NSAIDs may also elevate blood pressure and cause heart failure. The risk of heart attack and stroke achieved special notoriety with rofecoxib (Vioxx), a type of NSAID called a COX-2 inhibitor. It caused as many as 140,000 heart attacks in the . during the five years it was on the market (Vioxx was removed from the market in 2004). The regrettable experience with Vioxx raised awareness about the cardiovascular risk of NSAIDs, and led to further studies showing that the risk is not limited to Vioxx but is associated with all NSAIDs.
Other drugs are frequently used to support analgesics resist various types of pain or specific parts of the overall pain encounter. This is drugs like orphenadrine, cyclobenzaprine, trazadone and other drugs with anticholinergic capabilities which could be used together with opioids for reducing neuropathic pain. In case of painful musculoskeletal disorders again orphenadrine and cyclobenzaprine can be used as a muscle relaxants. Also, clonidine used as an analgesic for similar purpose and all of the mentioned drugs enhance the effects of opioids overall.