Drug Treatment Of Gout


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Drug Treatment Of Gout

  1. 1. DRUG TREATMENT OF GOUT Prof. Dr. Shah Murad [email_address]
  2. 3. GOUT <ul><li>also called crystal-induced arthritis , is an arthritic condition that occurs when uric acid crystals accumulate in the joints. </li></ul><ul><li>Gout usually affects the large joint of the big toe, but can also affect other joints, such as the knee, ankle, foot, hand, wrist and elbow. </li></ul><ul><li>In rare cases, it may later affect the shoulders, hips or spine. </li></ul><ul><li>Gout does not spread from joint to joint. </li></ul>
  3. 4. <ul><li>Uric acid is a substance that normally forms when the body breaks down waste products (called purines). </li></ul><ul><li>Uric acid is usually dissolved in the blood and passes through the kidneys into the urine. </li></ul><ul><li>For people with gout , the uric acid level in the blood is so high that uric acid crystals form and deposit in joints and other tissues. This causes the joint lining to become inflamed, resulting in sudden and severe attacks of pain, tenderness, redness and warmth. </li></ul>
  4. 5. <ul><li>After several years, the crystals can build up in the joints and surrounding tissues, forming large deposits, called tophi. </li></ul><ul><li>Tophi look like lumps under the skin and are often found in or near severely affected joints, on or near the elbow, over the fingers and toes, and in the outer edge of the ear. </li></ul>
  5. 6. <ul><li>Another condition, called pseudogout, is caused by deposits of calcium-based (instead of urate-based) crystals in the joints. </li></ul>
  6. 7. Although the exact cause is unknown, gout may be caused by <ul><li>genetic defect in metabolism, which causes overproduction and retention of uric acid </li></ul><ul><li>kidney impairment that prevents normal elimination of uric acid </li></ul><ul><li>thiazide diuretic medications (water pills) used to treat high blood pressure and heart failure </li></ul><ul><li>diseases of the blood cells and blood-forming organs, certain cancers and psoriasis </li></ul><ul><li>environmental factors, such as obesity , alcohol abuse and a purine-rich diet. </li></ul>
  7. 8. An episode of gout can be triggered by: <ul><li>drinking too much alcohol </li></ul><ul><li>eating too much of the wrong foods </li></ul><ul><li>surgery </li></ul><ul><li>sudden, severe illness </li></ul><ul><li>crash diets </li></ul><ul><li>injury to a joint </li></ul><ul><li>chemotherapy . </li></ul>
  8. 9. Symptoms of Gout <ul><li>Gout generally occurs in four (4) stages (asymptomatic, acute, intercritical and chronic) and has the following signs and symptoms: </li></ul><ul><li>(1)Asymptomatic stage - urate levels rise in the blood, but produces no symptoms </li></ul>
  9. 10. <ul><li>(2) Acute stage - symptoms usually lasting five to 10 days </li></ul><ul><li>sudden attack of joint pain </li></ul><ul><li>swelling </li></ul><ul><li>joints feel hot, tender and look dusty red or bruised </li></ul>
  10. 11. <ul><li>Intercritical stage - symptom-free intervals between gout episodes. </li></ul><ul><li>Most people have a second attack from six months to two years, while others are symptom-free for five to 10 years </li></ul>
  11. 12. (4) Chronic stage <ul><li>persistently painful joints with large urate deposits in the cartilage, membranes between the bones, tendons and soft tissues </li></ul><ul><li>skin over the deposits develop sores and release a white pus </li></ul><ul><li>joint stiffness </li></ul><ul><li>limited motion of affect joint </li></ul>
  12. 13. Diagnosis of Gout <ul><li>The diagnosis of gout is based on symptoms, blood tests showing high levels of uric acid, and the finding of urate crystals in joint fluid. </li></ul><ul><li>In chronic gout, x-rays show damage to the cartilage and bones. </li></ul>
  13. 14. MANAGEMENT <ul><li>Proper diet </li></ul><ul><li>Avoid or restrict foods high in purine (a substance that produces uric acid when broken down). </li></ul><ul><li>These foods include: brains, liver, kidneys, tripe, sweetbreads, tongue, shellfish (mussels and oysters), fish roe, scallops, peas, beans and an excessive amount of red meat. </li></ul><ul><li>Drink 10 to 12 eight-ounce glasses of non-alcoholic fluids daily. </li></ul>
  14. 15. <ul><li>Healthy lifestyle </li></ul><ul><li>Reduce alcohol consumption </li></ul><ul><li>Lose weight </li></ul>
  15. 16. <ul><li>Using medications for gout can be complicated, because the treatment needs to be tailored for each person and may need to be changed from time to time. </li></ul><ul><li>To relieve the pain and swelling of an acute attack, the doctor may prescribe nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, corticosteroid drugs, and/or adrenocorticotropic hormone (ACTH). </li></ul>
  16. 17. <ul><li>To prevent future attacks , the doctor may recommend colchicine, probenecid (Benemid, Parbenem or Probalan), sulfinpyrazone (Anturane), or allopurinol (Lopurin, Zurinol or Zyloprim). </li></ul><ul><li>To prevent or treat tophi , probenecid, sulfinpyrazone and allopurinol are recommended. </li></ul>
  17. 18. SPECIFIC DRUGS for Gout <ul><li>non-steroidal anti-inflammatory drugs (NSAIDS) </li></ul><ul><li>colchicine </li></ul><ul><li>corticosteroids </li></ul><ul><li>adrenocorticotropic hormone (ACTH) </li></ul><ul><li>allopurinol </li></ul><ul><li>probenecid </li></ul><ul><li>sulfinpyrazone </li></ul>
  18. 19. Colchicine
  19. 20. COLCHICINE <ul><li>It is used to treat acute flares of gouty arthritis and to prevent recurrent acute attacks. </li></ul><ul><li>Colchicine does not cure gout or take the place of other medicines that lower the amount of uric acid in the body. </li></ul><ul><li>It prevents or relieves gout attacks by reducing inflammation. </li></ul><ul><li>Colchicine may be used in 2 ways: some people take small amounts of it regularly for months or years, while others take large amounts of colchicine during a short period of time (several hours). </li></ul>
  20. 21. <ul><li>Colchicine, an alkaloid is identified as a tricyclic alkaloid, and it has pain-relieving and anti-inflammatory effects for gout which are linked to its ability to bind with tubulin . </li></ul>
  21. 22. <ul><li>Colchicine inhibits microtubule polymerization by binding to tubulin , one of the main constituents of microtubules . </li></ul><ul><li>Availability of tubulin is essential to mitosis , and therefore colchicine effectively functions as a &quot;mitotic poison&quot; or spindle poison </li></ul>
  22. 23. <ul><li>colchicine also inhibits neutrophil motility and activity, leading to a net anti-inflammatory effect. </li></ul><ul><li>Colchicine also inhibits uric acid ( urate ) crystal deposition, which is enhanced by a low pH in the tissues, probably by inhibiting oxidation of glucose and subsequent lactic acid production in leukocytes. </li></ul><ul><li>The inhibition of uric acid crystals is a vital aspect on the mechanism of gout treatment. </li></ul>
  23. 24. <ul><li>Pharmaceutical companies have developed a combination therapy to treat constipation-predominant irritable bowel syndrome which combines colchicine with the anti-inflammatory drug olsalazine . </li></ul>
  24. 25. <ul><li>Long term (prophylactic) regimens of oral colchicine are absolutely contraindicated in patients with advanced renal failure (including those on dialysis). </li></ul><ul><li>10-20% of a colchicine dose is excreted unchanged by the kidneys. </li></ul><ul><li>Colchicine is not removed by hemodialysis. </li></ul><ul><li>Cumulative toxicity is a high probability in this clinical setting. A severe neuromyopathy may result. The presentation includes a progressive onset of proximal weakness, elevated creatine kinase, and sensorimotor polyneuropathy. </li></ul>
  25. 26. <ul><li>Colchicine toxicity can be potentiated by the concomitant use of cholesterol lowering drugs (statins, fibrates). </li></ul><ul><li>This neuromuscular condition can be irreversible (even after drug discontinuation). </li></ul><ul><li>Accompanying dementia has been noted in advanced cases. </li></ul>
  26. 27. <ul><li>Other Side effects include gastro-intestinal upset and neutropenia . </li></ul><ul><li>High doses can also damage bone marrow and lead to anemia . </li></ul><ul><li>Note that all of these side effects can result from hyper-inhibition of mitosis </li></ul>
  27. 28. Toxicity <ul><li>Colchicine poisoning has been compared to arsenic poisoning: symptoms start 2 to 5 hours after the toxic dose has been ingested and include burning in the mouth and throat, fever , vomiting , diarrhea , abdominal pain and kidney failure . </li></ul><ul><li>These symptoms may set in as many as 24 hours after the exposure. Onset of multiple-system organ failure may occur within 24 to 72 hours. This includes hypovolemic shock due to extreme vascular damage and fluid loss through the GI tract , which may result in death. </li></ul>
  28. 29. <ul><li>Additionally, sufferers may experience kidney damage resulting in low urine output and bloody urine; low white blood cell counts (persisting for several days); anemia ; muscular weakness; and respiratory failure . </li></ul><ul><li>Recovery may begin within 6 to 8 days. There is no specific antidote for colchicine, although various treatments do exist </li></ul>