牙科常用止痛藥              義大醫院	 	 口腔外科                 陳文惠13年2月2日星期六
Pain                     Cellular&   Emo/onal&                     Damage      Experience   Tissue&Injury,&     Infec/on  ...
Cerebral Cortex : Interpretation      Limbic System (emotional Center)                                           CNS      ...
Cerebral Cortex : Interpretation                                                 X      Limbic System (emotional Center)  ...
Physiology             Pain of Inflammatory Origin                                   Cyclooxygenase                        ...
Physiology             Pain of Inflammatory Origin                                         Cyclooxygenase                  ...
Found in brain, kidney Found in most tissue, PLTs                              Not in PLTs Protect gastric mucosa13年2月2日星期六
Analgesics For Dental Pain              Non$                      Opioid       Adjunc7ve             Opioid              A...
Non-Opioid Analgesics13年2月2日星期六
Non-Opioid Analgesics             First-line drug             Lack of the unwanted side effect of opioid               Con...
Classification             Centrally acting : APAP               Highly effective inhibitor of COX-1 variant(CNS)          ...
Absorption             Rapidly absorbed from               Stomach and the upper small intestine             Effective pla...
Rate of Absorption             The product formulation             pKa of the drug             The pH in the stomach      ...
Rate of Absorption             The product formulation             pKa of the drug                  Antacid             Th...
Liver :     Metabolism    Metabolize                        Kidney :                       Excretion13年2月2日星期六
Common Rx             Acetaminophen               Ibuprofen                Naproxen               Ketoprofen             C...
Acetaminophen             Weak anti-inflammatory agent             More effective against COX effects in             the CN...
Indication             A suitable substitute in patients             with peptic ulcer disease,             hemophilia, or...
Dosage             The Single dose               Adult : 650 mg every 4 hours.               Children : 80-120mg , age & w...
Toxicity of APAP             Occurs when a toxic, highly             reactive metabolite of APAP             accumulates i...
Side Effect             Usually well tolerated in recommended             therapeutic dosages             Erythematous or ...
Ibuprofen             Ibuprofen : between 400 and 800 mg               Longer duration of action             Dose-dependen...
Ibuprofen        The current gold standard for surgical dental pain             Control pain at lower dosages (200-400mg q...
Side Effect             GI side effects : 5-15%               Been used with some success in p’ts with a               his...
Side Effect             Cross the placenta in animal studies             Evidence(+) of fetal risk : outweighs any        ...
Drug Interaction             Immediate-release aspirin 81mg daily               ≥ 400mg ibuprofen :interfere with aspirin’...
Drug Interaction             The proper timing of ibuprofen dosing             in relationship to aspirin therapy         ...
Naproxen             Well absorbed               Food delays the rate but not the extent               of absorption      ...
Naproxen             Plasma half-life is variable               Ranges from 14 hours in the young               Approximat...
Dosage             Naproxen (250,375,500mg tablets; 125 mg/5ml             suspension)               500mg initially, foll...
Side Effect             Cross the placenta and approximately 1%             is found in breast milk             GI side ef...
Side Effect             Pruritus and other dermatologic problem :             less often             Rarely : jaundice, im...
Ketoprofen             Plasma half-life : approximately 2 hours,             except in the elderly (longer half-life)     ...
Dosage             1st day dosage : 75mg q8H or 50mg q6h               Followed by 25 to 50mg q6-8h             Total dail...
Side Effect             30% : GI side effects               Reduced if taken with food or antacids             Increase pl...
Ketorolac             Adult: PO               Moderate to severe pain 10 mg 4-6 hrly.               Max: 40 mg/day.       ...
Other Common Side             Effect for COX inhibitor              Intolerance to COX inhibitors                history o...
GI Side Effect             GI distress, nausea and vomiting             Exacerbate the symptoms of peptic             ulce...
Ibuprofen              Aspirin             Diclofenac             Naproxen             Ketoprofen             Ketorolac13年...
Bleeding Tendency             COX-1 inhibitor               Impair platelet adhesion to tissue and               platelet ...
Renal Side Effect             COX inhibitors decrease the synthesis of renal             prostaglandins, decrease renal bl...
Pregnancy             APAP is a suitable substitute for ASA             and other COX-1 inhibitors in the             mana...
Alcohol Abuse             APAP :   maximum dose of 2000 mg daily.13年2月2日星期六
Adjunctive Drugs13年2月2日星期六
Enhance the efficacy of an analgesic or it             may have an analgesic activity of its own               Corticostero...
Corticosteroid             Function               Decrease swelling and post-OP pain               Reduce local congestion...
13年2月2日星期六
Side Effect         Aggravate glycemic control in DM patients             Uncontrolled DM: Only in lift-threatening situat...
Side Effect             Hypertension : unknown mechanism               Even with decreased sodium consumption             ...
Side Effect with                   Higher Dose             Behavioral change               Initial : insomnia and euphoria...
Use with Caution             Active peptic ulcer        Psychoses             Heart disease              DM             Hy...
Rational for Use                Hypothalamic-pituitary-adranal(HPA)                axis suppression                Increas...
Rational for Use             Short-term use               not induce HPA axis suppression               Nor higher inciden...
Rational for Use             Short-term use               not induce HPA axis suppression               Nor higher inciden...
Suggested Protocol             Consideration               Age : very young or elder =>               adjustment of dosage...
Suggested Protocol             Injectable               Immediately prior to surgery                  Dexamethasone sodium...
Suggested Protocol             Oral form : Dexamethasone              Before surgery              Less than 5 days13年2月2日星期六
Caution             P’t take glucocorticoids routinely               Consult the physician : temporary dosage             ...
Efficacy13年2月2日星期六
Efficacy of Analgesics     ASA#650#mg   =   APAP#650#mg   =   Ibuprofen*200*mg   =   Naproxen)Sodium)                      ...
3rd Molar Extraction             Diclofenac             Ibuprofen      The 95% confidence interval of the number needed to ...
Acute Post-OP Pain             Ibuprofen                                  APAP      The 95% confidence interval of the numb...
Clinical Guideline13年2月2日星期六
Suggested Protocol     MildPain             •  ingleExtrac.on,Rou.neRCT,SC/RP,gingivectomy     ModeratePain             • ...
NSAIDs                                                Ibuprofen 200-400     MildPain                                      ...
NSAIDs                                              Ibuprofen 200-400     MildPain                                    mg q...
NSAIDs                                             Ibuprofen 200-400     MildPain                                   mg q4-...
non-NSAIDs                                                APAP 650-1000mg                                                 ...
non-NSAIDs                                                APAP 650-1000mg                                                 ...
non-NSAIDs                                                APAP 650-1000mg                                                 ...
Additional Consideration             Daily ibuprofen < 2400mg , APAP < 4000mg             NSAIDs contraindicated in       ...
Periodontology 2000,   Vol. 46, 2008, 143–16413年2月2日星期六
13年2月2日星期六
13年2月2日星期六
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牙科止痛藥

  1. 1. 牙科常用止痛藥 義大醫院 口腔外科 陳文惠13年2月2日星期六
  2. 2. Pain Cellular& Emo/onal& Damage Experience Tissue&Injury,& Infec/on Unpleasant& Sensa/on13年2月2日星期六
  3. 3. Cerebral Cortex : Interpretation Limbic System (emotional Center) CNS Spinal Cord Nerve Fiber PNS Nociceptor or Pain Receptor13年2月2日星期六
  4. 4. Cerebral Cortex : Interpretation X Limbic System (emotional Center) CNS Spinal Cord X Analgesics X Nerve Fiber PNS Nociceptor or Pain Receptor13年2月2日星期六
  5. 5. Physiology Pain of Inflammatory Origin Cyclooxygenase Prostaglandins Induce pain perception Influence inflammation Stimulate elevated B.T, Affect the tone & permeability of B.V.13年2月2日星期六
  6. 6. Physiology Pain of Inflammatory Origin Cyclooxygenase Aspirin COX inhibitors ✘ Prostaglandins Induce pain perception Influence inflammation Stimulate elevated body temperature, Affect the tone & permeability of B.V.13年2月2日星期六
  7. 7. Found in brain, kidney Found in most tissue, PLTs Not in PLTs Protect gastric mucosa13年2月2日星期六
  8. 8. Analgesics For Dental Pain Non$ Opioid Adjunc7ve Opioid APAP Morphine Steroid3 NSAID Meperidine Codeine313年2月2日星期六
  9. 9. Non-Opioid Analgesics13年2月2日星期六
  10. 10. Non-Opioid Analgesics First-line drug Lack of the unwanted side effect of opioid Constipation, respiratory depression and physical dependence Not change the perception of sensory modalities other than pain13年2月2日星期六
  11. 11. Classification Centrally acting : APAP Highly effective inhibitor of COX-1 variant(CNS) Weak inhibitor of peripheral PG Peripheral acting: NSAIDs Non-selective COX inhibitor COX-2 inhibitor13年2月2日星期六
  12. 12. Absorption Rapidly absorbed from Stomach and the upper small intestine Effective plasma concentrations 30 to 60 minutes Peak concentrations About 2 to 3 hours.13年2月2日星期六
  13. 13. Rate of Absorption The product formulation pKa of the drug The pH in the stomach Vascularity of the absorptive surface Gastric emptying time13年2月2日星期六
  14. 14. Rate of Absorption The product formulation pKa of the drug Antacid The pH in the stomach Vascularity of the absorptive surface Gastric emptying time Food13年2月2日星期六
  15. 15. Liver : Metabolism Metabolize Kidney : Excretion13年2月2日星期六
  16. 16. Common Rx Acetaminophen Ibuprofen Naproxen Ketoprofen COX-2 inhibitor13年2月2日星期六
  17. 17. Acetaminophen Weak anti-inflammatory agent More effective against COX effects in the CNS Ability to reduce fever and relieve pain, with minimal effect on peripheral inflammation13年2月2日星期六
  18. 18. Indication A suitable substitute in patients with peptic ulcer disease, hemophilia, or other bleeding disorders, and for those individuals taking anticoagulants13年2月2日星期六
  19. 19. Dosage The Single dose Adult : 650 mg every 4 hours. Children : 80-120mg , age & weight Ceiling dose of 1000 mg The daily dose < 4000 mg for adults and 1200 mg for children13年2月2日星期六
  20. 20. Toxicity of APAP Occurs when a toxic, highly reactive metabolite of APAP accumulates in the liver ➡Serious, irreversible and occasionally fatal liver damage13年2月2日星期六
  21. 21. Side Effect Usually well tolerated in recommended therapeutic dosages Erythematous or urticarial skin rash may occur occasionally, sometimes accompanied by fever and mucosal lesions The mechanism of intolerance to APAP is unknown13年2月2日星期六
  22. 22. Ibuprofen Ibuprofen : between 400 and 800 mg Longer duration of action Dose-dependent increase in its analgesic and anti-inflammatory efficacy13年2月2日星期六
  23. 23. Ibuprofen The current gold standard for surgical dental pain Control pain at lower dosages (200-400mg q6h) Anti-inflammatory activity at higher dosages (600-800mg q6h) Ibuprofen 600mg q6h : controls most dental pain The max. adult daily dose : 2400 mg.13年2月2日星期六
  24. 24. Side Effect GI side effects : 5-15% Been used with some success in p’ts with a history of GI intolerance to other NSAIDs Less frequency Thrombocytopenia, rashes, headache, dizziness, blurred vision, fluid retention, edema, and toxic amblyopia When ocular disturbance (+): discontinued immediately13年2月2日星期六
  25. 25. Side Effect Cross the placenta in animal studies Evidence(+) of fetal risk : outweighs any analgesic benefits when ibuprofen is taken during the third trimester of pregnancy No known controlled studies examining the effects on the fetus during the 1st and 2nd trimesters13年2月2日星期六
  26. 26. Drug Interaction Immediate-release aspirin 81mg daily ≥ 400mg ibuprofen :interfere with aspirin’s antiplatelet effects, with its greatest effect occurring if its is administered less than 8hrs prior to aspirin13年2月2日星期六
  27. 27. Drug Interaction The proper timing of ibuprofen dosing in relationship to aspirin therapy Routine or long-term administration: At least 8 hrs before taking aspirin or 30-120 mins after taking aspirin13年2月2日星期六
  28. 28. Naproxen Well absorbed Food delays the rate but not the extent of absorption Peak plasma concentration : 2-4 hours , Concomitant administration of sodium bicarbonate : accelerate the rate of absorption13年2月2日星期六
  29. 29. Naproxen Plasma half-life is variable Ranges from 14 hours in the young Approximately twice this in the elderly because of decreased renal function13年2月2日星期六
  30. 30. Dosage Naproxen (250,375,500mg tablets; 125 mg/5ml suspension) 500mg initially, followed by 500mg q12h or 250mg q6-8h Total daily dose on D1 < 1250mg Thereafter the totally daily dose <1000mg Greater analgesic : 1500mg/d for limited period13年2月2日星期六
  31. 31. Side Effect Cross the placenta and approximately 1% is found in breast milk GI side effect : the same frequency as indomethacin but less severity Drowsiness, headache, dizziness, sweating, fatigue, depression and ototoxicity have been observed13年2月2日星期六
  32. 32. Side Effect Pruritus and other dermatologic problem : less often Rarely : jaundice, impairment of renal function, angioedema, thrombocytopenia and agranulocytosis All => seemly associated with prolonged treatment13年2月2日星期六
  33. 33. Ketoprofen Plasma half-life : approximately 2 hours, except in the elderly (longer half-life) >75y/o, initial dose decreased even with normal BUN levels13年2月2日星期六
  34. 34. Dosage 1st day dosage : 75mg q8H or 50mg q6h Followed by 25 to 50mg q6-8h Total daily dose of regular formulations <300mg Mildly impaired renal function <150mg More severe renal impairment(GFR <25ml/min) or end- stage renal impairment <100mg13年2月2日星期六
  35. 35. Side Effect 30% : GI side effects Reduced if taken with food or antacids Increase plasma Cr, especially in the elderly and/or those taking diuretics Renal function studies : routinely on p’t requiring long-term therapy13年2月2日星期六
  36. 36. Ketorolac Adult: PO Moderate to severe pain 10 mg 4-6 hrly. Max: 40 mg/day. Max duration: 7 days.13年2月2日星期六
  37. 37. Other Common Side Effect for COX inhibitor Intolerance to COX inhibitors history of asthma, nasal polyps and chronic urticaria Immunoglobulin E (IgE)-dependent hypersensitivity reactions leading to hypotension and respiratory collapse13年2月2日星期六
  38. 38. GI Side Effect GI distress, nausea and vomiting Exacerbate the symptoms of peptic ulcer disease and with chronic use, GI bleeding, ulceration and perforation can occur13年2月2日星期六
  39. 39. Ibuprofen Aspirin Diclofenac Naproxen Ketoprofen Ketorolac13年2月2日星期六
  40. 40. Bleeding Tendency COX-1 inhibitor Impair platelet adhesion to tissue and platelet aggregation Platelet inhibition with ibuprofen and naproxen Reversible APAP : suitable substitute13年2月2日星期六
  41. 41. Renal Side Effect COX inhibitors decrease the synthesis of renal prostaglandins, decrease renal blood flow ➡ Fluid retention, precipitate renal failure Risk factors include old age, chronic renal insufficiency, congestive heart failure, hepatic cirrhosis and concurrent use of diuretic drugs13年2月2日星期六
  42. 42. Pregnancy APAP is a suitable substitute for ASA and other COX-1 inhibitors in the management of mild-to-moderate pain13年2月2日星期六
  43. 43. Alcohol Abuse APAP : maximum dose of 2000 mg daily.13年2月2日星期六
  44. 44. Adjunctive Drugs13年2月2日星期六
  45. 45. Enhance the efficacy of an analgesic or it may have an analgesic activity of its own Corticosteroids : anti-inflammatory effects ➡ analgesia in some patients with pain of inflammatory origin. Some controversy13年2月2日星期六
  46. 46. Corticosteroid Function Decrease swelling and post-OP pain Reduce local congestion Diminish nerve damage, accelerate recovery of normal sensory perception13年2月2日星期六
  47. 47. 13年2月2日星期六
  48. 48. Side Effect Aggravate glycemic control in DM patients Uncontrolled DM: Only in lift-threatening situations Use steroid in DM patient : controversial Controlled DM Short time period at reduced dosage Careful monitoring of blood glucose levels Well-controlled type 1 DM : adjust daily insulin doses based on their current blood glucose values13年2月2日星期六
  49. 49. Side Effect Hypertension : unknown mechanism Even with decreased sodium consumption Monitor Hyperglycemia, glycosuria and sodium retention with edema or hypertension Short-term therapy : no contraindication13年2月2日星期六
  50. 50. Side Effect with Higher Dose Behavioral change Initial : insomnia and euphoria Then : depression Increased intracranial pressure Peptic ulcer Decreased Vit. D. and calcium absorption Increase in PLT and RBC numbers13年2月2日星期六
  51. 51. Use with Caution Active peptic ulcer Psychoses Heart disease DM Hypertension Osteoporosis Congestive heart failure Glaucoma Systemic infection Herpes simplex infection13年2月2日星期六
  52. 52. Rational for Use Hypothalamic-pituitary-adranal(HPA) axis suppression Increased infection Occurrence of inflammation and swelling after steroids are cleared from the body (approximately 2-3 days)13年2月2日星期六
  53. 53. Rational for Use Short-term use not induce HPA axis suppression Nor higher incidence of infection Antibody production : affected by large dosages of steroid but not by moderate dosage (20mg of prednisone/day)13年2月2日星期六
  54. 54. Rational for Use Short-term use not induce HPA axis suppression Nor higher incidence of infection Antibody production : affected by large dosages of steroid but not by moderate dosage (20mg of prednisone/day) Long-Term Use Infection Reactivate TB13年2月2日星期六
  55. 55. Suggested Protocol Consideration Age : very young or elder => adjustment of dosage Weight Surgical invasiveness13年2月2日星期六
  56. 56. Suggested Protocol Injectable Immediately prior to surgery Dexamethasone sodium phosphate 4-8mg IV or deep IM After the procedure : long-acting IM glucocorticoid, such as methylprednisolone acetate suspension 20-60mg via deep IM Not inject into small muscle13年2月2日星期六
  57. 57. Suggested Protocol Oral form : Dexamethasone Before surgery Less than 5 days13年2月2日星期六
  58. 58. Caution P’t take glucocorticoids routinely Consult the physician : temporary dosage increase Abrupt cessation of glucocorticoids after prolonged therapy : risk of adrenal insufficiency due to suppression of the HPA axis and may be fetal13年2月2日星期六
  59. 59. Efficacy13年2月2日星期六
  60. 60. Efficacy of Analgesics ASA#650#mg = APAP#650#mg = Ibuprofen*200*mg = Naproxen)Sodium) 220)mg > Ceiling doses of APAP (1000mg) 60mm Codeine Ibuprofen*400mg 650mg ASA+60mg Codeine 600mg APAP+60mg Codeine13年2月2日星期六
  61. 61. 3rd Molar Extraction Diclofenac Ibuprofen The 95% confidence interval of the number needed to treat (NNT) for at ieast 50% pain relief over 4 to 6 hours compared with placebo in third molar extraction trials." Adapted with permission from Macmillan Publishers Ltd: British Dental Journal (Barden J, et al. Br Dent J. 2004:197:407-411). Copyright 2004.13年2月2日星期六
  62. 62. Acute Post-OP Pain Ibuprofen APAP The 95% confidence interval of the number needed to treat (NNT) for at least 50% pain relief over 4 to 6 hours compared with placebo in acute postoperative pain trials.*^"13年2月2日星期六
  63. 63. Clinical Guideline13年2月2日星期六
  64. 64. Suggested Protocol MildPain •  ingleExtrac.on,Rou.neRCT,SC/RP,gingivectomy ModeratePain •  mplant,Perio.FlapOP,ApicalSurgery Severepain •  Impac.on,CompleximplantorPerio.OP13年2月2日星期六
  65. 65. NSAIDs Ibuprofen 200-400 MildPain mg q4-6H •  ingleExtrac.on,Rou.neRCT,SC/RP,gingivectomy ModeratePain •  mplant,Perio.FlapOP,ApicalSurgery Severepain •  Impac.on,CompleximplantorPerio.OP13年2月2日星期六
  66. 66. NSAIDs Ibuprofen 200-400 MildPain mg q4-6H •  ingleExtrac.on,Rou.neRCT,SC/RP,gingivectomy Ibuprofen 400-600 mg q4-6H ModeratePain x I then 400mg q4-6H or Ibuprofen 400-600 mg + APAP •  mplant,Perio.FlapOP,ApicalSurgery 500mg q6H x I then ibuprofen Severepain 400mg q4-6H •  Impac.on,CompleximplantorPerio.OP13年2月2日星期六
  67. 67. NSAIDs Ibuprofen 200-400 MildPain mg q4-6H •  ingleExtrac.on,Rou.neRCT,SC/RP,gingivectomy Ibuprofen 400-600 mg q4-6H ModeratePain x I then 400mg q4-6H or Ibuprofen 400-600 mg + APAP •  mplant,Perio.FlapOP,ApicalSurgery 500mg q6H x I then ibuprofen Severepain Ibuprofen 400-600mg + APAP 400mg q4-6H 500mg + hydrocodone 10mg •  Impac.on,CompleximplantorPerio.OP q6H x II then ibuprofen 400mg q4-6H13年2月2日星期六
  68. 68. non-NSAIDs APAP 650-1000mg q6H MildPain •  ingleExtrac.on,Rou.neRCT,SC/RP,gingivectomy ModeratePain •  mplant,Perio.FlapOP,ApicalSurgery Severepain •  Impac.on,CompleximplantorPerio.OP13年2月2日星期六
  69. 69. non-NSAIDs APAP 650-1000mg q6H MildPain •  ingleExtrac.on,Rou.neRCT,SC/RP,gingivectomy APAP 650+ hydrocodone 10mg q6H xI => APAP 650-1000mg ModeratePain Q6H •  mplant,Perio.FlapOP,ApicalSurgery Severepain •  Impac.on,CompleximplantorPerio.OP13年2月2日星期六
  70. 70. non-NSAIDs APAP 650-1000mg q6H MildPain •  ingleExtrac.on,Rou.neRCT,SC/RP,gingivectomy APAP 650+ hydrocodone 10mg q6H xI => APAP 650-1000mg ModeratePain Q6H •  mplant,Perio.FlapOP,ApicalSurgery APAP 650+ hydrocodone 10mg Severepain q6H xII => APAP 650-1000mg Q6H •  Impac.on,CompleximplantorPerio.OP13年2月2日星期六
  71. 71. Additional Consideration Daily ibuprofen < 2400mg , APAP < 4000mg NSAIDs contraindicated in History of GI ulceration Aspirin intolerance / Cross hypersensitivity Receiving anticoagulant13年2月2日星期六
  72. 72. Periodontology 2000, Vol. 46, 2008, 143–16413年2月2日星期六
  73. 73. 13年2月2日星期六
  74. 74. 13年2月2日星期六
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