Which organs does ketorolac (Non-Steroidal Anti-Inflammatory Drug (NSAID)) primarily affect?

Ketorolac's Effects on Organ Systems

Ketorolac primarily affects the kidneys, gastrointestinal tract, and cardiovascular system, with the most significant concern being its nephrotoxic effects through inhibition of prostaglandin synthesis. 1, 2

Renal Effects

• Ketorolac causes kidney injury primarily through inhibition of prostaglandin synthesis, which leads to decreased renal blood flow, potentially resulting in volume-dependent renal failure, interstitial nephritis, and nephrotic syndrome 1
• The renal system relies on prostaglandins for maintaining adequate renal perfusion, especially in compromised states, and NSAIDs like ketorolac inhibit this protective mechanism 1
• Long-term administration can result in renal papillary necrosis and other renal injury 2
• Acute renal failure associated with ketorolac is usually reversible after discontinuation of the drug 3

Risk Factors for Renal Complications

• Pre-existing renal disease, even if mild 4
• Advanced age (>60 years) 1
• Compromised fluid status 1
• Concomitant use of other nephrotoxic medications (e.g., cyclosporin, cisplatin) 1
• Heart failure or cirrhosis 1
• Use of ACE inhibitors or angiotensin receptor blockers 4

Gastrointestinal Effects

• Ketorolac can cause gastrointestinal bleeding and perforation due to its inhibition of COX-1, which is responsible for protecting gastric mucosa 5
• Risk factors for GI toxicity include age >60 years, history of peptic ulcer disease, significant alcohol use, and concurrent use of glucocorticoids or anticoagulants 5
• The risk of gastrointestinal bleeding with ketorolac is slightly higher than with opioids but increases markedly with high doses used for more than 5 days, especially in the elderly 6

Cardiovascular Effects

• Like other NSAIDs, ketorolac can increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke 2
• NSAIDs, including ketorolac, have been implicated in an uptick in cardiac events 5
• Ketorolac can cause reduced sodium excretion, leading to increased blood pressure (average increase of 5 mm Hg) 1

Hematologic Effects

• Ketorolac affects platelet aggregation and can alter hemostasis, increasing the risk of bleeding complications 2
• This effect is particularly concerning in patients with coagulation disorders or those on anticoagulant therapy 2
• Postoperative hematomas and other signs of wound bleeding have been reported with perioperative use of ketorolac 2

Mechanism of Action

• Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) that inhibits both COX-1 and COX-2 enzymes 5, 2
• This inhibition prevents the conversion of arachidonic acid to prostaglandins, reducing pain and inflammation 5
• COX-1 is active throughout the body and provides routine physiologic functions such as protection of gastric mucosa and vascular hemostasis 5
• COX-2 is expressed mainly by inflammatory cells and becomes active in response to inflammatory stimuli 5

Clinical Considerations

• Ketorolac should not be used for more than five days due to increased risk of adverse effects 2
• The lowest effective dose should be used for the shortest possible duration 2
• Ketorolac is contraindicated in patients with advanced renal impairment 2
• Regular monitoring of renal function is recommended when using ketorolac, especially in high-risk patients 7
• Alternative pain management options should be considered for patients with risk factors for ketorolac-induced organ toxicity 4

Pharmacokinetics

• Ketorolac is 100% absorbed after oral administration 2
• It is highly protein-bound (99%) in plasma 2
• The drug is primarily eliminated through the kidneys, with approximately 92% of a dose found in the urine (40% as metabolites and 60% as unchanged ketorolac) 2
• The half-life is between 4-6 hours in healthy individuals but can be prolonged to 6-19 hours in patients with renal impairment 2