nonsteroidal anti-inflammatory analgesics in pain management in dogs and cats. Can Vet J 1996;37:539-543.
80. Vane J. Foreword. Drugs 1994;47(Suppl 5):S-P.
81. Simmons DL, Botting RM, Robertson PM, Madsen ML, Vane JR. Induction of an acetaminophen-sensitive cyclooxygenase with reduced sensitivity to nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci USA 1999;96:3275-3280.