Opioids: Helpful or Harmful? - Palliative care

Opioids: Helpful or Harmful? - Palliative care

Opioids: Helpful or Harmful? Emerging knowledge and clinical experience Conflict of Interest None to declare Objectives Brief overview of areas of emerging knowledge Facilitated discussion of clinical experiences and evolution of clinical practice related to opioid therapy

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 Helpful, but New/nuanced understanding of opioid receptors and drug effects both acutely and chronically Palliative = Chronic Pain 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 Cellular Level Opioid 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 B i- m o d a l O p io id M o d u la tio n w ith D o s e B i-m o d a lly A c tin g O p io id R e c e p to r s , , . E x c i t a to r y M ode In h i b i t o r y M ode

+ G M 1 G a n g lio s id e G s B l o c k e d b y e ith e r C T X - A o r C T X -B G 1 B lo c k e d

by PTX A C /c A M P A C /c A M P P r o te in k in a s e K + c o n d u c ta n c e E x c i t a to r y e f f e c t s ( a n ti - a n a l g e s i a ) G

O C a 2+ c o n d u c ta n c e I n h i b i to r y e ffe c t s (a n a lg e s ia ) I dont understand this either Source: Mellar P Davis MD FCCP FAAHPM Paul Sloan MD Opioids: What is New and Potentially Good 2017 Annual Assembly of

Acute pain Opioid receptors are constitutionally activated by acute pain (independent of endorphins) -> reduces pain sensitivity and this can remain for months (or years?) Effect 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 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 Hyperalgesiaincreasing 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

Longterm Opioid Side Effects Increased infections Increased cancer relapses? Endocrinopathiescentral 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 longterm opioidsthere 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 Likely to Fail an Opioid Taper

Depression 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 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

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

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 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 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 Opioid antagonists Peripherally acting mu-opioid receptor antagonist (PAMORA) = Methylnaltrexone, Naloxegol naloxone 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 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

Recently Viewed Presentations

  • Resurrection: It changes Everything

    Resurrection: It changes Everything

    Typical response to opposition - fear. 16 And we have come to know and to believe the love that God has for us. God is love, and the one who remains in love remains in God, and God remains in...
  • Présentation PowerPoint

    Présentation PowerPoint

    With Interpoles specificitieseg fragments. Only data sets and collections. At Data center level. Assigning several DOI (with different prefixes) for the same data sets is forbidden. ENVRI FAIR ? GO FAIR ? DIrection du Numérique, de l'exploitation et des Opérations.
  • Star Wars

    Star Wars

    Harrison Ford/Han Solo. BIRTH DATE July 13, 1942 . EDUCATION . Ripon College. PLACE OF BIRTH . Chicago, Illinois. Harrison Ford is one of Hollywood's leading men, with an acting career that has spanned nearly 40 years and included iconic...
  • Extended Mast Terminal for Lightning Protection System Improvement

    Extended Mast Terminal for Lightning Protection System Improvement

    * * Content Introduction Lightning Data Lightning Protection System Experience on Improvement of LPS for HV and EHV lines Indonesia; Maritime Continent St. Petersburg, Rusia Java Island & Bali Bali Island East Java Overvoltage due to Lighnting at Transmission Lines...
  • Adverb Clauses - Shelby County Schools

    Adverb Clauses - Shelby County Schools

    Adverb Clauses An adverb clause is a dependent clause that modifies, or describes, the verb in the independent clause of a complex sentence. Just like adverbs, adverb clauses tell how, when, where, why, or under what condition. Subordinating Conjunctions Subordinating...
  • Power and the People, c1170-2016

    Power and the People, c1170-2016

    A tool developed during war to remove arrow heads from wounds without causing more damage. ... Plot the events on the mini timeline, giving their dates. TOPIC: ... The Boer War. Second World War. First World War.
  • Quality improvement - Quality data leads to quality connections:

    Quality improvement - Quality data leads to quality connections:

    QCancer® RAT is a tool to that can give a risk of a patient having a current but as yet undiagnosed cancer taking account of their risk factors and current symptoms. It does not give a diagnosis cancer, but a...
  • HANTAVIRUS: VIRAL EVOLUTION Chelsea, Zuania, Keerthana, Eduardo Transmission

    HANTAVIRUS: VIRAL EVOLUTION Chelsea, Zuania, Keerthana, Eduardo Transmission

    Uses nsRNA genome as a cap snatching device. steals end of host mRNA genome. migration of newly formed hantaviral proteins. Deterministic Model (ODEs) Conceptual Diagram. Stochastic Model (SDEs) Adds Brownian motion. Quasispecies (viral evolution)