Keeping up on arthritis meds

Any time you have a sore ankle, neck, or shoulder, you have a painful reminder of what the arthritis patient suffers all the time. Except that most arthritis is more than just joint pain. It’s also a complicated systemic disease. Its treatment includes a confusing array of medication: non-steroidal anti-inflammatory drugs–NSAIDs–analgesics, anti-rheumatics, steroids, and immunosuppressives.

To help your patients understand what these drugs do, you’ve got to keep up to date on the medications available now–changes in indications, recommended dosages, interactions with other drugs, and adverse reactions–and be aware of the investigational drugs you may be giving soon. This review will help you do just that.

Aspirin is still the drug of choice

Of the commonly used NSAIDs–acetylsalicylic acid, indomethacin, and phenylbutazone–ASA is still the preferred drug for the initial management of rheumatoid arthritis and osteoarthritis. It works as both an analgesic and an anti-inflammatory. The analgesic effect benefits patients with OA, a localized condition resulting from biochemical or biomechanical changes within the joint. Its anti-inflammatory action is especially important in treating RA, a systemic connective tissure disease marked by stiff, sore joints and swelling, redness, and tenderness in the surrounding tissues.

Because aspirin is such a common medication, it’s easy to treat its prescription in an offhand way: “Just take aspirin.” But for the arthritis sufferer, the benefits of the drug are highly dependent on correct dosage. While it’s possible to obtain pain-relief from 2,300 mg–about seven regular-strength tablets a day–4,000 to 6,000 mg are often necessary to achieve anti-inflammatory action. To maintain a therapeutic blood level, your patient must get into the habit of taking the drug at regular intervals, not just when pain intensifies. The first dose should be taken upon arising. However, it may take several hours before the drug’s therapeutic effect enables a patient to carry out his usual everyday activities.

To provide adequate blood levels through the night, time-release ASA preparations are sometimes useful. When the medication is taken at bedtime it not only helps the patient sleep through the night, but often decreases morning stiffness and pain as well.

In the dosages required to relieve arthritis, aspirin is a potent drug, not without danger. For this reason, blood samples may be drawn every few weeks during the early stages of management to monitor serum salicylate levels and determine the right dosage. The dosage shouldn’t raise salicylate levels above 30 mg/%, the toxicity threshold. Once the safest effective dosage is determined, serum salicylate levels are drawn periodically, as determined by the patient’s response.

Even a relatively low dose of aspirin can become toxic if your patient takes it along with other products that contain hidden salicylates. For example, Pepto-Bismol can provide the equivalent of eight 5-grain aspitin tablets when taken at the dosage recommended for travelers’ diarrhea (2 tablespoons every hour or half hour). That can be enough to cause toxicity when added to salicylates prescribed for arthritis.

Even relatively low salicylate levels can cause harmful GI side effects, including irritation and bleeding. You can’t always rely on positive results from an occult blood test to confirm the presence of bleeding. The best way to monitor bleeding is to have a baseline CBC done before therapy begins, with follow-up testing every four to six months.

To reduce the risk of bleeding, give the drug with food or milk. You might also suggest that the patient be switched to enteric-coated aspirin or non-acetylated salicylates, when necessary. The non-acetylated salicylates include salsalate (Disalcid), choline salicylate (Arthropan), magnesium salicylate (Magan), and choline magnesium salicylate (Trilisate). They produce less gastrointestinal irritation, and can be administered less often than aspirin.

When other NSAIDs are indicated

Physicians often prescribe indomethacin (Indocin) as an anti-inflammatory when patients don’t respond well to milder medications such as aspirin. Some patients experience prompt relief from the drug, others may not get any relief for several weeks.

You should caution patients on indomethacin to take the drug with milk or food to prevent GI irritation. Aldo be on guard for visual and renal complications. Patients on long-term regimens need regular eye exams. Elderly patients or others with kidney problems should be closely monitored.

Another potent NSAID, phenylbutazone, is generally given for only seven days at a time to manage acute inflammatory conditions. It’s rarely used for long-term treatment of rheumatoid arthritis because of its high incidence of GI, cardiovascular, hematologic, and cutaneou side effects. Sometimes, physicians will prescribed the drug for longer periods in treating anky-losing spondylitis, a rheumaic disease characterized by back pain and eventual fusion of the spine.

Some other non-steroidal anti-inflammatory drugs are listed on the following page. Several drugs may have to be tried to find the one that’s right for the patient.

For osteoarthritis and other conditions where patients need an analgesic but not an anti-inflammatory agent, aspirin remains the ideal medication. Approximately seven regular-strength tablets–2,300 mg–are given per day, just enough to ease pain. Patients who can’t tolerate aspirin can take acetaminophen.

When neither of these drugs controls the pain, the doctor often prescribes propoxyphene (Darvon). One precaution: Remind patients not to take Darvon with alcohol, tranquilizers, sedatives, or other CNS depressants.

Narcotics are not indicated for arthritis because it’s a chronic disease. Occasionally, patients in severe pain may receive codeine either alone or in combination with aspirin, acetaminophen, or propoxyphene. However, whenever possible, urge your patients to seek non-drug alternatives such as relaxation techniques, biofeedback, or transcutaneous electrical nerve stimulation (TENS).

Anti-rheumatics are the next step

When conservative drug treatment fails to provide adequate relief from the symptoms of rheumatoid arthritis, the physician will usually try anti-rheumatic compounds such as gold stars, D-penicillamine, and hydroxychloropine. They sometimes produce excellent results because they suppress the immune system, thus decreasing the inflammatory response.

Gold salts, for example, can produce dramatic, sustaines, remission. But if the treatment–called chrysotherapy–is discontinued, the inflammation often returns. Two types of injectable gold salts are available: aurothioglucose (Solganal), in an oil suspension, and gold sodium thiomalate (Myochrysine), in a water-soluble formula. Myochrysine may cause a transient effect called nitritoid crisis, that produces dizzines, blurred vision, flushing, joint pain, and occasionally anaphylactic shock. So observe patients for at least one hour after the first injection, and at least 15 minutes after subsequent doses.

A test dose of 10 mg IM is given the first week, followed by 25 mg the second week, then 50 mg the third week. After this, patients receive 25 to 50 mg per week until they improve, which sometimes takes three to six months. Because of this delayed response, other anti-inflammatory drugs are given at the same time.

After patient and doctor observe sustained improvement, the physician gradually reduces the number of injections to once a month. Some physicians wait until a cumulative dose of 1,000 mg is reached before switching to a maintenance program. Be sure to record the dose given after each injection to keep track of the total dosage.

Advise your patient to report rashes, mucosal ulcers, hematuria, and a metallic taste in his mouth because these adverse effects can indicate blood levels of the drug in the toxic range. If the drug is continued, serious complications, including renal damage and bone marrow suppression, can occur.

To monitor these potential dangers, the physician will probably request a urinalysis and CBC before each injection. Check these reports for blood or protein in the urine and for a decreased WBC or platelet count. If test results show abnormal findings, the physician will usually discontinue the drug or lower the dose.

Fortunately, problems usually show up early and disappear when the medication is stopped. With the exception of those experiencing hematologic and renal complications, patients who have reactions can often start taking the drug again later without suffering side effects.

A new oral preparation of gold salts called auranofin (Ridaura) was approved recently by the Food and Drug Administration. It’s expected to have fewer side effects than injectable gold salts.

Another anti-rheumatic agent that helps control the systemic effects of rheumatoid arthritis is D-penicillamine. At first, the doctor prescribes low oral doses–125 to 250 mg daily. Every two to four weeks, he increases the dosage until the therapeutic range is reached. This is usually 750 mg, given in equally divided doses of 250 mg each. Rarely is more than 1,000 mg daily prescribed. Because food, antacids, and ferrous sulfate interfere with the drug’s absorption, it’s best to give it an hour and a half before or after a meal, separated from other drugs by one hour.

Instruct patients to promptly report fever, rash, diarrhea, or ulcers because these may signal a toxic reaction. Watch for hematologic, renal, and cutaneous signs of toxicity by reviewing urinalysis and CBC reports every two to four weeks for proteinuria or a decrease in WBCs and platelets.

Hydroxychloroquine (Plaquenil), an anti-material drug, also has an anti-rheumatic effect. But it’s usually reserved for patients who don’t respond favorably to medications with less serious adverse side effects. Hydroxychlorine can cause rashes, retinopathy, peripheral neuropathy, and leukopenia. These effects usually stop when the drug is discontinued, but retinopathy can be permanent. So, recommend that patients taking the drug have eye examinations every three to six months during therapy to discover problems before they become serious.

Corticosteroids for acute flare-ups

Your patient with rheumatoid arthritis may need corticosteroids to suppress acute systemic inflammation. Prednisone and prednisolone are two drugs often used for this purpose, and they have fewer side effects than other medications.

When giving corticosteroids, the lowest effective dose is the most desirable one. The longer you give the drug, however, the higher the dose needed to get the same therapeutic effect. Higher doses are also needed during emotional trauma and surgery. These increased doses increase risk of toxicity.

Side effects of corticosteroids include GI ulcers, osteoporosis, hyperglycemia, fluid retention, skin lesions, infection, thrombi, and psychosis. Patients on long-term, high-dose therapy are also susceptible to aseptic necrosis–a condition that causes sclerosis and cystic changes in bone, especially the head of the femur.

sometimes, a corticosteroid is injected directly into a joint or its surrounding tissues. The drug can reduce pain and swelling in a severely inflamed joint while you wait for slower-acting drugs to take effect. The corticosteroid is often combined with a local anesthetic and given for RA or osteoarthritis. These injections shouldn’t be repeated in the same joint more than three or four times a year nor given when joint infection, fracture, or severe osteoporosis exists.

Clean the injection site well to avoid introducing bacteria into the joint. The patient will probably experience immediate pain relief, but some complain of increased pain caused by the medication. If this happens, advice the patient to apply ice for 15 minutes every hour for 24 to 48 hours.

Remind all patients who receive an intra-articular injection not to overuse the treated joint just because it feels so much better. Overuse can damage the joint.

Immunosuppressives are a last resort

when other attempts to control severe rheumatoid arthritis fail, drugs such as methotrexate, cyclophosphamide (Cytoxan), azathioprine (Imuran), or chlorambucil (Leukeran) can help. These drugs reduce the patient’s immune response to his disease. Dosages are lower for rheumatoid arthritis than for cancer treatment, so you may see less toxicity than you would in cancer patients. But even so, the side effects can be devastating, and these drugs are still considered experimental. Adverse reactions include malignancy, chromosome damage, infection, and bone marrow suppression.

One other experimental drug worth mentioning is dimethyl sulfoxide, DMSO. Although its effectiveness and safety are still being debated, you may find a number of patients using it as a topical agent because it’s available over the counter as a commercial solvent. Warn patients you suspect of using DMSO–they’ll have a garlic-like breath odor–that in many states the commercial formulas are too concentrated and may contain dangerous impurities.

Patients will use DMSO and other unproven treatmens because they’ve had no relief from traditional treatment. Indeed, all the drug therapy discussed above is aimed at relieving pain, reducing inflammation, and impeding systemic manifestations. There is no one drug that will cure arthritis.

As long as there is no cure, new drugs will be developed to treat the symptoms. And they’ll be heralded in the news media as the latest miracle cure, raising false hope for the millions of arthritis sufferers who live with chronic pain. It’s those patients who need the up-to-date, accurate information that we can provide.

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