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Ketorolac

Ketorolac or ketorolac tromethamine (marketed as Toradol® - generics have been approved) is a non-steroidal anti-inflammatory drug (NSAID) in the family of propionic acids, often used as an analgesic, antipyretic (fever reducer), and anti-inflammatory. Ketorolac acts by inhibiting bodily synthesis of prostaglandins. more...

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Ketorolac in its oral and intramuscular preparations is a racemic mixture of R-(+)(which is the salt 1H-Pyrrolizine-1-carboxylic acid,5-benzoyl-2,3-dihydro- ketorolac) and S-(-) (which does not have the 1H-Pyrrolizine-1-carboxylic acid,5-benzoyl-2,3-dihydro group) ketorolac.

The brand name Toradol was coined by the Syntex company of the United States.

This article does not cover Acular® or ophthalmic ketorolac.

Chemistry

Ketorolac, like other 2-arylpropionate derivatives (including ketoprofen, flurbiprofen, naproxen, ibuprofen etc.) contains a chiral carbon in the β-position of the propionate moiety. As such there are two possible enantiomers of ketorolac with the potential for different biological effects and metabolism for each enantiomer.

NSAIDs are not recommended for use with other NSAIDs because of the potential for additive side effects.

The protein-binding effect of most non-aspirin NSAIDs is inhibited by the presence of aspirin in the blood.

Mechanism of action

The primary mechanism of action responsible for Ketorolac's anti-inflammatory/antipyretic/analgesic effects is the inhibition of prostaglandin synthesis by competitive blocking of the the enzyme cyclooxygenase (COX). Like most NSAIDs, Ketorolac is a non-selective cyclooxygenase inhibitor.

As with other NSAIDs, the mechanism of the drug is associated with the chiral S form. Conversion of the R enantiomer into the S enantiomer has been shown to occur in the metabolism of ibuprofen; it is unknown whether it occurs in the metabolism of ketorolac.

Indications

Ketorolac is indicated for short-term management of pain (up to five days).

Contraindications

Ketorolac is contraindicated against patients with a previously demonstrated hypersensitivity to ketorolac, and against patients with the complete or partial syndrome of nasal polyps, angioedema, bronchospastic reactivity or other allergic manifestations to aspirin or other non-steroidal anti-inflammatory drugs (due to possibility of severe anaphylaxis).

Adverse effects

Similar to other NSAIDs. See inset "Ketorolac adverse effects."

Warnings and precautions

The most serious risks associated with ketorolac are, as with other NSAIDs, gastrointestinal ulcerations, bleeding and perforation; renal events ranging from interstitial nephritis to complete renal failure; hemorhage, and hypersensitivity reactions.

As with other NSAIDs, fluid and solute retention and edema have been reported with ketorolac; ketorolac elevated liver protein levels; it also inhibits platelet aggregation and may be associated with an increased risk of bleeding.

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Intravenous Ketorolac vs. Morphine for Acute Pain
From American Family Physician, 5/1/01 by Anne D. Walling

Patients who present to the emergency department following acute limb injury are often treated with intravenous morphine for analgesia. Although morphine is inexpensive and effective, it is also associated with serious adverse effects and has the potential for abuse. Intravenous nonsteroidal anti-inflammatory drugs (NSAIDs) could provide effective analgesia with fewer side effects, but they are substantially more expensive than morphine. Rainer and colleagues compared the effectiveness and relative costs of morphine and ketorolac as analgesia in patients with acute blunt limb injury.

They studied patients 16 years and older who presented to an emergency department in Hong Kong with isolated blunt limb injury. Patients who presented at night or on weekends were not included in the study. Other reasons for exclusion were dementia, hemorrhage, pregnancy, asthma, chronic lung disease and any contraindication to either of the study medications. The 149 eligible patients were randomly assigned to receive ketorolac (10-mg loading dose followed by 5 mg every five minutes to a maximal dosage of 30 mg, if required) or morphine (5-mg loading dose followed by 2.5 mg every five minutes to a maximal dosage of 15 mg, if required). With the assistance of a research nurse, patients completed a visual analog scale to assess pain levels at baseline and every five minutes for 30 minutes following the initial injection. Thereafter, pain was assessed every 30 minutes for 90 minutes and again after six hours. Routine observations and monitoring for adverse effects were maintained on all patients. The patients and staff did not know which drug had been injected.

The 75 patients who were treated with ketorolac were comparable to the 73 who received morphine with regard to age, sex, type and location of injury, and initial pain scores. The likelihood of pain relief at rest was higher in the patients who received morphine, but the difference was not statistically significant (see the accompanying table). Conversely, pain on activity was relieved to a greater extent with ketorolac, with the difference at the 75 percent level being statistically significant. Patients who received morphine had significantly more side effects, principally dizziness, drowsiness and nausea. Patient satisfaction was also significantly higher in the group that received ketorolac. When all additional related costs were taken into account, the mean cost of analgesia per person was significantly lower in the patients treated with ketorolac.

The authors conclude that intravenous ketorolac provides more effective pain relief with fewer adverse effects and reduced overall cost than morphine in the emergency department situation.

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