arthritis and pain medication

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

Click here: Second Opinion Arthritis Treatment Kit

Dealing with pain can be the hardest part of having arthritis or a related condition, but you can learn to manage it and its impact on your life.

The first step is knowing which type of arthritis or condition you have, because that will help determine your treatment. Before learning different management techniques, however, it's important to understand some concepts about pain.

Just as there are different types of arthritis, there are also different types of pain. Even your own pain may vary from day to day.

Each person needs a pain management plan. What works for one person may not work for someone else. You may need to try several different treatments before you find the one that works for you.

Pain is your body's alarm system that tells you something is wrong. When your body is injured, nerves in the affected area release chemical signals. Other nerves send these signals to your brain, where they are recognized as pain.

Pain often tells you that you need to act. For example, if you touch a hot stove, pain signals from your brain make you pull your hand away. This type of pain helps protect you.

Long-lasting pain, like the kind that accompanies arthritis or fibromyalgia, is different. While it tells you that something is wrong, it often isn't as easy to relieve. Managing this type of pain is essential to enhance your quality of life and sense of well-being.

• Inflammation, the process that causes the redness and swelling in your joints;
• Damage to joint tissues, which results from the disease process or from stress, injury or pressure on the joints;
• Fatigue that results from the disease process, which can make your pain seem worse and harder to handle;
• Depression or stress, which results from limited movement or no longer doing activities you enjoy. You can get caught in a cycle of pain, limited/lost abilities, stress and depression that makes managing pain and arthritis seem more difficult.

People react differently to pain for several reasons. Physical factors include the sensitivity of your nervous system and the severity of your arthritis. Emotional and social factors include your fears and anxieties about pain, previous experiences with pain, energy level, attitude about your condition and the way people around you react to pain.

Many people with arthritis have found that by learning and practicing pain management skills, they can reduce their pain.

• Increased disease activity
• Stress
• Overdoing physical activity
• Focusing on pain
• Fatigue
• Anxiety
• Depression

What can reduce pain?

• Positive attitude and pleasant thoughts
• Appropriate exercise
• Relaxation
• Medications
• Massage
• Distraction
• Topical pain relievers
• Humor
• Heat and cold treatments

Pain signals travel through a system of nerves in your brain and spinal cord. At times, your body tries to stop these signals by creating chemicals that help block pain signals. These chemicals, called endorphins, are morphine-like painkilling substances that decrease the pain sensation.

Different factors cause the body to produce endorphins. One example is your own thoughts and emotions. For example, a father who is driving his children is hurt in a car accident. He is so worried about his children that he doesn't feel the pain of his own broken arm. The concern for his children has caused the natural release of endorphins, which block the pain signal and prevent him from noticing the pain.

The body also produces endorphins in response to external factors, such as medicine. Codeine is one example of a powerful pain-blocking medication. Other external pain control methods, such as heat and cold treatments, can stimulate the body to either release endorphins or block pain signals in other ways.

Here are some important medicine groups that are used to treat arthritis pain:

Analgesics are drugs that relieves pain. There are many types of pain medications. Some pain medications are actually combinations of drugs that work together to relieve pain. Some pain medications are available over-the-counter (without a prescription), such as aspirin, acetaminophen, ibuprofen, and naproxen, or with a prescription, such as the narcotics oxycodone, propoxyphene, and codeine. Narcotic pain relievers can be habit-forming.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of drugs commonly used to treat arthritis because of their analgesic (pain-killing), anti-inflammatory, and antipyretic (fever-reducing) properties. The mechanism of action of NSAIDs is the inhibition of the enzyme cyclooxygenase, which catalyzes arachidonic acid to prostaglandins and leukotrienes. Arachidonic acid is released from membrane phospholipids as a response to inflammatory stimuli. Prostaglandins establish the inflammatory response.

inflammatory stimuli (disease, trauma)---->membrane phospholipids release arachidonic acid--->cyclooxygenase catalyzes arachidonic acid to prostaglandins and leukotrienes---->prostaglandins create an inflammatory response

Scientific studies have shown a correlation between concentration of the drug and effect, but do not explain the differences in individual patient responses. It is thought that the pharmacokinetic (process by which a drug is absorbed, distributed, metabolized, and eliminated) differences among the various NSAIDs may account for the variability in response.

• Pain and inflammation sometimes occur in a circadian rhythm (daily rhythmic cycle based on a 24 hour interval). Therefore NSAIDs may be more effective at certain times.
• NSAIDs are divided into two groups: those with plasma (blood) half-lives less than 6 hours (i.e. aspirin, diclofenac, ibuprofen) and those with half-lives greater than 10 hours (i.e. diflunisal, piroxicam, and sulindac). Since it takes three to five half-lives to stabilize blood levels, NSAIDs with longer half-lives require a loading dose to be given (large dose given initially). The "half-life" is the time it takes a drug to go down to half of its initial level.
• Prostaglandins, which are inhibited by NSAIDs, function in the body to protect the stomach lining, promote clotting of the blood, regulate salt and fluid balance, and maintain blood flow to the kidneys when kidney function is reduced. By decreasing prostaglandins, NSAIDs can cause stomach irritation, bleeding, fluid retention, and decreased kidney function.
• Synovial fluid (joint fluid) concentrations are 60% of plasma concentrations regardless of type of NSAID or its half-life. Synovial fluid is mostly the site of action of NSAIDs.
• NSAIDs are 95% albumin (protein) bound. The unbound fraction of the NSAID is increased in patients with low albumin concentrations such as in active rheumatoid arthritis and the elderly.
• Since NSAIDs bind to plasma proteins they may be displaced by or may displace other plasma-bound drugs such as coumadin, methotrexate, digoxin, cyclosporine, oral antidiabetic agents, and sulfa drugs. This interaction can enhance either therapeutic or toxic effects of either drug.
• Due to their different chemical properties some NSAIDs have substantial biliary (bile ducts, gallbladder) excretion (i.e. indomethacin , sulindac) and others are metabolized pre-excretion, while a few are excreted in the urine unchanged.
• NSAID studies which have shown a variation in patient response attribute a lower rate of adherence to one NSAID when other NSAIDs are known to be available. The response to and preference of an NSAID may relate to more than just symptom control.
• About 60% of patients will respond to any single NSAID. A trial period of three weeks should be given for anti-inflammatory effectiveness to be observed. About 10% of rheumatoid arthritis patients will not respond to any NSAID.
• A study in the United Kingdom revealed ibuprofen as the lowest risk for causing serious upper gastrointestinal distress. Naproxen, indomethacin, and diclofenac were viewed as an intermediate risk. Azapropazone, and piroxicam had the highest risk.
• Antipyretic and anti-inflammatory effects of NSAIDs can mask the signs and symptoms of infection.
• Adverse effects of NSAIDs which can occur at any time include renal (kidney) failure, hepatic (liver) dysfunction, bleeding, and gastric (stomach) ulceration.
• NSAIDs (particularly indomethacin) can interfere with the pharmacologic control of hypertension and cardiac failure in patients who take beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, or diuretics.
• Long-term use of NSAIDs may have a damaging effect on chondrocyte (cartilage) function.
• Commonly used NSAIDs include: Ansaid, Arthrotec, Aspirin, Cataflam, Clinoril, Daypro, Dolobid, Feldene, Ibuprofen, Indocin, Ketoprofen, Lodine, Meclomen, Mobic, Nalfon, Naproxen, Ponstel, Relafen, Tolectin, and Voltaren.

Glucocorticoids: Glucocorticoids are medications that include cortisone and related drugs. A glucocorticoid is hormone that predominantly affects the metabolism of carbohydrates and, to a lesser extent, fats and proteins (and has other effects). Glucocorticoids are made in the outside portion (the cortex) of the adrenal gland and chemically classed as steroids. Cortisol is the major natural glucocorticoid. The term glucocorticoid also applies to equivalent hormones synthesized in the laboratory. Glucocorticoid drugs are also called corticosteroids.

Corticosteroids have potent anti-inflammatory properties, and are used in a wide variety of inflammatory conditions such as arthritis, colitis, asthma, bronchitis, certain skin rashes, and allergic or inflammatory conditions of the nose and eyes. There are numerous preparations of corticosteroids including oral tablets, capsules, liquids, topical creams and gels, inhalers and eye drops, and injectable and intravenous solutions.

Dosage requirements of corticosteroids vary among individuals and the diseases being treated. In general, the lowest possible effective dose is used. Corticosteroids given in multiple doses throughout the day are more effective, but also more toxic, than if the same total dose is given once daily, or every other day.

Disease-Modifying Antirheumatic Drugs or DMARDs: While "first-line" medications (NSAIDs and corticosteroids) can relieve joint inflammation and pain, they do not necessarily prevent joint destruction or deformity. For patients with an aggressively destructive form of rheumatoid arthritis, medications other than NSAIDs and corticosteroids are needed. These "second-line" or "slow-acting" medicines (listed below) may take weeks to months to become effective. They are used for long periods of time, even years, at varying doses. If effective, they can promote remission, thereby retarding the progression of joint destruction and deformity. Sometimes a number of second-line medications are used together as combination therapy.

Hydroxychloroquine (Plaquenil) is related to quinine, and is used in the treatment of malaria. It is used over long periods for the treatment of rheumatoid arthritis. Side effects include upset stomach, skin rashes, muscle weakness, and vision changes. Even though vision changes are rare, patients taking Plaquenil should be monitored by an eye doctor (opthalmologist).

Sulfasalazine (Azulfidine) is an oral medication traditionally used in the treatment of mild to moderately severe inflammatory bowel diseases, such as ulcerative colitis and Crohn's colitis. Azulfidine is used to treat rheumatoid arthritis in combination with antiinflammatory medications. Azulfidine is generally well tolerated. Common side effects include rash and upset stomach. Because Azulfidine is made up of sulfa and salicylate compounds, it should be avoided by patients with known sulfa allergies.

Gold salts have been used to treat rheumatoid arthritis throughout most of this century. Gold thioglucose (Solganol) and gold thiomalate (Myochrisine) are given by injection, initially on a weekly basis for months to years. Oral gold, auranofin (Ridaura) was introduced in the 1980's. Side effects of gold (oral and injectable) include skin rash, mouth sores, kidney damage with leakage of protein in the urine, and bone marrow damage with anemia and low white cell count. Patients receiving gold treatment are regularly monitored with blood and urine tests. Oral gold can cause diarrhea. Gold is not used by many rheumatologists any longer.

Biological Response Modifiers (BRMs)--also known as Biologic DMARDS (Disease-Modifying Antirheumatic Drugs):: Substances that modify the body's response to infection and disease. The body naturally produces small amounts of these substances. Scientists can produce some of them in the laboratory in large amounts for use in treating cancer, rheumatoid arthritis, and other diseases.

BRMs used in biological therapy include monoclonal antibodies, interferon, interleukin-2 (IL-2), and several types of colony- stimulating factors (CSF, GM-CSF, G-CSF). Interleukin-2 and interferon are BRMs being tested for the treatment of advanced malignant melanoma. Interferon is a BRM now in use to treat hepatitis C.

The side effects of BRM therapy often include flu-like symptoms such as chills, fever, muscle aches, weakness, loss of appetite, nausea, vomiting, and diarrhea. Some patients develop a rash, and some bleed or bruise easily. Interleukin therapy can cause swelling. Depending on the severity of these problems, patients may need to stay in the hospital during treatment. These side effects are usually short-term and go gradually away after treatment stops.

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Arthritis and pain medication