Cox1&2

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Cox1&2

  1. 1. Pain Management
  2. 2. Why Treat Pain? <ul><li>Animals feel pain just like us </li></ul><ul><li>Unethical not to address pain </li></ul><ul><li>Animal owner and public concerns </li></ul><ul><li>Many anesthetics have no analgesic effect </li></ul><ul><ul><li>Which do? </li></ul></ul><ul><li>Pain results in poor anesthetic recovery </li></ul>
  3. 3. MYTHS “ Anesthetics mask symptoms” “ Patient will harm itself if there’s no pain” “ Pain is difficult to assess”
  4. 4. The Truth! <ul><li>Pain is BAD: </li></ul><ul><ul><li>Decreased cardiovascular function </li></ul></ul><ul><ul><li>Decresed appetite </li></ul></ul><ul><ul><li>Slows wound healing </li></ul></ul><ul><ul><li>Decreased immune function </li></ul></ul><ul><ul><ul><li>Greater chance of infection </li></ul></ul></ul><ul><ul><li>Increased fear and anxiety </li></ul></ul>
  5. 5. Use of Analgesics in Practice <ul><li>Overall = poor </li></ul><ul><ul><li>13-26% dog and cat spay/neuters receive analgesics </li></ul></ul><ul><ul><li>50-70% of non-neutering soft tissue surgery </li></ul></ul><ul><ul><li>>80% orthopedic surgery and severe trauma </li></ul></ul><ul><li>Why not better? </li></ul><ul><ul><li>DEA / theft concerns </li></ul></ul><ul><ul><li>Older vets not trained that way </li></ul></ul><ul><ul><li>Older drugs dangerous </li></ul></ul><ul><ul><li>Animals are stoic </li></ul></ul>
  6. 6. Pain Perception <ul><li>Pain sensor  nerve fiber  spinal cord  brain </li></ul><ul><li>Neurotransmitters>> </li></ul><ul><ul><li>Somatic ( superficial ) pain </li></ul></ul><ul><ul><li>Visceral ( internal organ ) pain </li></ul></ul><ul><ul><li>Bone pain </li></ul></ul>
  7. 7. Classification of Pain <ul><li>Intensity (scale of 1-10) </li></ul><ul><li>Acute, sharp, sudden, short </li></ul><ul><ul><li>Surgical pain </li></ul></ul><ul><ul><li>Responds well to drug tx </li></ul></ul><ul><li>Chronic, dull, prolonged </li></ul><ul><ul><li>Cancer or arthritis </li></ul></ul><ul><ul><li>Doesn’t always respond well to tx </li></ul></ul><ul><li>Referred (from somewhere else) </li></ul><ul><li>Hyperesthesia (increased sensitivity) </li></ul><ul><li>Neuropathic (Nerve damage) </li></ul><ul><ul><li>Poorly responsive </li></ul></ul>
  8. 8. Degree and Type of Pain Depend On <ul><li>The procedure </li></ul><ul><li>The animal </li></ul><ul><ul><li>Pain is an individual experience </li></ul></ul><ul><ul><ul><li>Tailor analgesic protocol to the patient </li></ul></ul></ul><ul><li>Analgesic administration </li></ul><ul><ul><li>Timing </li></ul></ul><ul><ul><li>Dosage </li></ul></ul>
  9. 9. Preemptive Analgesia <ul><li>If the body doesn’t sense the pain during the procedure, the pain will be easier to deal with post-operatively </li></ul><ul><ul><li>A patient in surgical anesthesia is not aware of pain, but the body is still responding  sensitizes the nervous system </li></ul></ul>
  10. 10. Preemptive Analgesia Results In <ul><li>Marked decrease in amount of analgesic medication needed post-operatively </li></ul><ul><li>Increased patient comfort </li></ul>
  11. 11. Balanced Anesthesia <ul><li>Several anesthetic drugs are combined into anesthetic protocol </li></ul><ul><li>Include analgesic </li></ul><ul><li>Synergism </li></ul><ul><ul><li>Smaller dosages needed </li></ul></ul><ul><ul><li>Decreased potential for side effects </li></ul></ul>
  12. 12. Monitoring Signs of Pain Facial Expression Vocalization Body Posture Abnormal Gait Decreased Activity Level Attitude Appetite Grooming Urination/Defecation Habits
  13. 13. Methods of Pain Control <ul><li>Non-pharmacological methods: </li></ul><ul><li>Endorphins = The body’s natural painkillers </li></ul><ul><li>Good nursing care </li></ul><ul><ul><li>Comfortable bedding </li></ul></ul><ul><ul><ul><li>Clean and dry </li></ul></ul></ul><ul><ul><li>Easy access to bathroom, food, water </li></ul></ul><ul><ul><li>TLC </li></ul></ul><ul><ul><li>Rotate recumbency </li></ul></ul><ul><ul><li>Allow time to sleep </li></ul></ul>
  14. 14. Non-pharmacological Methods <ul><li>Apply cold to site (acute- 1 st 24 hours) </li></ul><ul><ul><li>Decreases inflammation </li></ul></ul><ul><ul><li>Numbs </li></ul></ul><ul><li>Apply heat to site (chronic) </li></ul><ul><li>Massage </li></ul><ul><li>Acupuncture/acupressure </li></ul><ul><li>Complementary methods </li></ul><ul><ul><li>Herbs, laser, magnetic, chiropractic </li></ul></ul>
  15. 15. Pharmacologic Methods <ul><li>Opioids </li></ul><ul><li> 2 agonists </li></ul><ul><li>Steroids </li></ul><ul><li>NSAIDS </li></ul><ul><li>Local anesthetics </li></ul><ul><li>Chondroprotective drugs </li></ul>
  16. 16. Opioids
  17. 17. Opiate Receptors MOA? 4 types of receptors: mu kappa sigma delta Should we be wondering why fraternities/sororities name themselves after receptors of pain??
  18. 18. Opioids: Backbone of Analgesia <ul><li>Pure Agonists </li></ul><ul><ul><li>Morphine, oxymorphone, meperidine, hydromorphone, fentanyl </li></ul></ul><ul><li>Partial agonists, mixed agonist-antagonists </li></ul><ul><ul><li>Buprenorphine </li></ul></ul><ul><ul><li>Butorphanol </li></ul></ul><ul><li>Pure Antagonists (reversal of agonists) </li></ul><ul><ul><li>Naloxone </li></ul></ul><ul><li>ABUSE POTENTIAL </li></ul>
  19. 19. Opioid Administration <ul><li>Systemic: IV, SQ, IM, CRI </li></ul><ul><li>Intra-articular injection </li></ul><ul><li>Local injection </li></ul><ul><li>Epidural injection </li></ul><ul><li>Transdermal fentanyl patch </li></ul>
  20. 20. Opioid Effects <ul><li>GOOD: </li></ul><ul><ul><li>Great analgesia </li></ul></ul><ul><ul><li>Variable muscle relaxation </li></ul></ul><ul><ul><li>Sedation </li></ul></ul><ul><li>BAD: </li></ul><ul><ul><li>Respiratory depression </li></ul></ul><ul><ul><li>GI effects </li></ul></ul><ul><ul><ul><li>Vomiting </li></ul></ul></ul><ul><ul><ul><li>Defecation followed by constipation </li></ul></ul></ul>
  21. 21. Opioids (other effects) <ul><li>Excitement </li></ul><ul><ul><li>Panting </li></ul></ul><ul><ul><li>Vocalization </li></ul></ul><ul><ul><li>Noise sensitivity </li></ul></ul><ul><li>Depression of the cough center </li></ul><ul><ul><li>Advantage for? </li></ul></ul>
  22. 22. Fentanyl Patch <ul><li>Lag time: </li></ul><ul><ul><li>apply 6-12 hours prior to surgery in cats, </li></ul></ul><ul><ul><li>12-24 hours in dogs </li></ul></ul><ul><li>Lasts about 3 days (up to 6 in cats) </li></ul><ul><li>Variation in absorption rate </li></ul><ul><ul><li>Dose of patch (in micrograms/hr) </li></ul></ul><ul><ul><li>Avoid heat sources </li></ul></ul><ul><li>Excessive amounts can cause ataxia, sedation in dogs, excitement, disorientation, wide-eyed stare in cats </li></ul><ul><ul><li>Remove patch, can reverse </li></ul></ul>
  23. 23. Fentanyl Patch <ul><li>Applied to dorsal neck or shoulders, lateral thorax </li></ul><ul><li>Clip hair, clean skin with water only </li></ul><ul><li>Do not cut patch </li></ul><ul><ul><li>Can remove just part of backing if small animal </li></ul></ul><ul><li>Apply patch, hold firmly 2 minutes </li></ul><ul><li>Bandage </li></ul>
  24. 24. Opioid Partial Agonists <ul><li>Buprenorphine </li></ul><ul><li>Buprenex® </li></ul><ul><li>4-8 hour duration </li></ul>
  25. 25. Opioid Mixed Agonist-Antagonist <ul><li>Butorphanol </li></ul><ul><li>(Torbutrol®, Torbugesic®) </li></ul><ul><li>For mild to moderate pain </li></ul><ul><li>Duration 1 to 4 hours IM, SQ </li></ul><ul><li>Less abuse potential than agonists </li></ul>
  26. 26. Opioid Antagonists <ul><li>Naloxone </li></ul><ul><li>Used to reverse opiates/opioids </li></ul><ul><li>Remember: Reverses analgesia too! </li></ul><ul><li>May not last as long as the agonist </li></ul><ul><ul><li>Relapse =“renarcotization” </li></ul></ul><ul><li>Partial reversal with butorphanol possible </li></ul>
  27. 27. Alpha-2 Agonists “thiazines”
  28. 28. Alpha-2 Agonists <ul><li>MOA? </li></ul><ul><li>Examples: </li></ul><ul><ul><li>Xylazine (Rompun ® ) </li></ul></ul><ul><ul><li>Medetomidine (Domitor ® ) </li></ul></ul>Engages receptors in CNS >> decrease norepinephrine
  29. 29. Xylazine: Good Things <ul><li>Moderate analgesia </li></ul><ul><li>Potent sedative effect </li></ul><ul><li>Good muscle relaxation </li></ul>
  30. 30. Xylazine: Bad Things <ul><li>Bradycardia due to stimulation of the vagus nerve  heart block </li></ul><ul><li>Profound cardiac disturbances! </li></ul><ul><ul><li>Sensitizes the heart to catecholamines  Arrhythmias </li></ul></ul><ul><ul><li>Decreased cardiac output </li></ul></ul><ul><ul><ul><li>Hypotension (BP decreases by 1/4-1/3) </li></ul></ul></ul>#1 ?
  31. 31. Xylazine: More Bad Things <ul><li>Vomiting (sometimes used as emetic) </li></ul>
  32. 32. Xylazine: Reversal? <ul><li>Yohimbine is reversal agent </li></ul><ul><li>Mixed Alpha- antagonist (blocker) </li></ul><ul><li>Trade name “Yobine” </li></ul>
  33. 33. Medetomidine <ul><li>=DOMITOR® </li></ul><ul><li>More specific to CNS alpha-2 receptors </li></ul><ul><li>Alpha-2 so has reversal agent </li></ul><ul><ul><li>(Antisedan®) </li></ul></ul>Common name? Name?
  34. 34. Steroids = corticosteroids,glucocoticoids <ul><li>Examples: </li></ul><ul><ul><li>Prednisone = Prednisolone </li></ul></ul><ul><ul><li>Dexamethasone </li></ul></ul><ul><ul><li>Betamethasone </li></ul></ul><ul><ul><li>Solu-Delta-Cortef </li></ul></ul><ul><ul><li>Solu-Medrol </li></ul></ul><ul><li>Decrease pain </li></ul><ul><li>by decreasing inflammation </li></ul>
  35. 35. Steroids: MOA inhibit phospholipase A2>>> inhibits prostoglandin/leukotrienes COX-2 COX-1 Phospholipase A2 Steroids inhibit here NSAIDS inhibit here Membrane Phospholipid Arachidonic Acid “ Bad” Prostaglandins Pain/Inflammation “ Good” Prostaglandins GI Protection Renal Blood Flow Thromboxane “ Platelets”
  36. 36. Side Effects and Toxicity <ul><li>Iatrogenic hyperadrenocorticism </li></ul><ul><ul><li>“ Cushings Dz” </li></ul></ul><ul><li>Polyphagia </li></ul><ul><li>PU/PD </li></ul><ul><li>Glaucoma and cataracts </li></ul><ul><li>Gastric ulceration </li></ul><ul><li>Delayed wound healing </li></ul><ul><li>Immunosuppression </li></ul>
  37. 37. More ! <ul><li>Insulin resistance </li></ul><ul><li>Hepatopathy </li></ul><ul><li>CNS: restlessness, seizure activity </li></ul><ul><li>Infection </li></ul>
  38. 38. Non-Steroidal Anti-inflammatory Drugs ( NSAIDS ) <ul><li>Aspirin </li></ul><ul><li>Carprofen - Rimadyl ® </li></ul><ul><li>Etodolac - Etogesic® </li></ul><ul><li>Ketoprofen - Ketofen ® </li></ul><ul><li>Phenylbutazone – “Bute” </li></ul><ul><li>Flunixin - Banamine ® </li></ul><ul><li>(Acetaminophen - Tylenol ®) </li></ul>
  39. 39. NSAIDS <ul><li>Most have effective somatic (superficial) analgesic effect </li></ul><ul><li>Some have good visceral analgesic effect also </li></ul><ul><li>All take 30-60 minutes to take effect, even if injected </li></ul><ul><li>All have antiinflammatory properties </li></ul><ul><li>Reduce fevers </li></ul>
  40. 40. NSAIDS <ul><li>MOA: cyclooxygenase inhibitors >> prostaglandin inhibitors </li></ul><ul><li>Many side effects are due to “good” prostaglandin inhibition (COX 1): </li></ul><ul><ul><li>GI upset/ ulceration </li></ul></ul><ul><ul><li>Renal toxicity </li></ul></ul><ul><ul><li>Impaired platelet function </li></ul></ul>
  41. 41. NSAIDS: MOA inhibit cyclooxygenase>>> inhibits prostoglandin/thromboxane COX-2 COX-1 Phospholipase A2 Steroids inhibit here NSAIDS inhibit here Membrane Phospholipid Arachidonic Acid “ Bad” Prostaglandins Pain/Inflammation “ Good” Prostaglandins GI Protection Renal Blood Flow Thromboxane “ Platelets” Fever
  42. 42. NSAIDS - Metabolism <ul><li>Metabolized by the liver </li></ul><ul><li>Variation in metabolism between species </li></ul><ul><li>Aspirin half-life 12 hours in dogs, 1 hour in horses, 38 hours in cats </li></ul><ul><li>Many NSAIDS toxic to cats due to inability to metabolize them </li></ul><ul><li>Acetaminophen is toxic in dogs AND cats! </li></ul>
  43. 43. NSAIDS Inhibit Production of Protective GI Prostaglandins <ul><li>Erosion/ulceration of GI tract </li></ul><ul><li>Stomach upset </li></ul><ul><li>Inappetance </li></ul><ul><li>Vomiting </li></ul><ul><li>Diarrhea </li></ul><ul><li>Melena ? </li></ul>
  44. 44. Prostaglandins in the Kidneys <ul><li>Cause dilation of renal vasculature, allowing perfusion despite decreased blood pressure due to </li></ul><ul><ul><li>Shock </li></ul></ul><ul><ul><li>Dehydration </li></ul></ul><ul><ul><li>Blood loss </li></ul></ul><ul><ul><li>Anesthesia </li></ul></ul><ul><li>Inhibition of prostaglandin production can cause kidney cell death due to lack of perfusion </li></ul><ul><li>Only an issue if decreased BP </li></ul>
  45. 45. NSAIDS <ul><li>Cyclooxygenase inhibition  decreased thromboxane  decreases platelet adhesion/clumping  decreases clot formation and thromboemboli </li></ul>
  46. 46. TYPES of NSAIDs
  47. 47. Phenylbutazone <ul><li>COX1 and 2 Inhibitor </li></ul><ul><li>Very Potent </li></ul><ul><li>Commonly used in horses </li></ul><ul><li>Not recommended in dogs </li></ul><ul><ul><li>GI side effects common </li></ul></ul><ul><ul><li>NEVER IN CATS! </li></ul></ul>
  48. 48. Aspirin <ul><li>COX1 and 2 Inhibitor </li></ul><ul><li>Very short half-life in horses </li></ul><ul><li>Commonly used in dogs </li></ul><ul><ul><li>Buffered only </li></ul></ul><ul><ul><li>With food </li></ul></ul><ul><li>Use with caution in cats </li></ul><ul><ul><li>Can’t metabolize well </li></ul></ul><ul><ul><li>Half-life 38 hours </li></ul></ul><ul><ul><li>Dosed every 48-72 hours </li></ul></ul>
  49. 49. Neither Ibuprofen Nor Naproxen Is Recommended for Use in Cats Ibuprofen = “Advil” COX1 + COX2 Inhibitors Officially not recommended in dogs. most do OK if used like aspirin
  50. 50. Ketoprofen <ul><li>Ketofen ® (COX1 and COX2) </li></ul><ul><li>Licensed in horses </li></ul><ul><li>Approved for use in dogs and cats in Canada, Europe </li></ul><ul><li>Good analgesia, potent antipyretic </li></ul><ul><li>Injectable </li></ul><ul><ul><li>Limit use </li></ul></ul><ul><ul><li>Blood clotting </li></ul></ul>
  51. 51. Flunixin meglumine <ul><li>Banamine ® (COX1 and COX2) </li></ul><ul><li>Injectable </li></ul><ul><li>Horses </li></ul><ul><ul><li>Colic </li></ul></ul><ul><ul><li>Good analgesia </li></ul></ul><ul><li>Dogs </li></ul><ul><ul><li>GI side effects common, severe </li></ul></ul>
  52. 52. Carprofen <ul><li>Rimadyl ® </li></ul><ul><li>COX-2 inhibitor: “spares” “good” prostaglandins </li></ul><ul><li>Fewer side effects </li></ul><ul><li>DOGS ONLY </li></ul><ul><li>Black labs… </li></ul><ul><ul><li>0.06% of all dogs develop hepatic problems (rare) </li></ul></ul><ul><li>BID Dosing </li></ul>
  53. 53. Etodolac <ul><li>Etogesic ® </li></ul><ul><li>COX 1 and 2 Inhibition </li></ul><ul><li>Once daily administration </li></ul><ul><li>DOGS ONLY </li></ul>
  54. 54. Derramax <ul><li>Use in dogs </li></ul><ul><li>COX 2 Specific </li></ul><ul><li>SID dosing </li></ul><ul><li>$$ </li></ul>
  55. 55. “ Metacam” =Meloxicam <ul><li>COX-2 Specific </li></ul><ul><li>Use in dogs and cats </li></ul><ul><li>Liquid </li></ul><ul><li>Well tolerated </li></ul><ul><li>$$ </li></ul>
  56. 56. NSAID Precautions <ul><li>Use only 1 NSAID at a time </li></ul><ul><li>Never combine NSAIDS with glucocorticoids </li></ul><ul><ul><li>Gastric Ulceration </li></ul></ul><ul><li>Taper to lowest effective dose </li></ul><ul><li>Change to alternative NSAID if poor response </li></ul>
  57. 57. NSAID Contraindications <ul><li>Renal of hepatic dysfunction </li></ul><ul><li>Decreased circulating blood volume </li></ul><ul><li>Coagulopathies </li></ul><ul><li>GI disease </li></ul><ul><li>Pregnancy </li></ul>
  58. 58. Local Anesthetics
  59. 59. Local Anesthetics <ul><li>The “-caine” family: Lidocaine, bupivicaine, mepivicaine, proparicaine, tetracaine, etc. </li></ul><ul><li>MOA= Block nerve impulses by blocking Na+ channels in nerve membranes </li></ul>
  60. 60. Local Anesthetics <ul><li>Local infiltration of surgical site </li></ul><ul><li>Intravenous regional anesthesia </li></ul><ul><li>Intra-articular injection </li></ul><ul><li>Nerve blocks </li></ul><ul><li>Epidural </li></ul><ul><li>Topical on skin/ eye/ larynx </li></ul><ul><li>http://www.cvm.okstate.edu/courses/vmed5412/Lect23.asp </li></ul>
  61. 61. Commonly Used With Neuroleptanalgesic
  62. 62. Capsaicin <ul><li>Hot peppers </li></ul><ul><li>Excites then fatigues nerve transmission  local analgesia </li></ul><ul><li>Also get endorphin release </li></ul>
  63. 63. St. Johnswort <ul><li>Arthritic pain </li></ul><ul><li>Hypericin </li></ul><ul><ul><li>Stimulates neural inhibitory pathways  analgesia </li></ul></ul>
  64. 64. Chondroprotective Agents <ul><li>Nutraceuticals </li></ul><ul><ul><li>Chondroitin sulfate </li></ul></ul><ul><ul><li>Glucosamine </li></ul></ul><ul><ul><li>Hyaluronic acid </li></ul></ul><ul><ul><li>Building blocks for cartilage and synovial fluid </li></ul></ul>Examples: (oral) Synovi, Glycoflex (injectable) Adequan Can be mixed with many other ingredients (MSM, Creatine) to enhance effects.
  65. 65. Antibiotic Analogy to understand pain control <ul><li>Antibiotics prescribed based on clinical signs, not always based on culture and sensitivity </li></ul><ul><li>Rely on return to normal function to confirm diagnosis </li></ul><ul><li>If doesn’t help, add to or change drug protocol </li></ul><ul><li>May need a loading dose </li></ul><ul><li>May need a combination of drugs </li></ul>
  66. 66. Questions ??

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