Nsai ds 2010


Published on

Published in: Health & Medicine
  • Be the first to comment

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Nsai ds 2010

  2. 2. NSAIDs OR (Non-narcotic analgesics or non-opioid analgesics) <ul><li>Analgesic </li></ul><ul><li>Anti-pyretic </li></ul><ul><li>Anti-inflammatory </li></ul><ul><li>Antirheumatic </li></ul><ul><li>Anti-uricosuric </li></ul>
  3. 3. differ from opioid analgesics in several respects <ul><li>Effective only in superficial pain of somatic origin but not of deep visceral pain </li></ul><ul><li>Effective in pain of low to moderate intensity. </li></ul><ul><li>Cause respiratory depression only in very high doses. </li></ul><ul><li>Have no abuse liability. </li></ul>
  4. 4. Very common drugs as OTC sale <ul><li>Ponston </li></ul><ul><li>Paracetamol </li></ul><ul><li>Aspirin </li></ul><ul><li>Dispirin </li></ul><ul><li>Voren </li></ul><ul><li>Brufen </li></ul>
  5. 5. <ul><li>Block cyclo-oxygenase pathway of arachedonic acid origin in cell membrane </li></ul><ul><li>Block lipo-oxygenase pathway of AA origin </li></ul>
  6. 6. Shared toxicities due to inhibition of PG synthesis <ul><li>Gastric mucosal damage </li></ul><ul><li>Bleeding due to inhibition of platelet function </li></ul><ul><li>Limitation of renal blood flow: Na+ and water retention </li></ul><ul><li>Delay/prolongation of labor </li></ul><ul><li>Asthma and anaphylactic reaction in susceptible individuals </li></ul>
  7. 7. Uses/Indications <ul><li>As analgesic: Headache, toothache, myalgia. </li></ul><ul><li>As antipyretic. Effective in fever of any origin. </li></ul><ul><li>Acute rheumatic fever. Dose 4-6g/day </li></ul><ul><li>Rheumatoid arthritis. Dose 3-5g/day </li></ul><ul><li>Osteoarthritis </li></ul>
  8. 8. <ul><li>Post myocardial infarction and post stroke patients. Aspirin inhibits TXA2 synthesis in platelets. </li></ul><ul><li>Pregnancy induced hypertension and pre-eclampsia – imbalance between TXA2 and PGI2. </li></ul><ul><li>Patent ductus arteriosis. Aspirin can bring about closure </li></ul>
  9. 9. Individual Characteristics <ul><li>Aspirin displaces warfarin, naproxen, phenytoin, sulphonyl ureas, and methotrexate from plasma protein binding sites; toxicity of these drugs may occur. </li></ul><ul><li>Its anti-platelet action increases the risk of bleeding in patients on oral anti-coagulants. </li></ul>
  10. 10. <ul><li>Aspirin inhibits tubular secretion of uric acid, at low doses and antagonizes uricosuric action of probenecid. </li></ul>
  11. 11. Interactions <ul><li>Aspirin decreases the diuretic action of furosemide and thiazides and blocks the action of spironolactones. </li></ul>
  12. 12. Pharmacokinetics <ul><li>Aspirin is absorbed from stomach and intestine. </li></ul><ul><li>Its poor water solubility is the limiting factor in its absorption. </li></ul><ul><li>Microfining the drug and inclusion of an alkali (solubility is more at higher pH) enhances absorption. </li></ul>
  13. 13. <ul><li>However, higher pH also favours ionization thus decreasing the diffusible form. (>>>>>>> aspirin is acidic drug so remain unionized in acidic medium like in STOMACH >>>>>> so >>>>>>> is absorbed more in stomach than intestine >>>>> and so it causes acidity/gastric ulcer) </li></ul>
  14. 14. Metabolism <ul><li>Aspirin is deacetylated in liver and plasma. </li></ul><ul><li>It is conjugated with glycine and with glucoronic acid. </li></ul>
  15. 15. Adverse Effects of Aspirin <ul><ul><li>Hypersensitivity: Infrequent; urticaria, angioedema, anaphylactic reaction. </li></ul></ul>
  16. 16. <ul><ul><li>Side-effects that occur at analgesic dose (0.3-1.5g/day) are nausea, epigastric distress, increased occult blood loss in the stools, peptic ulceration. </li></ul></ul>
  17. 17. <ul><ul><li>Anti-inflammatory doses (3-6g/day) produce the syndrome called ‘salicylism’ – dizziness, tinnitus, vertigo, excitement, hyperventilation, electrolyte imbalance. </li></ul></ul><ul><ul><li>In children having viral infections (vericella, influenza), salicylate therapy may cause ‘Reye’s syndrome’ (hepatic encephalopathy) </li></ul></ul>
  18. 18. Acute salicylate poisoning <ul><ul><li>It is more common in children, manifestations are : </li></ul></ul><ul><ul><li>vomiting, dehydration, acidotic breathing, electrolyte imbalance, delirium, hallucinations, hyperpyrexia >>> convulsions >>> coma >>>>>>>> DEATH </li></ul></ul>
  19. 19. Management of salycylism <ul><li>It is symptomatic and supportive. </li></ul><ul><li>Most important is external cooling </li></ul><ul><li>I.V fluids with Na+, K+, HCO3-, and glucose. </li></ul><ul><li>Gastric levage. </li></ul><ul><li>Forced alkaline diuresis. </li></ul>
  20. 20. Precautions and contraindications <ul><li>Contraindicated in patients who are sensitive to it and in peptic ulcer, bleeding disorders, in children suffering from chicken pox or influenza ( risk of Reye’s Syndrome) </li></ul><ul><li>Aspirin should be avoided in diabetes, CHF </li></ul>
  21. 21. <ul><li>Aspirin should be stopped one week before elective surgery </li></ul><ul><li>Given during pregnancy it may be responsible for low birth weight babies. </li></ul><ul><li>If taken near term, aspirin may cause prolonged labour, greater blood loss (post-partum) and premature closure of ductus arteriosis </li></ul>
  22. 22. Compare effects, uses, PK and SE of <ul><li>Mefanamic acid (ponston) </li></ul><ul><li>Phenacetin (paracetamol) </li></ul><ul><li>Ibuprofen (brufen) </li></ul><ul><li>Diclofenac sodium (voren) </li></ul>
  23. 23. GOUT <ul><li>Disease that results from an overload of uric acid in the body. </li></ul><ul><li>This overload of uric acid leads to the formation of tiny crystals of urate that deposit in tissues of the body, especially the joints. </li></ul>
  24. 24. <ul><li>When crystals form in the joints it causes recurring attacks of joint inflammation (arthritis). </li></ul><ul><li>Chronic gout can also lead to deposits of hard lumps of uric acid in and around the joints and may cause joint destruction, decreased kidney function, and kidney stones. </li></ul>
  25. 26. <ul><li>It is often related to an inherited abnormality in the body's ability to process uric acid. </li></ul><ul><li>Uric acid is a breakdown product of purines that are part of many foods we eat. </li></ul>
  26. 27. <ul><li>An abnormality in handling uric acid can cause attacks of painful arthritis (gout attack), kidney stones, and blockage of the kidney-filtering tubules with uric acid crystals, >>>>>>>>> leading to kidney failure. </li></ul>
  27. 28. <ul><li>On the other hand, some people may only develop elevated blood uric acid levels (hyperuricemia) without having arthritis or kidney problems. </li></ul>
  28. 29. <ul><li>Gouty arthritis is typically an extremely painful attack with a rapid onset of joint inflammation. </li></ul><ul><li>The joint inflammation is precipitated by deposits of uric acid crystals in the joint fluid (synovial fluid) and joint lining (synovial lining). </li></ul>
  29. 30. <ul><li>Intense joint inflammation occurs as white blood cells engulf the uric acid crystals and chemical messengers of inflammation are released, causing >>>>>> </li></ul><ul><li>Pain, Heat, and Redness of the joint tissues. </li></ul>
  30. 31. Risk factors for gouty arthritis <ul><li>an inherited abnormality </li></ul><ul><li>obesity, </li></ul><ul><li>excessive weight gain (especially in youth), </li></ul><ul><li>moderate to heavy alcohol intake, </li></ul><ul><li>high blood pressure, and </li></ul><ul><li>abnormal kidney function </li></ul>
  31. 32. <ul><li>Certain drugs, such as thiazide diuretics (hydrochlorothiazide) , low-dose aspirin, niacin, cyclosporine, tuberculosis medications (pyrazinamide and ethambutol), can also cause elevated uric acid levels in the blood and lead to gout </li></ul>
  32. 33. <ul><li>A recent study demonstrated an increased prevalence of abnormally low thyroid hormone levels (hypothyroidism) in patients with gout. </li></ul>
  33. 34. Some conditions can precipitate acute attacks of gout <ul><li>dehydration, </li></ul><ul><li>injury to the joint, </li></ul><ul><li>fever, </li></ul><ul><li>excessive eating, </li></ul><ul><li>heavy alcohol intake, and </li></ul><ul><li>recent surgery. </li></ul>
  34. 35. Diagnosis <ul><li>Gout is suspected when a patient reports a history of attacks of painful arthritis, particularly at the base of the toes. </li></ul>
  35. 36. <ul><li>Ankles and knees are the next most commonly involved joints in gout. </li></ul><ul><li>Gout usually attacks one joint at a time, while other arthritis conditions, such as systemic lupus and rheumatoid arthritis, usually attack multiple joints simultaneously. </li></ul>
  36. 37. <ul><li>The most reliable test for gout is finding uric acid crystals in a sample of the joint fluid obtained by joint aspiration (arthrocentesis). </li></ul><ul><li>Arthrocentesis is a common procedure performed under local anesthesia. Using sterile technique, fluid is withdrawn (aspirated) from the inflamed joint using a syringe and needle. </li></ul>
  37. 38. <ul><li>The joint fluid is then analyzed for uric acid crystals and for infection. </li></ul><ul><li>Shiny, needle-like uric acid crystals are best viewed with a special polarizing microscope. </li></ul>
  38. 39. <ul><li>The diagnosis of gout can also be made by finding these urate crystals from material aspirated from tophi nodules and bursitis fluid. </li></ul>
  39. 40. <ul><li>Sometimes patients with a classic history and symptoms of gout can be successfully treated and presumed to have gout without undergoing arthrocentesis. </li></ul>
  40. 41. <ul><li>However, establishing a firm diagnosis is still preferable since other conditions can mimic gout. </li></ul><ul><li>These include another crystal-induced arthritis called pseudogout, psoriatic arthritis, rheumatoid arthritis, and even infection in the joint. </li></ul>
  41. 42. <ul><li>X-rays can sometimes be helpful and may show tophi-crystal deposits and bone damage as a result of repeated inflammations. </li></ul>
  42. 43. Management <ul><li>Change in life style </li></ul><ul><li>Change in diet </li></ul><ul><li>Medication </li></ul><ul><li>Surgery </li></ul>
  43. 44. <ul><li>There are two key concepts essential to treating gout. </li></ul><ul><li>First, it is critical to stop the acute inflammation of joints affected by gouty arthritis. </li></ul>
  44. 45. <ul><li>Second, it is important to address the long-term management of the disease in order to prevent future gouty arthritis attacks and shrink gouty tophi crystal deposits. </li></ul>
  45. 46. <ul><li>The treatment of an acute attack of gouty arthritis involves measures and medications that reduce inflammation. </li></ul><ul><li>Preventing future acute gout attacks is equally as important as treating the acute arthritis. </li></ul>
  46. 47. <ul><li>Prevention of acute gout involves maintaining adequate fluid intake, weight reduction, dietary changes, reduction in alcohol consumption, and medications to lower the uric acid level in the blood (reduce hyperuricemia). </li></ul>
  47. 48. <ul><li>Dietary changes can help reduce uric acid levels in the blood. </li></ul><ul><li>Since purine chemicals are converted by the body into uric acid, purine-rich foods are avoided. </li></ul><ul><li>Examples of foods rich in purines include shellfish and organ meats such as liver, brains, kidneys, and sweetbreads </li></ul>
  48. 49. <ul><li>There are three aspects to the treatment of gout with medications. </li></ul><ul><li>First, pain relievers such as acetaminophen (paracetamol) or other more potent analgesics are used to manage pain. </li></ul>
  49. 50. DRUGS used in GOUT <ul><li>NSAIDs (aspirin, brufen, probenecid, Naproxin, indocid) </li></ul><ul><li>Corticosteroids </li></ul><ul><li>Colchicine </li></ul><ul><li>Allopurinol </li></ul><ul><li>Febuxostat </li></ul>
  50. 51. <ul><li>Secondly, antiinflammatory agents such as nonsteroidal antiinflammatory drugs (NSAIDS), colchicine, and corticosteroids are used to decrease joint inflammation. </li></ul><ul><li>Finally, medications are considered for managing the chronic underlying metabolic derangement that causes hyperuricemia and gout. </li></ul>
  51. 52. NSAIDs <ul><li>NSAIDS such as indomethacin (Indocin) and naproxen (Naprosyn) are effective antiinflammatory medications for acute gout. </li></ul><ul><li>These medications are tapered after the arthritis resolves. </li></ul>
  52. 53. <ul><li>Common side effects of NSAIDS include irritation of the gastrointestinal system, ulceration of the stomach and intestines, and even intestinal bleeding. </li></ul><ul><li>Patients who have a history of allergy to aspirin or nasal polyps should avoid NSAIDS because of the risk of an intense allergic (anaphylactic) reaction. </li></ul>
  53. 54. COLCHICINE <ul><li>Colchicine for acute gout is administered by mouth to reduce inflammation as well as to prevent gouty arthritis attacks while correcting hyperuricemia with medications such as allopurinol (Zyloprim) or febuxostat (Uloric). </li></ul>
  54. 55. <ul><li>For acute attacks, it is given hourly or every two hours until there is significant improvement in pain or the patient develops gastrointestinal side effects such as severe diarrhea. </li></ul>
  55. 56. <ul><li>For prevention, it is given once or twice daily. </li></ul><ul><li>Other common side effects of colchicine include nausea and vomiting. </li></ul>
  56. 57. STEROIDS <ul><li>Corticosteroids such as prednisone, given in short courses, are powerful antiinflammatory agents for treating acute gout. </li></ul><ul><li>They can be administered orally or injected directly into the inflamed joint. </li></ul>
  57. 58. <ul><li>Corticosteroids can be prescribed to patients who have accompanying kidney, liver, or gastrointestinal problems. </li></ul><ul><li>Long-term chronic use of corticosteroids is discouraged because of serious long-term side effects. </li></ul>
  58. 59. <ul><li>In addition to medications for acute gout attacks, other drugs can be taken over prolonged periods to lower blood uric acid levels. </li></ul><ul><li>Lowering blood uric acid levels reduces the risk of recurrent attacks of arthritis, kidney stones, and kidney disease, and also slowly dissolves hard tophi deposits. </li></ul>
  59. 60. <ul><li>Medicines used to lower blood uric acid level work either by increasing the kidney's excretion of uric acid or by decreasing the body's production of uric acid from the purines in foods. </li></ul>
  60. 61. <ul><li>These medicines are generally not started until after the inflammation from acute gouty arthritis has subsided because they can worsen the attack. </li></ul><ul><li>If they are already being taken prior to the attack, they are continued and only adjusted after the attack has resolved. </li></ul>
  61. 62. <ul><li>Probenecid and sulfinpyrazone are medications that are commonly used to decrease uric acid blood levels by increasing the excretion of uric acid into the urine. </li></ul>
  62. 63. <ul><li>Since these drugs can, in rare instances, cause kidney stones, they should be avoided by those patients with a history of kidney stones. </li></ul><ul><li>These medications should be taken with plenty of fluid so as to promote the rapid passage of uric acid out of the urinary system in order to prevent kidney stone formation. </li></ul>
  63. 64. ALLOPURINOL <ul><li>Allopurinol  lowers the blood uric acid level by preventing uric acid production. </li></ul><ul><li>It actually blocks the metabolic conversion from purines in foods to uric acid. </li></ul>
  64. 65. <ul><li>This medication is used with caution in patients with poor kidney function, as they are at a particular risk of developing side effects, including severe rash and liver damage. </li></ul>
  65. 66. FEBUXOSTAT <ul><li>Febuxostat is used for the chronic management of hyperuricemia from gout. </li></ul><ul><li>Febuxostat has been shown to be more effective than allopurinol in preventing acute attacks of gouty arthritis and is effective in shrinking tophi deposits of uric acid in the tissues such as the fingers, elbows, and ears. </li></ul>
  66. 67. <ul><li>Because febuxostat is not significantly metabolized by the kidneys, it may have advantages over allopurinol in patients with underlying kidney disease. </li></ul><ul><li>While taking febuxostat, patients have uric acid and liver function blood tests monitored regularly. </li></ul>
  67. 68. HOME REMEDY <ul><li>Home remedies which can alleviate the symptoms of acute gout include resting and elevating the inflamed joint. </li></ul><ul><li>Ice-pack applications can be helpful to reduce pain and decrease inflammation. </li></ul>
  68. 69. <ul><li>Patients should avoid aspirin-containing medications, when possible, because aspirin prevents kidney excretion of uric acid. </li></ul>