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 85year-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
Endorphins Enkephalins
Opioids
Clonidine
Baclofen
2-methylserotonin
GABAB µ
§
Nociceptor
Midozalam
GABAA
a2
5-HT3
Citalopram
Dorsal Horn Cell
5-HT1B
Brookoff, 2000
Pain and Suffering
The Importance of Genetics
GENETICS
N
O
C
I
C
E
P
T
I
O
N
COMT
P
A
MORs
I
N
Placebo
Effect
COMT
Emotions
Cognition (vigilance)
Environment
2D6
Codeine
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
CognitiveBehavioural
Family therapy
Psychotherapy
MindfulnessBased Stress
Reduction
PHARMACOLOGIC
OTC medication
CAM
Topical medications
NSAIDs / COXIBs
DMARDs
Immune modulators
Tricyclics / AEDs
INTERVENTIONAL
I.A. steroids
I.A. hyaluronan
Trigger Pt Therapy
IMS / Prolotherapy
Nerve Blocks
Botox
Epidurals
Opioids
Orthopedic
Local anesthetic
Neurotomy
congeners
Neurectomy
Muscle relaxants
Implantable
Sympathetic agents stimulators
NMDA blockers
Implantable pain
CGRP blockers
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
in
s
Ho
dg
k
Ca
Ce
r
vix
a
hm
As
t
lo
m
a
My
e
MV
As
s
ET
OH
NS
AI
D
S
AI
D
Le
uk
em
ia
0
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
10th 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
Opioid Analgesic
Related ED Visits
50000
40000
30000
20000
10000
1996
1997
1998
1999
2000
2001
New Users of Illicit Drugs
in the Past Year
Pain Meds
THC
Cocaine
Ecstacy
Tranquilizers
Heroin
3,500,000
3,000,000
2,500,000
2,000,000
1,500,000
1,000,000
500,000
0
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
>6
5
-64
60
-59
55
-54
50
-49
45
-44
40
-39
35
-34
30
-29
26
-25
24
-23
22
-21
20
-19
18
-17
16
-15
14
12
--1
3
0
Age
U.S. National Household Survey on Drug Abuse, 2001
Prescription Opioid Addiction
Treatment Episode Data System, TEDS
2.00
1.50
1.00
0.50
20
01
20
00
19
99
19
98
19
97
0.00
19
96
Percent of total admissions
2.50
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