Allopurinol lowers the levels of uric acid in the body. It is available as tablets containing 100 or 300mg of the drug. A maximum daily dose of 600 mg is permissible to maintain the blood uric acid levels below 6 mg/dl. Liquid intake should be more than 2 liters a day. Avoid all forms of alcohol. Allopurinol may sometimes cause hypersensitivity (allergic) reactions such as itchy skin rashes. The risk of hypersensitivity reactions is further increased on concurrent administration of antibiotics such as Ampicillin and Amoxycillin. This adverse effect may be severe and sometimes life-threatening. Allopurinol is therefore started in small doses, and the dose is gradually increased over time. Other adverse effects of Allopurinol include gastrointestinal disturbances, itching of eyes, burning urination, and dizziness. Antacids impair the absorption of Allopurinol. The risk of adverse effects is increased by concurrent administration of anti-hypertensives such as Enalapril and diuretics. The doses of anti-diabetic drug Chlorpropamide and anti-coagulant Warfarin need to be adjusted as Allopurinol increases their efficacy.
Azathioprine is available commercially in the form of 25 mg and 50mg tablets. The usual dose is one 50 mg tablet taken twice a day (for a patient with 50 kg body weight). The dose is initially small and is gradually increased over the next few months. Gastrointestinal disturbances, malaise, fatigue, dizziness, and allergic skin rashes are occasional adverse effects of Azathioprine. It may also cause liver dysfunction, reduction in blood cells, and ecchymoses (bleeding under the skin). Therefore, regular blood tests are advisable while on this drug. This drug does not have any adverse effects on male or female fertility or fetus. Though secreted in breast milk for 2-8 hours after administration, Azathioprine is not reported to have any adverse effects on the breastfed infant.
Alendronate (70mg) and Risedronate (35mg) are administered on an empty stomach once a week. It is advisable to drink plenty of water (one glass – 200 ml) along with the tablet so that it reaches well into the stomach and does not hold up in the food pipe (esophagus). These tablets should never be broken or chewed to avoid drug contact with the food pipe. Further, it is not advisable to eat or lie down at least for half an hour after taking these drugs; instead, one should sit upright or stand up straight and carry out routine chores if required. These precautions must be followed meticulously, lest these drugs can cause severe swelling of the food pipe. Contact your doctor immediately in case of symptoms such as chest pain, heartburn, difficulty in swallowing, and blood in vomit or blackening of stools. These drugs may sometimes cause generalized body pain or unusual fractures of the femur bone. Thus, in case of pain in the groin or thighs, one must contact the doctor immediately. Given their adverse effects on teeth, dental hygiene (brushing twice daily) and regular dental check-ups are essential. If one has to undergo dental surgeries while on Bisphosphonate therapy, the dentist must be fully informed regarding the consumption of these drugs. Moreover, one should contact their dentist immediately in case of heaviness, pain, swelling of the jaw, or loosening of teeth.
Another drug belonging to Bisphosphonates, namely Ibandronate, is administered orally (5mg once a month) or intravenously (once in three months). Zoledronate is administered intravenously once a year. The intravenous route is preferred in patients with gastrointestinal disorders due to the possibility of compromised absorption.
The biological drugs such as Etanercept, Infliximab, Adalimumab, Rituximab, and Tocilizumab, though expensive, are highly effective in patients nonresponsive to conventional medications. These drugs control rheumatoid arthritis by different mechanisms of action, such as suppressing chemical mediators of inflammation (TNF, Interleukin) or modifying B type of lymphocyte cells. Detailed recommendations on their indications and usage have been published by the American College of Rheumatology, European League Against Rheumatism, Indian Rheumatology Association, and other international organizations. These drugs need to be prescribed by a rheumatologist only.
Etanercept is administered like insulin injection once or twice a week. Hospitalization is required for a 2–6-hour intravenous infusion of other drugs. Infection and cancer are significant adverse effects of these biological drugs. It is essential to investigate hidden tuberculosis even in the absence of symptoms, given the high prevalence. One should contact a doctor immediately even if minor symptoms (fever, sore throat, night sweats, burning micturition) appear. These drugs can cause local or generalized allergic reactions. Other adverse effects include loss of appetite, abdominal pain, weight loss, and appearance of nodes in the neck, axilla, or groins. Occasional adverse effects on the nervous system can lead to significant disability.
Large-scale, high-quality research is ongoing for the development of new drugs in rheumatoid arthritis. Various new drugs, though expensive, are now available in the market. Biosimilars, less expensive alternatives to biological medicines, are also available. These drugs are certainly a boon for patients with rheumatoid arthritis who do not respond adequately to standard therapy.
All adults need about 600-800 mg of Calcium every day. Post-menopausal women require around 1000mg of Calcium per day. A routine vegetarian diet along with two cups of milk contains 500 mg of elemental Calcium. A tablet containing 500 mg of elemental Calcium is therefore sufficient to fulfill our daily Calcium requirement. Excessive calcium intake leads to the accumulation of Calcium in the blood vessels. It increases the risk of heart attacks and stroke. Drugs suppressing gastric acid (Omeprazole, Pantoprazole) hamper the breakdown and absorption of Calcium by decreasing acid in the stomach. Diuretics (drugs increasing urine output) increase the calcium levels in our body. Calcium impairs the absorption of certain antibiotics (such as Ciprofloxacin, Tetracycline, etc.), Thyroxine, and iron from the gut. Calcium tablets should be taken along with food. Excessive intake of fibrous foods, such as green leafy vegetables in the diet decreases Calcium absorption. Various Calcium salts are available in the market. Of these, Calcium Carbonate is the least expensive and equally effective. Other Calcium compounds such as citrate maleate (possibly fewer chances of kidney stones), orotate, etc., are costlier and do not have any significant advantages over Calcium carbonate. The adverse effects of Calcium supplements include gastrointestinal disturbances and constipation. Iron supplements also cause constipation. Some patients do not tolerate simultaneous administration of Calcium and iron as they develop severe constipation with this combination. Calcium impairs the absorption of iron. Hence, it is advisable to take Calcium and Iron at least two hours apart.
Colchicine is the first-line drug used to treat inflammation due to the deposition of uric acid and other crystals in joints or other areas of the body. One tablet of Colchicine (0.5mg) should be taken immediately at the onset of pain. One more tablet can be taken after an hour or so. A maximum of eight tablets can be taken in a day. Some patients may experience diarrhea due to Colchicine. If used with other anti-inflammatory painkillers, just two pills a day may suffice. Colchicine needs to be continued in the dose of 2 tablets a day for 1-2 months after control of inflammation to avoid recurrence. Colchicine acts as an anti-inflammatory agent; it does not decrease the levels of uric acid. In case one misses a dose, that dose should be taken as soon as remembered. Colchicine has various adverse effects such as gastrointestinal disturbances, diarrhea, fatigue, numbness of limbs, and muscle pains (rare). Special precautions should be taken while administering Colchicine along with antibiotics such as Azithromycin and Fluconazole and cholesterol-lowering drugs such as Atorvastatin.
Cyclophosphamide is a highly effective drug administered intravenously every 2-4 weeks for 3-6 months. It may be prescribed for a longer duration in some patients. The dose varies from patient to patient according to the intensity of the disease. Cyclophosphamide injections may have immediate adverse effects such as allergic rashes, redness of skin (especially face), nasal stuffiness, vomiting, and diarrhea. Over time, loss of appetite, weight loss, darkening of nails and skin may develop in some patients. Some of these adverse effects, however, are controllable. Hair loss may occur after 3-6 weeks of therapy. However, hairs grow again once the drug is stopped. Suppression of bone marrow due to this drug leads to a reduction in various types of circulating blood cells. However, the cell counts normalize over the next two weeks. The next dose is reduced if cell counts do not normalize.
Cyclophosphamide is excreted through the kidneys (urine). Therefore, it is advisable to drink plenty of water (2-4 liters daily) and urinate every two hours at least two days before and after Cyclophosphamide injection to ensure proper excretion of the drug. Adequate water intake prevents the accumulation of the drug in the urinary bladder and averts the risk of bladder cancer. MESNA (2-Mercaptoethane sulfonate sodium) is administered along with to prevent bladder cancer. Gonadal suppression occurs after eight weeks of therapy. However, it normalizes in 90% of young patients on stopping the drug. Conception is contraindicated while on this drug and can be attempted four months after stopping the drugs. Breastfeeding, too, is not allowed. High doses of Cyclophosphamide may cause bloody stools, various cancers, swelling, and heart dysfunction. Smoking is strictly prohibited as it further increases the risk of cancers due to Cyclophosphamide.
Cyclophosphamide is also available in the form of 50 mg tablets. However, the maximum dose of 9 gm (i.e., two pills a day for three months) should not be exceeded as it increases the possibility of adverse effects. Therefore, intravenous administration is preferable because of rapid action and fewer adverse effects due to lower cumulative dose.
Cyclosporine and related drugs such as Tacrolimus are also expensive. Cyclosporine is available commercially in the form of 25, 50, and 100 mg capsules. It is administered up to 125 mg or more per day. Fatty substances such as ghee, oil, etc., enhance the absorption of Cyclosporine. Hypertension, an adverse effect seen in some cases, can be easily controlled by the administration of anti-hypertensive drugs. Anemia, swelling of gums, and unwanted hair growth may be seen in some patients. Darkening of skin, headache, tremulousness, bone pains are other adverse effects of Cyclosporine. It may also cause increased uric acid levels and kidney dysfunction. Hence, this drug should always be taken as prescribed by a specialist physician. Regular blood testing is mandatory.
This drug has the same mechanism of action as Allopurinol. It is generally used in patients with compromised kidney function. The initial dose of Febuxostat is 40-80 mg which may be gradually increased up to 160mg as the need be. Though Febuxostat has relatively lesser adverse effects, regular blood check is advisable for liver function. Febuxostat appears to be safer than Allopurinol in older people and patients with kidney disease.
Both Allopurinol and Febuxostat help in controlling uric acid levels; they do not cure the disease. Therefore, life-long treatment with these drugs is inevitable to maintain optimum blood uric acid levels.
Febuxostat tablet: 40 mg, 80mg
Quinine, earlier used in malaria, was obtained from the Cinchona bark. Hydroxychloroquine, a related compound, is presently used to reduce inflammation in arthritis. In addition, it lowers blood lipids and averts the development of diabetes to some extent. Moreover, it prevents the clotting of blood and reduces the risk of heart attacks. In combination with methotrexate, it protects from acute liver injury. Hydroxychloroquine should be taken at night, and prolonged exposure to sunlight be avoided to avoid pigmentation (darkening) of skin.
Furthermore, it should be taken after food to prevent hyperacidity. Prolonged use can affect eyes in the form of irritation of eyes, blurring of vision, altered vision, difficulty in focusing eyes, double vision, halos around lights, inability to see a part of an object, inability to move eyes, etc. It is, therefore, necessary for patients on hydroxychloroquine to visit an Ophthalmologist for the field of vision and other tests every 12 months. In animal experiments, the efficacy of Chloroquine (the precursor of hydroxychloroquine) increases if consumed along with the juice of neem leaves.
Hydroxychloroquine tablet: 200 /300/ 400 mg
Leflunomide is another important drug used in inflammatory arthritis. The tablet of Leflunomide is administered every day. The effects of the drug can be seen only after 3-5 months of continuous administration. Pregnancy is not allowed while taking this drug. The drug remains in our body for about two years after its discontinuation. Patients on Leflunomide desirous of conception can attempt so after an 11- day detoxification using Cholestyramine. Minor adverse effects of Leflunomide include hyperacidity and gastric upsets. The significant adverse effects include weakness, weight loss, high blood pressure, tingling and numbness of limbs, and vasculitis (inflammation of small blood vessels) rashes, especially on legs. Consumption of alcohol must be avoided because of the adverse effects of Leflunomide on the liver. Leflunomide, therefore, must be used under the supervision of an expert physician.
Leflunomide tablet: 10, 20 mg
Methotrexate, the primary drug in rheumatoid arthritis, shows its effects after about 2-3 months. Methotrexate is used in large doses in cancer treatment. A small weekly dose of 7.5 to 25 mg is sufficient in the management of rheumatoid arthritis. Methotrexate should never be taken every day. One should select any weekday and take the drug on that particular day without fail. Folic acid needs to be taken along with (at least 24 hours apart) methotrexate to avoid its adverse effects. Multivitamin tablets should also be avoided on the methotrexate day as most of them contain folic acid. Injection of Methotrexate causes less gastric upset and has the advantage of being effective in a lesser dose. Some antibiotics, theophylline (used in asthma), and a few other drugs need supervision if administered along with methotrexate. Methotrexate causes loss of appetite, swelling of gums, glossitis, reduced white blood cells, and liver dysfunction in some patients. It is, therefore, mandatory to check blood repeatedly as advised by the doctor. These adverse effects can be easily reversed by stopping the drug and giving an additional dose of folic acid. Once stabilized, methotrexate can be restarted in a lower dose. Methotrexate does not cause any adverse effects on the lungs. However, methotrexate suppresses immunity and increases the risk of cancer and infections such as herpes zoster and tuberculosis to a small extent. Consumption of alcohol must be avoided given the adverse effects of methotrexate on the liver.
Methotrexate tablet: 2.5, 5, 7.5, 10, 12.5, 15 mg.
Injection: 15 mg/ml ampoule, 25 mg/ml vial 2ml (50 mg)
Methotrexate Injection (once a week)
Methotrexate injection is administered with an insulin syringe on the thigh or abdomen.1 ml of liquid contains 25 mg of Methotrexate. The 1 ml insulin syringe is calibrated for 40 units which means that every four units of fluid contain 2.5 mg of methotrexate. Fill the insulin syringe according to the prescribed dose. Then, clean the skin with spirit or iodine. Hold your skin between your thumb and index finger (as if pinching). Insert the needle in an oblique direction and pull back the piston to confirm that the needle is not in any blood vessel. Inject the drug and remove the needle. Press for a while with the swab to stop bleeding, if any. This injection is almost painless as the needle is very thin. The injection is to be taken just once a week, whereas patients with diabetes take the injection one or more times every day.
Mycophenolate mofetil is available as a 500 mg tablet and is administered in two divided doses up to a maximum of 3 grams a day. It should ideally be taken on an empty stomach. Conception is not advisable while taking Mycophenolate. The drug must be stopped at least three months before conception. However, breastfeeding is safe. Adverse effects include gastrointestinal disturbances such as diarrhea, headache, generalized body pain, allergic rashes, and disturbed sleep. Progressive multifocal leukoencephalopathy is a serious adverse effect of this drug. The intensity of adverse reactions is directly proportional to the dose of this drug. Therefore, regular blood tests are a must while on Mycophenolate therapy.
Aspirin and Paracetamol (Crocin) are the drugs that reduce pain though they do not reduce inflammation in arthritis. The use of aspirin is less common due to its side effects, such as hyperacidity. Paracetamol is much safer and is available worldwide without a prescription. Paracetamol can be consumed up to 2-3 grams a day in 3-4 divided doses since its effect lasts for about 6-8 hours. Controlled release preparation is also available, which can be consumed twice daily. Paracetamol is a constituent of cough-cold remedies. Hence simultaneous use of these drugs can lead to overdosage of Paracetamol. Paracetamol can occasionally cause hyperacidity. Overdose can lead to liver toxicity manifesting as jaundice.
Paracetamol Tablet: 500, 650 mg; Controlled release tablet: 650, 1000 mg
This drug is from the sulfa group and may cause skin hypersensitivity in the form of itching, redness, and rashes. It is therefore started in a low dose which is gradually increased over few weeks. One should not worry about yellowish-orange discoloration of urine and tears due to the excretion of the drug in these fluids. The use of contact lenses should be avoided as they too may get discolored. The drug may cause stomach upset, loss of appetite and sometimes affect the liver and white blood cells. It is necessary to take folic acid along with sulfa drugs.
Sulphasalazine tablet (Sustained release): 500 and 1000 mg
Steroids (Glucocorticoids) are produced naturally in our body. Hydrocortisone, Prednisolone, Methylprednisolone, Betamethasone, and Deflazacort are the various synthetic compounds belonging to steroids. These drugs usually act for a prolonged period; for instance, a single dose of Prednisolone acts for one full day (18-25 hours), whereas, Betamethasone acts for almost two days (36-54 hours). Betamethasone, if administered daily, keeps on accumulating in our body, and hence the use of Betamethasone tablets should be discouraged. Steroids in our body are secreted in a cyclical pattern – their levels being highest at 8 am, leading to enthusiasm and freshness. Prednisolone should be administered at around 8 am after breakfast to coincide with this natural steroid cycle. The dose of Prednisolone can be small (up to 10 mg/day), medium (up to 30 mg/day), or more, depending on the severity of the disease. Apart from arthritis, steroids are also used to treat asthma, ulcerative colitis, skin diseases, allergies, kidney disorders, cancer, encephalitis, and many other conditions. These drugs have proven saving in many critically ill patients.
Steroids rapidly control inflammation associated with rheumatic conditions, thereby preventing joint damage. Pain also decreases due to control of inflammation. Guidelines for the safe use of steroids can be found in various Rheumatology textbooks and recommendations of various national and international associations. Steroids are used only in small doses for controlling rheumatoid arthritis. Methotrexate, the mainstay of drug treatment in rheumatoid arthritis, is effective only after 2-3 months. The risk of irreversible joint damage due to swelling is high during this period. The use of steroids, therefore, is inevitable during this period to prevent further joint damage. As the severity of the condition decreases, so does the dose of steroids. In most cases, the use of steroids can be stopped entirely once the disease is under control.
Proper care must be taken while using other drugs during steroid therapy. The doses of certain antibiotics, oral contraceptives, psychotherapeutic agents, and medications used in heart disease, blood pressure, and diabetes need to be altered if they are to be administered concurrently with steroids. The powder for arthritis available in the market appears to contain steroids. It should not be taken along with the drugs mentioned above. Limited use of salt in daily diet will prevent weight gain and a rise in blood pressure due to water retention in the body. Steroids should not be suddenly stopped if taken for more than three weeks. The dose is gradually tapered in such cases. Abrupt stopping of steroids can lead to disease flare. The dose of steroids is required to be slightly increased in patients undergoing surgery to alleviate the stress of operation.
Prolonged use of steroids has various adverse effects (refer box). A long list of such effects can discourage a patient from using steroid drugs. However, the use of steroids in small doses is not as dangerous as perceived by a layman. Non-steroidal anti-inflammatory painkillers are more harmful than steroids. It is just the stigma with steroids that leads to all the misconceptions about their use. Steroids in proper doses for an optimum period are, in fact, a boon for arthritis patients.
Adverse effects of prolonged use of steroids
- Loss of appetite, gastric disturbances, vomiting, hyperacidity, intestinal ulcers(rare)
- Thinning and dryness of skin, pimples (acne), reddish-purple discolored patches on the skin, stretch marks on hands, abdomen, chest, and thighs
- Hair loss, unwanted hair
- Moon face (deposition of fat on face), fat deposition on shoulders, abdomen, thighs, etc.
- Increase in blood levels of lipids (cholesterol and other fats), sugar and sodium, thus, increased risk of diabetes and hypertension
- Weakening of bones leading to increased risk of fractures, necrosis of thigh or other bones due to the compromised blood supply, and consequent loss of joint function
- Fatigue, muscle weakness – weakness of thigh muscles leading to inability to get up from sitting
- Increased risk of clot formation in the blood vessels, which may cause complete blockage of a blood vessel
- Masking of symptoms of infections leading to difficulty in early diagnosis, delayed healing of wounds, increased susceptibility to infections (common cold, flu, fever, etc. are frequent) due to a compromised immune system
- Cataract and glaucoma in the eyes
- Irregular menses, lethargy, lack of enthusiasm, sleeplessness, disturbed sleep, restlessness, agitation, confusion, mood swings, depression, suicidal tendency
- Growth retardation if used in large doses in children
- Dependence and addiction
Injections of steroids in joints:
Localized steroid injection in or around the joint is an important treatment for all kinds of arthritis. An intra-joint injection is comparable to an application of cream over a skin rash, except that injection becomes necessary because inflammation is inside the joint. It may so happen that a single joint remains swollen despite good disease control. In such cases, it is pragmatic to give a localized injection in such a joint instead of increasing the dose of drugs or adding a new drug. These injections can be administered in small or large joints alike. Inflammatory flares in osteoarthritis (disease of wear and tear) lead to inflammation and swelling due to fluid accumulation in the joint. Steroid injection in such cases is preceded by the removal of fluid from the joint. Such fluid aspiration along with steroid injection alleviates pain at least for about 3-4 months. A decrease in pain facilitates exercise, which in turn strengthens muscles of the joint.
Fluid may accumulate in a bursa (fluid-filled sac) around a joint (bursitis) or in and around the tendons (fibers joining muscles to bones) near a joint (tendonitis). In these cases, too, local steroid injections are helpful. These injections may also help for diagnostic purposes, as in gout or septic arthritis cases, where fluid needs to be withdrawn for testing the presence of uric acid crystals or organisms, respectively.
The steroid injected in joints is not absorbed to any significant extent in our body. Thus, systemic adverse effects such as hyperacidity and diabetes can be averted. Joint injections are frequently used in children with joint swellings. The injection site is sterilized to avoid the risk of infection and anesthetized to reduce pain during injection. No post-procedure care is needed except avoidance of overuse for 24 hours following injection.
Joint injections are not used in unstable or deformed joints, septic arthritis, risk of fractures, and blood clotting disorders. Rarely (1 in 1500 cases) intra-articular injections may be followed by sepsis. Depigmentation may sometimes occur at the site of injection. However, it disappears with time, and the skin becomes normal after a few months. The skin may thin out in some cases. Steroid crystals can trigger a sudden swelling and severe pain immediately after injection. In these cases, a good painkiller and ice-pack are helpful. However, it is advisable to contact your doctor immediately if the joint becomes warm and reddish with intense pain and fever two-three days after injection.
Endorphins are opium-like chemicals that are normally present in our body. Opiate drugs can thus be effectively used for pain relief. Tramadol is a very mild opiate with a unique mode of action. Combined use of Paracetamol and Tramadol is more effective and less harmful. Dizziness, nausea, and headache are some of the side effects that can be more pronounced during the initial days of usage of Tramadol. However, such side effects can be managed with symptomatic treatment. One should avoid driving during the initial few days of Tramadol usage. Alcohol should be avoided as it increases the adverse effects of Tramadol.
Codeine (a constituent of cough suppressant syrups), Oxycodone, Buprenorphine are other opiate painkillers. Some of these prescription drugs are very cheap. However, constipation and the possibility of addiction and tolerance (body becoming used to the drug necessitating increasing dose over time) are important concerns about these drugs.
Tramadol tablet: 50 mg; Controlled release tablet: 100 mg
The daily requirement of Cholecalciferol (Vitamin D3) is 800-1000 IU. It is quite inexpensive and commercially available as powder or granules (60000 IU) administered with water or milk. Fatty substances such as ghee, cream, butter enhance the absorption of Vitamin D. Injections containing 600,000 IU of vitamin D3 are also available. Calcitriol, an expensive form of Vitamin D, is needed only in patients with kidney or parathyroid diseases. Therefore, calcium supplements need to be administered along with Vitamin D. Hypervitaminosis D (excess Vitamin D in the body) can cause headaches, excessive sweating, increased thirst, weakness, fatigue, diarrhea, increased urination (diuresis), and weight loss.