Mount Sinai Pain Fellowship Lecture Series

1. Overview and Medical Management of Cancer Pain YuryKhelemsky, M.D. Anesthesiology and Pain Medicine

4. 1300 outpatients with metastatic cancer approximately 2/3 had cancer-associated pain

6. 540 hospitalized cancer patients found that 85 percent of those with bone involvement had pain which required analgesic medication compared to only 5 percent of those with leukemia

7. 200 patients referred to a specialized cancer pain clinic, pain was caused by tumor growth in about 80 percent of cases.

10. #1, mild pain, utilizes nonopioid and adjuvant drugs.

11. #2, an opioid is added for increasing pain.

12. #3, most severe pain, more potent opioids are used. This approach is designed to be simple to understand and usable around the world.

15. Realize that anxiety and depression may exacerbate, rather than exaggerate, the pain.

17. Faces Pain Scale, originally designed for use in children, may be useful in cognitively-impaired patients

18. McGill Pain Questionnaire (MPQ): best, but not self administered and takes up to 20 min

19. Memorial Pain Assessment Card: rapid assessment

21. Pathophysiology:noxious mechanical, thermal, or chemical stimuli which trigger nociceptors. Ischemia, inflammation, and perhaps substances produced by a nearby tumor may sensitize nociceptors to ordinarily nonnoxious stimuli.

23. Often associated with nausea and diaphoresis

24. Examples of primary and referred visceral pain in patients with cancer include the pain associated with pancreatic cancer, small bowel obstruction, and pleuritis

25. Mechanisms not well characterized, but visceral autonomic afferents may be involved

27. Usually constant but may be interrupted by paroxysms of dramatically increased pain. There may be no area of tenderness, or areas of exquisite sensitivity to normally innocuous stimuli (allodynia).

28. Symptoms and signs of autonomic instability (eg, tachycardia, sweating)

30. Demyelinated axons may become sites of ectopic activity and aberrant (ephaptic) conduction of C or A-delta fiber impulses

31. NMDA receptors may be involved in perception and maintenance of neuropathic pain is suggested by the response to treatment with ketamine (also methadone).

33. Opioid Therapy

35. Evidence to support improved efficacy of combination drugs (i.e. percocet, etc.) is limited in cancer pain

36. NSAIDs (ketorolac) may also be useful in the treatment of neuropathic pain

38. Dyspepsia and Gastric Ulceration: relative protection with coxibs. Take with food, misoprostol, H2 Blockers, PPI.

39. Nephrotoxicity: prescribe with caution in CRI

40. Hepatotoxicity: even at recommended doses, esp. with EtOH use or starvation. LFT elevations usually mild and reversible after d/c Rx.

41. HTN: all may increase BP

45. Not clear if low-dose co-administration of ASA mitigates risk

47. Predictably induce tolerance to and physical dependence on their effects. Despite the development of tolerance to opioid analgesia, disease progression is usually responsible for increasing analgesic requirements

49. Initial agents: start with short half-life drugs (morphine, oxycodone, fentanyl, etc.). Once pain becomes constant transition to longer acting agents.

51. Levorphanol t(1/2): 16hrs

52. Excellent oral bioavailability even in short bowel conditions

53. Rectal, SL, IV

54. Both difficult to titrate as initial duration of action (4-6hrs) much shorter than t(1/2), may lead to accumulation during initial 2-5 days. Consider starting as PRN.

55. Methadone may be effective for neuropathic pain and prevention of tolerance due to NMDA antagonism in dorsal horn

58. Double-blind, randomized, crossover comparison of tramadol and morphine in 20 patients with severe cancer pain.Equivalent pain ratings were achieved with both drugs. Constipation and nausea were less severe and total side effects were fewer with tramadol.

60. Like tricyclic antidepressants, it lowers the seizure threshold, so avoid in patients with brain tumors

61. Less likely to cause respiratory depression and constipation than equianalgesic doses of pure opioids, but does cause dizziness, nausea, dry mouth, and sedation.

62. Can accumulate in renal failure, decrease dose

63. Avoid use in patients taking SSRI, SNRI, TCA (seratonin syndrome)

65. Agonist/Antagonist: Pentazocine, Nalbuphine, Butorphanol

66. All have ceiling effect

67. Sigma receptor agonism ((pentazocine (Talwin) and butorphanol (Stadol)) may cause delirium

69. After five or six half-lives(steady state plasma concentration), one day for morphine, the basal daily opioid requirement is determined and a long-acting opioid preparation is substituted (75% total requirment). This should be provided regularly to prevent most pain.

70. An additional short-acting opioid (5 to 15 percent of the basal daily requirement) is made available for breakthrough pain every 3-6 hrs.

73. Onset of analgesia 12-14hrs after application and continues 16-24hrs after removal. Some patients may require q48h (not q72h) reapplication

75. Hydromorphone is the drug of choice

77. 25 to 50 percent dose reduction to account for incomplete cross-tolerance for large dose conversions

78. Additional short-acting opioid should be made available while titrating the new drug to achieve stable analgesia

85. Choice of drug is empiric, no clearly superior drug

86. Amitriptyline, imipramine, or doxepin are more sedating.

87. Nortriptyline is less sedating; Desipramine has fewest S/E

88. Best given in evening due to sedation

89. Greater analgesia is seen with higher doses

90. Persistent treatment esssential: may take 4-6wks for analgesia

92. Antihistaminergic: sedation and weight gain

93. alpha-1 and alpha-2 adrenergic blockade contribute to orthostatic hypotension and tachycardia.

94. Most of these side effects diminish with time (except dry mouth) and are not life-threatening

96. Carbamazepine: start 100mg q12h. Sedation, vertigo, ataxia, hyponatremia, skin reactions, reversible hepatotoxicity, bone marrow suppression, rarely aplastic anemia (monitor CBC and LFTs).

98. Clonazepam may be an effective coanalgesic when used for lancinating neuropathic pain and myoclonus

100. Hydroxyzine (50 to 100 mg IM) may be used in conjunction with opioids for acute pain and for cancer pain.

102. Topical lidocaine may provide temporary relief of oral mucositis

104. A Cochrane analysis of two randomized placebo-controlled trials concluded calcitonin provides no benefit to patients with metastatic bone pain.

107. Topical capsaicin has been useful for the treatment of mucocutaneous neuropathic pain, postmastectomy pain, PHN.

108. Studies have been complicated by difficulty in blinding because the active preparation causes a burning sensation.

110. N/V: due to direct effect on chemoreceptor trigger zone, enhanced vestibular sensitivity, and slower gastric emptying. Tolerance develops quickly.

111. If nausea follows meals, use metoclopramide. If occurs with movement use meclizine.

112. Otherwise, use 5HT3 antagonists (ondansetron).

114. Not all are equally constipating (fentanyl less than morphine)

115. All must be on colace and senna prophylaxis

116. Treat (if not obstructed) with lactulose, polyethylene glycol, magnesium citrate, bisacodyl suppository, sodium phosphate, oral mineral oil, etc.

117. Methylnaltrexone: peripherally acting opioid antagonist. 8mg (38-61kg), 12mg (62-114kg) SC qd.

118. Naloxone po (1-12mg): 3% bioavailable

120. Modafinil, a novel, nonamphetamine does not produce tolerance and may cause fewer side effects

122. Questions?