Pain Management current concepts - Updated May 2010

1. Carlos Leal M.D. Director Orthopedic Research Laboratory Director of Knee Surgery & Sports Medicine Fellowship Bosque University Orthopedic Department Bogotá DC, Colombia Current Management of Postoperative Pain

9. Effective postoperative pain management has a humanitarian role, But there are additional medical and economic benefits for rapid recovery and discharge from hospital.

12. INJURY GATE Various factors: physical, emotional, cognitive or behavioural open or close the gate PAIN experienced depending on how far gate open or closed

13. INJURY GATE Various factors: physical, emotional, cognitive or behavioural open or close the gate PAIN experienced depending on how far gate open or closed

21. Pain as a Health Problem

25. Our most frequent problems Chronic Musculoskeletal Pain

28. The use of analgesics to mask the pain caused by sports injuries is not recommended for long term health. Masking the pain may enable an athlete to continue playing their sport in the short term, but in the longer term, removing the body’s sensory receptors of pain can leave the athlete worse off. .

29. It may also have the effect of significantly impairing their performance.

30. Pain or sports injuries are often the main reasons athletes end up consulting physicians. Instead of merely treating the pain, athletes should be encouraged to treat the cause of the pain

34. Pain Assessment

36. IASP Postop Pain Protocols International Association for the Study of Pain

37. Ablation surgery IV Morphine Tens Nerve/Spinal Block Opioid derivates NSAIDS + Codein NSAIDS Aspirin Acetaminophen Pain Intensity Scale Treatment International Association for the study of Pain

50. Pain and Inflammation Pathways Tissue Damage Pro-Inflammatory Response COX Araquidonic Acid Prostaglandins Pain Fever Inflammation

51. NSAID Actions Most NSAIDs act as non-selective inhibitors of the ciclooxygenase, inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes Cyclooxygenase catalyzes the formation of prostaglandins and thromboxane from arachidonic acid Prostaglandins act (among other things) as messenger molecules in the process of inflammation.

56. The widespread use of NSAIDs has meant that the adverse effects of these relatively safe drugs have become increasingly prevalent. Gastrointestinal Renal Cardiovascular Other… NSAIDS Adverse Effects

59. NSAIDS Cardiovascular Adverse Effects Kearney et al., BMJ 2006;332:1302–1308 A recent meta-analysis of all trials comparing NSAIDs found an 80% increase in the risk of myocardial infarction with both newer COX-2 antagonists and high dose traditional anti-inflammatories compared with placebo All NSAIDs are associated with a doubled risk of symptomatic heart failure in patients without a history of cardiac disease

60. NSAIDS Cardiovascular Adverse Effects In patients with such a history, use of NSAIDs was associated with more than 10-fold increase in heart failure If this link is found to be causal NSAIDs are estimated to be responsible for up to 20% of hospital admissions for congestive heart failure

62. NSAIDS Renal Adverse Effects In renal failure the kidney is trying to maintain renal perfusion pressure by elevated Angiotensin II levels Angiotensin II also constricts the afferent ateriole into the glomerulus in addition to the efferent arteriole it normally constricts

64. NSAIDS are good, but more research is needed to improve safety and increase efficacy

65. Discovery of COX-2 Selective inhibition of COX-2 results in anti-inflammatory action without disrupting gastroprotective prostaglandins. Daniel L. Simmons Brigham Young University

66. Discovery of COX-2 COX-1 is a constitutively expressed enzyme with a "house-keeping" role in regulating many normal physiological processes COX-2 is an enzyme expressed in inflammation and it is inhibition of COX-2 that produces the desirable effects of NSAIDs.

67. Discovery of COX-2 OXICAMS and COXIBS Proved Efficacy and Safety FDA and EMEA approval under revision due to validation of Cardiovascular Adverse Effects

68. Pain research history 1936 1949 1952 1958 1965 1978 1982 1998 2002 MYOCHRYSINE CORTONE HYDROCORTONE DECADRON INDOCID (Indometacina) DOLOBID (Diflunisal) CLINORIL (Sulindac) VIOXX (Rofecoxib) ARCOXIA (Etoricoxib)

69. Etoricoxib N N Cl S O 2 CH 3 C 3

71. Etoricoxib world clinical program Phase I / Pharmacology : 651 subjects Phase II / Clinical: OA, RA : 4888 patients. EDGE: GI tolerance: 2 studies OA: 3953 patients, 90 mg RA: 2032 patients, 90 mg. MEDAL: CV safety OA: 8940 patients (6769:60mg; 2171: 90mg) RA: 2846 patients, 90 mg. >30.000

72. Lancet. 2006 Nov 18;368(9549):1771-81

73. PostOp Pain Results Max Pain Relief Score 5 4 3 2 1 0 6 7 8 12 24 Time (hr) Cambio promedio con ± EE Initial Analgesic Effect with Etoricoxib 120 mg= 24 min Initial Analgesic Effect with Ibuprofen 400 mg.= 32 min Clin Therapeutics 2004;26:667-672. 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Placebo Ibuprofen 400 mg ETORICOXIB 60 mg ETORICOXIB 120 mg

74. PostOp Pain Results Average Pain Relief Score 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ETORICOXIB 120 mg Naproxen 550 mg Paracetamol 600mg /codeín 60 mg Placebo Time (Hours) Post-dose Puntuación promedio de AD ± EE 0 1 2 3 4 5 6 7 8 10 12 20 24 Clin Therapeutics 2004;26:667-672.

76. PostOp Pain Results Oxicodone/paracetamol 10/650< mg (n=100) Time (Hours) Post-dose Clin Therapeutics 2004;26:667-672. 10 8 6 4 2 0 12 14 16 20 24 Puntuación ±EE 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Placebo (n=25) ETORICOXIB120 mg (n=100) 18 22

77. PostOp Pain Results Was “Rescue”medication needed ? % Patients that required rescue medication Clin Therapeutics 2004;26:667-672. *p<0.010 para Etoricoxib vs. oxicodona/paracetamol; p<0.001para Etoricoxib vs. placebo **p<0.010 para oxicodona/paracetamol vs. placebo Porcentaje ±SE 90 80 70 60 50 40 30 20 10 0 Oxicodone/Paracetamol 10/650 mg (n=100) Etoricoxib 120 mg (n=100) Placebo (n=25) 41.0** 22.0* 72.0 100

78. Tolerance Profile Vs. Oxicodone Adverse effects results Oxicodone/ Etoricoxib paracetamol 120 mg 10/650 mg Placebo (%) patients (n=100) (n=100) (n=25) Any AE 32 (32.0)** 71 (71.0) 6 (24.0) AE related to treatment 9 (9.0)** 64 (64.0) 2 (8.0) Common AE Dizziness 2 (2.0) 38 (38.0) 1 (4.0) Nausea 4 (4.0)** 33 (33.0) 0 (0.0) Vomit 0 (0.0)** 20 (20.0) 0 (0.0) Drowsiness 0 (0.0) 19 (19.0) 1 (4.0) Post Op Alveolitis 15 (15.0) 15 (15.0) 2 (8.0) Headache 3 (3.0) 6 (6.0) 0 (0.0)

79. Etoricoxib Farmacokinetics Linear Kinetics Dose Dose Concentration Concentration Max. 1h Biodisponibility 100% Effects Lasts 24 hs (72%) Effect Starts at 24 Minutes (50%) Not affected by food intake Stable after 7 days

81. Medication Interaction INR ↑ Dose Microdosis Monitor MTX Monitor BP

82. Safety Profile % Adverse effects Clin Therapeutics 2004;26:667-672.

83. Safety Profile % Adverse Effects Retired due to AE EA TGI. EA HTA Clin Therapeutics 2004;26:667-672.

84. GI Adverse Effects *p<0.001 para placebo y etoricoxib vs. naproxeno Incidencia (%) 0 Etoricoxib 120 mg (n=236) 10 20 30 40 70 100 80 22.7* 72.0 50 60 90 Naproxeno 1000 mg (n=235) Etoricoxib 120 mg (n=216) 17.4* 58.7 Ibuprofeno 2400 mg (n=218) Incidencia (%) 0 10 20 30 40 70 100 80 50 60 90 AR - OA OA Placebo (n=229) 23.2* Placebo (n=221) 19.7* Patients with gastric ulcers or erosions diagnosed with endoscopy 12 weeks treatment Clin Therapeutics 2004;26:667-672.

85. Endoscopy studies comparing Etoricoxib in OA & RA *p<0.001 vs. naproxeno; **p<0.001 vs. ibuprofeno; ***p=0.007 vs. ibuprofeno Datos en Archivo, MSD. Incidence of GI Ulcers  3 mm - 12 weeks 25 Incidencia Acumulada, porcentaje (± IC 95%) Incidencia Acumulada, porcentaje (± IC 95%) 0 OA o AR 5 10 15 20 25 35 30 Etoricoxib 120 mg (n=251) 7.42* 25.27 Naproxeno 1000 mg (n=244) Placebo (n=247) 1.35* OA 0 5 10 15 20 8.12*** Etoricoxib 120 mg (n=221) 17.02 Ibuprofeno 2400 mg (n=226) 1.86** Placebo (n=233) Clin Therapeutics 2004;26:667-672.

86. Cardiovascular adverse effects Note: * p<0.05 vs. Pbo

87. Lancet. 2006 Nov 18;368(9549):1771-81

88. Use with caution… Pregnancy: 6-9 month Alergies Severe renal Insufficiency Moderate liver insufficicency Hiperlipidemia, heavy smokers Dehidration

90. In accute pain 120 mg once a day Etoricoxib

91. In Rheumathoid Arthritis 90 mg once a day Etoricoxib

92. in Osteoarthrosis 60 mg once a day Etoricoxib

93. In chronic low back pain 60 mg once a day Etoricoxib

96. “ In the new world there will be no pain…” Apc 7,17;21,4

100. CURSO DE INSTRUCCIÓN EN MEDICINA DEL DEPORTE SANTA MARTA, COLOMBIA OCTUBRE 2 & 3 DE 2009 IROTAMA RESORT – GOLF - MARINA