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牙科止痛藥
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牙科止痛藥

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  • 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. Pain Cellular& Emo/onal& Damage Experience Tissue&Injury,& Infec/on Unpleasant& Sensa/on13年2月2日星期六
  • 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. 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. 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. 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. Found in brain, kidney Found in most tissue, PLTs Not in PLTs Protect gastric mucosa13年2月2日星期六
  • 8. Analgesics For Dental Pain Non$ Opioid Adjunc7ve Opioid APAP Morphine Steroid3 NSAID Meperidine Codeine313年2月2日星期六
  • 9. Non-Opioid Analgesics13年2月2日星期六
  • 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. 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. 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. 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. 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. Liver : Metabolism Metabolize Kidney : Excretion13年2月2日星期六
  • 16. Common Rx Acetaminophen Ibuprofen Naproxen Ketoprofen COX-2 inhibitor13年2月2日星期六
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Ibuprofen Aspirin Diclofenac Naproxen Ketoprofen Ketorolac13年2月2日星期六
  • 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. 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. 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. Alcohol Abuse APAP : maximum dose of 2000 mg daily.13年2月2日星期六
  • 44. Adjunctive Drugs13年2月2日星期六
  • 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. 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. 13年2月2日星期六
  • 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. 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. 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. 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. 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. 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. 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. Suggested Protocol Consideration Age : very young or elder => adjustment of dosage Weight Surgical invasiveness13年2月2日星期六
  • 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. Suggested Protocol Oral form : Dexamethasone Before surgery Less than 5 days13年2月2日星期六
  • 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. Efficacy13年2月2日星期六
  • 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. 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. 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. Clinical Guideline13年2月2日星期六
  • 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. 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. 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. 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. 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. 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. 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. 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. Periodontology 2000, Vol. 46, 2008, 143–16413年2月2日星期六
  • 73. 13年2月2日星期六
  • 74. 13年2月2日星期六

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