Pain can be acute or chronic. Chronic pain has been broadly classified into two types: nociceptive and neuropathic. Nociceptive pain can be treated with nonopioid analgesics or opioids. Neuropathic pain is less responsive to opioids; adjuvant medicines such as antidepressants and anticonvulsants are often used to treat neuropathic pain. Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects.

Pain can be acute or chronic. Chronic pain has been broadly classified into two types: nociceptive and neuropathic. Nociceptive pain is generally treated with nonopioid analgesics and opioids. Antidepressants and anticonvulsants have been used to treat neuropathic pain. Combining two different types of analgesics may nprovide an additive analgesic effect without increasing adverse effects.

To prevent irreversible damage to joints and minimize toxicities associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, disease modifying anti-rheumatic drugs (DMARDs) are now used early in the treatment of rheumatoid arthritis (RA). The DMARDs listed in the table on page 84 have no immediate analgesic effects, but can control symptoms and have been shown to delay and possibly stop progression of the disease. The NSAIDs listed in the table on page 88 have analgesic and anti-inflammatory effects, but may not affect the disease process. Oral corticosteroids can rapidly relieve joint symptoms and control systemic manifestations, but their chronic use is associated with many complications.

Patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) may be asking their health care providers if they should continue, and some may be asking for alternatives. For most patients taking nonspecific NSAIDs, it would be reasonable to continue. For those who are taking the COX-2 selective celecoxib (Celebrex) because they cannot tolerate the gastrointestinal (GI) effects of nonspecific NSAIDs, it seems reasonable to continue at doses no higher than 100 mg b.i.d. or 200 mg once daily; at these dosages cardiovascular risk has been no higher than with placebo. All NSAIDs, including COX-2 inhibitors, can decrease renal blood flow and cause fluid retention, hypertension and renal failure, especially in the elderly and in patients who take diuretics. The unpublished study that led to an FDA alert on an increased cardiovascular risk with naproxen (Naprosyn, and others) was conducted in patients older than 70. See NSAID addendum

At a US Senate hearing prompted by the withdrawal of Vioxx, an FDA officer cited 5 drugs as potentially dangerous. It may be useful to revisit Medical Letter reviews of these drugs.

With the removal of Vioxx from the market and concerns about cardiovascular toxicity with other selective COX-2 inhibitors, patients are looking for safe alternatives, and manufacturers of other drugs are looking for additional market share. The COX-2 inhibitors first became popular because they have less upper GI toxicity than older less selective NSAIDs, at least in the short term, in patients not taking aspirin.

Rofecoxib (Vioxx - Merck) has been withdrawn from the market due to an increased risk of cardiovascular complications associated with its long-term use. The question remains whether all selective COX-2 inhibitors carry the same risk. Full-page advertisements in newspapers for celecoxib (Celebrex - Pfizer), the most widely used COX-2 inhibitor, assure the public that it does not.

Drugs for treatment of migraine attacks are listed in the table on page 64. All of the oral drugs are most effective if taken early in an attack when the pain is mild (H Christoph-Diener et al, Neurology 2004; 63:520). Drugs for prevention of migraine are listed in the table on page 65. Treatment of migraine in the emergency room, which may involve use of intravenous drugs, is not included here.

Low-dose aspirin is widely used as an antiplatelet drug to reduce the risk of cardiovascular disease (Medical Letter 2000; 42:18). Recent reports suggest that the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen (Motrin, and others) may decrease the efficacy of aspirin for this indication. The manufacturer of Tylenol is capitalizing on these reports by advertising that aspirin-taking patients who need pain relief should use acetaminophen instead of ibuprofen.

Three types of analgesic drugs are available: non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; opioids; and adjuvant drugs that are not usually thought of as analgesics, such as antidepressants, which can act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Combining two different types of analgesics may provide an additive analgesic effect without necessarily increasing adverse effects.

Most peptic ulcers not caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with infection of the gastric mucosa by the gram-negative bacilli Helicobacter pylori. The majority of NSAID-related ulcers are gastric. H. pylori infection causes both duodenal and gastric ulcers. Eradication of H. pylori promotes healing and markedly decreases recurrence of both duodenal and gastric ulcers (A Shiotamni and DY Graham, Med Clin North Am 2002; 86:1447; FKL Chan and WK Leung, Lancet 2002; 360:933). The first step in the management of peptic ulcers is the diagnosis and treatment of H. pylori.

Many different drugs are now used to treat rheumatoid arthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs), listed in the table on page 26, have analgesic and anti-inflammatory effects, but may not affect the disease process. Corticosteroids can provide rapid relief of joint symptoms and control of systemic manifestations, but chronic use is associated with many complications. The "disease-modifying" anti-rheumatic drugs (DMARDs), listed on page 29, have no immediate analgesic effects, but can control symptoms and may delay progression of the disease (American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines, Arthritis Rheum 2002; 46:328). Interactions of anti-rheumatic drugs with other drugs are listed in The Medical Letter Handbook of Adverse Drug Interactions, 2003.

Related Articles Since Publication

Increasing use of rofecoxib (Vioxx) and celecoxib (Celebrex), both selective inhibitors of cyclooxygenase-2 (COX-2), for treatment of arthristis has been accompanied by concerns that they may increase risk of thrombotic cardiovascular events.

Selective COX-2 Inhibitors and Bleeding Risk: An Additional Note - The Medical Letter article on Drugs for Pain (August 21, 2000) stated that the selective COX-2 inhibitors celecoxib (Celebrex) and rofecoxib (Vioxx) do not inhibit platelet aggregation or bleeding time. Perhaps we should have added, as we did in discussing use of these drugs in rheumatoid arthritis (July 10, 2000), that both celecoxib and rofecoxib, if given with warfarin (Coumadin, and others), increase INR and prothrombin time values and may increase the risk of bleeding.

Three types of analgesic drugs are available: first, non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; second, opioids; and third, drugs not usually thought of as analgesics, which act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Non-opioids can be given concurrently with opioids for an additive analgesic effect.

Many different drugs are now used to treat rheumatoid arthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic and anti-inflammatory effects, but may not affect the disease process. The "disease-modifying anti-rheumatic"drugs (DMARDs) have no immediate analgesic effects, but can control symptoms and may delay progression of the disease.

Meloxicam, a nonsteroidal anti-inflammatory drug (NSAID) with some cyclooxygenase-2 (COX-2) selectivity in vitro, has been approved by the FDA for treatment of osteoarthritis.