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Pharmacologic Treatments of Pain

Pharmacologic Treatments of Pain . PMRC Nursing Module Kim Chapman RN, MSc(N), CON(C) Clinical Nurse Specialist, Oncology October 2, 2009. Learning Objectives. Understand the spectrum of pain pharmacology Choose pharmacologic treatment options in chronic and cancer pain

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Pharmacologic Treatments of Pain

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  1. Pharmacologic Treatments of Pain PMRC Nursing Module Kim Chapman RN, MSc(N), CON(C) Clinical Nurse Specialist, Oncology October 2, 2009

  2. Learning Objectives • Understand the spectrum of pain pharmacology • Choose pharmacologic treatment options in chronic and cancer pain • Identify the more common side effects and strategies to manage those side effects

  3. Mr. Pain’s Story 57 yr. old male diagnosed with small cell lung cancer. Has a lg. mass in his LUL along with mediastinal & (lt.) hilar adenopathy, extensive liver mets. MI in 2002 - takes ASA daily; peptic ulcer disease - takes losec daily Active until about 1 mos. ago. Lost ~10 lbs. in the last 2-3 mos. Poor nutritional intake. Constipated. ++ ascites. Enlarged liver. Jaundiced. Arrived for day 1 of his 1st chemotherapy (etoposide & cisplatin) with c/o abdominal pain.

  4. Mechanistic Approach to Pain Somatic Superficial NOCICEPTIVEPAIN Deep Visceral MIXED Central Peripheral NEUROPATHIC PAIN Others Ashby MA et al. 1992 51:153-161

  5. Nociceptive: Somatic pain • skin, muscle, connective tissue or bone • dull, sharp, aching, stabbing, throbbing, or pressure • well-localized • usually associated with tissue damage as well as inflammatory processes • eg. bone mets., pressure ulcer, infiltrated IV, incision Nociceptive: Visceral pain • organs or tissue • gnawing, cramping, aching, sharp, colicky, dull, or sharp • localized or referred • eg. hepatomegaly, bladder spasms

  6. Neuropathic pain • nerve involvement centrally or peripherally • may arise as a direct consequence of a lesion or disease affecting the somatosensory system (IASP 2007) • sharp, tingling, burning, shooting, pins & needles, allodynia, burning, or lancinating

  7. Pain Assessment Findings • P – Provocation & Palliation – lying, hiccups; certain positioning, heat, medication, relief of hiccups, relief of anxiety, sleep (BPI) • Q – Quality of Pain - Classic neuropathic pain both anterior thigh areas with the usual burning, stinging, & sharp pain along with allodynia - possibly due to femoral nerve obstruction or paraneoplastic syndrome. (LANSS). Dull, achy pain in abdominal area - nociceptive pain (BPI) • R – Region & Radiation - Pain moves from place to place; always persistent (BPI) • S – Severity (on a 0-10 scale) - Pain score of 8-9 at rest and 10 + with activity (ESAS & BPI) • T – Timing – constant unless using pain medication; time of day does not appear to influence pain experience (BPI) BPI – Brief Pain Inventory; LANSS- ESAS - Edmonton Symptom Assessment System

  8. Key Patient Outcomes Mr. Pain verbalizes that pain is reduced or relieved to his satisfaction. Mr. Pain uses pharmacologic and non-pharmacologic interventions. Mr. Pain participates in activities of daily living with appropriate medications.

  9. What pharmacologic approach would you use?

  10. Your Selection Opioids Non-Opioid Analgesics Adjuvant Medications (Co-analgesics)

  11. *Codeine *Hydrocodone **Tramadol Morphine Hydromorphone Oxycodone Methadone Fentanyl Sufentanyl Levorphanol Meperidine Naloxone/Pentazocine Pharmacological: Opioids Codeine combination products (>7 million prescriptions/yr) Oxycodone combination products (>1 million prescriptions/yr)

  12. Analgesics Acetaminophen NSAIDS (Anti-inflammatory medications) Adjuvant Medications (Co-analgesics) Anticonvulsants (carbamazepine, phenytoin, gabapentin, pregabalin) Antidepressants (amitriptyline, nortriptyline, desipramine) NMDA blockers Corticosteroids (dexamethasone) Antispasmodic agents (baclofen) Bisphosphonates (pamidronate, zoledronic acid) Pharmacological: Non-Opioid

  13. So, Where’s the roadmap?

  14. The Analgesic Stepped Approach Increasing Pain Severe Pain Moderate Pain Fentanyl Hydromorphone Methadone Morphine Oxycodone (+/- nonopioid) (+/- adjuvants) Mild Pain Codeine Oxycodone Tramadol (+/- nonopioid) (+/- adjuvants) Acetaminophen ASA NSAIDs/COXIBs (+/- adjuvants) World Health Organization. Cancer Pain Relief, with a Guide to Opioid Availability. Geneva, Switzerland: WHO, 1996. Leppert W, Luczak J. The role of tramadol in cancer pain management – a review. Support Care Cancer 2005;13:5-17.

  15. Mr. Pain’s Story • GP started him on hydromorphone contin • ↓ in pain • developed hives, urticaria & constipation

  16. Basic Considerations: Patient opioid exposure & experience Patient fears (stigma) Caregiver & physician attitudes, preferences & biases Compliance Convenience Cost Side effects Pharmaco-clinical Considerations: Patient sensitivities/allergies Administration & absorption limitations Metabolism & clearance Opioid profile Opioid Therapy: Getting Started Fine PG. Journal of Pain, Aug. 2001

  17. Hydromorphone: Key Points • ~ 5 x more potent than morphine • Fewer drug interactions • May be used cautiously in renal failure • Very soluble - up to 300 mg/ml • Available in oral liquid, IR tablets, CR capsules, IR suppositories, & injectable form. • Less sedation, less pruritis, less constipation & vomiting than morphine

  18. Physical Dependence pts. are physically acclimatized to the presence of the drug occurs with long-term opioid use pts will experience withdrawal if drug is withheld if opiod withdrawn quickly then withdrawal Predictable Tolerance Given dose that relieved pain no longer produces the same degree and duration of relief Addiction both physical & psychological components continuous craving & need for effects other than originally intended results in compulsive drug seeking behaviours the 4 C’s: impaired control over drug use, compulsive use, craving, continued use despite harm (consequences) Pain & Substance Abuse (Victoria House, 1998; Wickham, 2001)

  19. Screening for Addiction/Misuse Risk • Previous history of substance abuse/addiction • Family history of drug abuse &/or addiction • Previous “chemical coping” with life stresses • Significant psychiatric history • Previous high risk behaviours (esp. criminal activity) • High risk home environment

  20. Which opioid(s) would you use with Mr. Pain?

  21. Opioid Therapy: Which Approach? • Start with an IR opioid & titrate to effect When dose stable  CR opioid • fastest method for pain relief • Start with CR opioid & titrate dose q 1-3 days (or when side effects stable) • for stable, chronic pain • Start with CR opioid baseline dose & use IR opioid to titrate • once weekly (may be as soon as q2-4 days in patients with cancer), add the total daily dose of IR to the CR dose and repeat weekly until dose stable

  22. IR vs. CR Oral Opioids Note: These studies were conducted in healthy volunteers, or post-op

  23. IR vs. CR Oral Opioids

  24. Mr. Pain’s Story • GP switched to an equianalgesic dose of morphine i.e. 100mg BID. • Uticaria disappeared. No change in hives or constipation. • c/o mild, infrequent nausea. • Started to become agitated & experienced hallucinations.

  25. Opioid Rotation Changing one opioid to another When: if pain is or has been relieved with original opioid, but toxicity limits further dose titration Approximate dose ratio of two opioids required to produce a similar degree of analgesia “equianalgesic tables”

  26. Opioid Equianalgesic Doses 60-134mg oral morphine /day = 25 ug/hr td fentanyl1 Jovey R. et al. Managing Pain. p. 109 1 Health Cnada, 2009

  27. Morphine • “Natural” drug derived from opium poppy. • It’s the old standard NOT the gold standard. • Very effective orally (first pass through liver). • Duration of action for oral IR is ~ 4 hrs. & parenteral is ~ 3-4 hrs. • Active metabolites may accumulate in renal insufficiency leading to toxicity; not recommended in renal failure. • Fluctuating plasma levels can lead to variable efficacy & side effects. In the elderly bioavailability can be as low as 30%. • More sedating & GI s.e. than the semi-synthetic opioids. • More CNS effects in elderly (sedation, confusion, hallucinations) • •Histamine release (pruritis)

  28. What next?

  29. Codeine • 10% of the overall population lacks the enzyme (CYP450 2D6) required to metabolize codeine to active drug morphine • 2-5% of the population have relatively high amounts of the converting enzyme • Ceiling dose is 600 mg/day • Most constipating of all opioids • Some SSIs (Paxil, Prozac, Cymbalta) inhibit the conversion of codeine to morphine IR: 15mg, 30mg, 60mg tablets CR: 50, 100, 150, 200mg tablets

  30. Oxycodone Hydrochloride • Strong semisynthetic opioid; potency 2x > morphine • Conversion to oxymorphone may be inhibited by drugs such as fluoxetine • CR form is OxyContin®. • Dose initiation: 10mg q12h for opioid naïve • No pharmacological dose ceiling for pure opioid agonists. • Can be used with close monitoring in renal failure IR: 5, 10, 15mg tablets CR: 10, 20, 40, 80mg Jovey, R. et al Managing Pain 2008 , Pg 96

  31. Methadone • Powder, capsule, liquid, suppositories • Long half-life (q8h). Half-life variable making it unpredictable with repeated doses  sudden severe toxicity. • Variable equianalgesic dose to other opioids • Individual titration with close monitoring is extremely important • Special authorization from Health Canada • Many drug interactions with CYP450 3A4 • Less constipating; does not cause metabolite accumulation; less expensive • A good option in neuropathic pain

  32. Cytochrome P450 Drug Interaction Table University of Indiana Department of Medicine www.drug-interactions.com

  33. Fentanyl • Use if difficulty with oral meds; compliance issue; intractable side-effects • 25ug. of Fentanyl range is 60 - 134 mg oral morphine equivalents1 • 60mg of morphine or equivalent before switching to the 25ug. patch; 45mg if 12.5ug. patch. • When applying 1st patch continue with other pain medication x 24 hrs. • Rate of absorption can be affected by: fever, soap, oils, alcohol, shaving skin Duragesic patch: 12.5, 25, 50, 75, 100 ug. 1Health Canada, January 2009

  34. Sufentanil (sufenta) • Approximately 5 to 10 times more potent than fentanyl • Relieves pain by stimulating opiate receptors in CNS25-50 mcg SL/buccal. • Good choice for use just before activity. • Pt. teaching re: taking it.

  35. Tylenol # 3 • 300mg acetaminophen + 30mg of codeine in each tablet • 12 x Tylenol #3 (usual daily dose) = 3.6g total daily dose of acetaminophen & 360mg of codeine – this exceeds what is safely recommended for chronic use in healthy patients

  36. Acetaminophen*- Suggested Dose Ceilings 4 gm/day > 10 days in healthy, well-nourished patients – short-term use in healthy patients 3.2 gm / day for chronic use in healthy patients 2.6 gm / day chronically in at risk patients *Daily alcohol consumption, warfarin, fasting, a low protein diet, cardiac or renal disease increase the risk of hepatotoxicity Latta, 2000 http://pain.mc.duke.edu/mild_pain.cfm

  37. Tramadol • An opioid analgesic with a dual mechanism of action (weak affinity to the Mu receptor + inhibits the reuptake of serotonin & norepinephrine) • Recommended for the tx. of moderate - moderately severe pain. • CR tramadol can be initiated in opioid naïve at lowest dose • Less constipating then codeine • Maximum 400mg/day

  38. Immediate release (Tramacet) One tablet is 37.5mg Tramadol HCL/ 325mg of acetaminophen Maximum dose is 8 tablets per 24hours Beneficial for acute pain Extended release (Zytram XL1, Ralivia, Tridural) Doses 100mg, 150mg, 200mg, 300mg, and 400mg If on IR tramadol calculate 24 hr. dose & initiate total daily dose rounded down to nearest 100 mg, titrate up to max. of 400mg/day Tramadol Dosing

  39. What is the appropriate intervention for Pain’s opioid therapy? • Discontinue morphine and initiate tramadol. • Switch from MS Contin to OxyContin • Administer MS Contin once a day, rather than every 12 hours • Change dose of morphine and add a co-analgesic.

  40. Drug Selected: Oxycodone • Oxycontin 60mg (40mg & 20mg) BID • Oxy-IR 10mg q1hr. prn for BTP

  41. Breakthrough Pain • Always have BTP ordered: ensure it is adjusted if regular dose is adjusted. • 30-50% of regular dose q4hrs. (you may want to use 1/10 to 1/6 of the total daily dose usually q1hr.) • Same drug is usually used; may use other drugs. • >/= 3 doses BTP/24 hours add to regular dose • If pain is not improved after 1-2 BTP increments re-evaluate cause of pain.

  42. Based on Mr. Pain’s description of his pain, would you consider a co-analgesic?

  43. What co-analgesic would you add to Mr. Pain’s pain management plan? • Baclofen • Neurontin • Zoledronic acid • Nortiptyline

  44. What was Prescribed? • Neurontin (gabapentin) • 100mg BID x 2 days • 100mg TID x 2 days • 200mg TID daily • Baclofen 5mg q8hr • Senokot-S 2 tabs. at hs

  45. Which of the following side effects will you need to monitor when neurontin is initiated? • Constipation, nausea, itching, tremors, and hallucinations • Sedation, dizziness, nausea, confusion, and lower extremity edema • Ataxia, nausea, alterations in liver enzymes, and weight gain • Ataxia, nausea, vomiting, and diarrhea

  46. Neurontin • Proven indications: postherpetic neuralgia (PHN) & diabetic neuropathy • Widely considered to be first-line (co-analgesic) agent for neuropathic pain despite off label status • Fewest drug interactions of all AEDs • Common adverse effects: somnolence, dizziness, fatigue, ataxia, S & S of CNS depression

  47. Neurontin • 100-300mg mg qhs; PHN initiate at 300mg day 1, 600mg day 2 in divided dose, 900mg day 3 in divided dose, & titrated further as needed up to 1800-3600mg • Supplied in 100mg, 300mg, 400mg, 600mg, 800mg capsules • Dose reduction needed in renal compromise • Morphine increases the neurontin concentration in the blood

  48. What Other Co-analgesics are there?

  49. Antiepileptic Drugs • Neurontin • Pregablin (lyrica) • Lamotrigine • Well-tolerated with proven efficacy in neuropathic pain caused by neurotoxic anti-retroviral therapy in HIV-positive patients • Carbamazepine 100-200mg BID • Valproate 250mg daily to TID

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