Clinical Textbook of Addictive Disorders 3rd ed - R. Frances, S. Miller, A. Mack (Guilford, 2005) WW

17. Pain and Addiction 389logical processes, whereas the “inducible” COX-2 is mostly produced as part ofthe inflammatory cascade. A higher selectivity for the COX-2 isozyme is thereforedesirable in order to achieve higher analgesic and anti-inflammatory activitieswith fewer adverse effects. The various NSAIDs vary in their COX-2 selectivity.Commercially available drugs with high COX-2 selectivity comprisecelecoxib and valdecoxib; at a relatively low dose, meloxicam is also highlyselective. The appropriate positioning of the COX-2 selective drugs is still controversial;they are most clearly appropriate in patients who have not toleratedthe nonselective COX-1/COX-2 inhibitors and those at increased risk of gastrointestinalcomplications.The potential for toxicity during NSAID therapy influences the decisionto initiate therapy, the selection of drug, and the approach to dosing and monitoring.The most important toxicities are gastrointestinal, renal, and cardiovascular.Approximately 10% of patients treated with a nonselective COX-1/COX-2 NSAID experience clinically important gastrointestinal toxicity, and gastricor duodenal ulcers occur in about 2% (Loeb, Ahlquist, & Talley, 1992). Therisk of gastrointestinal toxicity is increased with advanced age (older than 60years old), higher NSAID dose, concomitant administration of a corticosteroid,a history of ulcer disease or previous gastrointestinal complication fromNSAIDs, and possibly by heavy alcohol or cigarette consumption (Hernandez-Diaz & Rodriguez, 2000; Loeb et al., 1992). The risk of ulcer can be reduced butnot eliminated (Mamdani et al., 2002) by use of the selective COX-2 inhibitorsor by concurrent administration of gastroprotective therapy, including a protonpump inhibitor (e.g., omeprazole), misoprostol (a prostaglandin analogue), or aH2 blocker (La Corte, Caselli, Castellino, Bajocchi, & Trotta, 1999).Renal function depends on both COX-1 and COX-2 isoforms; consequently,any NSAID can cause serious renal toxicity, including acute renal failureand hyperkalemia. NSAIDs should be used with caution in those with renaldisease, and all patients should have regular monitoring of renal function. Thenonselective COX-1/COX-2 NSAIDs can cause a bleeding diathesis by interferingwith platelet activity; this potential toxicity does not occur with theCOX-2 selective agents. Symptomatic coronary artery disease during treatmentwith the selective COX-2 drug, rofecoxib, recently led to the withdrawal of thisdrug from the U.S. market. At the present time, this problem is not believed tobe a class effect. Patients at risk for atherothrombotic disease who are treatedwith a COX-2 selective drug should also receive aspirin therapy.Adjuvant Analgesics. Adjuvant analgesics are drug that have primary indicationsother than pain but can be analgesic in some pain conditions (Lussier &Portenoy, 2003). This category is extremely diverse, representing numerousdrugs in many classes (Table 17.7). Some of these drugs have analgesic propertiesin several pain syndromes and are therefore referred as “multipurpose