Opioid-Sparing Benefit of NSAIDs

Opioid-sparing benefit of NSAIDs

Because NSAIDs do not activate opioid receptors, they can provide additive pain relief when combined with an opioid analgesic.(8,68) Thus, combining an NSAID with an opioid analgesic may provide adequate pain control with a clinically significant reduction in opioid dosage.(69) This opioid-sparing effect of NSAID therapy allows the clinician to diminish the side effects associated with opioid therapy without sacrificing pain control.(68,70)

However, nonselective NSAIDs have clinically significant adverse effects that differ from those of opioids, which have dose-dependent side effects. It is not always possible to predict which patients are at increased risk of developing an NSAID-induced side effect.(69) Furthermore, catastrophic or irreversible idiosyncratic side effects, which are not always preceded by a minor side effect, may occur without any warning.(8,69)

Clinical factors that increase the risk of an unacceptable adverse effect with traditional NSAID therapy are often present in patients with cancer, limiting the clinical utility of these agents.(65,69) For example, the risk of developing NSAID-associated agranulocytosis is greater in cancer patients who are often pancytopenic as a consequence of their cancer treatments. Similarly, aspirin-associated platelet dysfunction via acetylation of surface proteins is more likely to be clinically significant in cancer patients who are often thrombocytopenic due to chemotherapy or radiation therapy.(66,68,69) In these patients, nonacetylated salicylates (eg, salsalate, choline magnesium trisalicylate) or even acetaminophen are routinely used as alternatives to traditional NSAIDs.(66,68) The potential for toxicity is increased when both salicylates and nonselective NSAIDs are combined with methotrexate therapy.

NSAID-associated GI side effects such as dyspepsia are also more likely to occur in cancer patients, who often experience GI toxicities following chemotherapy.(68) The possibility of developing NSAID-associated GI ulceration, perforation, or frank bleeding is more likely to develop in cancer patients who often are thrombocytopenic, or to become clinically significant in patients who are chronically anemic as a consequence of their treatment.(68,69)

Coxibs: another option for cancer pain management

Oncologists are replacing nonselective NSAIDs, nonacetylated salicylates, and acetaminophen with coxib therapy, chosen for its safety profile. Surgical oncologists are exploring the use of coxibs both preoperatively, as preemptive analgesic therapy, and during the postoperative period to reduce opioid usage and speed the recovery process.

Guidelines for the use of NSAIDs, largely empiric, are drawn from extensive clinical experience.(70) Some anecdotal reports have found that celecoxib is less effective than traditional nonselective NSAIDs in managing cancer pain. Conversely, rofecoxib (25 mg/day or 50 mg/day) seems to be more effective than nonselective NSAIDs in managing cancer pain when combined with an opioid.

Conclusion

There are several patient groups other than high-risk arthritis patients that may benefit from coxib therapy. The data from epidemiological studies suggest that chronic use of NSAIDs may have a chemopreventive effect on the development of AD, and some clinical trials have shown a slowing of AD symptoms with NSAID treatment. A recent prospective study found that nonselective NSAIDs may be protective against AD.(71) The benefits of coxib treatment of AD are under study and will become known in the coming years.

Preclinical studies suggest that COX-2 inhibition should be a therapeutic target for the chemoprevention of CRC. One coxib is indicated for the treatment of the premalignant condition FAP. Depending on the outcome of current clinical trials, coxibs may be approved soon for adjunctive treatment and/or chemoprevention of CRC.

Palliative care clinicians and oncologists are increasingly using coxibs to manage cancer pain because of their opioid-sparing effect and their lack of the adverse effects typically associated with NSAID or opioid therapy.

Lema MJ. Emerging options with coxib therapy. Cleve Clin J Med 2002;69:SI76-84.