1. PAIN MANAGEMENT Terry J. Baumann, Pharm.D., BCPS tbaumann@mhc.net
Clinical Pharmacy Pain Practitioner
Clinical Manager
Department of Pharmacy
Munson Medical Center
Traverse City, Michigan
Dr. Terry Baumann is a clinical pharmacist with the Pain Control Services and clinical manager of the pharmacy department at Munson Medical Center. He has served in this capacity for the last nine years. He currently is an adjunct assistant professor of pharmacy at Ferris State University and previously spent six years teaching graduate and postgraduate students at Wayne State University. In addition he serves on a number of hospital committees and from was president of the Michigan Society of Hospital Pharmacists.
Dr. Baumann holds a board certification as a pharmacotherapy specialist and is a diplomat of the American Academy of Pain Management. He has performed extensive research and is widely published in the areas of pain management and drug therapy, and has spoken at numerous national conferences and seminars. In addition, as a coauthor, he is a past recipient of the American Society of Health Systems Pharmacists’ prestigious research award presented for outstanding contribution to the literature of research in hospital pharmacy.
After graduating from Alma College with a B.S. degree in biology, and serving a year in Volunteers in Service to America (VISTA), Terry earned a B.A. in education and a doctor of pharmacy degree with high distinction from the University of Kentucky. He then completed a two-year hospital pharmacy residency at Albert B. Chandler Medical Center in Lexington, Kentucky.

2. OBJECTIVE

3. 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)

4. 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)
Health-care professionals spend an incredible amount of prolonged effort in nursing facility settings at disease modification (for example [e.g.], hypertension, diabetes, congestive heart failure). We spend much less time on symptomatic and supportive care (e.g., pain control).1 To some older persons, the term “pain” may be a metaphor for serious disease or death. Thus, they often describe pain in other terms of discomfort or aching, or may not mention it at all.2 In addition, residents of nursing facilities often feel pain is a natural part of growing older and/or do not want to be seen as complainers.1,3 Additionally, age-related pain has not been well studied, leaving the clinician with very little science upon which to base practice decisions.1 Ferrell,4 in 1991, pointed out that of eleven leading textbooks on geriatric medicine, only two had chapters devoted to pain. He also noted that a review of eight geriatric nursing textbooks revealed less than eighteen pages devoted to pain out of 5,000 total pages in those texts. These factors all contribute to the problem of the under-treatment of pain in nursing facilities.

5. 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 % % % %

6. 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

8. 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.
Man- and woman-kind have been trying to figure out what pain is and how to fix it since Adam and Eve. It is probably how the medical profession got its start. Initially, we thought it was punishment. Today, we have categorized it, dissected it, and given it a very proper definition: “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.”11 This DOES NOT describe pain very well. SUFFERING, TRAUMA, EMOTION-- that is pain!

9. ALTERNATIVE DEFINITION OF PAIN
Pain is whatever the patient says/feels it is, existing whenever
he or she says/indicates it does.
Margo McCaffery, R.N., has been given credit for the following definition: “Pain is whatever the patient says it is, existing whenever he/she says it does.”12 I believe this gets closer to what most of us know as pain. However, Karen Feldt, R.N., points out this definition does not address those patients who cannot speak.18 Thus the addition of says/feels and says/indicates is appropriate.
In general, the experience of pain is highly subjective. Not to trust or believe the patient is pure folly.

10. 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
Acute pain is what follows trauma and usually is gone when the body heals. It has a well-defined onset, usually associated with signs of autonomic activity: tachycardia, hypertension, diaphoresis, hydriasis, and pallor. It is best treated by recognizing the cause.13
Chronic pain persists well beyond the time it would normally take the body to heal. In fact, it is often hard to identify a specific event or injury that caused the pain. In contrast to acute pain, autonomic activity often is not present. This may lead clinicians to think the patient does not look like he or she is in pain, when indeed the suffering from pain is quite severe. Often one sees depression, sleep problems, and family problems.13
Cancer pain usually has a definable cause and can be acute (sometimes a recurring, acute pain) or chronic. It often has both components.13

11. CHARACTERISTICS OF ACUTE AND CHRONIC/PERSISTENT PAIN
CHARACTERISTICS ACUTE PAIN CHRONIC/PERSISTENT PAIN
Relief of Pain Highly Desirable Highly Desirable
Dependence & Unusual Common
Tolerance
Physiological Usually Not Present Often a Problem
Component
Organic Cause Common Often Not Present
Family & Environ Small Significant
ment Involvement
Sleep Problems Unusual Common
Treatment Goal Cure Rehabilitation
& Acceptance
The major differences between acute and chronic pain are certainly worth noting. One important fact that does not differ is that relief from the pain is highly desirable. An important difference is in the treatment goals. In chronic pain, one seldom will see a cure. Acceptance and increase in functional ability are much more realistic goals. In acute pain, a cure is usually the main treatment goal. Dependence and tolerance are not problems in acute pain, even with the use of opioids. However, in chronic painful conditions, these potential problems must be monitored. Long-term psychological uncertainties and the need to counsel and involve family and friends (e.g., divorce, depression, anxiety) are usually not seen with acute pain, but are often very large components of chronic pain. An organic cause is usually present in acute pain, but is often not identifiable in chronic pain. And finally, sleep disorders are common in chronic pain and are unusual (if pain is being treated effectively) in acute pain.15

12. 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

13. Pendulum Swings (according to TJB)
Under-treatment of cancer pain ( ’s)
Development of sustained release opioids (1980’s)
Development of devices that allowed patients to deliver own opioids (1980’s)
Better definition of addiction ( ’s)
Use of opioids in chronic pain ( ’s)
Guidelines for use of opioids ( )
Better defined use of opioid in non-cancer pain? ?
????

14. 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 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)

15. 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

16. Evidence of Opioid Misuse
Misuse of Opioids Doubles Over Five-Year Period (CDC MMWR 2010;59: )
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): )
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): )
Risk clear what about solution ?

17. “Perfect Storm” of increasing pain and increasing opioid misuse, abuse and diversion (ref #74)

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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 (
3) REMS implementation responsibility falls on pharmaceutical companies
4) Administrative requirements

24. 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 non-cancer pain
Add maximum duration of 90 days for continuous (daily) use for non-cancer pain
Response (Professionals for Rational Opioid Monitoring and Pharmacotherapy)

25. 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

26. 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)

27. IF WE CANNOT ASSESS PAIN, WE WILL NEVER BE ABLE TO RELIEVE PAIN.
The importance of assessment can never be overstated. How can we expect to understand what is going on with a patient without systematic, consistent, and thorough assessment? Betty Ferrell states it well: “If we cannot assess pain, we will never be able to relieve pain.”12
Betty R. Ferrell, Ph.D.

28. ASSESSMENT OF PAIN Long duration, long-standing functional impairment
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
Always respect the complaint. There may be an evident physical process or a masked depression, but a patient who says he or she has pain MUST be believed. Dr. Foley5 cites evidence that the majority of pain complaints in the elderly have a definable cause. Learn the exact onset (when possible) of pain, the circumstances around the onset, where the pain is located, what makes it worse and what makes it better. Have the patient describe the pain (i.e., sharp, dull, burning) and find out if it spreads to anywhere else. Ask the patient to describe the severity (e.g., 0=no pain; 10=worst pain ever experienced) and ask if the pain is always in the same place or if it moves around. During this assessment, you are trying to establish if this is acute pain, chronic pain, or cancer-related pain.5,17
Remember, acute pain will have a distinct onset, be of short duration, and have physical evidence (e.g., increased blood pressure, diaphoresis). Chronic pain is of longer duration (six months or longer)4, may be associated with functional impairment and/or neuropathic pain.

29. 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.
CONSIDER ONSET, WHAT MAKES PAIN BETTER OR WORSE, LOCATION, DESCRIPTION, SEVERITY, AND DOES PAIN MOVE?
Do not forget to assess ALL pain complaints. Patients often will have several overlapping pain problems (e.g., arthritis and diabetic neuropathy and a broken limb) that may take varying management strategies.
Finally, one must not forget to look at the history of psychiatric illness, anxiety, depression, suicidal ideation.5

30. 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
All the medications used within the last six months should be reviewed. This review should include: dose, duration of use, frequency of use, reason for use, and perception of efficacy. All recreational drug use (including alcohol) should be reviewed. Ask the patient what worked, how well it worked, and what did not work. Don’t forget allergies, and products residents may be getting from loved ones and self-dosing (e.g., over-the-counter products, especially acetaminophen). Finally, nutritional supplements may be playing a role and so may the latest in-vogue alternative therapies (e.g., melatonin).20

31. 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.
Treatment plans for pain should be developed using the initial assessment tools and, whenever possible, include input from the patient and family. Remember that it is often unrealistic to expect complete relief. These plans should be continually reevaluated in a systematic and ongoing process with a functional end point as the goal. The plan should be changed when needed with documentation of the initial plan and any changes. This process should never end.

32. 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
PLoS = Public Library of Science
The Joint Commission. Sentinel Event Alert. 2012;(49):1-5.
Davies EC et al. PLoS One. 2009;4(2):e4439. .

33. Evidence from The Joint Commission Sentinel Event Database
Other-Excessive Dosing, interaction, adverse drug reactions
The Joint Commission. Sentinel Event Alert. 2012;(49):1-5.

34. Selected Risk Factors for Oversedation and Respiratory Depression
Sleep apnea or sleep disorder diagnosis
Use of other sedating drugs
Pre-existing pulmonary or cardiac disease, dysfunction, or major organ failure
Morbid obesity
Snoring
Older age
Thoracic or other surgical incisions that may impair breathing
No recent opioid use
Post-surgery status
Opioid habituation
Smoker
Longer length of time receiving general anesthesia
Risk is 2.8 times hgher for 61-70, 5.4 times higher for 71-80, 8.7 times higher for >80.
The Joint Commission. Sentinel Event Alert. 2012;(49):1-5.

35. Actions suggested by TJC
Monitoring Guidelines/Policies
Assessment Procedures
Standardized Order Sets
Second Level Review
Safe
Technology
Effective Processes
Education
Training
Effective
Tools
Bar Code Scanning
Smart Pumps
EtCO2 monitoring
Computer Decision Support Alerts
Mention under effective processes the /reporting/tracking and analyzing events for quality improvement purposes
We recently changed the hard stop on the Alaris pumps on dilaudid from 1.1 to 0.99 on both PCA and Cont. infusion dose to prevent 10 fold dose errors that were being reported.
Orientation
Newsletters
Healthstream
Encourage multi-modal adjuvant therapies
Assessment Tools
Pain Scales
Risk Assessment Tools

36. 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
Sleep Apnea 2
Three or more opioids prescribed
Opioid naïve 4
Total number of patients analyzed = 14. BMI: body mass index.
SCr: serum creatinine. BZD: benzodiazepine.

37. Opioid Risk Assessment Project
Risk Factor
Number
Obesity (BMI > 30) 4
Respiratory Disease
Renal Dysfunction (SCr > 1.5)
Concomitant BZD’s/muscle relaxants
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.

38. 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

39. 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
Terry – would this be a good segway for your fentanyl MUE here?? I can mention that we have done one on fentanyl & have a meperidine one in process; then turn it over to you so can share your info??

40. Key to effective use is individualization and proper titration
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
The next step on the analgesic ladder is the use of opioids. Their pharmacologic profiles depend on affinity for receptors. Pure opiate agonists (e.g., morphine) relieve pain and have a similar side-effect profile, while pure opiate antagonists (i.e., naloxone) displace the agonists and reverse both adverse effects as well as analgesia. “Partial agonists and antagonists (i.e., pentazocine) compete with agonists for opiate receptor sites and, depending on the inherent ability to either stimulate or block these sites, exhibit mixed agonist-antagonist activity. Mixed agonist-antagonist agents with analgesic activity appear to exhibit selectivity for analgesic receptor sites.”25 This has the potential to produce analgesia with fewer side effects but has the disadvantage of reaching a ceiling effective dose. The agonist has no ceiling effective dose.
“In usual doses, opioid analgesics do not eliminate pain; instead, they decrease its unpleasantness. Patients report that although their pain is still present, it no longer bothers them. The effects of the analgesics are also relatively selective and, at normal therapeutic concentrations, these agents do not decrease sensitivity to touch, sight, or hearing, or impair intellectual functioning; however, as the dosage increases, so do the undesirable side effects.”16 Some variability is seen in the onset of action and duration of action.25
There continues to be much debate on the sensitivity of the elderly to opioids. Short-term studies have shown that the elderly may be more sensitive to the pain-relieving effects of these agents. Other studies have shown no differences.4 As stated earlier, this confusion can lead to under-treatment. Titration, with appropriate starting doses and assessment, may minimize this problem.

41. 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
Much anecdotal evidence exists, despite lack of systematic study, suggesting that the elderly may be more prone to opioid adverse effects.4 Mood changes, including agitation and paradoxical excitement, can occur,1 but these effects can be minimized with careful titration. In addition, potential cognitive disturbances are also best handled with careful titration and proper assessment. Remember, pain itself often causes agitation, anxiety, and cognitive disturbances. In these cases, only adequate opioid titration will abate the symptoms.
Somnolence, drowsiness, and the chance for increased gait disturbances (and more falls) also can be seen with opioid analgesics. Somnolence and drowsiness can be used in determining proper opioid dosing. Note that adequate pain relief and the ability to then fall asleep, should not be confused with opioid-induced somnolence. When drowsiness is a significant problem, management techniques include: careful drug history (is the patient on a medication potentiating the sedative effects of the opioid [benzodiazepine]?), reducing individual doses, giving the drug more frequently but at a lower dose, or switching to a drug with a shorter half-life (e.g., switching from methadone to morphine).5

42. 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
Respiratory depression is potentially the most serious problem associated with the opioids. It most often occurs in patients who are opioid-naive given relatively large doses. It is usually accompanied by sedation and mental clouding. Once again, careful titration will prevent this problem. Tolerance quickly develops, and it is not unusual in chronic or cancer pain to see the elderly tolerate very large doses of opioid analgesic. Caution is advised in patients with a significant degree of respiratory problems.5
Opioid analgesics stimulate the chemoreceptor trigger zone and can produce nausea and vomiting. In most cases, tolerance develops rather rapidly, but it is reasonable to switch to another opioid or use non-sedating anti-nausea medications (e.g., metoclopramide).5
Urinary retention (secondary to increased sphincter tone), pruritus (secondary to histamine release), and rarely, exacerbation of asthma (secondary to histamine release) can also be seen.25

43. 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 analgesics produce a decrease in GI peristalsis and intestinal secretion. This is to be expected and unlike other opioid adverse effects, this is not transient; and although tolerance may develop, it is a very slow process. Clinicians must anticipate this to prevent constipation , dry hard stools, or GI obstruction. Careful attention must be given to diet (plenty of fiber and fluid), and the use of stimulants, stool softeners, and bulk-producing laxatives.5

44. 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
Tolerance develops with all effects of opioids at different rates and with much patient variation. It can easily be confused with a change in pain status and can be minimized with regular dosing. Clinicians should increase the dose to achieve effective analgesia with minimal side effect change. DO NOT be overly concerned with the size of the dose. Efficacy and minimal side effects are the end points.

45. 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
Dependence, although much feared and often confused with addiction, is rarely seen with short-term opioid use. In fact, even when used for extended periods of time the medical use of opioids rarely, if ever, leads to drug abuse or iatrogenic addiction. Abrupt discontinuation, however, may lead to signs and symptoms of withdrawal. Discontinuation is best achieved with a weaning process that is predicated on how long and why the patient has been on opioids.5 Any resident on opioid therapy for more than two weeks who must discontinue therapy should be considered a candidate for weaning. Pseudoaddiction, in which residents are considered to demonstrate drug-seeking behavior secondary to inadequate pain relief, may be a much bigger problem than addiction.

46. 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
Tolerance develops with all effects of opioids at different rates and with much patient variation. It can easily be confused with a change in pain status and can be minimized with regular dosing. Clinicians should increase the dose to achieve effective analgesia with minimal side effect change. DO NOT be overly concerned with the size of the dose. Efficacy and minimal side effects are the end points.

47. 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)
Tolerance develops with all effects of opioids at different rates and with much patient variation. It can easily be confused with a change in pain status and can be minimized with regular dosing. Clinicians should increase the dose to achieve effective analgesia with minimal side effect change. DO NOT be overly concerned with the size of the dose. Efficacy and minimal side effects are the end points.

48. 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
Opioids vary greatly in equianalgesic doses. In addition, the studies that establish such doses are seldom done in the elderly, and cross tolerance is very difficult to measure. Dosing guidelines can be helpful, but must only be used as a guide. Experience, titration, and reassessment are the keys to successful dosing conversions.25

49. 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

50. 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

51. 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?

52. 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?

53. 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?

54. 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?

55. OPIOID ANALGESICS Allergies True allergies rare
Chance of cross sensitivity decreased between
Morphine-like agonists
Meperidine-like agonists
Methadone-like agonists
True opioid allergies are rare. When they do occur, switching to another opioid analgesic class may be warranted. The chances of cross sensitivity between morphine-like agonists (morphine, hydromorphone, oxymorphone, levorphanol, codeine, hydrocodone, oxycodone), meperidine-like agonists (meperidine and fentanyl), and methadone-like agonists (methadone and propoxyphene) are decreased, although caution is always advised. For the purposes of cross sensitivity, the mixed agonist-antagonists should be grouped with the morphine-like agonists.25

56. 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 remains the standard with which other opiate drugs should be compared in elderly persons, because its effects are the best understood and the most predictable. Thus, MORPHINE is an opiate that clearly can be used for severe pain in most nursing facility patients.”1 Myths about morphine include: it is the drug of last resort, it causes unmanageable side effects, it sedates the patient too much, morphine causes addiction, and tolerance is a large life-threatening problem.

57. 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
Very little of morphine is eliminated unchanged by the kidney, however one active metabolite (morphine-6-glucuronide) is eliminated by the kidney and may accumulate in patients with renal impairment.54
“Therapeutic doses of morphine have minimal effects on blood pressure, cardiac rate, or cardiac rhythm when patients are supine; however, morphine does produce venous and arteriolar vessel dilation, and orthostatic hypotension may result. Hypovolemic patients, those whose blood pressure is being maintained by sympathetic outflow, and patients with acute myocardial infarction are more susceptible to morphine-induced cardiovascular changes (e.g., decrease in blood pressure). Because morphine prompts a decrease in myocardial oxygen demand in ischemic cardiac patients, it is often considered the opioid of choice when using opioids to treat pain associated with myocardial infarction.”25

58. 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
One reason morphine is so useful and remains the drug of choice for acute severe pain in nursing facilities is its dosage form and administration route flexibility. In the preferred oral route, patients can receive immediate-release tablets, liquid, or sustained-release formulations (Q 24 vs. Q 12 vs. Q8). The bioavailability of immediate- release morphine via the sublingual route has not been well studied. Anecdotally, it is used in some hospice settings with varying degrees of success. Rectal morphine, on the other hand, has a proven record and is commercially available. Morphine can be given by the IM route, infused subcutaneously, and infused intravenously. Epidural and intrathecal routes are employed in some cancer and chronic pain patients as well as in the postoperative population (usually epidural).

59. 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
A transdermal patch is available which has proved very useful in the treatment of cancer pain and chronic nonmalignant pain. This system can deliver medication effectively for 72 hours. The drug “depots” in the upper skin layers; thus hours is needed after the patch has been applied to reach an effective blood level of fentanyl. If a dose is changed, it may take up to six days to reach steady state. This property makes it difficult to titrate and is best used after a patient has established analgesic efficacy with oral agents. It should not be used in acute pain.25 Ferrell1 feels the potential for overdose in the nursing facility patient is very high, and this system should not be used in the “opioid-naive” elderly. Increased body temperature can change the way the transdermal patch delivers fentanyl. Use caution when residents have high fevers.

60. FENTANYL Many transmucosal dosage forms now available
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
Some of these disadvantages may be overcome as the patch will soon be available in a lower dosage strength, and a patient-controlled release mechanism is now being developed. In addition a flavored sugar lozenge will soon be available for the treatment of breakthrough cancer pain.

61. 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 should be used only in moderate pain. The analgesic effect is due to the metabolism of 10% of codeine to morphine, however, its antitussive actions probably involve codeine.54 It works best when combined with acetaminophen, aspirin, or NSAIDs. Since there are so many codeine combination products, caution is advised when reviewing “prn” use due to the increased potential for peripheral analgesic overdose. Even though codeine may not be as efficacious as morphine, it shares morphine’s propensity to induce tolerance, dependence, and constipation.25

62. 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 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

63. 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)
Hydrocodone and oxycodone are seen most often in combination products with aspirin or acetaminophen. They have shown effectiveness in moderate to severe pain and share morphine’s overall pharmacology25. Even though oxycodone has been placed in the schedule II drug category and hydrocodone in the schedule III category, they share similar analgesic efficacy. This often causes confusion since some states require triplicate schedule II prescription forms which would include oxycodone and exclude hydrocodone.25

64. 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)
Oxycodone is also available in a sustained-release dosage form. Tablets in 10, 20, 40, and just-released 80 mg can be given every 12 hours for severe pain.

65. HYDROMORPHONE IV Dose = POTENTIAL DANGER-DANGER
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
Hydromorphone is more potent than morphine, has more favorable oral absorption properties (making it a favorite street drug), and is very soluble. These characteristics make it useful when highly concentrated narcotic solutions are needed (i.e., high dose subcutaneous infusions, intrathecal administration). Its overall pharmacology is very similar to that of morphine.25

66. 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
Oxymorphone and levorphanol are morphine-like agonists. Oxymorphone can be administered rectally or it can be injected. It shares all of morphine’s characteristics and offers no advantages. It is NOT used in long term care facilities. Levorphanol can be administered orally or by injection. It has an extended half-life when compared to morphine and has been used in chronic pain and cancer pain. It offers no clear advantage over sustained-release products Since it may accumulate in the elderly, it should be avoided in nursing facility patients.

67. MEPERIDINE Contraindicated in renal failure
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
Meperidine is particularly hazardous in the elderly.1 The metabolite normeperidine can accumulate and get into the CNS, causing tremor, muscle twitching, and possible seizures. Since normeperidine is excreted renally, this agent is contraindicated in renal failure or renal insufficiency. The combination of monoamine oxidase inhibitors and meperidine can lead to excitation syndrome, hyperpyrexia, and convulsions. It is less potent, with a shorter analgesic duration than morphine. If used, this drug should be given at higher doses and at more frequent intervals. Several studies have shown this is often not done Meperidine is effective orally but doses at least three times higher than parenteral doses must be given to achieve efficacy. In most settings, meperidine offers no advantages over morphine.25

68. METHADONE Ref 55,56,57 Longer duration of action than morphine
Long half-life (30.4 +/ 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 is an effective analgesic in the treatment of moderate to severe pain. It is inexpensive, can be taken orally or by injection, has an extended duration of action, and has a pharmacologic profile similar to morphine. Chronic pain and cancer patients benefit from this agent. However, it is to be used with caution if at all in the elderly because of its propensity to accumulate, leading to oversedation and somnolence.1,25

69. 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

70. Methadone Conversion 20 mg Oral Oxycodone = 30 mg Oral Morphine
ORAL MOPHINE EQUIVALENT DAILY DOSE
= NON-METHADONE : METHADONE
Mg Ratio
= :1
= :1
= :1
= :1
> = :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 = ?

71. 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

72. 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
????
Opioids vary greatly in equianalgesic doses. In addition, the studies that establish such doses are seldom done in the elderly, and cross tolerance is very difficult to measure. Dosing guidelines can be helpful, but must only be used as a guide. Experience, titration, and reassessment are the keys to successful dosing conversions.25

73. 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)
?????
Opioids vary greatly in equianalgesic doses. In addition, the studies that establish such doses are seldom done in the elderly, and cross tolerance is very difficult to measure. Dosing guidelines can be helpful, but must only be used as a guide. Experience, titration, and reassessment are the keys to successful dosing conversions.25

74. 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
Opioids vary greatly in equianalgesic doses. In addition, the studies that establish such doses are seldom done in the elderly, and cross tolerance is very difficult to measure. Dosing guidelines can be helpful, but must only be used as a guide. Experience, titration, and reassessment are the keys to successful dosing conversions.25

75. 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
????
Opioids vary greatly in equianalgesic doses. In addition, the studies that establish such doses are seldom done in the elderly, and cross tolerance is very difficult to measure. Dosing guidelines can be helpful, but must only be used as a guide. Experience, titration, and reassessment are the keys to successful dosing conversions.25

76. 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
Opioids vary greatly in equianalgesic doses. In addition, the studies that establish such doses are seldom done in the elderly, and cross tolerance is very difficult to measure. Dosing guidelines can be helpful, but must only be used as a guide. Experience, titration, and reassessment are the keys to successful dosing conversions.25

77. 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)
?????
Opioids vary greatly in equianalgesic doses. In addition, the studies that establish such doses are seldom done in the elderly, and cross tolerance is very difficult to measure. Dosing guidelines can be helpful, but must only be used as a guide. Experience, titration, and reassessment are the keys to successful dosing conversions.25

78. 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
Opioids vary greatly in equianalgesic doses. In addition, the studies that establish such doses are seldom done in the elderly, and cross tolerance is very difficult to measure. Dosing guidelines can be helpful, but must only be used as a guide. Experience, titration, and reassessment are the keys to successful dosing conversions.25

79. Questions

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