Emerging knowledge and clinical experience Conflict of Interest None to declare Objectives Brief overview of areas of emerging knowledge F acilitated discussion of clinical experiences and evolution ID: 637856
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Slide1
Opioids: Helpful or Harmful?
Emerging knowledge and clinical experienceSlide2
Conflict of Interest
None to declareSlide3
Objectives
Brief
overview of areas of emerging knowledge
F
acilitated discussion of clinical experiences and evolution
of
clinical practice related to opioid therapySlide4
Historical Context
The mean opioid dose at St Christopher ‘s hospice in the 1970s was
30
mg of morphine per day
Hey Doc Can We Cut Down on the Pain Pills?
Current Status of Opioid Tapering Guidelines and How to Do it
Mellar
Davis, MD FAAHPM Mary Lynn McPherson, Pharm D Eric
Prommer
, MD, FAAHPM Kathryn A. Walker, Pharm D Slide5
Helpful, but…
New/nuanced understanding of opioid receptors and drug effects both acutely and chronically
Palliative = Chronic
P
ain management (unless clear disease progression/end-of-life)?
Opioid reduction as therapeutic measure
Source: Mellar P Davis MD FCCP FAAHPM Paul Sloan MD Opioids: What is New and Potentially Good 2017 Annual Assembly of Hospice and Palliative Care Slide6
Cellular Level
O
pioid receptors have many subtypes, variants; receptors form heterodimers
Downstream effects (
beta-
arrestin
, dynorphin)
Opioids from different classes produce different physiologic
effects
How do we separate analgesia from analgesic tolerance and various toxicities?
Source:
Mellar
P Davis MD FCCP FAAHPM Paul Sloan MD Opioids: What is New and Potentially Good 2017 Annual Assembly of Hospice and Palliative Care Slide7
I don’t understand this either…
Source: Mellar P Davis MD FCCP FAAHPM Paul Sloan MD Opioids: What is New and Potentially Good 2017 Annual Assembly of Hospice and Palliative Care Slide8
Acute pain
O
pioid
receptors
are constitutionally
activated by acute pain
(independent of endorphins) -> reduces pain sensitivity and this can remain for months (or years?
)
E
ffect
can be reversed by inverse agonists and exogenous opioids can interfere with this mechanism and prolong pain
Source:
Mellar
P Davis MD FCCP FAAHPM Paul Sloan MD Opioids: What is New and Potentially Good 2017 Annual Assembly of Hospice and Palliative Care Slide9
Chronic Pain Concepts
Catastrophization
, Depression
Central Sensitization and
Chronification
of pain – neuroplasticity
Opioid Syndrome:
• Unresolved pain
•
Frequent breakthrough doses despite stable
disease (escalation
independent of disease
course)
•
Withdrawal interpreted as recurrent or persistent disease
•
Analgesic tolerance at high doses
•
Hyperalgesia
‐increasing unpleasantness to
pain
and sensitivity
•
Altered social and occupational interactions
•
Distorted insight as to risks and harms to opioid therapy
Hey
Doc Can We Cut Down on the Pain Pills?
Current Status of Opioid Tapering Guidelines and How to Do it
Mellar
Davis, MD FAAHPM Mary Lynn McPherson, Pharm D Eric
Prommer
, MD, FAAHPM Kathryn A. Walker, Pharm D Slide10
Long‐term Opioid Side Effects
• Increased infections
• Increased cancer relapses?
•
Endocrinopathies
–central
hypogonadism
• Osteoporosis
•
Sarcopenia
• Falls and fractures
• Delayed healing of fractures
• Opioid induced depression
• Wound dehiscence
• Complex sleep apnea –obstructive and central
• Increased cardiovascular mortality
• COPD exacerbations/Pneumonia
• Increase mortality in at risk populations –COPD and chronic non – cancer pain
• Similar effects will be observed in patients with cancer on long‐term opioids‐there is no “opioid adverse effect immunity” with cancer
Hey Doc Can We Cut Down on the Pain Pills?
Current Status of Opioid Tapering Guidelines and How to Do it
Mellar
Davis, MD FAAHPM Mary Lynn McPherson, Pharm D Eric
Prommer
, MD, FAAHPM Kathryn A. Walker, Pharm D Slide11
Likely to Fail an Opioid Taper
D
epression and pain together
High
pain intensity prior to
taper
Experience of withdrawal prior to taper
Female
Smokers
No evidence-based guidelines, but some
literature to support different strategies
Hey Doc Can We Cut Down on the Pain Pills?
Current Status of Opioid Tapering Guidelines and How to Do it
Mellar
Davis, MD FAAHPM Mary Lynn McPherson, Pharm D Eric
Prommer
, MD, FAAHPM Kathryn A. Walker, Pharm D Slide12
Future Strategies
Combining opioids:
Better analgesia? Increased side-effects, e.g.
addiction?
Partial agonists?
Full analgesic response without side-effects? (buprenorphine)
Drugs with agonist/antagonist effects?
Full agonists can be added
to relieve pain
without
withdrawal
Strategic use of antagonists
Use of adjuvants to mitigate harmful effects
Source: Mellar P Davis MD FCCP FAAHPM Paul Sloan MD Opioids: What is New and Potentially Good 2017 Annual Assembly of Hospice and Palliative Care Slide13
Combining opioids
Some preclinical and clinical evidence for oxycodone + morphine, but not enough
evidence to
determine utility
Preclinical studies on fentanyl + morphine
Methadone + morphine: methadone synergy effects unrelated to NMDA, but (weak) clinical studies of
coanalgesic
methadone suggest benefit actually came from simply reducing the morphine
Source: Mellar P Davis MD FCCP FAAHPM Paul Sloan MD Opioids: What is New and Potentially Good 2017 Annual Assembly of Hospice and Palliative Care Slide14
Combining Opioids
Therapeutic windows can be narrow
Variables multiply: genetic variation, pain phenotype, region
Source: Mellar P Davis MD FCCP FAAHPM Paul Sloan MD Opioids: What is New and Potentially Good 2017 Annual Assembly of Hospice and Palliative Care Slide15
Buprenorphine
Seems to work differently in many ways
Possible synergy with other opioids
No
RCT
– need proper studies to determine utility, i.e. efficacy/adverse
effects Suboxone
now general ODB benefit; patch is expensive
Can cause withdrawal if rotation attempted from greater than 45-60 mg MEDD
Source: Mellar P Davis MD FCCP FAAHPM Paul Sloan MD Opioids: What is New and Potentially Good 2017 Annual Assembly of Hospice and Palliative Care Slide16
Agonist/antagonist Agents
Nalbuphine
Butorphanol
Source: Mellar P Davis MD FCCP FAAHPM Paul Sloan MD Opioids: What is New and Potentially Good 2017 Annual Assembly of Hospice and Palliative Care Slide17
Opioid antagonists
Peripherally acting mu-opioid receptor antagonist (
PAMORA
) =
Methylnaltrexone
,
Naloxegolnaloxone within
Targin
,
Suboxone
has minimal bioavailability via GI route – NB liver
disease increases systemic
absorption
Isomers of opioid antagonists that do not bind the opioid receptor but have good adjuvant effects
Source: Mellar P Davis MD FCCP FAAHPM Paul Sloan MD Opioids: What is New and Potentially Good 2017 Annual Assembly of Hospice and Palliative Care Slide18
Use of adjuvants
Haloperidol – preclinical studies – potential to mitigate adverse effects of methadone
NSAID
gabapentinoids
Source:
Mellar
P Davis MD FCCP FAAHPM Paul Sloan MD Opioids: What is New and Potentially Good 2017 Annual Assembly of Hospice and Palliative Care