Osteoarthritis

Description

Medications

Many medications are available for relieving the symptoms of osteoarthritis. In fact, a major 2003 analysis indicated that, at this time, drug therapy is generally more effective than non-drug treatments (e.g., surgery, acupuncture). The following are some of the medications used in mild to severe cases:

• Acetaminophen (Tylenol, Anacin-3, Panadal, Phenaphen, Valadol, and others) for mild to moderate osteoarthritis. This is usually the first choice, although a major analysis in 2003 reported that it was less effective than NSAIDs in reducing osteoarthritic pain. Furthermore, a major 2003 study found that it was no more effective than placebo.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 medications for moderate to severe arthritic pain.
• Capsaicin (Zostrix) is an ointment prepared from the active ingredient in hot chili peppers that has been helpful for relieving painful areas in other disorders. It may have some value for fibromyalgia patients.
• Tramadol (Ultram) is a pain reliever that has some properties that are similar to narcotics. It is not as addictive, however, and may be an alternative for patients who do not respond to NSAIDs or less potent agents.
• Narcotic pain relievers, such as oxycodone, oxymorphone, or morphine, may be necessary for severe pain that does not respond to less potent pain relievers.

Alternative treatments, specifically glucosamine sulfate and chondroitin sulfate, are showing promise in a number of studies for improving pain and treating osteoarthritis.

Acetaminophen

Acetaminophen (Tylenol, Anacin-3, Panadal, Phenaphen, Valadol, and others) is currently the first choice for treating osteoarthritis. This is usually the first choice, although a major analysis in 2003 reported that it was less effective than NSAIDs in reducing pain. In fact, a well-conducted 2003 study, in fact, found that it was no more effective than placebo for patients with osteoarthritis. In the same study, diclofenac (Voltaren), a prescription NSAID, provided significant relief.

Side Effects. Acetaminophen is inexpensive and generally safe. It poses far less of a risk for gastrointestinal problems than NSAIDs and does not appear to pose a risk for miscarriage, as NSAIDs do, even when used regularly.

It does have some adverse effects, however, and the daily dose should not exceed 4 grams (4000 mg). Patients who take high doses of this drug for long periods are at risk for liver damage, particularly if they drink alcohol and do not eat regularly. It may pose a small risk for serious kidney complications in people with preexisting kidney disease, although it is still the drug of choice for people with impaired kidney function. There is some evidence that taking even more than 2 grams (2000 mg) a day for the long term may confer a risk of ulcers and bleeding comparable to that of NSAIDs. This finding needs to be confirmed, however. It also may interact with certain medications, including the blood thinner warfarin.

The kidneys are responsible for removing wastes from the body, regulating electrolyte balance and blood pressure, and the stimulation of red blood cell production.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs. The most common are the following:

• Over-the-counter NSAIDs include aspirin, ibuprofen (Advil, Nuprin, Motrin IB, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
• Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), nabumetone (Relafen), dexibuprofen (Seractil), indomethacin (Indocin).
• Topical NSAIDs delivered in gels, creams, or patches are proving to reduce arthritic pain and pose less of a risk for gastrointestinal complications associated with oral NSAIDs. Topical forms that contain diclofenac (Pennsaid, Oxa Sat) are now available outside the US. Others showing promise contain the NSAIDs eltenac, ibuprofen, or ketoprofen. One interesting agent combines NSAIDs with fish oil compounds, which have anti-inflammatory effects.

Regular use of even over-the-counter NSAIDs may be hazardous for anyone and has been associated with the following side effects:

• Ulcers and gastrointestinal bleeding. This is the major danger with long-term use of NSAIDs.
• Increased blood pressure. Most NSAIDs appear to pose this risk, with higher risks observed with piroxicam (Feldene), naproxen (Aleve), and indomethacin (Indocin). (Sulindac has the smallest effect and aspirin has no risk.) People with hypertension, severe vascular disease, kidney, or liver problems and those taking diuretics must be closely monitored if they need to take NSAIDs.
• May delay the emptying of the stomach, which could interfere with the actions of other drugs. The elderly are at special risk.
• Dizziness.
• Tinnitus (ringing in the ear)
• Headache.
• Skin rash.
• Depression has also been noted.
• Confusion or bizarre sensation (in some higher-potency NSAIDs, notably indomethacin).
• Possible higher risk for miscarriage (particularly if the NSAID is taken for more than a week or around the time of conception).
• Kidney abnormalities have been reported in people taking NSAIDs, which resolve when the drugs are withdrawn. Any sudden weight gain or swelling should be reported to a physician. Anyone with kidney disease should avoid these drugs.
• There is a slight risk for liver abnormalities.

Note on interactions: Of great concern is research suggesting taking NSAIDs with aspirin might reduce the benefits of aspirin or other heart protective drugs. Diabetics taking oral hypoglycemics may need to adjust the dosage if they also need to take NSAIDs because of possible harmful interactions between the drugs.

Click the icon to see an image of a gastric ulcer.

COX-2 Inhibitors (Coxibs)

Celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra) are known as COX-2 (cyclooxygenase-2) inhibitors, or coxibs. They inhibit an inflammation-promoting enzyme called COX-2. Others, such as etoricoxib, are under investigation. Meloxicam (Mobicox) is a related drug known as a COX-2 preferential.

Evidence is increasing that the coxibs are significantly less harmful to the gastrointestinal (GI) tract than common NSAIDs. In an important 2003 study, Celebrex had a significantly better safety record in the GI tract than NSAIDs and had lower rates of ulcers even in patients who also needed to take aspirin to prevent heart attacks. Another 2003 study also suggested that rofecoxib was safer for the GI tract than NSAIDs. Some early evidence also suggests that, like NSAIDs, they may be partially protective against colon cancer and possibly even Alzheimer's disease.

In spite of their potential promise, some researchers believe that inhibiting COX-2 may have some negative side effects over the long term. The effects of these drugs on the heart particularly require clarification. The following are possible adverse effects or complications:

• Some studies have reported a higher incidence of heart attacks in patients taking Vioxx compared to those taking standard NSAIDs. There were limitations to these studies, however, and 2003 study of 67,000 elderly patients found no higher risk compared to patients taking other NSAIDs or none of these drugs. Some (but not all evidence) suggests that the COX-2 inhibitors may increase the risk for blood clots. On the other hand, some studies have suggested that the anti-inflammatory effects, at least in Celebrex and meloxicam (Movicox), may have beneficial effects on blood vessels that would be heart protective.
• Celebrex or Vioxx can increase in blood pressure, with Vioxx having the greater effect.
• A few cases of neurologic side effects (hallucinations) have been observed with higher doses of Celebrex or Vioxx.
• Coxibs may have some adverse effects on kidney function, particularly in elderly people, which is similar to the effects of standard NSAIDs. Liver abnormalities, which are side effects of many drugs, have also been reported with coxibs and need further follow-up.
• They may have negative effects on pregnancy and fertility.
• Some severe allergic reactions have been reported in patients taking valdecoxib (Bextra). People allergic to sulfa drugs may be at particular risk.Anyone who develops a rash after taking these agents should stop taking them immediately.
• Patients who are sensitive to aspirin should discuss coxibs with their physician. Some may be safer for these individuals than others.

Coxibs can interfere with other drugs taken concurrently. Patients taking anticoagulant drugs such as warfarin may experience a higher risk for bleeding with the use of these agents. The use of coxibs can interfere with many other drugs taken concurrently, including lithium, methotrexate, and many others taken for heart disease, high blood pressure, or epilepsy. Patients should discuss all other medications with their physician.

COX-2 inhibitors are also significantly more expensive than traditional NSAIDs, costing about $80 per month, compared to about $15 for an NSAID like naproxen. Although they pose a lower risk for ulcers than NSAIDs, this risk is small for most NSAID users, so choosing coxibs may be justified only in patients with evidence of GI bleeding. More research is needed.

Capsaicin

Capsaicin is a component of hot red peppers and may bring pain relief when used as a skin cream (Zostrix). This is the only skin preparation that does more than just mask pain or reduce it temporarily. Capsaicin seems to reduce a substance in the body, known as substance P, which contributes both to inflammation and the delivery of pain impulses from the central nervous system. A small amount of capsaicin must be applied to the area of inflammation about four times a day. During the first few days of use, the patient will experience a warm, stinging sensation when the cream is applied. This sensation goes away, and pain relief usually begins within one to two weeks.

Tramadol

Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) It can cause nausea but does not cause severe gastrointestinal problems, as NSAIDs can. Some patients experience severe itching. A combination of tramadol and acetaminophen (Ultracet) is now available and provides more rapid pain relief than tramadol alone with more long-lasting benefits than acetaminophen. Side effects are the same as for each of these agents.

Narcotics

Narcotics, pain-relieving and sleep-inducing drugs that act on the central nervous system, are the most powerful medications available for the management of moderate to severe pain. There are two types of narcotics:

• Opiates, which are derived from natural opium (e.g., morphine and codeine).
• Opioids, which are synthetic drugs. They include oxycodone (Percodan, Percocet, Roxicodone, Oxycontin), hydrocodone (Vicodin), and oxymorphone (Numorphan).

Although the use of narcotics for arthritic pain is controversial, many studies have suggested that they are rarely addictive for pain sufferers except among patients with a history of substance abuse. Some experts, then, believe that opioids have a place in osteoarthritis treatment when milder drugs are not effective or appropriate. The use of such agents is very beneficial when included as part of a comprehensive pain management program. Such a program involves screening prospective patients for possible drug abuse and then regularly monitoring those who are taking it, adjusting the dose as necessary to achieve an acceptable balance between pain relief and side effects. Common side effects include anxiety, constipation, nausea and vomiting, dizziness, drowsiness, paranoia, urinary retention, restlessness, and labored or slow breathing. Unfortunately, opioid abuse among young people is a major concern.

Corticosteroids

When pain becomes a major problem and less potent pain relievers are ineffective, physicians may resort to corticosteroid (steroid) injections, usually by administering a shot into the affected joint every three months. Corticosteroid shots are useful only if inflammation is present in the joint. Relief from pain and inflammation is of short duration, and this treatment is rarely used for chronic osteoarthritis. They may not be as effective for women as for men.

Corticosteroids mask pain and the patient must be very careful to avoid over-use of the affected joints. Patients are usually advised not to have more than two or three injections a year, since there is some concern that repeated injections over the long term may be harmful. A reassuring 2003 study found no greater disease progression in people who had injections every three months for two years compared to those who were given sham injections on the same schedule. (On the other hand, corticosteroids also produced no greater improvements in functioning.) Because long-term use of corticosteroids has many potentially serious side effects, steroid medications are never given orally or systemically for the treatment of osteoarthritis.

Experimental Therapies

Bisphosphonates. Bisphosphonates, such as alendronate (Fosamax) and risedronate (Actonel), are important agents in preventing bone loss in people with osteoporosis. They are currently being investigated for osteoarthritis as well. For example, a 2002 study found that they were very beneficial in reducing bone loss after knee replacement surgery.

Lidocaine Patch. Lidocaine, a local anesthetic, is available in patch form (Lidoderm) and has been used specifically for herpes zoster pain. Early studies are suggesting that it may provide significant relief for people who suffer from osteoarthritis with very few adverse effects, even with continuous use of four patches a day. If further studies support its benefits, the patch could prove to be an important treatment

Additional Investigative Therapies. Other therapies under investigation include agents that aim at stopping the disease process itself.

• Tetracycline antibiotics, such as doxycycline, may have a role to play in treating osteoarthritis. Laboratory studies are reporting that, at low concentrations, the drug reduces the production of collagenases, which are enzymes critical to disease development and progression. Human trials are under way.
• Licofelone is drug that inhibits both the COX enzyme plus an inflammatory substance called Lipoxygenase 5. Early trials indicate they may be effective and safer than either NSAIDs or COX-2 inhibitors, though further study is needed
• NO-NSAIDs are experimental agents that combine nitric oxide with NSAIDs. Nitric oxide increases blood flow in the mucous lining and secretions of mucus and bicarbonate. Combining nitric oxide with NSAIDs may reduce the adverse effects on the GI tract. In addition, according to one study, an experimental NO-aspirin also had the heart protective properties of aspirin without its gastrointestinal problems.
• Diacerein inhibits an inflammatory substance in arthritic joints called interleukin-1b. It has shown some promise in European trials, with a 2002 study reporting it to be as effective as NSAIDs.
• An amino acid-like substance called oxaceprol is also under investigation.
• Two trials of gene therapies that either fight joint degradation or strengthen cartilage are under way.

And in a nod to low-tech therapies of the past. Russian researchers report that leeches, whose saliva contains anesthetic compounds as well as the anticoagulant hirudin, brought lasting relief when attached to arthritic knees for an hour and twenty minutes.A German study using leeches also reported rapid pain relief with sustained improvement after four weeks.