Pharmacodynamics and mechanism of action
Ketorolac is a non-selective NSAID and acts by inhibiting the two enzymes COX-1 and COX-2, which are normally responsible for the conversion of arachidonic acid to prostaglandins. The COX-1 enzyme is constitutively active and is found in platelets, gastric mucosa, and vascular endothelium. The COX-2 enzyme mediates inflammation, pain, and fever.
Therefore, inhibition of the COX-1 enzyme is associated with an increased risk of bleeding and gastric ulcers, whereas the desired anti-inflammatory and analgesic properties are associated with inhibition of the COX-2 enzyme. Therefore, despite its efficacy in pain management, ketorolac should not be used long-term because it increases the risk of serious adverse effects such as gastrointestinal bleeding, peptic ulceration, and perforation.
Pharmacokinetics
Ketorolac is rapidly and completely absorbed after oral administration, with bioavailability after oral administration of approximately 80%. Maximum plasma concentratione is reached 20-60 minutes after administration. Over 99% of the dose is bound to plasma proteins in the blood. Ketorolac is metabolized by hydroxylation or conjugation in the liver. The enzymes involved mainly include CYP2C8 and CYP2C9. Ketorolac is excreted primarily through the kidneys, with approximately 92% of the dose excreted through the kidneys. The remainder is excreted in the stool.
Drug Interactions
Probenecid may increase the likelihood of adverse reactions when taken with ketorolac. The risk of gastrointestinal effects is increased if potassium supplements, aspirin, other NSAIDs, corticosteroids, or alcohol are taken at the same time. The risk of bleeding increases with concomitant use of clopidogrel, cefoperazone, valproic acid, cefotetan, eptifibatide, tirofiban, and ticlopidine. Anticoagulants and thrombolytic medications also increase the likelihood of bleeding.
