CLINICAL PRACTICE AND
SAFETY IN PERSISTENT PAIN
MANAGEMENT
Chris Herndon, PharmD
Associate Professor
Southern Illinois University Edwardsville
Disclosures
• Nothing to disclose
Objectives
• Define tolerance, addiction, hyperalgesia, misuse, abuse,
diversion, and aberrant drug taking behaviors
• Describe the risks versus benefits of opioid therapy in the
treatment of persistent noncancer pain
• Identify methods for stratifying risk of misuse among
patients with chronic pain
• Develop monitoring strategies for patients requiring
chronic opioid therapy based on risk level
Important Definitions
• Dependence
• Addiction (substance abuse disorder)
• Aberrant drug taking behavior
• Misuse
• Abuse
• Diversion
• Tolerance
• Pseudo-addiction (oligo-analgesia)
• Hyperalgesia
The Challenge in Treatment
Untreated or
undertreated
pain
Overdose,
abuse,
diversion
Important Definitions
• Dependence
a physiologic, receptor response to an exogenous substance and
the result from removing that substance
• Addiction (substance abuse disorder)
• Aberrant drug taking behavior
• Misuse
• Abuse
• Diversion
• Tolerance
• Pseudo-addiction (oligo-analgesia)
• Hyperalgesia
Important Definitions
• Dependence
• Addiction (substance abuse disorder)
Impaired control over drug use, compulsive use, continued use
despite harm, cravings
• Aberrant drug taking behavior
• Misuse
• Abuse
• Diversion
• Tolerance
• Pseudo-addiction (oligo-analgesia)
• Hyperalgesia
Important Definitions
• Dependence
• Addiction (substance abuse disorder)
• Aberrant drug taking behavior
Any drug-related behaviors other than taking the med exactly as
prescribed
• Misuse
• Abuse
• Diversion
• Tolerance
• Pseudo-addiction (oligo-analgesia)
• Hyperalgesia
Important Definitions
• Dependence
• Addiction (substance abuse disorder)
• Aberrant drug taking behavior
• Misuse
• The use of a medication, FOR THERAPEUTIC INTENT, other than
exactly as directed by the prescriber
• Abuse
• Diversion
• Tolerance
• Pseudo-addiction (oligo-analgesia)
• Hyperalgesia
Important Definitions
• Dependence
• Addiction (substance abuse disorder)
• Aberrant drug taking behavior
• Misuse
• Abuse
The use of a substance for a non-medical purpose to alter one’s
state of conciousness
• Diversion
• Tolerance
• Pseudo-addiction (oligo-analgesia)
• Hyperalgesia
Important Definitions
• Dependence
• Addiction (substance abuse disorder)
• Aberrant drug taking behavior
• Misuse
• Abuse
• Diversion
Knowingly transferring a controlled substance to a recipient other
than for whom the substance is prescribed
• Tolerance
• Pseudo-addiction (oligo-analgesia)
• Hyperalgesia
Important Definitions
• Dependence
• Addiction (substance abuse disorder)
• Aberrant drug taking behavior
• Misuse
• Abuse
• Diversion
• Tolerance
A state of pharmacological adaptation to a drug in which either
efficacy or side effects diminish over time and higher doses are
required to maintain effect
• Pseudo-addiction (oligo-analgesia)
• Hyperalgesia
Important Definitions
• Dependence
• Addiction (substance abuse disorder)
• Aberrant drug taking behavior
• Misuse
• Abuse
• Diversion
• Tolerance
• Pseudo-addiction (oligo-analgesia)
exhibiting aberrant or addicted behaviors due to undertreatment of a
legitimate pain syndrome
• Hyperalgesia
Important Definitions
• Dependence
• Addiction (substance abuse disorder)
• Aberrant drug taking behavior
• Misuse
• Abuse
• Diversion
• Tolerance
• Pseudo-addiction (oligo-analgesia)
• Hyperalgesia
A phenomenon in which stimuli that hurt induce a response greater
than expected. Opioid-induced hyperalgesia is represented by a
worsening of pain with escalation of dose
Webster LR, Fine PG. Approaches to improve pain relief while minimizing abuse liability. J Pain 2010;
11(7):602-611.
Guidelines on opioid use
Guideline
Yes or No?
Caveats
Chou (APS & AAPM)
Yes, moderate to
severe pain ; benefits
outweigh risks
Risk assessment,
strict monitoring, and
exit strategies
Am Geriatrics Society
Yes, moderate to
severe pain; benefits
outweigh risks
What is conventional
practice for pain
syndrome?
Is prescriber qualified
or should specialist be
consulted
Trescot (ASIPP)
Maybe, severe pain;
benefits must strongly
outweigh risks
Provides decision
algorithm and
extensive review, no
clear recs
1. Chou R, et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain
2009;10(2):113-130.
2. American Geriatrics Society. Pharmacologic management of persistent pain in older persons. J Am Geriatr Soc
2009;57:1331-1346.
3. Trescot AM, et al. Opioids in the management of chronic non-cancer pain: An update of American Society of
Interventional Pain Physicians’ Guidelines. Pain Physician 2008;11(2 Suppl):S5-S62.
Cochrane Systematic Review:
Long-term opioid management for chronic noncancer pain
Route
Discontinued Discontinued
AE
Lack of
Efficacy
Oral (n=3040)
22.9%
10.3%
Transdermal
(n = 1628)
12.1%
5.8%
Intrathecal
(n = 231)
7.6%
Aberrant
Behavior
0.27%
7.6%
Noble M, Treadwell JR, Tregear SJ, Coates VH, Wiffen PJ, Akafomo C, Schoelles KM. Long-term opioid
management for chronic noncancer pain. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.:
CD006605. DOI: 10.1002/14651858.CD006605.pub2
What is considered “high dose”
Walker JM, et al. Chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing. J Clin Sleep Med
2007;3(5):455-461.
How and what should we monitor (inpatient)?
• Opioid induced sedation
• Ramsay
• Pasero Opioid-Induced Sedation Scale (POSS)
• Respiratory depression
• Respiratory rate < 8? 10?
• Continuous pulse-oximetry
• End-tidal capnography
Jarzyna D, et al. American Society for Pain Management Nursing guidelines on monitoring for opioid-induced sedation and
respiratory depression. Pain Management Nursing 2011;12(3):118-145.
Validated Risk Assessment Tools
Acronym of toolα
Number of questions
Completion
Time to complete
SOAPP®-R
24 items
Self-report
< 10 minutes
DIRE
7 items
Clinician administered
< 5 minutes
ORT
5 items
Clinician administered
< 5 minutes
COMM
40 items
Self-report
< 10 minutes
CAGE
4 items
Either
< 5 minutes
PDUQ
42 items
Clinician administered
20 minutes
STAR
14 items
Self-report
< 5 minutes
SISAP
5 items
Clinician administered
< 5 minutes
PMQ
26 items
Self-report
< 10 minutes
α - SOAPP®-R (Screener and Opioid Assessment for Patient’s in Pain-revised); DIRE (Diagnosis, Intractability, Risk, and Efficacy); ORT
(Webster’s Opioid Risk Tool); COMM (Current Opioid Misuse Measure); CAGE (Cut-down, Annoyed, Guilt, Eye-opener); PDUQ
(Prescription Drug Use Questionnaire); STAR (Screening Tool for Addiction Risk); SISAP (Screening Instrument for Substance Abuse
Potential); PMQ (Pain Medication Questionnaire)
Example of common screening tool
Opioid Risk Tool
Family history of substance abuse
Female
Male
Alcohol
1 point
3 points
Illegal drugs
2 points
3 points
Prescription drugs
4 points
4 points
Personal History of Substance abuse
Female
Male
Alcohol
3 points
3 points
Illegal Drugs
4 points
4 points
Prescription Drugs
5 points
5 points
Age (16 yrs to 45 yrs)
1 point
1 point
Preadolescent sexual abuse
3 points
0 points
Depression
1 point
1 point
ADD, OCD, Bipolar, or Schizophrenia
2 points
2 points
Low Risk 0 – 3 points, Moderate Risk 4 – 7 points, High Risk > 8 points
Webster LR, Webster RM. Predicting aberrant behaviors in opioid treated patients. Pain Med 2005;6(6)432-42.
Opioid Metabolism
Phase I
Enzyme(s)
Metabolite (s)
Phase II
Enzyme/Metaboli
te
Buprenorphine
CYP 3A4
Norbuprenorphine
UGT/ Glucoronides
Codeine
(Prodrug)
CYP 2D6, CYP 3A4
Morphine,
Noroxycodone
UGT/ Glucoronides
Fentanyl
CYP3A4
Norfentanyl
N/A
Hydrocodone
CYP 2D6
CYP 3A4
Hydromorphone
Norhydrocodone
UGT/Glucoronides
Hydromorphone
N/A
N/A
UGT/Glucoronides
Methadone
CYP 3A4, 2D6,
2C19, 2C8, 2C9,
2B6
EDDP
N/A
Morphine
N/A
N/A
UGT/Glucoronides
(A)
Oxycodone
CYP 2D6
CYP 3A4
Oxymorphone
Noroxycodone
UGT/Glucoronides
Oxymorphone
N/A
N/A
UGT/Glucoronides
Tapentadol
CYP2D6, 2C9 &
2C19 (all minor)
Inactive metabolites
UGT/Glucoronides
Drug Testing
• Biological specimens
• Urine, blood, hair, saliva, sweat, and nails
• All have different specificity and sensitivity
• Urine mostly preferred
• Ease of collection
• Possibly higher drug concentrations and longer detection window
Urine Drug Screen
• Immunoassay
• Most commonly used
• Disadvantage – false positives
• Gas chromatography – mass spectrometry (GC –MS)
• Confirmatory test for specific drug
• More sensitive and reliable
• Disadvantage - Cost
* Know which test your institution uses are what compounds are being
tested
Length Detection Time in Urine
Drug
Time
Codeine
48 Hours
Hydromorphone
2 -4 Days
Methadone
3 Days
Morphine
48 – 72 Hours
Oxycodone
2 -4 Days
Alcohol
7 – 12 Hours
Cocaine
2 -4 Days
Marijuana
Single Use
Moderate Use (4x’s/week)
Daily Use
Long – Term Heavy Smoker
3 Days
5 – 7 Days
10 – 15 Days
> 30 Days
Moeller KE, Lee KC, Kissack JC. Urine drug screening: practical guide for clinicians. Mayo Clin Proc.
2008;83(1): 66-76.
Achieving Safe
Use While Improving
Patient Care
Presented by CO*RE
Collaboration for REMS Education
www.core-rems.org
Presented by CO*RE
Collaboration for REMS Education
www.corerems.org
Collaborative for
REMS Education
Patient Counseling Document
Required for CR / LA REMS
• DO
• Read the med guide
• Take exactly as prescribed
• Flush unused meds down toilet
• Call healthcare provider for med advise or SE
• DON’T
• Give your medicine to others
• Take medicine unless prescribed for you
• Stop taking your medicine without direction
• Break, chew, crush, dissolve, or inject your medicine
• Drink alcohol while taking this medicine
http://www.er-la-opioidrems.com/IwgUI/rems/pdf/patient_counseling_document.pdf. Accessed 10/12/12.
Patient-Prescriber Agreement Form
Required for TIRF REMS
Appropriate Documentation
• The 4 “As” of pain management
• Analgesia
• Adverse effects
• Aberrant drug taking behavior
• Activity
• Diagnosis, prognosis, and correlation of symptoms
Pathways for primary care
Chronic Disease Management
Principles
Risk
assessment
Policies and
expectations
Education /
referral
Treatment
agreements
Risk
management
Assessment
Opioid risk
tools
Office visits
Individual
Consent
PMP review
Validated
scales
Psychiatric
screens
Nursing
utilization
Group
Educational
Drug
screening
The 4 “A”s
Previous
record review
ED utilization
Punitive
Pill count
Frequency of
visits
Refill policies
Conduct
agreements
Case
discussion
Non-pharm
adherence
VAS: visual analog scale; NRS: numeric rating scale; BPI: Brief Pain Inventory; MPQ: McGill Pain Questionnaire; NPRS:
Neuropathic Pain Rating Scale
Conclusions