Drug Resource Center
Arthritis And Arthritic Disorders
Until recently, conventional medical treatment for arthritic conditions relied on two categories of medications: nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying drugs.
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Until recently, conventional medical treatment for arthritic conditions relied on two major categories of medications:
- Those that reduce symptoms of inflammation, such as nonsteroidal anti-inflammatory drugs (NSAIDs)
- Disease-modifying drugs (also called remittive agents, immunosuppressive or immunomodulatory medications), which work to slow the underlying autoimmune disease process, such as rheumatoid arthritis or lupus
In most cases, more than one type of medication is needed to control the symptoms over time.
Anti-Inflammatory Drugs (NSAIDs And Corticosteroids)
NSAIDs are a class of drugs that relieves the symptoms associated with many forms of arthritis by slowing the body's production of prostaglandins. Prostaglandins are responsible for the characteristics of inflammation — swelling, pain, stiffness, redness and warmth. NSAIDs are also analgesics, or pain relievers, separate of their anti-inflammatory effect; the anti-inflammatory effect is generally experienced only with moderate or high doses. In the United States, there are more than 20 different NSAIDs approved by the Food and Drug Administration, each with slightly different characteristics, but more alike than different. Aspirin is the most well-known anti-inflammatory agent. Other NSAIDs include ibuprofen (Motrin, Nuprin or Advil, for example), naproxen (Naprosyn, Aleve) and indomethacin (Indocin).
The most common side effect associated with NSAIDs is stomach upset. Sometimes, stomach problems can be minimized if the medications are taken with meals, milk or antacids. Even so, stomach irritation remains a common problem. In a small number of patients (2 percent to 4 percent per year of those taking NSAIDs in moderate or high doses on a regular basis), an ulcer develops that may bleed, cause obstruction or perforation requiring surgery.
Newer NSAIDs, such as celecoxib (Celebrex), are as effective as the older NSAIDs but cause fewer ulcers. (These newer drugs are called "Cox-II selective" because they primarily inhibit one enzyme called Cox-II, rather than inhibiting both Cox-I and Cox-II, as the older drugs do.) However, one study showed that for people at highest risk (those with recent bleeding ulcer), up to 10 percent of those treated with celecoxib developed a new ulcer; in addition, the risk was similar for these high-risk patients when taking an older drug (diclofenac) combined with a drug to protect the stomach (omeprazole). Just how safe these drugs are for the stomach in persons at lower risk of ulcers remains an area of some controversy and active research; current recommendations suggest reserving the Cox-II inhibitors for people at higher risk of ulcer disease (such as those who are also taking corticosteroids or who have had an ulcer in the past). For high-risk patients, avoiding NSAIDs is an even safer option.
Because aspirin has an anticoagulant effect — that is, because it inhibits the blood's ability to clot — people who take a lot of aspirin (or any of the older "nonselective" NSAIDs) may bleed or bruise easily. Other important side effects include kidney injury, allergic reactions, fluid retention and elevation of blood pressure. The cost of the different NSAIDs varies dramatically, from pennies per day to $2 per day or more; whether the differences in their side effect profiles are worth the added cost is often unclear.
For persons taking low-dose aspirin (for example, about 80 milligrams) for heart protection and another NSAID for pain, the aspirin should be taken first, at least an hour before the other NSAID so that the benefits to the heart will not be lost.
The most powerful anti-inflammatory agents are corticosteroids. These are synthetic versions of the body's hormone, cortisone, that are produced in small quantities by the adrenal gland. Synthetically produced corticosteroids are used to reduce inflammation and suppress activity of the immune system. The most commonly prescribed are prednisone and dexamethasone.
Corticosteroids can produce dramatic improvement within a day or two. However, they tend to have little lasting benefit. Too many corticosteroid injections into a joint may damage it. Long-term use of oral corticosteroids often produces troubling side effects, such as weight gain, rounding of the face, high blood pressure, acne, easy bruising, cataracts, thinning of the skin and bone and an increased risk of diabetes and infection. When taken along with NSAIDs, there is a markedly increased risk of stomach ulcers.
Doctors prefer to prescribe a short course of corticosteroids to relieve acute symptoms and then gradually decrease the dosage. In all cases, the possible benefits are weighed against the possible side effects. And because side effects occur more frequently when corticosteroids are taken over long periods of time at high doses, these drugs are typically prescribed at the lowest effective dosage with ongoing efforts to reduce it further.
Disease-Modifying Antirheumatic Drugs
When a person's arthritis is due to rheumatoid arthritis or systemic lupus erythematosus, disease-modifying antirheumatic drugs may be recommended. Many of these medications are actually borrowed from other diseases, such as cancer and malaria. Antimalarials include chloroquine (Aralen) and hydroxychloroquine (Plaquenil). Drugs considered to be even more powerful in these diseases include methotrexate (Rheumatrex), sulfasalazine and azathioprine (Imuran). All of these agents act to suppress inflammation, presumably through their effects on the immune system, and also have a risk of more serious side effects.
It may take weeks or even months before these drugs produce any beneficial effect. During the time it takes for these drugs to work, your doctor may recommend that you take an NSAID or a corticosteroid as well.
As with any medication, the disease-modifying antirheumatic drugs can have problematic side effects. Various drugs in this category can cause diarrhea, rashes, anemia (decrease in red blood cells), leukopenia (low white blood cell count) and increased risk of infection. In general, when a drug works by suppressing the immune system, there is an increased risk of infection. In addition, methotrexate can cause serious liver and lung problems. Some antimalarial drugs can affect the eyes. It is therefore necessary that use of these drugs be carefully monitored.
Gold salts, another disease-modifying antirheumatic drug, have been used to treat arthritis for more than half a century; however, the way in which they work is not entirely clear. It is rare now for physicians to prescribe gold. Recent advances in research and technology have yielded promising new anti-arthritis therapies, including leflunomide (Arava), tofacitinib (Xelianz) and drugs that suppress the action of tumor necrosis factor (TNF).
Leflunomide reduces the action of immune cells by impairing a protein required for DNA synthesis. Tofacitinib reduces inflammation by interfering with enzymes inside white cells. Anti-TNF drugs seem to slow the destruction of the joints by disrupting the activity of TNF, a substance that promotes inflammation and joint damage. Examples of drugs that block the effects of TNF include:
- adalimumab (or Humira, injected under the skin)
- certolizumab (or Cimzia, injected under the skin)
- etanercept (or Enbrel, injected under the skin)
- golimumab (or Simponi, injected under the skin)
- infliximab (or Remicade, injected intravenously)
Anakinra (Kineret) inhibits a different chemical mediator of inflammation called interleukin-1 (IL-1) while tocilizumab (Actemra) inhibits interleukin-6 (IL-6). Other injectable medications for rheumatoid arthritis include abatacept (Orencia), which prevents certain immune cells from causing inflammation, and rituximab (Rituxan), which acts against certain antibody-producing immune cells (called B-cells). Belimumab (Benlysta) also inhibits the activity of B-cells and is the first new drug approved for systemic lupus erythematosus in decades.
Medical research is also looking into ways of restraining the body's autoimmune response before it is triggered, including efforts to develop a vaccine against arthritis. Loss of excess weight can also be helpful.
Although much of conventional anti-arthritis medications are palliative, that is, they treat the symptoms, much of the newer research, and the therapies that hopefully will emerge, may provide much more substantial relief and perhaps even cure.
Pain Relievers That Don't Treat Inflammation
In the most common form of arthritis, osteoarthritis, there is typically little or no inflammation. As a result, managing pain may be the primary focus of medical therapy. Pain relievers such as acetaminophen (Tylenol) may then be sufficient to control the pain. Other medications that may reduce symptoms of osteoarthritis include NSAIDs, other pain relievers or an injectable medication called hyaluronate (although its effects are modest). Although NSAIDs reduce inflammation, they also have analgesic effects. So their benefit for osteoarthritis may be unrelated to their ability to reduce inflammation.
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