1/21/14. Cancer Related Pain: Case-Based Pharmacology. Conflicts of Interest. Learning Objective

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1 Cancer Related Pain: Case-Based Pharmacology Jeannine M. Brant, PhD, APRN, AOCN Oncology Clinical Nurse Specialist Nurse Scientist Billings Clinic Conflicts of Interest Jeannine Brant has served on the speakers bureau for Genentech Oncology Learning Objective Employ practical suggestions for reducing barriers in the optimal management of patients with cancer-related pain 1

2 Overview Pain is a significant problem in patients with cancer Often the most feared aspect of the disease Multiple guidelines exist to guide clinicians in the diagnosis and management of pain q Pain can be adequately managed in over 95% of patients Advanced practitioners have a professional and ethical responsibility to adequately manage pain throughout the cancer trajectory Pathophysiology and Pharmacology of Pain Perception Relaxation Distraction Hypnosis Modulation Antidepressants Dorsal horn of the spinal cord Transmission Opioids NMDA Antagonists Alpha-2 Adrenergic Anticonvulsants Transduction NSAIDs Massage Ice/Heat Modified from Brant J. (2013). Pain at the end of life. In Palliative care nursing: A guide to practice, 3rd ed. Victoria, Australia: Ausmed. 58-year-old patient with stage IV renal cell cancer (diagnosed July 2013) Admitted to the hospital with intractable shoulder and rib pain Nephrectomy 1 yr prior Scans revealed recurrent disease with bone metastases Placed on an intractable pain protocol Continuous infusion of IV morphine 4 mg/hr Patient-controlled bolus dose 2 mg every 10 min as needed Total morphine use for 24 hr is 150 mg Meet Mike Discharge plan Lives in a rural area with few resources Baseline pain stable Breakthrough pain intractable, unable to lie on the radiation table due to pain; has 7 treatments remaining 2

3 Mike is ready for discharge. What would his dose of oral morphine be if he is taking 150 mg IV morphine/day? A. 75 mg of morphine CR every 12 hr B. 75 mg of morphine CR every 8 hr C. 150 mg of morphine CR every 12 hr D. 150 mg of morphine CR every 8 hr Equianalgesic Conversion Opioid Oral Parenteral Morphine 30 mg 10 mg Oxycodone 20 mg NA Hydromorphone 7 mg 1.5 mg Fentanyl 25 µg transdermal fentanyl ~ 75 mg oral morphine American Pain Society. (2008). Principles of analgesic use in the treatment of acute pain and cancer pain (6th ed.). Glenview, IL: APS Press. What would you recommend for breakthrough pain? A. 10 mg IV morphine prior to each radiation treatment B. Oral hydromorphone 4 mg every 2 hr as needed C. Transmucosal fentanyl 200 µg per dosing recommendations D. Morphine sulfate IR 45 mg every 2 hr as needed 3

4 Dosing and Titration Perform titration after reaching steady state q Average 4-5 half-lives for IR opioids q Average 2-3 days for CR opioids (or >) Titrate 24-hr dose by 33% 100% Keep breakthrough dose at approximately 10% 20%; higher with severe incident pain Consider dose reduction for incomplete cross tolerance q 50% 75% with good pain control q 0% 25% with poor pain control American Pain Society. (2008). Principles of analgesic use in the treatment of acute pain and cancer pain. 6th ed. Glenview, IL: APS Press; NCCN. (2013). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ). Adult cancer pain. Version Novel Fentanyl Products Approved rapid onset opioids q Transmucosal fentanyl citrate (1998); Actiq q Fentanyl buccal tablet (2006); Fentora q Fentanyl buccal soluble film (2009); Onsolis q Sublingual fentanyl (2011); Abstral q Fentanyl nasal spray (2011); Lazanda q Fentanyl sublingual spray (2012); Subsys In consideration of Mike s somatic pain (bone pain), what coanalgesics would you recommend? A. Nonsteroidal anti-inflammatory agent such as naproxen B. Anticonvulsant such as gabapentin C. Tricyclic antidepressant such as amitriptyline D. A combination of these options 4

5 Meet Mary Mary is a 56-year-old patient with stage IV bladder cancer (liver, lungs, bone metastases) q Admitted to the hospital with increasing pain in her right femur that radiates down her right leg X-ray of the femur q A lytic destructive process of the right femoral shaft and impending pathologic fracture Prior treatment q Chemotherapy: cisplatin, gemcitabine, docetaxel, ifosfamide q Currently on a phase I clinical trial q External beam radiation therapy to her pubic bone and sacrum What type of pain do you think Mary has? A. Somatic B. Visceral C. Neuropathic D. Combination More on Mary s Case Rod placed in femur for stabilization Radiation q 2,000 cgy in 5 fractions to right femur q 800 cgy in 1 fraction to left femur q Samarium injection Pain medication q Morphine sulfate CR 160 mg every 8 hr q Morphine sulfate IR 60 mg every 2 hr prn q Gabapentin 2,400 mg/day Pain scores continued at 8/10 5

6 How would you modify Mary s pain management plan? A. Continue to titrate the morphine B. Add a coanalgesic such as an NSAID or an antidepressant C. Rotate to an alternative opioid D. Rotate the route: Consider IV or intraspinal Pathophysiology and Pharmacology of Pain Perception Relaxation Distraction Hypnosis Modulation Antidepressants Dorsal Horn of the Spinal Cord Transmission Opioids NMDA Antagonists Alpha-2 Adrenergic Anticonvulsants Transduction NSAIDs Massage Ice/Heat Modified from Brant J. (2013). Pain at the end of life. In Palliative care nursing: A guide to practice, 3rd ed. Victoria, Australia: Ausmed. Mary s Case Continued Rotation to IV morphine Mary was started on intractable pain protocol q Morphine continuous infusion (CI) q Optional PCA bolus at 50% of the CI rate q Titration by 33% every hour as needed for pain 4 ü Guidelines say up to 50% 100% q Total oral morphine/day = 1,080 mg q IV dose = oral dose 3 = 360 mg/24 hr ü 15 mg morphine/hr with 7 mg PCA bolus ü Titrated to comfort (36 mg/hr and 18 mg bolus) q Signs of jerking and twitching PCA = patient-controlled analgesia 6

7 How would you manage the myoclonus? A. Rotate opioid B. Rotate route of administration C. Midazolam drip D. Dantrolene End of Life Palliative Education Resource Center. Myoclonus Management Development of myoclonus q Rotate to hydromorphone q Morphine use 1,500 mg/24 hr q 1,500 mg morphine = 10 morphine x mg HM 1.5 mg HM q 10 x = 2,250 mg; x = 225 mg HM/24 hr q 10 mg/hr CI with 5 mg PCA bolus Myoclonus resolved Patient up walking in the halls comfortable and ready for discharge Case Continued Pain scores escalated 10/10 within 24 hr Epidural placement q Temporary placement: 1 mg PF HM/hr: 10 IV: 1 epidural q Permanent placement: Tunneled catheter q Bupivacaine 0.25% added when pain scores escalated 10/10 q Midazolam IV push and gtt used for sedation between intractable pain episodes Patient discharged home with epidural catheter Comfortable at home for 1 wk q Pain scores escalated: IV lidocaine and IV fentanyl trials with comfort for 12 hr q Patient requested palliative sedation ü Epidural HM at 60 mg/hr with 0.25% bupivacaine ü Midazolam 90 mg/hr 7

8 Lipophilic Methadone Overview q Significant tissue distribution Protein bound q Slow release and long duration of action No known active metabolites NMDA activity. May decrease tolerance and inhibit neuropathic pain High oral bioavailability. Parenteral form may not be an advantage Cost-effective NMDA = N-methyl-D-aspartic acid Trafton, J. A., et al. (2009). Curr Pain Headache Rep, 13(1), 24-30; Brant, J. M., et al. (2010). J Adv Pract Oncol, 1(3), Methadone Conversion Morphine Equivalent Dose Conversion Ratio < 90 mg 1 methadone: 4 MS mg 1: mg 1: ,000 mg 1:15 > 1,000 mg 1:20 American Pain Society. (2008). Principles of analgesic use in the treatment of acute pain and cancer pain. 6th ed. Glenview, IL: APS Press; Weschules, D. J., et al. (2008). Pain Med, 9(5), Preventing Methadone Oversedation Should only be prescribed by experienced clinicians Use prescribing guidelines for all opioids Double-check opioid conversions and doses of methadone Beware of drug-drug interactions 8

9 Be kind, for everyone is having a hard battle. ~Plato 9

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