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.
Notes de l'éditeur
Headaches are one of the three most common complaints in the emergency department and comprise of up to 5% of all visits. . Recommended treatment may include triptans, dihydroergotamine (DHE), phenothiazines, or nonsteroidal anti-inflammatory drugs (NSAIDs). Ketorolac, a NSAID, is a common medication prescribed in the emergency department practice setting for the diagnosis of migraine headache.
The “migraine generator” located in the brain stem is responsible for triggering the trigeminovascular system. The “migraine generator” includes the neuromodulatory locus coeruleus (noradrenergic), dorsal raphe nucleus (serotonergic), and periaqueductal gray region (pain modulation).
The pain of a migraine is often unilateral, occurring around the temple or the eye. The pain normally peaks 2 to 12 hours from the onset of the attack. For mild to moderate migraines, the first-line drugs are NSAIDs and aspirin.
Ketorolac is in the NSAID subclass. By inhibiting the conversion of arachidonic acid, the neuroinflammatory compounds prostaglandin, prostacyclin, and thromboxane (mediators of pain and inflammation) are blocked.
The enzyme cyclooxygenase (COX) can present as COX-1 and COX-2. The enzyme COX-1 produce protective prostaglandins found in the gastrointestinal (GI) tract and kidneys. The enzyme COX-2 produce protective prostaglandins in the kidneys and broad sites of inflammation.
Gastrointestinal irritation may include nausea, vomiting, diarrhea, hemorrhage, perforation, pain, and ulcer. Frequent monitoring of patients with renal disease is needed with long-term NSAID use as it is known to cause renal function abnormalities.
Aspirin will reduce the protein binding of ketorolac; however, the amount of free ketorolac concentrations will remain to same. The clinical significance of this interaction is not known, however, administration of both ketorolac and aspirin is highly discouraged due to the possibility of an adverse reaction.
A common concern with ketorolac is prescribing the correct dose of medication. With electric charting, it has become easy to click a wrong button. Multiple options of the medication are available from the drop box, which can lead to errors on a busy day in the clinic. You may have ordered two 30-milligram intermuscular (IM) ketorolac, but input two 60-milligram IM ketorolac. Luckily, the pharmacist is responsible for authorizing the correct dose of medication for the patient. After collaborating with the physician, he or she will make the corrections as needed. This mistake can be improving by communicating this common error with the physicians and with the nurses. Information and awareness are key to improving knowledge and decision making.
