Second Generation NSAIDs (COX-2 Inhibitors)

Another type of NSAID that treats pain is COX-2. In addition to treating mild to moderate pain, COX-2 inhibitors also suppresses inflammation, reduces fever, and treat the pain of dysmenorrhea.

Prototype and Other Medications

Celecoxib – Medication Classification: COX-2 Inhibitors

The only prototype COX-2 inhibitor NSAID is celecoxib.

Expected Pharmacologic Action

COX-2 specific inhibitor NSAIDs are second-generation NSAIDs that were developed with the hope that the adverse drug reactions related to COX-1 would be minimized. These include the COX-1 effects on the stomach, kidneys, and platelets. However, some COX-1 adverse drug reactions decreased, while others increased. The gastric adverse drug reactions of COX-2 specific inhibitor NSAIDs are less, the renal impairment adverse drug reactions are similar to COX-1 and COX-2 inhibitors, and vasoconstriction combined with platelet aggregation actually increases risk of cardiovascular events. COX-2 inhibitors do still effectively suppress pain and inflammation.

Adverse Drug Reactions

The adverse drug reactions of celecoxib include gastric upset, diarrhea, heartburn, nausea, and gastric ulceration. But these effects are less of a problem than with COX-1 inhibitors. Renal dysfunction, cardiovascular, and cerebrovascular events are adverse drug reactions that can still occur with clients who take a COX-2 inhibiting NSAID.

Interventions

When caring for clients taking celecoxib, monitor for and report gastric upset, heartburn, nausea, diarrhea, and GI bleeding. It’s also a good idea to test for and treat Helicobacter pylori infection prior to beginning long-term NSAID therapy. For clients at high risk for gastric bleeding, talk to the provider about prescribing a proton pump inhibitor you can give concurrently during therapy. Monitor intake and output and watch for low urine output and fluid retention. Also, monitor for rapid rises in BUN and creatinine, which reflect decreased kidney function. When the provider starts NSAID therapy, recommend that the medication is only used for short periods of time and in low doses to help minimize adverse drug reactions. Monitor for manifestations of myocardial infarction and cerebrovascular accident due to the risk of thromboembolic events. And if you need to give celecoxib for long-term therapy, recommend low-dose aspirin to prevent those thromboembolic events.

Administration

When administering celecoxib, give it 2 hours before or after magnesium or aluminum-based antacids. Throughout therapy, continue to monitor for the medication’s therapeutic effects.

Client Instructions

When you provide instructions for clients on long-term NSAID therapy with a COX-2 inhibitor medication, reinforce the use of low-dose aspirin once daily to reduce the risk of heart attack and stroke. Instruct clients taking celecoxib to take the medication with food, milk, or 8 ounces of water, and to avoid alcohol to minimize gastrointestinal effects. Tell them to report persistent gastric irritation and manifestations of gastrointestinal bleeding, as well as changes in urine output, weight gain, or manifestations of fluid retention such as edema or bloating. Emphasize the need to report chest pain or heaviness, shortness of breath, sudden and severe headache, numbness, weakness, visual disturbances, or confusion.

Safety Alert

There is continuing research on the safety of celecoxib. Increased risk of gastrointestinal complications can relate to the length of time clients take the medication or the client’s age, as well as concurrent ingestion of alcohol or smoking. Increased risk of thromboembolic events can relate to the length of time clients take celecoxib, as well as a previous history of heart disease. In the meantime, clients taking a COX-2 inhibitor should be aware of the early manifestations of gastrointestinal bleeding such as coffee-ground emesis or black, tarry-looking stools; myocardial infarction such as heaviness in the chest and/or shortness of breath; and stroke such as one-sided numbness or weakness and confusion. These manifestations indicate the need for immediate medical care.

Contraindications and Precautions

Use of celecoxib is contraindicated in clients who are pregnant. It’s a teratogenic medication during the third trimester, causing premature closure of the ductus arteriosus. Celecoxib is also contraindicated for clients who have severe hepatic or kidney impairment, children younger than 18, clients with gastrointestinal bleeding, anemia, pain from coronary artery bypass grafting, and allergy to celecoxib, sulfa, and/or sulfonamides. Use celecoxib with caution in clients with alcohol use disorder, heart failure, cardiovascular disease, hypertension, diabetes mellitus, asthma, a history of GI bleeding or peptic ulcer disease, mild or moderate liver and/or renal impairment, and cerebrovascular accident. If you relate each of these disorders back to the effects that the COX inhibitor NSAIDs cause in the body, you should find a relationship.

Interactions

Celecoxib interacts with furosemide, decreasing its diuretic effects. Fluconazole, can increase celecoxib levels. Celecoxib increases the anticoagulant effects of warfarin. Glucocorticoids and alcohol increase the risk of bleeding. The antihypertensive effects of ACE inhibitors decrease when you give them concurrently with celecoxib, and there is an increase in the risk of lithium carbonate toxicity.