Transcript Slides [PowerPoint]

PAIN MANAGEMENT
Terry J. Baumann, Pharm.D., BCPS
[email protected]
Clinical Pharmacy Pain Practitioner
Clinical Manager
Department of Pharmacy
Munson Medical Center
Traverse City, Michigan
OBJECTIVE
Geek
• A performer often billed as a wild man
whose act usually includes biting off the
head of a live chicken or snake (Merriam Webster’s
Dictionary 10th Edition)
THE PROBLEM
• 116 million Americans suffer chronic/persistent pain
(Institute of Medicine’s Committee on Advancing Pain Research publication
“Relieving Pain in America” 2011)
– Direct medical costs AND loss of productivity - $560 – 635 billion per
year
– Conflicting problems of untreated pain AND opioid abuse ADDS to this
overall cost
• Morbidity secondary to pain twofold greater in patients
over 60
• Seen in 40-85% of patients in long term care facilities
• One month before death, 66% report pain frequently or
all the time
• In chronic/persistent non-cancer patients 50% respond to
treatments with reduction in pain of 30% (ref #75)
PAIN IN AMERICA
• Phone survey-Hart Research Associates July 2003 (1,004
adults)
• 76% personally/family member/friend suffer from chronic
pain-57% personally
• Pain types
–
–
–
–
–
Back pain – 28%
arthritis/joint pain – 19%
Headaches/migraines – 17%
Knee pain – 17%
Shoulder pain 7%
• Every age group affected
–
–
–
–
18-34 -- 54%
35-49 -- 56%
50-64 -- 63%
65+ -- 57%
PAIN IN AMERICA
• 75% make life-style adjustments
– 20% Disability from work, 17% change jobs, 13% help with daily
living, 13% move to another home
• 90% did seek professional help
–
–
–
–
–
–
Rx 69% (58% effective)
Chiropractic Tx (54% effective)
Surgery 32% (54% effective 0
Physical therapy 48% (48% effective)
OTC medications 79% (41% effective)
Other Tx 20% (40% effective)
• 72% physicians supportive, 51% of bosses supportive
• 57% would be willing to pay an extra $1.00 a week in
taxes to pay for more pain research
DEFINITION OF PAIN
Pain is an unpleasant sensory and emotional
experience associated with actual or potential tissue
damage, or described in terms of such damage.
ALTERNATIVE DEFINITION OF PAIN
Pain is whatever the patient says/feels it is, existing
whenever
he or she says/indicates it does.
TYPES OF PAIN
• ACUTE
– Follows injury
– Generally disappears when injury heals
– Well-defined temporal onset
• CHRONIC
– Persists beyond expected healing time
– Cause may be hard to define
• CANCER
– Definable cause
– Can be acute, recurrent, or chronic
CHARACTERISTICS OF ACUTE AND
CHRONIC/PERSISTENT PAIN
CHARACTERISTICS ACUTE PAIN
CHRONIC/PERSISTENT PAIN
Relief of Pain
Highly Desirable
Highly Desirable
Dependence &
Tolerance
Unusual
Physiological
Component
Usually Not Present
Organic Cause
Common
Family & Environment Involvement
Small
Sleep Problems
Unusual
Treatment Goal
Cure
Common
Often a Problem
Often Not Present
Significant
Common
Rehabilitation
& Acceptance
Trends
• Acute procedural pain (surgery, labor and delivery) well
addressed (ref #71)
• Chronic pain continues to be inadequately addressed (40%
report ineffective treatment) (ref #71)
– A subpopulation exists where opioids do not help and
may make overall situation worse
• Analgesic ADEs and errors large problem
• Recognition/perception that prescription opioids are a large
part of illicit drug use problem
Pendulum Swings
(according to TJB)
• Under-treatment of cancer pain (1960-1970’s)
• Development of sustained release opioids (1980’s)
• Development of devices that allowed patients to deliver
own opioids (1980’s)
• Better definition of addiction (1980-1990’s)
• Use of opioids in chronic pain (1990-2010’s)
• Guidelines for use of opioids (2001-2010)
• Better defined use of opioid in non-cancer pain? 2011 - ?
• ????
NEWS STORIES ABOUT OPIOIDS
• Survey: Illegal Drug Use, Prescription Medication Abuse Increased
Among Americans (AFP 9/17/10)
• Nation’s Hospitals Seeing Increase in Overdoses Related to Opioid
Prescriptions (Tulsa World 7/17/11)
• Growing number of Newborns have Painkiller Addiction (NPR/WUSF
2/17/11)
• Deaths from Rx Painkillers Still Rising (Med page today 2/17/11)
• Inappropriate Use of Prescription Pain Relievers Caused Nearly
425,000 ER Visits in 2009 (CBS affiliate KHQA-TV Hannibal MO,
8/8/12)
• Drug overdoses tripled in New York City 1990-2006 and most of
increase due to growing abuse of prescription pain meds (New York
Times 2/12/12)
• 11th straight year deaths due to drug overdoses increased –
pharmaceuticals “especially, opioid analgesics, have driven increase
(ABC World News 2/19/13)
NEWS STORIES ABOUT OPIOIDS
• CDC Director calls painkiller overdoses an epidemic (State
WV Journal 11/2, The Oregonian 11/2, CBS Evening News 11/1, Los Angeles
Times 11/2, NPR 11/2, HealthDay 11/2, Medscape 11/2)
– “More Americans now die from overdosing on
painkillers than from overdosing on heroin and cocaine
combined”…”deaths linked to opioid pain relievers
such as OxyContin, Vicodin, and Opana have become
an epidemic…the rate of deaths has more than tripled in
the past decade” CDC Director Thomas Frieden
Evidence of Opioid Misuse
• Misuse of Opioids Doubles Over Five-Year Period (CDC MMWR
2010;59:705-709)
– ED cases involving nonmedical use of opioid analgesics increased
from 144,600 (2004) to 305,900 (2008)
• Patients receiving higher doses of opioids at higher risk of overdose
(Ann Intern Med. 2010, 152(2): 85-92.)
– Close supervision of higher risk patients warranted
• Unintentional drug overdose is second leading cause of death in US
with 40% due to Rx opioids (NEJM. 2010, Nov 18; 363: 1981)
• Among patients receiving opioid prescriptions for pain, higher doses
were associated with increased risk for over overdose death (JAMA.
2011, 305(13): 1315-1321)
– Risk clear what about solution ?
“Perfect Storm” of increasing
pain and increasing opioid
misuse, abuse and diversion
(ref #74)
TREATING CRONIC NONCANCER
PAIN WITH OPIOIDS (ref 76)
• AAPM AND APS believe Rx of opioids should be
extension of good professional practice
– Evaluation of patient-physical exam, pain history, pain
impact on patient, review of previous diagnostic
studies, drug history, coexisting diseases/conditions
– Treatment plan-consideration of all aspects of treatment
(behavioral, physical therapy, noninvasive techniques,
physical and psychosocial support, and medication)
• If opioid trial selected risks should be explained to patient and
family, and informed consent OR signed agreement
obtained
• NO TRIAL WITHOUT COMPLETE ASSESSMENT OF
PAIN COMPLAINT
TREATING CHRONIC NONCANCER
PAIN WITH OPIOIDS (ref #76)
• AAPM AND APS believe Rx of opioids should be
extension of good professional practice
– Consultation as needed
• Pain specialist, psychologist, pharmacist
– Periodic review of treatment efficacy
• Assess functional state of patient, continued analgesia, side
effects, quality of life, indications of medication misuse, use
urine drug screens
– Documentation
• Reason for opioid, overall treatment plan, periodic review
TREATING CHRONIC NONCANCER
PAIN WITH OPIOIDS
• Evaluate risk factors for abuse (ref #76)
– Personal history of alcohol or drug abuse
– Family history of alcohol or drug abuse
– Younger age and presence of psychiatric conditions
– Use of screening tools
• Screener and Opioid Assessment of Patients with
Pain (SOAPP version 1 or SOAPP-R)
• Opioid Risk Tool
TREATING CHRONIC NONCANCER
PAIN WITH OPIOIDS
• Signs of drug seeking behavior (DEA)
–
–
–
–
–
Unusual behavior in waiting room
Extremes in dress (way over or under dressed)
Comes in at irregular hours (on call doc only)
Must be taken care of NOW
Reluctant or unwilling to provide reference information, no
regular physician
– Traveling through town, visiting relative, no permanent
address
– Uses child or elderly person when seeking pain medications
– Pressures care giver with guilt
TREATING CHRONIC NONCANCER
PAIN WITH OPIOIDS
• Watch for diversion (ref 54)
• Patients continually trying to fill Rx early despite dose
agreements
• Frequent reports of lost or stolen Rx
• Use multiple pharmacies and multiple prescribers
• Is noncompliant with other treatments
• Unusual quantity
• Quantity looks altered
• Reports allergies to all other drugs
Risk Evaluation and Mitigation Strategies
(REMS)
• FDA approved class-wide REMS for long acting opioids (2012)
– 1) Prescriber training (provided by manufacturer and not
mandatory)
– 2) NEW Medication Guides (www.er-la-opioidrems.com)
– 3) REMS implementation responsibility falls on pharmaceutical
companies
– 4) Administrative requirements
Petition Letter to FDA
(Pain and Palliative Care PRN, List serve, posted Richard Wheeler,
8/1/12)
• 37 Physicians (Physicians for Responsible Opioid Prescribing)
• Strike the term “moderate” from the indication for use of opioids in
non-cancer pain
• Add maximum daily dose, equivalent to 100mg of morphine for noncancer pain
• Add maximum duration of 90 days for continuous (daily) use for noncancer pain
• Response (Professionals for Rational Opioid Monitoring
and Pharmacotherapy)
Dr. Jeffry Fudin (posted 1/23/2013)
• IT IS NOT OK TO:
– Drink alcohol with opioids
– Use someone else’s medication
– Take more medication than instructed
BALANCING NEWS STORIES
ABOUT OPIOIDS
• “Taking legal, FDA approved opioid medications as
prescribed, under the direction of a physician for pain
relief, is safe and effective, and only rarely leads to
addiction. When properly used, these medications rarely
give a “high”-they give relief. And, most importantly, they
allow many people to resume their normal lives”
Dr. James Campell, Professor of Neurosurgery at
Johns Hopkins Medical Center, past president
Of the American Pain Society, and Chairman of
The American Pain Foundation (ref 53)
IF WE CANNOT ASSESS PAIN, WE WILL
NEVER BE ABLE TO RELIEVE PAIN.
Betty R. Ferrell, Ph.D.
ASSESSMENT OF PAIN
• Careful history
– Believe the patient and family
• When you dislike patients, pain is taken less
seriously (ref #77)
– Assess the nature of the pain
— Acute pain
– Distinct onset, short duration, physical signs
— Chronic/Persistent pain
– Long duration, long-standing
functional impairment
– Consider neuropathic pain
ASSESSMENT OF PAIN
• CONSIDER ONSET, WHAT MAKES PAIN BETTER
OR WORSE, LOCATION, DESCRIPTION, SEVERITY,
AND DOES PAIN MOVE?
• Consider multiple pain types and/or sites.
• Assess psychosocial status
– Emotional, Social, Cultural
• Assess functional status.
MEDICATION HISTORY
• All medications used in the
past six months
– Dose
– Duration of use
– Frequency of use
– Reason for use
– Perception of efficacy
• Social drug use (Do not forget alcohol)
• What worked, how well they worked, what did
not
• Side effects
• Allergies
• Nonprescription drug use
• Nutritional supplements
• Alternative therapies
PAIN TREATMENT PLAN
DEVELOPMENT
• Develop treatment plans using assessment tools and,
whenever possible, include patient and family input.
• Remember in chronic pain it is unrealistic in most cases to
expect COMPLETE relief of pain.
• Do systematic and ongoing reassessments with functional
end points in mind.
• Change the plan as needed.
• Document the plan and all changes.
• The process should never end.
The Joint Commission
Sentinel Event Alert
 Issue 49 concerning the safe use of opioids in hospitals was
published on August 8, 2012
 Opioid analgesics rank among drugs most frequently associated
with adverse drug events (as high as 16% in one trial)
 This may be due to:
– Lack of knowledge about potency differences
– Improper prescribing and administration of multiple opioids
and modalities of administration
– Inadequate monitoring
The Joint Commission. Sentinel Event Alert. 2012;(49):1-5.
Davies EC et al. PLoS One. 2009;4(2):e4439.
.
Evidence from The Joint Commission
Sentinel Event Database
The Joint Commission. Sentinel Event Alert. 2012;(49):1-5.
Selected Risk Factors for Oversedation and Respiratory
Depression
 Sleep apnea or sleep
disorder diagnosis
 Morbid obesity
 Snoring
 Older age
 No recent opioid use
 Post-surgery status
 Opioid habituation
 Longer length of time
receiving general anesthesia
 Use of other sedating drugs
 Pre-existing pulmonary or
cardiac disease, dysfunction, or
major organ failure
 Thoracic or other surgical
incisions that may impair
breathing
 Smoker
The Joint Commission. Sentinel Event Alert. 2012;(49):1-5.
Actions suggested by TJC
• Monitoring
Guidelines/Policies
• Assessment
Procedures
Effective
• Standardized
Processes
Order Sets
• Second Level
Review
•
•
•
•
Orientation
Newsletters
Healthstream
Encourage multi-modal
adjuvant therapies
Safe
Technology
Education
Training
•
•
•
•
Bar Code Scanning
Smart Pumps
EtCO2 monitoring
Computer Decision
Support Alerts
Effective
Tools
• Assessment Tools
• Pain Scales
• Risk Assessment Tools
Opioid
Risk Assessment Project
Risk Factor
Number
Obesity (BMI > 30)
5
Respiratory Disease
7
Renal Dysfunction (SCr > 1.5)
6
History of Chronic Pain
9
Concomitant BZD’s/muscle relaxants
5
Sleep Apnea
2
Three or more opioids prescribed
7
Opioid naïve
4
Total number of patients analyzed = 14. BMI: body mass index.
SCr: serum creatinine. BZD: benzodiazepine.
Opioid
Risk Assessment Project
Risk Factor
Number
Obesity (BMI > 30)
4
Respiratory Disease
4
Renal Dysfunction (SCr > 1.5)
4
Concomitant BZD’s/muscle relaxants
4
Sleep Apnea
2
Three or more opioids prescribed
5
Total number of chronic pain patients analyzed = 8. BMI: body mass index.
SCr: serum creatinine. BZD: benzodiazepine.
Additional Strategies to Improve Patient
Care & Safety
• Pain Resource Nurse
– Adopted from University of Wisconsin Pain Resource
Nurse Program
– On-going education
• Pain Committee
• Ad Hoc Opioid Safety Committee
– PCA Monitoring
– Risk Assessment/increased monitoring
• Continuous End-Tidal CO2, SPO2, monitoring
– Pasero opioid-induced sedation scale
Additional Strategies to Improve Patient
Care & Safety
• Pain Medication Order Set
– Hydromorphone IV doses adjusted
• Fentanyl patch – computer prompts
– Patient has chronic pain?
– Pain is stable in severity?
– Patient has “significant” opioid use?
• Methadone
• DUE – Fentanyl
OPIOID ANALGESICS
• Pharmacologic activity depends on affinity for opiate
receptors.
• Agents do not eliminate pain, but decrease its
unpleasantness.
• Some variability in onset and duration of action.
• Key to effective use is individualization
and proper titration
OPIOID ANALGESIC ADVERSE
EFFECTS
• Mood changes (minimized with careful titration)
– Dysphoria (may be seen as agitation in elderly)
– Euphoria or paradoxical excitement
• Cognitive disturbances (minimized with careful titration)
• Somnolence (minimized with careful titration)
– Drowsiness
– Inability to concentrate; apathy
– Increase in falls
OPIOID ANALGESIC ADVERSE
EFFECTS
• Respiratory depression (minimized with careful titration)
– RARE after receiving several weeks
•
•
•
•
•
Nausea and vomiting (tolerance usually develops)
Increased sphincter tone
Urinary retention
Histamine release
Pruritus
– Rarely, exacerbation of asthma
OPIOID ANALGESIC ADVERSE
EFFECTS
• Decreased gastrointestinal motility and secretion
– Unlike most other adverse effects that are transient or are avoided
with careful titration, this IS TO BE EXPECTED!
– Methylnaltrexone (Relistor) sub-q (Block receptors in GI
tract)
– Use an aggressive bowel regimen
• Lots of fluid
• Plenty of dietary fiber
• Stimulants
• Stool softeners
– by themselves are often ineffective
• Bulk-producing laxative ??
OPIOID ANALGESIC ADVERSE
EFFECTS
Consensus statement American Academy of Pain Medicine (AAPM), American Pain
Society (APS), American Society of Addiction Medicine (ASAM) Feb 2001
• Tolerance – a state of adaptation in which exposure to a
drug induces changes that result in a diminution of one or
more of the drug’s effects over time.
– Always a possibility
– Easily confused with change in pain status
– May be minimized with regular dosing
– Increase dose to achieve effective analgesia
OPIOID ANALGESIC ADVERSE
EFFECTS
Consensus statement American Academy of Pain Medicine, American Pain Society,
American Society of Addiction Medicine Feb 2001
• Physical Dependence – a state of adaptation that is
manifest by a drug class specific withdrawal syndrome that
can be produced by abrupt cessation, rapid dose
reduction, decreasing blood level of the drug, and/or
administration of an antagonist.
– Rarely seen with short-term use
– Slow wean will prevent withdrawal symptoms
• determined by length of time on therapy and why on
therapy
OPIOID ANALGESIC ADVERSE
EFFECTS
Consensus statement American Academy of Pain Medicine, American Pain Society,
American Society of Addiction Medicine Feb 2001
• Addiction – a primary, chronic, neurobiologic disease,
with genetic, psychosocial, and environmental factors
influencing its development and manifestations. It is
characterized by behaviors that include one or more of the
following: impaired control over drug use, compulsive use,
continued use despite harm, and craving.
– Inability to take meds as Rx’d, frequent lost/stolen Rx,
Doc shopping, isolation, intoxication
– No single event is diagnostic of addictive disorder,
diagnosis is pattern of behavior over time
OPIOID ANALGESIC ADVERSE
EFFECTS
Consensus statement American Academy of Pain Medicine, American Pain Society,
American Society of Addiction Medicine Feb 2001
• Addiction – a primary, chronic, neurobiologic disease,
with genetic, psychosocial, and environmental factors
influencing its development and manifestations. It is
characterized by behaviors that include one or more of the
following: impaired control over drug use, compulsive use,
continued use despite harm, and craving.
– Usually not seen in chronic pain, risk is unknown,
exposure to drugs only one of etiologic factors
– An individual’s behavior that may suggest addiction
sometimes a reflection of unrelieved pain or problems
unrelated to addiction (Pseudoaddiction)
OPIOID ANALGESICS
• Equianalgesic dosing
– Can use reference guides (better tables being
developed)
– Use only as a guide
– Individual titration and constant reassessment a
must
– What-How well-How long-End Point
Opioid Conversion Chart
• Demystifying Opioid Conversion
Calculations (A guide for effective dosing)
Mary Lynn McPherson – American Society
of Health System Pharmacists, Bethesda,
MD 2010.
(Whose “slide rule” are you using????)
Terry Baumann e-mail
[email protected]
Other Opioids and
Conversions
• Need to know
– What is being treated
– How is patient doing on present dose
– How long has the patient been treated on this
dose
– What are the other drugs used to treat the
patient
– What is the end point
Case Studies
• 77 YO female
• “Cancer” Pain
• Taking 10, oxycodone 5mg/acetminophen
325mg daily
• Physician wants to switch to fentanyl patch
• Check table = 25 mcg/hr every 72 hours
• Correct?
Case Studies
•
•
•
•
Compression Fracture
Terminal COPD
Long standing lymphoma
Severe pain (10/10) when moves, otherwise pain
2/10
• Was on 1-2 tablets a day until resent visit to
daughter
• No other pain medications
• New dose?
Case Studies
• Low back pain (10 years)
• Terminal COPD, history of breast cancer 15 years
ago
• Pain on scale 5/10
• Has taken the same amount if
oxycodone/acetaminophen with very little change
for 6 months
• Taking no other pain medications
• New dose?
Case Studies
• Aggressive breast cancer with metastasis, new low
back pain, pain in right leg
• Pain scale 9/10 most of time
• Taking 1-2 oxycodone/acetaminophen 5/325 until
two weeks ago with pain 3/10, two days ago
patient on 6 of above, yesterday 10
• Patient also on lorazepam and ibuprofen
• New Dose?
OPIOID ANALGESICS
• Allergies
– True allergies rare
– Chance of cross sensitivity decreased between
• Morphine-like agonists
• Meperidine-like agonists
• Methadone-like agonists
MORPHINE
• NOT drug of last resort
• Drug of choice for severe acute pain
• Morphine myths
– Causes unmanageable side effects
– It sedates patient too much
– Morphine causes “addiction”
– Tolerance a huge problem
MORPHINE
• Metabolism
– Very little excreted unchanged
– Morphine-6-glucuronide is renally
eliminated
• decrease dose and careful
titrate in patients with renal
impairment
• Cardiovascular effects
• IV time to peak 15 minutes –
duration 2-4 hours
MORPHINE
• Dosage forms/routes
– Oral
• Immediate release
– Solution - Caution - (100 mg/5ml,
20mg/5ml , 10mg/5ml )vs
/tablet
• Sustained release
– q24 vs q12 vs q8
– EMBEDA (no more than every 12 hours)
» Naltrexone released when product
crushed blunting effect of morphine
– Inhalation
– Rectal
– Parenteral
• Subcutaneous/IM/IV,
• Epidural (DepoMorphine)/intrathecal
FENTANYL
• Transdermal patch available
– q 72 hours
– 12-24 hours to steady state (depots in skin)
– 6 days after increasing dose to steady state
– Chronic nonmalignant pain and cancer
pain only
– Increased body temperature can change the
way patch delivers fentanyl
FENTANYL
• Formulation (FDA approved November 1998) Oral
Transmucosal Fentanyl Citrate (Actiq)-flavored sugar
lozenge for treatment of breakthrough cancer pain
– Many transmucosal dosage forms now
available
– Lower strength patch (may be better suited for
nursing facility patients)
– Buccal tablets available (not mcg to mcg same as
lozenge)
– Some Patches can burn patient in MRI
CODEINE
• Moderate pain only
– analgesia due to morphine metabolite
– antitussive actions probably involve codeine
– Many are advocating STOPPING its use in Peds
• In kids with polymorphism in genes coding for
CYP2D6 isoenzyme (which transforms codeine to
morphine) risk of death increase – ultra-rapid
transformation of codeine to morphine
• No better than ibuprofen in reducing pain?
• Works best when combined with acetaminophen or
NSAID
• Watch acetaminophen in combination product
• Same propensity as morphine to produce tolerance,
dependence, and constipation
CODEINE
Ref 91
• One to 7 of every 100 persons are ultrarapid metabolizers
• FDA’s safety review of codeine - 10 pediatric deaths and 3 overdoses
between 1969 and 2012. The children were aged 21 months to 9 years;
many were recovering from tonsil or adenoid surgery for obstructive
sleep apnea. All received codeine that was within the recommended
dose range. Signs of overdose developed within 1 to 2 days.
• The new boxed warning and contraindication state that codeine
should not be used for postoperative pain management in children
undergoing tonsillectomy or adenoidectomy.
• Codeine can be prescribed only for children with other types of pain if
the benefits are expected to outweigh the risks
• Children taking codeine should be monitored closely for signs of
morphine overdose
OXYCODONE AND HYDROCODONE
• Most often seen in combination products with
aspirin or acetaminophen
• Use in moderate to severe pain
• Hydrocodone Schedule II ???
• Different schedules, same efficacy
• Same pharmacology as morphine
• Long Acting Hydrocodone
(Zohydro)
SUSTAINED-RELEASE OXYCODONE
• 10, 20, 40, 80 mg dosage forms
– Q 12 hour dosing
• Breakthrough medication
- Immediate-release oxycodone
- Oxecta – New formulation
• Use in chronic pain
• Formulations Changing (induced by
misuse)
– Purdue ER Oxycodone (hard plastic
polymer making tablet hard to crush)
HYDROMORPHONE
• More potent than morphine
• Fast oral absorption
– Favorite street drug
• Very soluble
– Use when need a highly concentrated narcotic solution
(intrathecal, subcutaneous)
• Pharmacology very similar to morphine
• ER Hydromorphone (Exalgo) – {REMS}
– Osmotic release oral release alters pharmacokinetics
thus decreasing abuse potential
• IV Dose = POTENTIAL DANGER-DANGER
OTHER MORPHINE-LIKE AGONISTS
• Oxymorphone
– Can be administered rectally and by injection
– Offers no advantages over morphine
- Extended Release and immediate release
oral solids available 2006
• Levorphanol
– Extended half-life
– Effects similar to morphine
– Should not be used in the elderly as it may
accumulate
MEPERIDINE
• Particularly HAZARDOUS in the elderly
– Normeperidine accumulation can lead to
delirium and seizures
– Contraindicated in renal failure
– Interaction with MAOIs
• Less potent and shorter duration than morphine
– If administered, should be at higher doses
and more often is not
– Oral dose usually underdosed
• NO advantages over morphine
METHADONE
Ref 55,56,57
• Longer duration of action than morphine
– Long half-life (30.4 +/- 16.3 hours) (May range from 8-56 hours)
– Must individually dose because of long unpredictable half-life
• QTc interval proglongation
–
–
–
–
–
Disclose to all patients
Look for history of heart disease, arrhythmias, syncope
Pretreatment ECG, follow up 30 days (all patients)
Additional ECG follow up > 100 mg day
QTc 450 ms – 500 ms consider risks vs benefit
• Increased deaths in northern Michigan
• Can be taken orally or by injection
• Inexpensive
– 100 tablets AWP 40mg OxyContin=$440.82
– 100 tablets AWP 10mg methadone=$13.74
METHADONE
Ref 55,56
• Dose ratios to achieve equianalgesia influenced by
previous opioid
– Tolerance to opioids may be dependent on NMDA
receptor
– At high morphine doses, metabolites may produce
constant activation of NMDA receptor, requiring more
morphine to maintain pain relief
• Can even see severe myoclonic jerking
– Conversion to Methadone (which has NMDA
antagonist activity) and no excititory metabolites can
result in dramatic decrease in the MS requirements as
excititory metabolite effects are blunted and over time
decreased
• Has been noted to stop myoclonic jerking
Methadone Conversion
ORAL MOPHINE EQUIVALENT DAILY DOSE
= NON-METHADONE : METHADONE
Mg
Ratio
0-99
=
4:1
100-299
=
8:1
300-499
=
12:1
500-999
=
15:1
>1000
=
20:1
20 mg Oral Oxycodone = 30 mg Oral Morphine
Patient on 100 mg Oxycodone Q12 Hours
Equal to 300 mg Oral Morphine Equivalents (24 hours)
300/12 = 25
Oral Methadone dose = ?
Methadone59
• Suggestions when initiating Methadone
– Carefully note dose and length of therapy of previous
opioid use
– Carefully use NEWER ratios for conversion
– Note degree of opioid tolerance
– Carefully consider age, general condition, and medical
status of patient
– Consider concurrent medication
– Type, severity, and duration of pain
– Acceptable balance between pain symptoms and
analgesia
OPIOID ANALGESIC USE
High Risk Patients in Hospital
• 47 YO white female, 60 kg, recently moved into area from
another state, no LMD, 10 year history of low back pain, 20 pack
year smoker, occasional alcohol use, in MVA with multiple
fractures, Med Red shows no meds
• Put on hydromorphone PCA for 2 days, pain 9/10 most of time,
able to ambulate well, converted to hydrocodone
10mg/acetaminophen 325 mg every 4 hours, uses maximum
daily dose, pain 9/10 most of time
• Near discharge, patient reveals use of “friends” vicodins daily
(several in AM and several PM) before admission
• ????
OPIOID ANALGESIC USE
High Risk Patients in Hospital
• 55 YO white female, 90 kg, admitted for back surgery, 4 year
history methadone use, present dose 80 mg BID, non smoker,
occasional alcohol use
• Put on hydromorphone PCA post surgery, once on floor pain
15/20, patient in obvious discomfort
• Patient reveals “fired” from pain clinic week before surgery
(never told anyone)
• ?????
OPIOID ANALGESIC USE
High Risk Patients in Hospital
• Use principles previously mentioned (High Risk,
AND Obvious need for opioids)
• Treat acute pain
– Use FUNCTION as assessment tool
• Keep patient on equianalgesia
– Verify opioid history
– MAPS report
• Assess opioid abuse risk factors
• Develop long term plan and Communicate
OPIOID ANALGESIC USE
High Risk Patients in Hospital
• 47 YO white female, 60 kg, recently moved into area from
another state, no LMD, 10 year history of low back pain, 20 pack
year smoker, occasional alcohol use, in MVA with multiple
fractures, Med Red shows no meds
• Put on hydromorphone PCA for 2 days, pain 9/10 most of time,
able to ambulate well, converted to hydrocodone
10mg/acetaminophen 325 mg every 4 hours, uses maximum
daily dose, pain 9/10 most of time
• Near discharge, patient reveals use of “friends” vicodins daily
(several in AM and several PM) before admission
• ????
OPIOID ANALGESIC USE
High Risk Patients in Hospital
• Worked to find LMD to accept patient
• Communicated problem to office (obvious high risk to
abuse opioids)
• Sent patient out with limited supply (7 days) opioid
and specific visit date with LMD
• Discussed case with multidisciplinary pain clinic
– Will accept after patient establishes relationship
with LMD
OPIOID ANALGESIC USE
High Risk Patients in Hospital
• 55 YO white female, 90 kg, admitted for back surgery, 4 year
history methadone use, present dose 80 mg BID, non smoker,
occasional alcohol use
• Put on hydromorphone PCA post surgery, once on floor pain
15/20, patient in obvious discomfort
• Patient reveals “fired” from pain clinic week before surgery
(never told anyone)
• ?????
OPIOID ANALGESIC USE
High Risk Patients in Hospital
• Restarted methadone (1/2 dose as IVPB) and continued PCA,
pain controlled within few hours
• Re-established baseline methadone dose (put into system as
PRN)
• Over several days convert to oral IR oxycodone and methadone
with patient able to participate in all post op activities
• Communicated with patient’s LMD and pain clinic
– Plan to continue methadone short term with “breakthrough”
opioids , pain clinic to guide patient opioid therapy with
LMD, with plan for eventual opioid wean
• Struck agreement with patient to accept plan
Questions
BIBLIOGRAPHY
1. Gallagher RM. Primary care and pain medicine. Med Clin N Am.
1999:;83(3):555-583
2. Semenchuk M, Adjuvant analgesic for management of neuropathic pain.
Pharmacy Newswatch. Biezer JL ed. Park-Davis. 1999;(6) no 1.
3. Dellemijn P. Are opioids effective in relieving neuropathic pain? Pain.
1999;80:453-462.
4. Elliot KJ. Taxonomy and mechanisms of neuropathic pain. Seminars in Neurology.
1994;14(3):195-205.
5. Bennett GJ. Neuropathic pain: new insights, new interventions. Hospital Practice.
1998;Oct:95-114.
6. Sindrup SH, Jensen TS. Efficacy of pharmacological treatments of neuropathic pain:
an update and effect related to mechanism of drug action. Pain. 1999;83(3):389-400.
7. Rowbotham M, Harden N, Stacey B, et al. Gabapentin for the treatment of
postherpetic neuralgia. JAMA. 1998;280:1837-1842.
8. Gonzales GR. Central pain. Seminars in Neurology. 1994;14(3):255-262.
9. Johnson RW. Herpes zoster and postherpetic neuralgia. Drugs and Aging.
1997;10(2):80-94.
10. Cornblath DR. Diagnosis and treatment of painful diabetic neuropathy.
Family Practice Recertification. 1999;21(14):55-71.
11. Management of cancer pain. Agency for health care policy and research.
Clinical Practice Guideline. Number 9. 1994, p 34-35.
12. McCleane GJ. Intravenous infusion of phenytoin relieves neuropathic pain:
a randomized, double-blind, placebo-controlled, crossover study. Anesth Analg.
1999;89(4):985-988.
13. Backonja M, Behdoun A, Edwards DR, et al. Gabapentin for the treatment of
symptomatic painful neuropathy in patients with diabetes mellitus. JAMA. 1998;
280:1831-1836.
14. Morello CM, Leckband SG, Stoner CP, et al. Randomized double-blind study
comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral
neuropathy pain. Arch Intern Med. 199159(16):1931-1937.
15. McCleane G. 200 mg daily of lamotrigine has no analgesic effect in neuropathic
pain: a randomized, double-blind, placebo controlled trial. Pain. 1999;83(1):105-107.
16. Kawamataa T, Omote K, Kawamata M, et al. Premedication with oral
dextromethorphan reduces postoperative pain after tonsillectomy. Anesth Analg.
1998;86:594-597.
17. Henderson DJ, Withington BS, Wilson JA, et al. Perioperative dextromethorphan
reduces postoperative pain after hysterectomy. Anesth Analg. 1999;89:399-402.
18. Mercadante S, Casuccio A, Genovese G. Ineffectiveness of dextromethorphan in
cancer pain. J Pain Symptom Manage. 1998;16(5)317-322.
19. McQuay HJ, Carroll D, Jadad AR, et al. Dextromethorphan for the treatment of
neuropathic pain: a double-blind randomized controlled crossover trial with integral
n-of-1 design. Pain. 1994;59(1):127-133.
20. Nelson KA, Park KM, Robinovitz E, et al. High dose oral dextromethorphan
versus placebo in painful diabetic neuropathy and postherpetic neuralgia. Neurology.
1997;48(5):1212-1218.
21. Sang CN. NMDA-receptor antagonists in neuropathic pain: experimental methods
to clinical trials. J Pain Symptom Manag. 2000;19(1 suppl):S21-5.
22. Robbins WR, Staats PS, Levine J, et al. Treatment of intractable pain with topical
large-dose capsaicin: preliminary report. Anesth Analg. 1998;86(3):579-583.
23. Rowbotham MC, Davies PS, Verkempinck C, et al. Lidocaine patch: double-blind
controlled study of a new treatment method for post-herpetic neuralgia. Pain. 1996;
65(1):39-44.
24. Galer BS, Harle J, Rowbotham MC. Response to intravenous lidocaine infusion
predicts subsequent response to oral mexilitine: a prospective study. J Pain Symptom
Manage. 1996;12(3):161-167.
25. Bowsher D. The effects of pre-emptive treatment of postherpetic neuralgia with
amitriptyline: a randomized double-blind, placebo-controlled trial. J Pain Symptom
Manage. 1997;13(6):327-331.
26. Rowbotham MC. Postherpetic neuralgia. Seminars in Neurology. 1994;14(3):
247-254.
27. Byas-Smith MG, Max MB, Muir J, et al. Transdermal clonidine compared to
placebo in painful diabetic neuropathy using a two-stage ‘enriched enrollment’
design. Pain. 1995;60(3):267-274.
28. Dellemijn PL, Vanneste JA. Randomized double-blind active-placebo-controlled
crossover trial of intravenous fentanyl in neuropathic pain. Lancet. 1997;349(9054):
753-758.
29. Dellimijn PL, Van Duijn H, Vanneste JA. Prolonged treatment with transdermal
fentanyl in neuropathic pain. J Pain Symptom Manage. 1998;16(4):220-229.
30. Watson CP, Babul N. Efficacy of oxycodone in neuropathic pain: a randomized
trial in postherpetic neuralgia. Neurology. 1998;50(6):1837-1841.
31. Harati Y, Gooch C, Swenson M, et al. Double-blind randomized trial of tramadol
for the treatment of the pain of diabetic neuropathy. Neurology. 1998;50(6):1842-1846.
32. Sindrup SH, Andersen G, Madsen C, et al. Tramadol relieves pain and allodynia
in polyneuropathy: a randomized, double-blind, controlled trial. Pain.
1999;83(1):85-90.
33. Ruoff GE. Slowing thre initial titration rate of tramadol improves tolerability.
Pharmacotherapy. 1999;19(1):88-93.
34. Jaeger H, Maier C. Calcitonin in phantom limb pain: a double-blind study. Pain.
1992;48(1):21-27.
35. Ertas M, Sagduyu A, Arac N, et al. Use of levodopa to relieve pain from painful
symmetrical diabetic neuropathy. Pain. 1998;75(2-3):257-259.
36. Saper, JR ed. Post-herpetic neuralgia: new perspectives. Topics In Pain
Management Current Concepts and Treatment Strategies. Lippincott Williams &
Wilkins, Baltimore MD. 2000;15(8)25-26.
37. Katz NP. MorpiDex (MS:DM) double-blind, multidose studies in chronin pain
patients. J Pain Symptom Manage. 2000;19:s37-s41
38 Kaiko RF, et. al. Pharmacokinetic-pharmacokinetic relationships of controlled-release
oxycodone. Clin Pharmacol Ther. 1996;59:52-61.
.
39. Baumann TJ. Et al. Pain Management. In:Dipiro JT, Tlabert TL, Yee GC, Matzke
GR, Wells BG, Posey LM eds. Pharmacotherapy: A Phathophysiologic
Approach.
40. McCaffery M, Pasero C.ed. Pain. Clinical Manual. 2nd Edition. St Louis,
MO: Mosby; 1999.
41. Dellemijn P. Are opioids effective in relieving neuropathic pain? Pain.
1999;80:453-462.
42. Catella-Lawson F, et al. Cyclooxygenase inhibitors and the antiplatelet effects on
aspirin. NEJM 2001;345(25):1809-1817.
43. Mukherjee D, et al. Risk of cardiovascular events associated with selective Coc-2
Inhibitors. JAMA 2001;286(8):P954-959.
44. Herdon C, et al. Management of opioid-induced gastrointestinal effects in patients
Reveiving palliative care. Pharmacotherapy 2002;22(2):240-250.
45. Pharmacy Practice News. May 2001; 39-40.
46. ASHP News and Views July 2001; 6.
47. Desbiens NA, et al. Pain and suffering in seriously ill hospitalized patients. JAGS.
2000;48: s183-s186.
48. Gebhart,F. New drug may eliminate opioid side effects. Hospital Pharmacist
Report. 2001;December:11.
49. California jury rules doctor’s undertreatment of pain ins grounds for elder abuse.
Last Acts Quarterly. 2001; Summer (9):1and 8.
50. www.StopPain.org
51. News. Federal reports say oxycodone abuse is on the rise. AJHP. 2001;58:11751179.
52. Statement Purdue Pharma. October 2001.
53. Balancing news stories about opioids: a statement on the value of opoids for people
With severe pain. Analgesia. 2001;12(2):1.
54. Pharmacists’ responsibilities in managing opioids: a resource. APHA Special Report
2002 adv board Brushwood DB, Finely R, Giglio JG, Heit HA.
55. Anderson R, et al. Accuracy in equianalgesic dosing: conversion dilemmas. Journal
of pain and Symptom Management. 2001;21(5):397-406.
56. Gracely R. Methadone:history and recommendations for use in analgesia. APS
Bulletin. September/October 2000;10(5):1&8-9.
57. Krantz MJ, et al. QTc interval screening in methadone treatment. Annals of
Internal Medicine. 2009; 150(6):1-9.
58. Elliot VS. FDA, CDC, scrutinty follows surge in accidental opioid overdoses.
AMNews. Amednews.com, Posted Feb 9, 2009.
59. Dworkin RG. Et al. Advances in Neuropathic Pain. Arch Neurol. 2003; 60:
1524-1534.
60. Westanmo AD. Et al. Duloxetine:A balanced and selective norepinephrine and serotonin
61. Goldstein DJ, et al. Duloxetine vs. placebo in patients with painful diabetic
neuropathy. Pain. 2005;116(1-2):109-118.
62. Gauthier-Lewis M, et al. Pharmacologic options for the management of
diabetic peripheral neuropathy. Formulary. 2005;40:438-451.
63. Faria. Lyrica (pregabalin). Pharmacy Times. 2005;Nov:44.
64. Sneker BF et al. Pregabalin: A new neuromodulator with broad therapeutic
indications. Ann Pharmacother 2005;39:2029-2037.
65. Finnerup NB, et al. Algorighm for neuropathic pain treatment: an evidence
based proposal. Pain. 2005;118:289-305.
66. Anderson R, et al. Accuracy in equianalgesic dosing: conversion dilemmas.
Journal of pain and Symptom Management. 2001;21(5):397-406.
67. Gracely R. Methadone:history and recommendations for use in analgesia.
APS Bulletin. September/October 2000;10(5):1&8-9.
68. Adpoted from “Methadone use in the hospice setting:safe, effective, cost
efficient” by McCormick BY, Fisch MJ MD Anderson Cancer Center,
Houston Texas
69. Krantz MJ, et al. Torsades de pointes associated with very high dose
methadone. Ann Intern Med 2002;137:501-504.
70. Moulin DE, et al. Pharmacological management of chronic neuropathic painconsensus statement and guidelines from the Canadian Pain Society. Pain Res
Manag. 2007; 12: 13-21.
71. Approaches to Pain Management. Ed Porche RA. 2010. Joint Commission
Resources.
72. http://static.howstuffworks.com/gif/pain-1.gif (access 10/8/11)
73. An Economic Analysis of the Cost and Benefits Associated with Regular
Urine Drug Testing for Chronic Pain patients in the United States. Laffer
Associates: Millennium Research Institute. October 2011
74. Herndon, C. Pain management: Time for pharmacists to take action.
Pharmacist Today. Supplement, Pain Management Update. September:
2010; 1.
75. Walsh N. Little progress seen in treating chronic pain. MedPage. June 23,
2011. (Quote from Dennis C Turk MD and colleagues form the University of
Washington.
76. Chou R, et al. Opioid Treatment Guidelines. The Journal of Pain. 10 (2),
2009: 113-130.
77. Ruddere L, et al. When you dislike patients, pain is taken less seriously. Pain.
Oct 152 (10);2011, 2342-7.
78. http://www.celebritysentry.com/post/detroit-lions-rashied-davis-agree-toterms-on-1-yeardeal/
79. O’Connor AB, Dworkin RH. Treatment of neuropathic pain: An overview of
recent guidelines. The American Journal of Medicine. 2009;122:S22-S32.
80. http://www.drugdevelopmenttechnology.com/projects/licofelone/licofelone7.html
81. American Geriatarics Society Panel. Pharmacologic Management of Pain in
Older Persons. JAGS. 2009; 57:1331-1346
82. Hendon CM et al. Management of Chronic Nonmalignant Pain with
Nonsteroidal Antiinflammatory Drugs. Pharmacotherapy. 2008;28(6):788-805.
83. Watkins et al. Aminotransferase elevations in healthy adults receiving 4 grams
of acetaminophen daily: A randomized controlled trial. JAMA. 2006;296:8793.
84. http://www.nsaids.info/nsaids/worldwide-use-of-nsaids/
85. Oldenhof J, et al. Effect of maxium OTC doses of naproxen sodium or
acetaminophen on low-dose aspirin inhibition of serum thromboxane B2. Curr
Med Res Opin. 2010; 26:1497-1504.
86. Bombardier C, et al. Comparison of upper gastrointestinal toxicity of
rofecoxib and naproxen in patients with rheumatoid arthritis. NEJM
2000;343:1520-1528.
87. Bresalier RS, et al. Cardiovascular events associated with rofecoxib in
colorectal adenoma chemoprevention trial. NEJM 2005;352:1092-1102.
88. Lanza, FL, et al. Guidelines for prevention of NSAID-related ulcer
complications. Am J Gastroenterol 2009;104:728-738.
89. http://www.ofirmev.com/Overview.aspx
90. Solomon DH, et al. The comparative safety of analgesics in older adults with
arthritis. Ach Int Med. 2010, Dec 13/27; 170:1968.
91. Formulary. Accessed February 2, 2013.
http://formularyjournal.modernmedicine.com/formulary-journal/news/userdefined-tags/codeine/fda-warns-about-codeine-postop-pain-children