©2011 MFMER | slide-1 Cancer Pain: Bridging the Knowledge Gap – Linking Musculoskeletal Medicine...
-
Upload
tracy-brown -
Category
Documents
-
view
221 -
download
4
Transcript of ©2011 MFMER | slide-1 Cancer Pain: Bridging the Knowledge Gap – Linking Musculoskeletal Medicine...
©2011 MFMER | slide-1
Cancer Pain:Bridging the Knowledge Gap – Linking Musculoskeletal Medicine with Opioid Therapy
Andrea L. Cheville, MD, MSCEProfessor and Research ChairDepartment of Physical Medicine and RehabilitationMayo Clinic, Rochester
AAPMR Annual AssemblyOctober 3, 2015
PAIN
“Pain is a more terrible Lord of mankind
than even death itself.”Albert Schweitzer
Overview
• Physiatric culture is opioid ambivalent• Function versus comfort??1
• Opioid-based pharmacotherapy is the international standard of care for cancer pain management
• “Dose to effect or side effect” is the longstanding paradigm
• Cancer is dynamic and deadly
©2011 MFMER | slide-3
1. Richard D. Zorowitz; Randall J. Smout; Julie A. Gassaway; Susan D. Horn. Usage of Pain Medications During Stroke Rehabilitation: The Post-Stroke Rehabilitation Outcomes Project (PSROP). Volume 12, Issue 4 (Fall 2005), pp. 37-49.
©2011 MFMER | slide-4
WHO Analgesic Ladder1
• Rung III - for severe pain: “strong” opioid, +/- nonopioid, +/- adjuvant
• Rung II - for moderate pain: “weak” opioid, +/- nonopioid, +/- adjuvant
• Rung I - for mild pain: nonopioid (NSAID’S, acetaminophen), +/- adjuvant
• Effectively manages neuropathic pain2,31. WHO. Cancer Pain Relief with a Guide to Opioid Availability. Zurich: World Health Organization; 1996.2. Grond S, Radbruch L, Meuser T, Sabatowski R, Loick G, Lehmann KA. Assessment and treatment of neuropathic cancer pain following WHO guidelines. Pain. Jan 1999;79(1):15-20.3. Mishra S, Bhatnagar S, Gupta D, Nirwani Goyal G, Jain R, Chauhan H. Management of neuropathic cancer pain following WHO analgesic ladder: a prospective study. Am J Hosp Palliat Care. Dec-2009 Jan 2008;25(6):447-451.
©2011 MFMER | slide-5
What are opioids?
©2011 MFMER | slide-6
©2011 MFMER | slide-7
Morphine
HydrocodoneDiacetyl-morphine
Oxycodone
Codeine
©2011 MFMER | slide-8
Methadone
MeperidineFentanyl
Visceral cancer pain
• Associated with distention• Colicky• Dull achy
• Challenging to localize
• Pharmacotherapy• Anti-inflammatories
• Dexamethasone• Delta receptor agonists
©2011 MFMER | slide-9
Incident cancer pain
• Temporal profile
©2011 MFMER | slide-10
©2011 MFMER | slide-11
Adapted from Weinberg DS, et al. Clin Pharm Ther. 1988;44:337.
0
10
20
30
40
50
60
70
80
Mea
n %
Abs
orbe
d
Mor
phine
(5.0)
Oxyco
done
(2.5)
Levor
phan
ol (1
.0)
Hydro
morph
one (
1.0)
Naloxo
ne (1
.0)
Meth
adon
e (5.0
)
Heroin
(2.5)
Meth
adon
e (0.8
)
Fentan
yl (0
.5)
Bupren
orph
ene (
0.1)
Opioid (dose in mg)
Rate of onset = route + lipophilicity
©2011 MFMER | slide-12
Morphine Oxycodone Fentanyl
Octanol/H2O partition 1.4 0.71 8132
coefficient (lipid solubility)
Keo T1/2 17 min3 N/A 3-5 min2 (time into CNS) N/A=Not available.
1 - Oxycontin PI. 2 - ACTIQ PI. 3 - Kramer TH, d’Amours RH, Buetner C. Clin Pharmacol Ther. 1996;59:132.
Lipid Solubility and CNS Equilibrium Times
Transmucosal fentanyl products
• Abstral® (fentanyl) sublingual tablets
• Actiq® (fentanyl citrate) oral transmucosal lozenge
• Fentora® (fentanyl buccal tablet)
• Lazanda® (fentanyl) nasal spray
• Onsolis® (fentanyl buccal soluble film)
• Subsys® (fentanyl sublingual spray)
• Generic equivalents
©2011 MFMER | slide-13
Fentanyl Concentration-Time Profiles – Different Routes of Administration
©2011 MFMER | slide-14
Ketamine
• NMDA antagonist
• History in pediatric anesthesia
• Analgesic and anti-inflammatory
• May induced dissociative states
• Dosing• Intranasal 10-50 mg.1
• Sublingual 25 mg.2
©2011 MFMER | slide-15
1. Carr D, Goudasa LC , Denman WT, et al. Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study. Volume 108, Issues 1–2, March 2004, Pages 17–27
2. Mercadante S, Arcuri E, Ferrera P, et al. Alternative Treatments of Breakthrough Pain in Patients Receiving Spinal Analgesics for Cancer Pain. Volume 30, Issue 5, November 2005, Pages 485–491.
Osseous cancer pain
©2011 MFMER | slide-16
©2011 MFMER | slide-17
Polypharmacy
• Antiresorbtives• Bisphosphonates• Denosumab (Xgeva)
• Anti-inflammatories• Dexamethasone• NSAIDs
• Co-analgesics• Calcitonin• Ion channel stabilizers• SNRIs
• Opioids
©2011 MFMER | slide-18
Opioids for neuropathic cancer pain
©2011 MFMER | slide-19
Cannot generalize from other neuropathic pain states
• RCT gabapentin ineffective for chemotherapy-induced peripheral neuropathy1
©2011 MFMER | slide-20
1. Rao RD, Michalak JC, Sloan JA. Efficacy of gabapentin in the management of chemotherapy-induced peripheral neuropathy. Cancer Volume 110, Issue 9, Pages 2110–2118
Opioids are effective for neuropathic pain
©2011 MFMER | slide-21
CR oxycodone for DM-related Neuropathic Pain
Objective: Evaluate analgesic efficacy and safety
Study Design: 6-week, double-blind, randomized parallel study in 160 subjects
Treatments: CR oxycodone 10 to 60 mg q12h versus placebo
Concomitant: NSAIDs, acetaminophen, and adjuvants
Medications: permitted at stable dose
Duration of Pain: 1) Physical evidence of polyneuropathy confirmed by abnormality on neurologic exam: sensory, motor, or reflex abnormality. 2) Pain 5 in both feet
Neuropathic Pain 2° Diabetic NeuropathySubject Daily Diary VAS
0
2
4
6
8
10
Basel
ine 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42
PLACEBO CR OXYCODONE
Overall Treatment P = < .002
Day
OxycodonePlacebo
Leas
t S
quar
e M
eans
Day
Larger context
• Stage IV lung cancer is rapidly progressive
• Lung metastasizes to osseous and neural tissues• Severe pain more common that in other cancers
• Uncouple acetaminophen
©2011 MFMER | slide-24