2. CANCER PAIN MANAGEMENT PAMELA M. SUTTON, M.D. FAAHPM DECEMBER 2013

3. “ TOTAL PAIN ” “EVERYTHING HURTS” PHYSICAL PAIN EMOTIONAL PAIN SOCIAL PAIN SPIRITUAL PAIN

4. PAIN ASSESSMENT PATIENT RATES INTENSITY/SEVERITY OF PAIN ON SCALE OF ZERO TO TEN LOCATION QUALITY (ACHING, BURNING, SHOOTING) DURATION (INTERMITTENT OR CONTINUOUS) WHAT MAKES PAIN BETTER/WORSE

5. CAUSES OF PHYSICAL PAIN IN CANCER Bone Metastases-50% Nerve Injury(neuropathic)or compression-25% Cancer treatments-19%

6. NOCICEPTIVE vs. NEUROPATHIC PAIN

7. TREATMENT OF PHYSICAL PAIN TREAT UNDERLYING ILLNESS ELEVATE PAIN THRESHOLD INTERRUPT PAIN TRANSMISSION

8. WORLD HEALTH ORGANIZATION 3 STEP METHOD FOR CANCER PAIN RELIEF (“Analgesic Ladder”) STEP 1. “NON-OPIOID” +/- ADJUVANT If pain persists or worsens, go to: STEP 2. MILD OPIOID +/- NON-OPIOID +/- ADJUVANT If pain persists or worsens, go to: STEP 3. STRONG OPIOID +/- NON OPIOID+/-ADJUVANT

9. ANALGESIC LADDER ORAL MEDICATION IS PREFERRED EASE OF ADMINISTRATION STEADY BLOOD LEVELS SAFETY

10. ANALGESIC LADDER OPIOIDS DO NOT ALWAYS RELIEVE PAIN! NON-OPIOID ADJUVANTS AND/OR OTHER PAIN METHODS MAY BE NECESSARY.

11. ANALGESIC LADDER PAIN TREATMENT SUCCESSFUL IN 90% OF PATIENTS WITH PROPER MEDICATION USE

12. WORLD HEALTH ORGANIZATION 3 STEP METHOD FOR CANCER PAIN RELIEF (“Analgesic Ladder”) STEP 1. “NON-OPIOID” +/- ADJUVANT If pain persists or worsens, go to: STEP 2. MILD OPIOID +/- NON-OPIOID +/- ADJUVANT If pain persists or worsens, go to: STEP 3. STRONG OPIOID +/- NON OPIOID+/-ADJUVANT

13. NON-OPIOID ANALGESIC PARACETAMOL 500-1000 MG EVERY 4-6 HOURS Advantages: Available, cheap, effective for mild pain. Disadvantages: Potential liver toxicity. Not anti-inflammatory. Not best choice for bone pain.

14. NON-OPIOID ANALGESICS NSAID’S Advantages: Anti-inflammatory effects helpful for bone pain. Dosage may be less frequent than paracetamol. Disadvantages: Potential GI/renal side effects and interference with platelet function.

15. NSAIDS SALICYLATES Aspirin PROPRIONIC ACIDS Ibuprofen--every 6 hours; liquid Naproxen--every 12 hours ACETIC ACIDS Diclofenac--every 8 hours Ketorolac (Toradol)--oral or parenteral; short term use only

16. NSAIDS COX 2 INHIBITORS Celecoxib Less GI toxicity (not perfect); Less anti-platelet activity Potential Renal/Cardiovascular Toxicity

17. OPIOIDS 1) CODEINE, MORPHINE 2) SEMISYNTHETIC HYDROCODONE BUPRENORPHINE (MIXED AGONIST/ ANTAGONIST) 3) SYNTHETIC METHADONE (DOLOPHINE) FENTANYL (DURAGESIC) TRAMADOL

18. CONCERNS ABOUT OPIOIDS 1. ADDICTION Physical Dependence and Psychological Craving 2. TOLERANCE Rarely a practical problem. Dose can be increased if tolerance occurs. 3. RESPIRATORY DEPRESSION Rarely a problem when appropriate dose of oral narcotic is titrated to level of pain.

19. CONCERNS ABOUT OPIOIDS 4. LETHARGY Sleepiness may occur in first hours/days but usually improves. 5. NAUSEA Occurs in less than half of patients. May resolve. 6. CONSTIPATION Frequent problem--should be anticipated with stool softener/laxative on a daily basis. Avoid bulk laxatives.

20. WORLD HEALTH ORGANIZATION 3 STEP METHOD FOR CANCER PAIN RELIEF (“Analgesic Ladder”) STEP 1. “NON-OPIOID” +/- ADJUVANT If pain persists or worsens, go to: STEP 2. MILD OPIOID +/- NON-OPIOID +/- ADJUVANT If pain persists or worsens, go to: STEP 3. STRONG OPIOID +/- NON OPIOID+/-ADJUVANT

21. POSSIBLE STEP TWO OPIOIDS (for moderate pain) CODEINE TRAMADOL HYDROCODONE

22. STEP TWO OPIOIDS CODEINE 30 mg orally is approximately equal in analgesic effect to 650 mg of aspirin. When 30 mg codeine and 650 mg aspirin are combined, the analgesic effect equals or exceeds 60 mg codeine.

23. STEP TWO OPIOIDS HYDROCODONE May be packaged with paracetamol or ibuprofen. Beware of associated toxicity.

24. STEP TWO OPIOIDS TRAMADOL Synthetic mu agonist opioid Reportedly exerts additional analgesic effect by inhibition of serotonin and noradrenaline reuptake.

25. STEP THREE OPIOIDS (for severe pain) MORPHINE METHADONE (Dolophine) FENTANYL (Duragesic) BUPRENORPHINE

26. STEP THREE OPIOIDS MORPHINE  PROTOTYPE OPIOID  SHORT AND LONG-ACTING TABLETS, LIQUID, CONCENTRATE, SUPPOSITORIES, IV/SUBQ, EPIDURAL, INTRATHECAL  ACTIVE METABOLITES CAN CAUSE TOXICITY IN RENAL FAILURE

27. STEP THREE OPIOIDS METHADONE (Dolophine) SYNTHETIC MU AGONIST AND POSSIBLE NMDA RECEPTOR ANTAGONIST (May help neuropathic pain) ORAL/IV/SUBQ

28. STEP THREE OPIOIDS METHADONE (Dolophine) TRICKY TO TITRATE VARIABLE CLINICAL EFFECT. (May accumulate and cause lethargy and potential respiratory depression. ) EFFECTIVE IN LOW DOSES IN SOME PATIENTS WITH POOR RELIEF FROM HIGH DOSE MORPHINE.

29. STEP THREE OPIOIDS FENTANYL (Duragesic) SHORT-ACTING SYNTHETIC, PACKAGED AS THREE DAY PATCH 25 MCG PATCH APPROXIMATELY EQUIVALENT TO 15 MG ORAL MORPHINE NOT FOR QUICK TITRATION (ANALGESIC EFFECT PEAKS ABOUT 17 HOURS AND LINGERS THAT LONG WHEN REMOVED) MAY BE ABSORBED QUICKLY IF TEMP ELEVATION (BEWARE RESPIRATORY DEPRESSION)

30. STEP THREE OPIOIDS FENTANYL BEWARE ORAL MUCOSAL PRODUCTS: UNCLEAR DOSING, RAPID ABSORPTION

31. STEP THREE OPIOIDS BUPRENORPHINE (sublingual tablet, transdermal patch) CAN BE USED FOR MODERATE TO SEVERE PAIN MAY INDUCE WITHDRAWAL IN OPIOID DEPENDENT PATIENTS

32. ADJUVANTS IMPORTANT TO TREATMENT OF NEUROPATHIC PAIN ANTIDEPRESSANTS ANTICONVULSANTS ANESTHETICS

33. ANTIDEPRESSANTS  TRICYCLICS  amitriptyline(Elavil)  nortriptyline(Pamelor)  SSRI’s  paroxetine(Paxil)  Others:  venlafaxine (Effexor)  mirtazipine (Remeron)  duloxetine (Cymbalta)

34. ANTICONVULSANTS gabapentin (Neurontin) pregabalin (Lyrica) clonazepam (Klonopin)

35. ANESTHETICS FOR PAIN Lidocaine IV, Ointment, Lidoderm Patch EMLA Ketamine Oral, IV, Subq OTHER TOPICAL PREPARATIONS Capsaicin SUMMARY CANCER PAIN CAN AND MUST BE RELIEVED OBTAIN THOROUGH HISTORY AND PHYSICAL EXAM ADMINISTER MEDICATION ON A REGULAR BASIS ACCORDING TO THE ANALGESIC LADDER STEP 1. NON-OPIOID +/- ADJUVANT If pain persists or worsens, go to: STEP 2. MILD OPIOID + NON-OPIOID +/- ADJUVANT If pain persists or worsens, go to: STEP 3. STRONG OPIOID +/- NON-OPIOID+/-ADJUVANT OFFER EMOTIONAL SUPPORT REASSESS PAIN AND EFFECTIVENESS OF TREATMENT FREQUENTLY

36. PAIN SUMMARY PAIN MUST BE RELIEVED THOROUGH HISTORY AND PHYSICAL EXAM MEDICATION ON A REGULAR BASIS ACCORDING TO THE ANALGESIC LADDER STEP 1. NON-OPIOID +/- ADJUVANT STEP 2. MILD OPIOID +/- NON-OPIOID +/- ADJUVANT STEP 3. STRONG OPIOID +/- NON-OPIOID+/-ADJUVANT EMOTIONAL SUPPORT REASSESS PAIN AND EFFECTIVENESS OF TREATMENT FREQUENTLY

37. OPIOID EQUIVALENCE 5 MG OF OF IV OR SUBQ MORPHINE EVERY 4 HOURS = 15 MG OF IMMEDIATE RELEASE ORAL MORPHINE EVERY 4 HOURS = 25 MCG FENTANYL PATCH EVERY 3 DAYS

38. USEFUL REFERENCES ASSESSING AND TREATING PAIN; UNIPAC THREE, AAHPM, 2012. CANCER PAIN RELIEF, WORLD HEALTH ORGANIZATION, GENEVA, 1986. EDUCATION FOR END OF LIFE CARE (EPEC) PROJECT,2003; NORTHWESTERN UNIVERSITY SCHOOL OF MEDICINE created with AMA & ROBERT WOOD JOHNSON FOUNDATION, CHICAGO, ILL. FERRANTE, FM; ‘‘Principles of Opioid Pharmacotherapy: Practical Implications of Basic Mechanisms”, J. of PAIN and SYMPTOM MANAGEMENT; May 1996, Vol. 11, No 5. FOLEY, KM; “The Treatment of Cancer Pain”,NEJM;1985, 313:84-95. MANAGEMENT OF CANCER PAIN, Clinical Practice Guideline #9; AHCPR Publication #94-0592, March 1994. PRIMER OF PALLIATIVE CARE, 5 th Edition; AAHPM, 2010.