Major Research Findings

Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID) that has been widely used for the treatment of inflammatory pain, such as osteoarthritis. 24 Ketorolac tromethamine has strong anti-inflammatory and analgesic properties. 24 However, traditional methods of administration, such as oral administration and injections, often result in high systemic exposure, leading to adverse events such as gastric ulceration and bleeding. 24 To address this issue, a topical delivery system for ketorolac tromethamine via cataplasm has been developed. 24 This cataplasm, based on a three-dimensional mesh structure formed by the cross-linking of dihydroxyaluminum aminoacetate (DAAA) and sodium polyacrylate, has shown promising results in reducing systemic exposure and side effects. 24

Reasons for Side Effects

Ketorolac’s side effects are thought to be caused by its inhibition of both COX-1 and COX-2. 23 COX-1 is essential for protecting the stomach, and its inhibition can lead to side effects such as gastric ulcers and bleeding. 23 COX-2 is involved in the inflammatory response and its inhibition contributes to pain relief. However, COX-2 also plays a crucial role in protecting the kidneys, and its inhibition can lead to side effects such as nephrotoxicity. 23 Ketorolac, when combined with other medications, can have increased side effects. 2 Ketorolac carries a higher risk of side effects in older adults and individuals with kidney disease. 2 Additionally, ketorolac can interact with other medications. 2 It is recommended to avoid ketorolac during pregnancy and breastfeeding. 2

Common Side Effects

Gastrointestinal Issues

Ketorolac can cause gastrointestinal issues such as gastric ulcers and bleeding. 24 17 23 2 11 Ketorolac’s inhibition of COX-1, which is important for protecting the stomach, increases the risk of gastrointestinal issues. 23 Higher doses of ketorolac increase the risk of gastrointestinal issues. 2 Long-term use of ketorolac can also increase the risk of gastrointestinal issues. 2

Nephrotoxicity

Ketorolac can cause nephrotoxicity. 17 2 Ketorolac’s inhibition of COX-2, which is important for protecting the kidneys, increases the risk of nephrotoxicity. 23 Higher doses of ketorolac increase the risk of nephrotoxicity. 2 Long-term use of ketorolac can also increase the risk of nephrotoxicity. 2 Older adults and individuals with kidney disease are at an increased risk of nephrotoxicity from ketorolac. 2

Bleeding

Ketorolac can increase the risk of bleeding. 17 23 2 21 22 Ketorolac inhibits blood clotting, increasing the risk of bleeding. 23 Higher doses of ketorolac increase the risk of bleeding. 2 Long-term use of ketorolac can also increase the risk of bleeding. 2 Patients at an increased risk of bleeding, such as those with a history of gastric ulcers or bleeding, or those taking anticoagulants, should avoid using ketorolac. 2

Delayed Wound Healing

Ketorolac can delay wound healing. 17 Ketorolac can inhibit collagen synthesis, which may delay wound healing. 17 Patients at an increased risk of delayed wound healing, such as those who have undergone surgery, individuals with diabetes, or those who are malnourished, should avoid using ketorolac, or have their wounds monitored closely if using it. 17

Other

Ketorolac can cause side effects such as indigestion, diarrhea, constipation, dizziness, headache, tinnitus, visual disturbances, rash, itching, and hives. 9 14 10 6 3 The dosage of ketorolac can vary from patient to patient. 2 Ketorolac should be used only as directed by a healthcare provider. 2 If any side effects occur while using ketorolac, seek immediate medical attention. 2

Side Effects Management

Gastrointestinal Issues

To prevent gastrointestinal issues, ketorolac should be taken with food or in combination with a proton pump inhibitor. 2 11 The dose of ketorolac should be minimized as much as possible to reduce the risk of gastrointestinal issues. 2 Regular endoscopy should be considered for those using ketorolac long-term to detect the early signs of ulcers or other issues. 2

Nephrotoxicity

To prevent nephrotoxicity, ketorolac should be avoided in patients with impaired kidney function. 2 The dose of ketorolac should be minimized as much as possible to reduce the risk of nephrotoxicity. 2 Regular kidney function tests should be conducted while using ketorolac to ensure normal kidney function. 2

Bleeding

To prevent bleeding, ketorolac should be avoided in patients at an increased risk of bleeding. 2 The dose of ketorolac should be minimized as much as possible to reduce the risk of bleeding. 2 Regular blood tests should be conducted while using ketorolac to check for any signs of bleeding. 2

Delayed Wound Healing

To prevent delayed wound healing, ketorolac should be avoided in patients at an increased risk of delayed wound healing. 17 The dose of ketorolac should be minimized as much as possible to reduce the risk of delayed wound healing. 17 Patients at an increased risk of delayed wound healing should avoid using ketorolac, or if using it, have their wounds monitored regularly. 17

Comparison Between Studies

Similarities

Many studies have shown that ketorolac is effective in managing postoperative pain. 24 9 17 12 7 14 19 10 1 6 16 11 3 5 8 20 However, many studies have also shown that ketorolac can cause side effects such as gastric ulcers and bleeding. 24 17 2 11 23 21 22 8 The side effects of ketorolac vary depending on the dose and method of administration. 2

Differences

The methods and dosages of ketorolac administration vary between studies. 24 9 17 12 7 14 19 10 1 6 16 11 3 5 8 20 The study populations also differ. 24 9 17 12 7 14 19 10 1 6 16 11 3 5 8 20 Therefore, it can be challenging to compare the results of different studies. 24 9 17 12 7 14 19 10 1 6 16 11 3 5 8 20

Real-Life Application Precautions

Ketorolac should be used as directed by a healthcare provider to alleviate pain. 2 It is important to be aware of the risks of side effects when using ketorolac. 2 Seek immediate medical attention if any side effects occur while using ketorolac. 2 Ketorolac can interact with other medications. 2 Ketorolac should be avoided during pregnancy and breastfeeding. 2 Older adults and individuals with kidney disease are at an increased risk of side effects from ketorolac. 2

Limitations of Current Research

Research on the side effects of ketorolac is still limited. 2 23 Further research is needed to thoroughly investigate the side effects of ketorolac. 2 23 The side effects of ketorolac vary from patient to patient. 2 Research on ketorolac side effects does not cover all patients. 2

Future Research Directions

Further research is needed to thoroughly investigate the side effects of ketorolac. 2 23 Research is needed to develop methods for preventing or mitigating the side effects of ketorolac. 2 23 Identifying patients at a higher risk of ketorolac side effects and determining whether they should avoid using it should be studied. 2

Conclusion

Ketorolac should be used as directed by a healthcare provider to alleviate pain. 2 It is crucial to be aware of the potential for side effects when using ketorolac. 2 Seek immediate medical attention if any side effects occur while using ketorolac. 2