Understanding Ketorolac: An Interprofessional Approach

1. Understanding Ketorolac: An
Interprofessional Approach
Ben Roberts
Lamar University
Last edited: November 4, 2017

2. Description and Indications for Use
 Ketorolac – belongs to a group of meds known as NSAIDs
(non-steroidal anti inflammatory drugs)
 Used to treat moderately severe pain that is acute, not
chronic due to increased risk of adverse drug reactions
 Mechanism of action: inhibits prostaglandins thus
reducing pains associated with inflammatory process

3. Intended Drug Response from Usage
 Manage acute moderately severe pain through the IV, IM, or oral routes of
administration
 Oral route of administration intended to be given after IV or IM administration
 Drug may not be used for greater than 5 days
 Regardless of route
 Important teaching opportunity for patients
 More is not always better!
 Higher doses do not create greater analgesic effect but it will increase the
likelihood of adverse drug reactions!
 Higher doses are associated with increased duration of analgesia effects
 Ketorolac usage associated with decreased opiate requirements to manage
acute pain
 Do you think this would contribute positively to the drug epidemic seen in the
United States? (5 minute class discussion)

4. The Nitty Gritty
(nitty gritty refers to side effects & contraindications)
 Inhibits platelet function
 Decreased platelet function = greater risk of bleeding!
 Not to be used in conjunction with anticoagulants or NSAIDs
 Contraindications
 Increased risk of myocardial infarction and CVA
 Mechanism not fully understood
 Patients with history of gi bleeding’
 Peptic ulcer
 Intestinal perforation
 Renal insufficiency
 Drug has risk of nephrotoxicity

5. Drug-Drug Interactions
 Aspirin – both inhibit platelet function and compete for binding sites
 SSRI – increased risk of hallucination and gi bleed
 Lithium – decreased renal clearance of Lithium
 Decreased renal clearance means higher serum levels
 Can lead to seizures (Ain’t nobody got time for that!)
 Probenecid
 Both drugs use same excretion pathway in kidney
 Imagine everyone in a concert trying to go out the same exit at the same time! It would
be slow, cause delays, and increase likelihood of harm!!

6. Pharmacokinetics
 Pharmacokinetics
 100% bioavailability despite administration route
 You have two hands….ketorolac has two parts
 S-enantiomer – possess analgesic effect
 Cleared by kidneys quickly causing shorter half life (2.5 hours)
 Peak analgesic effect 1-2 hours after administration
 Analgesic effect experienced for 4-6 hours by patient
 R-enantiomer – does not have therapeutic effect
 Highly protein bound (99% protein bound)
 Decreased albumin levels cause more free drug
 Metabolized by liver
 Glucuronidation – removes toxic substance
 Excreted by kidneys
 60% is nonmetabolized
 40% is metabolized liver by products

7. Pharmacogenomics
 Pharmacogenomics – the study of genetics affect pharmacological responses
 New field of study….little research on ketorolac’s pharmacgenomic
 Pharmocogenomic can be used to our benefit
 Celebrex use decrease colon cancer relapse in patients with CYP2C9 mutation
 No study found to see if ketorolac has same effect
 Current evidence is conflicting
 Some studies show ketorolac has no pharmacogenomic considerations
 Some studies show the opposite:
 CYP2C9 mutations affect drug metabolism and increased risk of gi bleed
 ABCC2 mutations can affect biliary excretion of ketorolac and lead to hepatotoxicity

8. Knowledge is power…so do something with it!
(Ketorolac Clinical Applications)
 Provide patient education
 Example: sign/symptoms of gi bleed, 5 day use only
 Provide suggestions to other healthcare team members
 Example: has baseline or recent kidney functions tests been performed
 Be aware of contraindications
 Examples:
 Has your patient had a history of gi bleed?
 Does your patient have decreased kidney impairment?
 Is your patient also on aspirin?

9. References
 Baxter Healthcare Corporation (2006 January). Intravenous dilution guideline – ketorolac tromethamine. Retrieved from http://www.globalrph.com/ketorolac_dilution.htm
 Benedict, D. (2017, November 2). Personal interview
 Brocks, D.R. & Jamali, F. (1992 December). Clinical pharmacokinetics of ketorolac tromethamine. Clinical Pharmacokinetics, 23(6), 415-427. Retrieved from
https://link.sprnger.com/article/10.2165%2F00003088-199223060-00003
 DrugLib (n.d.). Toradol – description and clinical pharmacology. Retrieved from http://www.druglib.com/druginfo/toradol/description_pharmacology
 Fresenius Kabi USA, LLC (2017 March). Ketorolac tromethamine [PDF file]. Retrieved from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=950b7295-3f68-4027-ac2b
-2f7d0f5f8ef9
 G.D. Searle LLC (2005, June 15). Toradol. Retrieved from https://www.rxlist.com/toradol-drug.htm
 Genetic Home Reference (2017, October 24). What is pharmacogenomics? Retrieved from https://ghr.nlm.nih.gov/primer/genomicresearch/pharmacogenomics
 Institute of Safe Medication Practices (n.d.). About ISMP. Retrieved from http://www.ismp.org/about/default.aspx
 King, N. (2016, June 22). GeneSight analgesic combinatorial pharmacogenomic test. Retrieved from https://genesight.com/wp-content/uploads/2017/05/GeneSight-Sample
-Reports.pdf
 Morell, S. (2017, November 2). Personal interview
 Prescribers’ Digital Reference (n.d.). Ketorolac tromethamine – drug summary. Retrieved from http://www.pdr.net/drug-summary/Ketorolac-Tromethamine-Tablets-
ketorolactrometham ine-1793.3935
 Reactome (2011, September 20). Pathway: glucuronidation. Retrieved from http://www.pathwaycommons.org/pc/record2.do?id=486025
 Ricciotti, E., & FitzGerald, G. (2012, May 1). Prostaglandins and inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(5), 986-1000. doi: 10.1161/ATVBAHA.110.2074 49
 Roche (2008, December). Ketorolac [PDF file]. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019645s019lbl.pdf
 RxList (2017). Drug interactions with ketorolac iv and probenecid oral. Retrieved from https://www.rxlist.com/drug-interactions/ketorolac-iv-and-probenecid-oral-interaction.htm
 United States National Library of Medicine (2017, September 21). Ketorolac. Retrieved from https://medlineplus.gov/druginfo/meds/a693001.html
 Yiannakopoulou, E. (2013). Pharmacogenomics of acetylsalicylic acid and other nonsteroidal anti-inflammatory agents: clinical implications. European Journal of Clinical
Pharmacology, 69(7), 1369-1373. doi:10.1007/s00228-013-1477-9