Ketorolac chemical structure
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Toradol


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. 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. more...

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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.

Image:Ketorolac bottles.jpg

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.

Notes

Ketorolac is not recommended for pre-operative analgesia or co-administration with anesthesia because it inhibits platelet aggregation.

Ketorolac is not recommended for obstetric analgesia because it has not been adequately tested for obstetrical administration and has demonstrable fetal toxicity in laboratory animals.

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Pain relief in those recovering from chemical dependency
From American Family Physician, 11/15/04 by Robert L. Hatch

TO THE EDITOR: I enjoyed the article on the care of patients who are recovering from chemical dependency in the November 15, 2003, issue of American Family Physician. (1) This important issue has received little attention in the general medical literature. The article provides an excellent overview of the special factors one should consider when treating recovering persons. Many well-meaning physicians, unaware of these considerations, have unknowingly pushed a recovering person toward relapse by prescribing an avoidable mood-altering medication. The consequences of relapse are often grave, including destroyed relationships, incarceration, and death. Understanding these issues and following the suggestions outlined by the authors can help physicians play an important role in preventing relapses.

In addition to the authors' excellent suggestions about the management of cough in people recovering from chemical dependency, the use of albuterol inhalers should be considered. Albuterol inhalers are not mood altering, and they effectively control cough associated with bronchitis. (2) In my experience, albuterol is even more effective for cough in recovering patients than it is in the general population. This is not surprising, because most recovering patients have smoking histories, and many have inhaled a wide variety of potential lung toxins (such as marijuana, cocaine, and toxins from homemade pipes made from aluminum cans).

The authors (1) discuss acute pain management, but the topic of postoperative pain deserves additional attention. Following many surgical procedures, patients have no choice but to use medications that have the highest potential for triggering relapse. Recovering patients generally feel trapped between accepting the use of these substances they have worked hard to avoid or suffering unnecessarily. Physicians should reassure the patient that many thousands of persons recovering from chemical dependence have undergone major surgery and remained in recovery. The patient should be encouraged to be as active as possible in recovery efforts during the perioperative period (e.g., attending 12-step meetings, meditating).

Following surgery, adequate pain relief should be provided; however, it is important not to overshoot the necessary dose because this will lead to avoidable euphoria. The physician should be attentive for objective signs of uncontrolled pain (such as vital-sign changes, apprehension, difficulty moving) and unnecessarily high doses (such as the patient nodding out during conversation or being difficult to arouse). The patient may require substantially higher doses of medication than usual, and, especially in the early recovery period, may have a very high tolerance. Because of cross-tolerance, this high tolerance may extend to substances the patient never abused.

In my experience, parenteral ketorolac (Toradol) is an effective adjunct that provides adequate relief while using much lower doses of opiates. On discharge, ongoing adequate pain relief should be provided, but the patient should be switched to non-mood-altering medications as soon as possible. Patients should be instructed to adhere precisely to the scheduled dosing of mood-altering drugs and may have someone else keep the bottle and administer the medication. If the dosage is insufficient, the patient should contact the physician to discuss increasing the dose and/or frequency. Following these suggestions can help keep patients on course with their recovery following surgery and allay many of their concerns

REFERENCES

(1. Jones EM, Knutson D, Haines D. Common problems in patients recovering from chemical dependency. Am Fam Physician 2003;68:1971-8.

(2.) Gonzales R, Sande MA. Uncomplicated acute bronchitis. Ann Intern Med 2000;133:981-91.

EDITOR'S NOTE: This letter was sent to the authors of "Common Problems in Patients Recovering from Chemical Dependency," who declined to reply.

ROBERT L. HATCH, M.D.

University of Florida College of Medicine

Dept. of Community Health and Family Medicine

1600 S.W. Archer Rd. Room

G1-019 Gainsville, FL 32610

COPYRIGHT 2004 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group

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