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![Page 1: Optimizing Opioids in Pain Management Roman D. Jovey, M.D. Physician Director Alcohol & Drug Treatment Program Credit Valley Hospital Complex Pain Consultant.](https://reader036.fdocuments.in/reader036/viewer/2022062407/56649e225503460f94b0f97c/html5/thumbnails/1.jpg)
Optimizing Opioids in Pain Optimizing Opioids in Pain ManagementManagement
Roman D. Jovey, M.D.Physician Director
Alcohol & Drug Treatment ProgramCredit Valley Hospital
Complex Pain ConsultantMississauga, Ontario, Canada
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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.
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The Dorsal Horn SynapseThe Dorsal Horn Synapse
BaclofenBaclofenEndorphinsEndorphins
OpioidsOpioidsEnkephalinsEnkephalins
ClonidineClonidine
2-methylserotonin2-methylserotonin
GABAB µ§
a2
5-HT3Nociceptor
MidozalamMidozalam CitalopramCitalopram
5-HT1BDorsal Horn Cell
GABAA
Brookoff, 2000Brookoff, 2000
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Pain and SufferingPain and Suffering The Importance of Genetics The Importance of Genetics
Environment
SUFFERINGSUFFERING
PP
AA
II
NN
NNOOCCIICCEEPPTTIIOONN
Emotions
Cognition (vigilance)
GENETICS
COMTCOMT
MORs
Codeine
Placebo Effect
2D6
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Clinical Significance Clinical Significance of the Basic Science of Painof 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
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Why use opioids at all?Why use opioids at all?
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Chronic Pain- Chronic Pain- Treatment OptionsTreatment Options
PHYSICALPHYSICAL PSYCHOLOGICPSYCHOLOGIC PHARMACOLOGICPHARMACOLOGIC INTERVENTIONALINTERVENTIONAL
Normal activitiesAquafitnessPhysio Passive ActiveStretchingConditioningWeight trainingSplinting / TapingTENSTMS / TCNSMassageChiropracticAcupunctureDolphin
HypnosisStress ManagementCognitive-BehaviouralFamily therapyPsychotherapyMindfulness- Based Stress Reduction
OTC medicationCAMTopical medicationsNSAIDs / COXIBsDMARDsImmune modulatorsTricyclics / AEDs
OpioidsLocal anestheticcongenersMuscle relaxantsSympathetic agentsNMDA blockersCGRP blockers
I.A. steroidsI.A. hyaluronanTrigger Pt TherapyIMS / ProlotherapyNerve BlocksBotoxEpiduralsOrthopedicNeurotomyNeurectomyImplantable stimulatorsImplantable pain pumps
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Future PharmacotherapiesFuture Pharmacotherapies
CGRP antagonist NMDA blockers Cannabinoids COX inhibitors Bradykinin antagonists Glutamamte antagonists Substance P and Neurokinin antagonists Tetrodotoxin / Omega conotoxins CCK blockers TRPVR1 agonist
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Opioids continue to be our Opioids continue to be our most potent pain relievermost potent pain reliever
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Treating Chronic Pain… Treating Chronic Pain… PharmacotherapyPharmacotherapy
BENEFIT RISK
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AcetaminophenAcetaminophen
Used for mild-moderate nociceptive pain Good evidence in post-op pain No placebo-controlled evidence in chronic
arthritis pain (Case, 2003)
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Acetaminophen – not a benign drugAcetaminophen – 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.
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U.S. Mortality Data, 1997U.S. Mortality Data, 1997
0
5000
10000
15000
20000
25000
Singh G. Am J Med 1998Wolfe M. NEJM, 1999
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If you take an NSAID > 2 mo…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 10th World Congress on Pain, 2002
http://www.jr2.ox.ac.uk/bandolier/booth/painpag/nsae/nsae.html
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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
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COXIBsCOXIBs
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
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NSAIDs and COXIBsNSAIDs 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
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Adjuvant AnalgesicsAdjuvant AnalgesicsToxicityToxicity
Carbamazepine – liver, hematological Valproic Acid – liver, hematological Gabapentin – liver Tricyclics – cardiac, anticholinergic Mexiletine – cardiac, liver, hematological Topiramate - kidney stones
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Opioids have never been Opioids have never been shown to cause organ shown to cause organ damage when taken damage when taken
therapeutically.therapeutically.
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Opioids are physically the Opioids are physically the safest pain reliever safest pain reliever
available.available.
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Opioids can cause harm Opioids can cause harm when they are misused.when they are misused.
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Prescription Opioid AbusePrescription Opioid AbuseDAWN Data – United StatesDAWN Data – United States
10000
20000
30000
40000
50000
60000
70000
80000
90000
100000
1996 1997 1998 1999 2000 2001
Opioid AnalgesicRelated ED Visits
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New Users of Illicit Drugs New Users of Illicit Drugs in the Past Year in the Past Year
0
500,000
1,000,000
1,500,000
2,000,000
2,500,000
3,000,000
3,500,000
1965 1970 1975 1980 1985 1990 1995 1999 2000
Pain Meds
THC
Cocaine
Ecstacy
Tranquilizers
Heroin
U.S. National Household Survey on Drug Abuse, 2001
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Past Year Abuse or Dependence (DSM IV) Past Year Abuse or Dependence (DSM IV) on Alcohol or Illicit Drugs by Age on Alcohol or Illicit Drugs by Age
0
5
10
15
20
25
%
Age
U.S. National Household Survey on Drug Abuse, 2001
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Prescription Opioid AddictionPrescription Opioid AddictionTreatment Episode Data System, TEDSTreatment Episode Data System, TEDS
0.00
0.50
1.00
1.50
2.00
2.50
1996
1997
1998
1999
2000
2001
Per
cent
of t
otal
adm
issi
ons
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It really comes down to a It really comes down to a question of balancequestion of balance
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Appropriate Use vs Abuse:Appropriate Use vs Abuse:Maintaining the BalanceMaintaining 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
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Can we predict who will Can we predict who will misuse prescribed opioids?misuse prescribed opioids?
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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
Risk factors for misuse / addictionRisk factors for misuse / addiction
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Opioidology 101Opioidology 101Optimizing opioid use for pain
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When to Consider Opioid Therapy When to Consider Opioid Therapy for Chronic Pain …for Chronic Pain …
Failure of usual treatments
Unrelieved pain
+
Decreased QoL+
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Opioids work best Opioids work best when dosed to effect when dosed to effect
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Dosing to effect means…Dosing to effect means…
Reasonable pain reliefReasonable pain relieforor
Unmanageable Unmanageable andand persistent persistent side effectsside effects
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Some people respond to a Some people respond to a small dose. Others require a small dose. Others require a
much higher dose to much higher dose to adequately treat their pain.adequately treat their pain.
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Each patient responds Each patient responds uniquely to a given opioid at uniquely to a given opioid at
a given dose with an a given dose with an individual side effect individual side effect
response.response.
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Opioid Side EffectsOpioid 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)
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Stable dose, titrated, scheduled, LTO Stable dose, titrated, scheduled, LTO does not cause clinically significant does not cause clinically significant cognitive impairment: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
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The response to an excess of The response to an excess of side effects vs. pain relief is to side effects vs. pain relief is to
switch opioidsswitch opioids
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Optimizing Opioid TherapyOptimizing 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
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Treatment Goals Treatment Goals
Decrease pain
Improve function
Minimize adverse effects
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Opioids are not magic !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.
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We have a responsibility to society to prescribe and monitor carefully to minimize as much as possible the harm due to misuse and diversion
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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
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““Men stumble over the truth from time Men stumble over the truth from time to time, but most pick themselves up to time, but most pick themselves up
and hurry off as if nothing happened.”and hurry off as if nothing happened.”
Winston Churchill Winston Churchill