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
