Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Ketorolac NSAID Action Pathway
Homo sapiens
Drug Action Pathway
Ketorolac is an NSAID used to treat moderate to severe pain, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, menstrual disorders, and headaches. Ketorolac possesses anti-inflammatory, analgesic, and antipyretic activity. It targets the prostaglandin G/H synthase-1 (COX-1) and prostaglandin G/H synthase-2 (COX-2) in the cyclooxygenase pathway. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 convert arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase, or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. Ketorolac inhibits the action of COX-1 and COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. Fever is triggered by inflammatory and infectious diseases. Cytokines are produced in the central nervous system (CNS) during an inflammatory response. These cytokines induce COX-2 production that increases the synthesis of prostaglandin, specifically prostaglandin E2 which adjusts hypothalamic temperature control by increasing heat production. Because ketorolac decreases PGE2 in the CNS, it has an antipyretic effect. Antipyretic effects result in increased peripheral blood flow, vasodilation, and subsequent heat dissipation. This drug is administered as a nasal spray, an oral tablet/capsule, an intramuscular or intravenous injection, or as an ophthalmic solution.
References
Ketorolac NSAID Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Brocks DR, Jamali F: Clinical pharmacokinetics of ketorolac tromethamine. Clin Pharmacokinet. 1992 Dec;23(6):415-27. doi: 10.2165/00003088-199223060-00003.
Pubmed: 1458761
Litvak KM, McEvoy GK: Ketorolac, an injectable nonnarcotic analgesic. Clin Pharm. 1990 Dec;9(12):921-35.
Pubmed: 2292174
Macario A, Lipman AG: Ketorolac in the era of cyclo-oxygenase-2 selective nonsteroidal anti-inflammatory drugs: a systematic review of efficacy, side effects, and regulatory issues. Pain Med. 2001 Dec;2(4):336-51. doi: 10.1046/j.1526-4637.2001.01043.x.
Pubmed: 15102238
Buckley MM, Brogden RN: Ketorolac. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs. 1990 Jan;39(1):86-109. doi: 10.2165/00003495-199039010-00008.
Pubmed: 2178916
Kauffman RE, Lieh-Lai MW, Uy HG, Aravind MK: Enantiomer-selective pharmacokinetics and metabolism of ketorolac in children. Clin Pharmacol Ther. 1999 Apr;65(4):382-8. doi: 10.1016/S0009-9236(99)70131-1.
Pubmed: 10223774
Yarboro TL Sr: Intramuscular Toradol, gastrointestinal bleeding, and peptic ulcer perforation: a case report. J Natl Med Assoc. 1995 Mar;87(3):225-7.
Pubmed: 7731074
Valitalo PA, Kemppainen H, Kulo A, Smits A, van Calsteren K, Olkkola KT, de Hoon J, Knibbe CAJ, Allegaert K: Body weight, gender and pregnancy affect enantiomer-specific ketorolac pharmacokinetics. Br J Clin Pharmacol. 2017 Sep;83(9):1966-1975. doi: 10.1111/bcp.13311. Epub 2017 May 14.
Pubmed: 28429492
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings