Transcript Changing Views in the Management of Short
Optimizing Opioids in Pain Management
Roman D. Jovey, M.D.
Physician Director Alcohol & Drug Treatment Program Credit Valley Hospital Complex Pain Consultant Mississauga, Ontario, Canada
April 1, 2003 An 89-year-old man who smothered his 85 year-old wife in her nursing home bed to end her pain will face murder charges, U.S. prosecutors said yesterday. Morris Meyer, who uses a wheelchair, told police his wife had begged him to help her die, so he made his way to her bed and held a pillow over her face.
The Dorsal Horn Synapse
Baclofen Endorphins Enkephalins Opioids Clonidine 2-methylserotonin
Nociceptor
GABA B µ § a 2 5-HT 3 Midozalam Citalopram GABA A
Dorsal Horn Cell
5-HT 1B Brookoff, 2000
Pain and Suffering The Importance of Genetics GENETICS Placebo Effect N O C E P I T I C O N COMT MORs 2D6 Codeine P A I N COMT Emotions Cognition (vigilance) Environment SUFFERING
Clinical Significance of the Basic Science of Pain
Not all pains are the same
Not all patients have the same pain sensitivities
Not all patients have the same pain relief from opioids
Not all patients have the same side effects of opioids
Not all opioids are the same
Not all opioid receptors are the same Not all mu opioid receptors are the same Pasternak, 2001
Why use opioids at all?
Chronic Pain Treatment Options PHYSICAL Normal activities Aquafitness Physio
Passive
Active Stretching Conditioning Weight training Splinting / Taping TENS TMS / TCNS Massage Chiropractic Acupuncture Dolphin PSYCHOLOGIC Hypnosis Stress Management Cognitive Behavioural Family therapy Psychotherapy Mindfulness Based Stress Reduction PHARMACOLOGIC INTERVENTIONAL OTC medication CAM Topical medications NSAIDs / COXIBs DMARDs Immune modulators Tricyclics / AEDs Opioids Local anesthetic congeners Muscle relaxants Sympathetic agents NMDA blockers CGRP blockers I.A. steroids I.A. hyaluronan Trigger Pt Therapy IMS / Prolotherapy Nerve Blocks Botox Epidurals Orthopedic Neurotomy Neurectomy Implantable stimulators Implantable pain pumps
Future Pharmacotherapies
CGRP antagonist
NMDA blockers
Cannabinoids
COX inhibitors
Bradykinin antagonists
Glutamamte antagonists
Substance P and Neurokinin antagonists
Tetrodotoxin / Omega conotoxins
CCK blockers
TRPVR1 agonist
Opioids continue to be our most potent pain reliever
Treating Chronic Pain… Pharmacotherapy BENEFIT RISK
Acetaminophen
Used for mild-moderate nociceptive pain
Good evidence in post-op pain
No placebo-controlled evidence in chronic arthritis pain
(Case, 2003)
Acetaminophen – not a benign drug
Hepatotoxicity
GI bleeding / perforation
Chronic renal failure
Hypertension
Zimmerman, 1995, 2000; Bromer, 2003; Garcia Rodriguez, 2001; FDA 2004; Health Canada Feb. 2003; Curhan 2002.
U.S. Mortality Data, 1997 25000 20000 15000 10000 5000 0 Le uk em ia AID S NS AID s ET OH M VA s My elo ma As thm a Ca Ce rvi x Ho dg kin s
Singh G. Am J Med 1998 Wolfe M. NEJM, 1999
If you take an NSAID > 2 mo…
1/5 chance of an endoscopic ulcer
1/70 chance of a symptomatic ulcer
1/150 chance of a bleeding ulcer
1/1200 chance of dying Henry McQuay 10 th World Congress on Pain, 2002 http://www.jr2.ox.ac.uk/bandolier/booth/painpag/nsae/nsae.html
Approximately 1900 Canadians die annually due to NSAID-related adverse effects *
Canadian Arthritis Society www.arthritis.ca
* more than the total number of deaths due to MVCs, fires and gunshot wounds combined
COXIBs
Concurrent ASA nullifies the GI protective effect
Increased cardiovascular risk (Vioxx) Howard PA, 2004 Topol E, NEJM 2004
Delayed fracture healing in animals Simon AM. 2002 Gerstenfeld LC, 2004
NSAIDs and COXIBs
10-17% of patients develop increased BP Cheng HF. Hypertension, 2004
Acute and chronic kidney toxicity
DeMaria AN. JPSM 2003
Double the risk of hospitalization for CHF Garcia-Rodriguez LA. Epidemiology 2003
Increased miscarriage risk Li DK. BMJ 2003
Adjuvant Analgesics Toxicity
Carbamazepine – liver, hematological
Valproic Acid – liver, hematological
Gabapentin – liver
Tricyclics – cardiac, anticholinergic
Mexiletine – cardiac, liver, hematological
Topiramate - kidney stones
Opioids have never been shown to cause organ damage when taken therapeutically.
Opioids are physically the safest pain reliever available.
Opioids can cause harm when they are misused.
Prescription Opioid Abuse DAWN Data – United States
100000 90000 80000 70000 60000 50000 40000 30000 20000 10000 1996 1997 1998 1999 2000 2001 Opioid Analgesic Related ED Visits
New Users of Illicit Drugs in the Past Year 3,500,000 3,000,000 2,500,000 2,000,000 1,500,000 1,000,000 500,000 0 Pain Meds THC Cocaine Ecstacy Tranquilizers Heroin 1965 1970 1975 1980 1985 1990 1995 1999 2000
U.S. National Household Survey on Drug Abuse, 2001
Past Year Abuse or Dependence (DSM IV) on Alcohol or Illicit Drugs by Age 25 20
%
15 10 5 0
12 --1 3 14 -1 5 16 -1 7 18 -1 9 20 -2 1 22 -2 3 24 -2 5 26 -2 9 30 -3 4 35 -3 9 40 -4 4 45 -4 9 50 -5 4 55 -5 9 60 -6 4
Age
>6 5 U.S. National Household Survey on Drug Abuse, 2001
Prescription Opioid Addiction Treatment Episode Data System, TEDS
2.50
2.00
1.50
1.00
0.50
0.00
19 96 19 97 19 98 19 99 20 00 20 01
It really comes down to a question of balance
Appropriate Use vs Abuse: Maintaining the Balance
The FEW who misuse prescribed opioids should not penalize the OVERWHELMING MAJORITY who use opioids appropriately
Treat pain sufferers + minimize drug diversion
Assess for risk factors Prescribe carefully Monitor behaviours suggestive of misuse/abuse, or addiction
Can we predict who will misuse prescribed opioids?
Risk factors for misuse / addiction
Family history
Previous history of alcohol abuse / addiction
Previous history of drug abuse / addiction
Serious untreated psychiatric problems
Previous criminal behaviour
High risk home environment
Opioidology 101
Optimizing opioid use for pain
When to Consider Opioid Therapy for Chronic Pain … Unrelieved pain
+
Decreased QoL
+
Failure of usual treatments
Opioids work best when dosed to effect
Dosing to effect means…
Reasonable pain relief or Unmanageable and persistent side effects
Some people respond to a small dose. Others require a much higher dose to adequately treat their pain.
Each patient responds uniquely to a given opioid at a given dose with an individual side effect response.
Opioid Side Effects
Nausea/constipation Sedation during titration (driving, work) Pruritis/sweats Dysphoria/psychotomietic effects Dry mouth/urinary retention Hyperalgesia/myoclonus Opioid-induced edema Hormonal effects Reflux symptoms (Immune dysfunction)
Stable dose, titrated, scheduled, LTO does not cause clinically significant cognitive impairment:
Hendler N. et al. Amer J Psychiatr 1980 Zacny JP. Exp Clin Psychopharmacol 1995 Vainio A. et al. Lancet 1996 Zacny JP. Addiction 1996 Lorenz J. et. al. Pain 1997 Haythornthwaite JA, et al. JPSM 1998 Sjogren P,et al. Pain; 2000 Galski T, et al. JPSM 2000 Chapman S. Clin J Pain 2002 Sabatowski R. et al. JPSM 2003 Tassain V. et al. Pain; 2003 Fishbain DA. Et al. JPSM 2003
The response to an excess of side effects vs. pain relief is to switch opioids
Optimizing Opioid Therapy “In short, we need to move beyond inadequate trials of single opioids at fixed doses to sequential opioid trials, titration for individual patients, and management of side effects.”
K. Foley, M.D. NEJM 2003; 348(26):2688-9
Treatment Goals
Decrease pain
Improve function
Minimize adverse effects
Opioids are not magic !
Not all pains in all patients will respond.
Opioids have side effects - like any other medication
High risk patients on therapeutic opioids can manifest abuse / addiction.
Prescribed opioids can be diverted.
We have a responsibility to society to prescribe and monitor carefully to minimize as much as possible the harm due to misuse and diversion
BUT…
Opioids are our most potent pain reliever They do not cause organ damage They are underutilized due to exaggerated fears of addiction One cannot predict response without a trial of therapy They work best as part of a multi-modal treatment approach
“Men stumble over the truth from time to time, but most pick themselves up and hurry off as if nothing happened.” Winston Churchill