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Chemical Compound Review

ketorolac     5-(phenylcarbonyl)-2,3- dihydro-1H...

Synonyms: Ketoralac, Ketorolaco, Macril, Ketorolacum, rac-ketorolac, ...
 
 
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Disease relevance of ketorolac

 

Psychiatry related information on ketorolac

  • RESULTS: Pretreatment with ketorolac had a selective effect on the postburn injury hyperalgesia, reducing the increase in pain intensity (P<0.05) but not the decline in pain threshold [5].
  • RESULTS: For all treatment groups, there was no significant difference in extent or adequacy of sedation, incidence of oxygen desaturation, patient amnesia, time of procedure, or vital signs (except for a relative procedural tachycardia in the ketorolac and placebo groups as compared to baseline) [6].
  • No significant differences between eyes treated with ketorolac 0.4% and placebo were observed in patient cooperation, and ocular pain or discomfort during or immediately after surgery [7].
  • RESULTS: No significant decrease in corneal sensory thresholds was found with diclofenac or ketorolac compared with control at baseline (P = .50), 7 minutes (P = .41), or 15 minutes (P = .82) [8].
  • There was a significant difference between the groups in the average and daily pain rating, with the ketorolac therapy group reporting significantly less pain [9].
 

High impact information on ketorolac

 

Chemical compound and disease context of ketorolac

 

Biological context of ketorolac

 

Anatomical context of ketorolac

 

Associations of ketorolac with other chemical compounds

 

Gene context of ketorolac

  • RESULTS: Administration of SC-236 to cirrhotic animals did not produce significant renal effects, whereas administration of the nonselective COX-1/COX-2 inhibitor, ketorolac, resulted in a marked reduction in urine volume, urinary excretion of prostaglandins, and glomerular filtration rate and in a significant impairment in renal water metabolism [1].
  • These findings suggest that (R)- ketorolac may possess analgesic activity that is independent of COX inhibition and may be associated with reduced ulcerogenic potential compared to effects exhibited by (S)- ketorolac [32].
  • RESULT(S): Postoperative adhesion scores were significantly reduced in all groups of animals treated with IL-10 or ketorolac [33].
  • To extend these observations, we examined the (R)- and (S)- enantiomers of RS- ketorolac, (S)- ketorolac exhibited potent COX1 and COX2 enzyme inhibition, whereas (R)- ketorolac was > 100-fold less active on both COX subtypes [32].
  • A series of studies is reviewed that assesses the relationship between cytokines released at the site of tissue injury and NSAID analgesia, and the in vivo selectivity of a selective cyclooxygenase (COX)-2 inhibitor (celecoxib) in comparison to a dual COX-1/COX-2 inhibitor (ketorolac) [34].
 

Analytical, diagnostic and therapeutic context of ketorolac

  • Analgesia after intravenous ketorolac developed more slowly but was sustained better than morphine [35].
  • In this randomized, double-blind study, 26 volunteers received ketorolac, 30 mg intramuscularly four times a day for 5 days, and placebo, two capsules orally four times a day for at the last 2 study days [20].
  • METHODS: Based on a crossover study in 12 healthy volunteers, the extent and rate of absorption of ketorolac, delivered by a patch, were found by estimating the input rate function of the drug [21].
  • Ninety-two children from 3 to 12 years of age were given intravenous morphine or ketorolac by titration, or ketorolac by bolus injection for moderate or severe postsurgical pain in a double-blind randomized parallel-group study [35].
  • NSAIDs for the chemoprevention of oral cancer: promise or pessimism?: Commentary re J. L. Mulshine et al., randomized, double-blind, placebo-controlled, phase IIB trial of the cyclooxygenase inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia. Clin. Cancer Res., 10: 1565-1573, 2004 [36].

References

  1. Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites. Bosch-Marcè, M., Clària, J., Titos, E., Masferrer, J.L., Altuna, R., Poo, J.L., Jiménez, W., Arroyo, V., Rivera, F., Rodés, J. Gastroenterology (1999) [Pubmed]
  2. Parenteral ketorolac: the risk for acute renal failure. Feldman, H.I., Kinman, J.L., Berlin, J.A., Hennessy, S., Kimmel, S.E., Farrar, J., Carson, J.L., Strom, B.L. Ann. Intern. Med. (1997) [Pubmed]
  3. Ketorolac vs chlorpromazine in the treatment of acute migraine without aura. A prospective, randomized, double-blind trial. Shrestha, M., Singh, R., Moreden, J., Hayes, J.E. Arch. Intern. Med. (1996) [Pubmed]
  4. Population pharmacodynamic model for ketorolac analgesia. Mandema, J.W., Stanski, D.R. Clin. Pharmacol. Ther. (1996) [Pubmed]
  5. Reduction of postburn hyperalgesia after local injection of ketorolac in healthy volunteers. Lundell, J.C., Silverman, D.G., Brull, S.J., O'Connor, T.Z., Kitahata, L.M., Collins, J.G., LaMotte, R. Anesthesiology (1996) [Pubmed]
  6. Intravenous ketorolac tromethamine versus meperidine for adjunctive sedation in upper gastrointestinal endoscopy: a pilot study. Dies, D.F., Clarkston, W.K., Schratz, C.L. Gastrointest. Endosc. (1996) [Pubmed]
  7. Efficacy of topical ketorolac tromethamine 0.4% for control of pain or discomfort associated with cataract surgery. Price, M.O., Price, F.W. Current medical research and opinion. (2004) [Pubmed]
  8. Effect of topical diclofenac and ketorolac on patient discomfort and corneal sensitivity. Narváez, J., Kroll, P., Guzek, J.P. Journal of refractive surgery (Thorofare, N.J. : 1995) (2002) [Pubmed]
  9. The use of topical ketorolac 0.5% for pain relief following cyclophotocoagulation. Birt, C.M. Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye. (2003) [Pubmed]
  10. NSAID-induced gastric damage in rats: requirement for inhibition of both cyclooxygenase 1 and 2. Wallace, J.L., McKnight, W., Reuter, B.K., Vergnolle, N. Gastroenterology (2000) [Pubmed]
  11. Aspirin and salicylate induce apoptosis and activation of caspases in B-cell chronic lymphocytic leukemia cells. Bellosillo, B., Piqué, M., Barragán, M., Castaño, E., Villamor, N., Colomer, D., Montserrat, E., Pons, G., Gil, J. Blood (1998) [Pubmed]
  12. Cyclooxygenase regulates human oropharyngeal carcinomas via the proinflammatory cytokine IL-6: a general role for inflammation? Hong, S.H., Ondrey, F.G., Avis, I.M., Chen, Z., Loukinova, E., Cavanaugh, P.F., Van Waes, C., Mulshine, J.L. FASEB J. (2000) [Pubmed]
  13. Risk of hospitalization for upper gastrointestinal tract bleeding associated with ketorolac, other nonsteroidal anti-inflammatory drugs, calcium antagonists, and other antihypertensive drugs. García Rodríguez, L.A., Cattaruzzi, C., Troncon, M.G., Agostinis, L. Arch. Intern. Med. (1998) [Pubmed]
  14. Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. Gillis, J.C., Brogden, R.N. Drugs (1997) [Pubmed]
  15. Prevention of hearing loss in experimental pneumococcal meningitis by administration of dexamethasone and ketorolac. Rappaport, J.M., Bhatt, S.M., Burkard, R.F., Merchant, S.N., Nadol, J.B. J. Infect. Dis. (1999) [Pubmed]
  16. Efficacy and tolerability of newer antihistamines in the treatment of allergic conjunctivitis. Bielory, L., Lien, K.W., Bigelsen, S. Drugs (2005) [Pubmed]
  17. Intraocular penetration of periocular ketorolac and efficacy in experimental uveitis. Rabiah, P.K., Fiscella, R.G., Tessler, H.H. Invest. Ophthalmol. Vis. Sci. (1996) [Pubmed]
  18. Double-blind evaluation of short-term analgesic efficacy of orally administered dexketoprofen trometamol and ketorolac in bone cancer pain. Rodríguez, M.J., Contreras, D., Gálvez, R., Castro, A., Camba, M.A., Busquets, C., Herrera, J. Pain (2003) [Pubmed]
  19. Enantiomer-selective pharmacokinetics and metabolism of ketorolac in children. Kauffman, R.E., Lieh-Lai, M.W., Uy, H.G., Aravind, M.K. Clin. Pharmacol. Ther. (1999) [Pubmed]
  20. Effects of ketorolac tromethamine on hemostasis in volunteers. Conrad, K.A., Fagan, T.C., Mackie, M.J., Mayshar, P.V. Clin. Pharmacol. Ther. (1988) [Pubmed]
  21. Passive versus electrotransport-facilitated transdermal absorption of ketorolac. Park, K., Verotta, D., Gupta, S.K., Sheiner, L.B. Clin. Pharmacol. Ther. (1998) [Pubmed]
  22. Ketorolac potentiates morphine in postoperative patient-controlled analgesia. Picard, P., Bazin, J.E., Conio, N., Ruiz, F., Schoeffler, P. Pain (1997) [Pubmed]
  23. Cyclooxygenase inhibitor ketorolac or mast cell stabilizers: immunologic challenges in cancer therapy. Khatami, M. Clin. Cancer Res. (2005) [Pubmed]
  24. Phase I safety assessment of intrathecal ketorolac. Eisenach, J.C., Curry, R., Hood, D.D., Yaksh, T.L. Pain (2002) [Pubmed]
  25. In altering the release of glucocorticoids, ketorolac exacerbates the effects of systemic immune stimuli on expression of proinflammatory genes in the brain. Blais, V., Zhang, J., Rivest, S. Endocrinology (2002) [Pubmed]
  26. Comparative Effects of the Nonsteroidal Anti-inflammatory Drug Nepafenac on Corneal Sensory Nerve Fibers Responding to Chemical Irritation. Acosta, M.C., Luna, C., Graff, G., Meseguer, V.M., Viana, F., Gallar, J., Belmonte, C. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  27. Clinical pharmacokinetics of ketorolac tromethamine. Brocks, D.R., Jamali, F. Clinical pharmacokinetics. (1992) [Pubmed]
  28. Ibuprofen-mediated reduction of hypoxia-inducible factors HIF-1alpha and HIF-2alpha in prostate cancer cells. Palayoor, S.T., Tofilon, P.J., Coleman, C.N. Clin. Cancer Res. (2003) [Pubmed]
  29. Role of prostanoids in regulation of the renin-angiotensin-aldosterone system by salt intake. Höcherl, K., Kammerl, M.C., Schumacher, K., Endemann, D., Grobecker, H.F., Kurtz, A. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  30. Increased lithium serum and red blood cell concentrations during ketorolac coadministration. Cold, J.A., ZumBrunnen, T.L., Simpson, M.A., Augustin, B.G., Awad, E., Jann, M.W. Journal of clinical psychopharmacology. (1998) [Pubmed]
  31. Cyclooxygenase 2 (COX-2) inhibition increases the inflammatory response in the brain during systemic immune stimuli. Blais, V., Turrin, N.P., Rivest, S. J. Neurochem. (2005) [Pubmed]
  32. Preclinical enantioselective pharmacology of (R)- and (S)- ketorolac. Handley, D.A., Cervoni, P., McCray, J.E., McCullough, J.R. Journal of clinical pharmacology. (1998) [Pubmed]
  33. Immunomodulation with interleukin-10 and interleukin-4 compared with ketorolac tromethamine for prevention of postoperative adhesions in a murine model. Holschneider, C.H., Nejad, F., Montz, F.J. Fertil. Steril. (1999) [Pubmed]
  34. Analgesia and COX-2 inhibition. Dionne, R.A., Khan, A.A., Gordon, S.M. Clinical and experimental rheumatology. (2001) [Pubmed]
  35. Comparison of intravenous ketorolac with morphine for postoperative pain in children. Maunuksela, E.L., Kokki, H., Bullingham, R.E. Clin. Pharmacol. Ther. (1992) [Pubmed]
  36. NSAIDs for the chemoprevention of oral cancer: promise or pessimism?: Commentary re J. L. Mulshine et al., randomized, double-blind, placebo-controlled, phase IIB trial of the cyclooxygenase inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia. Clin. Cancer Res., 10: 1565-1573, 2004. Goodin, S., Shiff, S.J. Clin. Cancer Res. (2004) [Pubmed]
 
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