This document analyzes the use of ketorolac for migraine headaches. It begins by explaining the pathophysiology of migraines, involving the trigeminovascular system and vasodilation. It then discusses how ketorolac works to inhibit COX enzymes and decrease prostaglandin precursors to provide relief. While ketorolac and other NSAIDs are first-line treatments for mild to moderate migraines, the document notes the challenges in demonstrating ketorolac's efficacy for severe migraines based on a specific study. It concludes by emphasizing the importance of considering a patient's full medical history and medication profile to safely apply ketorolac in a clinical setting.

1. Ketorolac: An Analysis of
Its Use on Migraine Headaches
Rebekah K. Ahlborn
MSNE 5356
Lamar University

2. Migraines and Ketorolac

3. Pathophysiology of Migraine Headaches
 The pain originates from the trigeminovascular system of the cerebrum
 The trigeminovascular system regulates the environment and activates
neuropeptides, which cause vasodilation and inflammation
 The “migraine generator” is activated by emotion, stress, circadian rhythm
disruption, light, odors, and smells received from the cerebral cortex
 The impulse travels through cranial nerve VII (facial nerve) causing dilation of
cranial blood vessels, release of neuroinflammatory compounds, and thus, more
vasodilation
(Arcangelo & Peterson, 2013)

4. Ketorolac’s response when treating
Migraine Headache
 NSAIDS employ their anti-inflammatory action in two ways:
 Inhibit the conversion of arachidonic acid to prostaglandin, prostacyclin, and
thromboxane
 Arachidonic acid is converted through the enzyme cyclooxygenase (COX)
 Interfering with protein kinase activation
(Arcangelo & Peterson, 2013)
 Ketorolac, specifically inhibits COX-1 and COX-2 enzymes, resulting in a decrease
of prostaglandin precursors
(Ketorolac, 2016)

5. Ketorolac’s response when treating
Migraine Headache
 NSAIDS are the first-line medication for mild to moderate migraines.
 Triptans are the first-line medication for moderate to severe migraines.
(Arcangelo & Peterson, 2013)
 In the research conducted by Taggart et al. (2013), it was difficult to demonstrate
the effectiveness of ketorolac on severe migraine headaches because of the diverse
treatments completed before arriving to the emergency department, which will
alter the course of treatment while in the emergency department.

6. Potential Interaction
 Avoid concomitant use of ketorolac with other medications classified as a NSAID or
aspirin.
 Ketorolac can increase the effect and/or toxicity of:
 Drugs with antiplatelet properties, anticoagulatns, aspirin, NSAIDs, potassium spring diuretics,
vancomycin, and vitamin K antagonists
 The levels of ketorolac can be increased by:
 ACE inhibitors, ARBs, antidepressants, corticosteroids, and cyclosporine
 Ketorolac can decrease the effects of:
 ACE inhibitors, ARBs, beta-blockers, loop diuretics, salicylates, and anticonvulsants
(Ketorolac, 2016)

7. Adverse Drug Reaction and Side Effects
 Edema
 Hypertension
 Dizziness
 Drowsiness
 Headache
 Other neurologic effects that may
impair the patient’s abilities
 Skin rash
 Tinnitus
 Bruising or easy bleeding
(Ketorolac, 2016)
“The most common adverse
events of NSAIDs occur in the GI
and renal systems”
(Arcangelo & Peterson, 2013, p. 541)

8. Pharmacokinetics
 Onset of action: ~30 minutes
 Peak effect: ≤2-3 hours
 Duration: 4-6 hours
 Absorption: oral bioavailability 100%
 Distribution: ~13 L; poor penetration
into CSF
(Ketorolac Tromethamine Injection, 2014)
 Metabolism: Hepatic
 Half-life elimination: 2-6 hours;
prolonged 30%-50% in elderly; up to
19 hours in renal impairment
 Excretion: urine (92%)

9. Ketorolac Binding
 Highly bound to plasma protein (99.2%)
 Aspirin is known to affect the protein binding of ketorolac
(Ketorolac Tromethamine Injection, 2014)

10. Improving Communication
 Patient safety is our biggest concern
 Every medication has potential for harm or error
 Collaborating with the pharmacist to increase the awareness in common
medications errors
 In-services, PowerPoints, e-mails
 Information from the auxiliary departments point of view will increase teams’
awareness and improve knowledge and decision making
(Hughes, 2008)

11. Application to the Practice Setting
 Know the patient’s medical history and current medication in conjunction with the
ordered medication in the emergency department
 Ketorolac has multiple drug-drug interaction and is contraindicated in patients with a
history of renal impairment, cardiovascular thrombotic events, or gastrointestinal
irritation
 Avoid concomitant use of ketorolac with other medications classified as a NSAID or
aspirin
(Ketorolac Tromethamine Injection, 2014)
 Increased awareness of common medication errors associated with ketorolac may
improve patient safety, knowledge, and decision making

12. References
Arcangelo, V., & Peterson, A. (2013). Pharmacotherapeutics for advanced practice: A
practical approach (3rd ed.). Philadelphia, PA: Lippincott, Williams, & Wilkins.
Foster, A., Mobley, E., & Wang, Z. (2007). Complicated pain management in a CYP450 2D6
poor metabolizer. Pain Practice, 7(4), 352-356.
Hughes, R. (2008). Patient safety and quality: An evidence-based handbook for nurses (6th ed.).
Rockville, MD: Agency for Healthcare Research and Quality.
Ketorolac. (2016). Epocrates Plus for Apple iOS (Version 16.11) [Mobile application software]
Ketorolac Tromethamine Injection. (2014). Sagent Pharmaceuticals [Data file]. Retrieved from
http://www.sagentpharma.com/wp-content/uploads/2014/11/Ketorolac_PI.pdf
Taggart, E., Doran, S., Kokotillo, A., Campbell, S., Villa-Roel, C., & Rowe, B. ( 2013). Ketorolac in
the treatment of acute migraine: A systematic review. Headache, 53,
277-287.