Ketorolac chemical structure
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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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Prochlorperazine more effective than ketorolac for pediatric migraine
From Journal of Family Practice, 6/1/04

Brousseau DC, Duggy SJ, Anderson AC, Linakis JG. Treatment of pediatric migraine headaches. A randomized, double-blind trial of prochlorperazine versus ketorolac. Ann Emerg Med 2004; 43:256-262.

* CLINICAL QUESTION

Is ketorolac more effective than prochlorperazine in the treatment of pediatric migraine in the emergency setting?

* BOTTOM LINE

Prochlorperazine (Compazine) is more effective than ketorolac (Toradol) in the treatment of children presenting to the emergency department with migraine. One additional child will experience headache relief for every 4 children receiving prochlorperazine instead of ketorolac. (LOE=1b)

* STUDY DESIGN

Randomized controlled trial (double-blinded)

* SETTING

Emergency department

* SYNOPSIS

This study is a start in the right direction toward clearing up the lack of information regarding treatment of pediatric migraine in the emergency department. The investigators recruited 62 children aged 5 to 18 years presenting with migraine in either of 2 pediatric emergency departments. Migraine was defined as recurrent headache with at least 3 of the following symptoms: an aura; unilateral location; throbbing pulsatile pain; nausea, vomiting, or abdominal pain; relief after sleep; and a family history of migraine.

Using concealed allocation, researchers randomized patients deemed to require intravenous medication to receive either prochlorperazine 0.15 mg/kg, up to 10 mg, or ketorolac 0.5 mg/kg, up to 30 mg, over 10 minutes. Children not experiencing at least a 50% reduction in pain within 60 minutes were given the alternative study drug and evaluated again.

Using the Nine Faces Pain Scale, 85% of prochlorperazine-treated children and 55% of ketorolac-treated patients experienced at least a 50% relief in pain (number needed to treat [NNT]=4; 95% confidence interval [CI], 2-13). One third of children treated with prochlorperazine achieved complete relief, compared with 7% of children receiving ketorolac (NNT=4; 95% CI, 2-13). Headache recurrence within the following 2 days occurred at a similar rate in both groups (27% and 31%, respectively).

COPYRIGHT 2004 Dowden Health Media, Inc.
COPYRIGHT 2004 Gale Group

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