Post on 11-Aug-2015
December 4, 2014
Optimizing Treatment for Pain Patients and the Opioid Safety
Initiative
V2
Shannon DeGrote, PharmD Amina Ghalyoun, PharmDJaclyn Sievers, PharmD
Objectives
I. Distinguish different types of pain and identify
appropriate first line treatments
II. Manage side effects of opioid use
III. Identify the goals and measures of the opioid
safety initiative
IV. Interpret urine drug screens
V. Recognize recent FDA changes in opioid
scheduling
Epidemiology
“The total number of opioid-related deaths in the United States (>100,000 between 1999 and
2010) far exceeds the number of US military casualties in the Vietnam War (58,000).”
1. Baumann TJ, Strickland JM, Herndon CM. Pain Management. In: Dipiiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill; 2011:539-541.
2. Bohnert AS, Illgen MA, Galea S, McCarthy JF, Blow FC. Accidental Poisoning Mortality Among Patients in the Department of Veterans Affairs Health System Med Care. Apr 2011;49(4):393-3963. Franklin, Gary M, MD. Opioids for Chronic Noncancer Pain. American Academy of Neurology. 2014;83:1277-1284.
Pain“An unpleasant sensory and emotional experience associated with actual or potential tissue damage”
Rosenquist, EWK, MD. Definition and pathogenesis of Chronic Pain. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on November 18, 2014.)
Pathophysiology
Baumann TJ, Strickland JM, Herndon CM. Pain Management. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill; 2011:539-541.
Types of Pain
Description
Somatic • Skin, bone, joint, muscle or connective tissue• Presents with throbbing and well localized
sensation of pain
Visceral • Pain from an internal organ• Feeling of pain from different area other than
location of organ
Neuropathic • Nerve damage • Pain described as burning, tingling, shock like, or
shooting pain
Baumann TJ, Strickland JM, Herndon CM. Pain Management. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill; 2011:539-541.
Acute versus Chronic Pain
Acute Pain Chronic Pain
Duration Hours to weeks More than 3 months
Causes Surgery, traumaPain due to a chronic disease or condition
Prognosis Predictable Unpredictable
Complicating Issues UncommonDepression, anxiety,
financial issues
Treatment Primary analgesics Multimodal
Baumann TJ, Strickland JM, Herndon CM. Pain Management. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill; 2011:539-541.
Common Examples of Chronic Pain
Osteoarthritis
Neuropathic pain
Fibromyalgia
Somatic pain
OsteoarthritisDamage to protective cartilage in any joint of the body, most commonly hands, knees, hips and spine
• Acetaminophen (APAP)• Non-steroidal anti-inflammatory drugs (NSAIDs)
First line
• Topical & intra-articular analgesics
Second line
• Opioids
Third line
1. Hochberg, Marc C., Roy D. Altman, Karine Toupin April, et al. Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies in Osteoarthritis of the Hand, Hip, and Knee. American College of Rheumatology. 2012;64(4):465-474.
2. Kalunian KC. Initial pharmacologic therapy of osteoarthritis. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.
3. Kalunian KC. Treatment of osteoarthritis resistant to initial pharmacologic therapy. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.
Neuropathic PainNerve damage in any area of the body, commonly feet and hands, described as tingling or burning pain, weakness and numbness
• Tricyclic antidepressants (TCAs): amitriptyline, nortriptyline• Anti-epileptics (AEDs): gabapentin, pregabalin*• Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs):
venlafaxine, duloxetine*• Central & topical analgesics
First line
• AEDs: carbamazepine, oxcarbazepine, topiramate• Opioids
Second line
1. Attal N, Cruccu G, Baron R, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol. 2010;17:1113-88.2. National institutte for health and care excellence. NICE clinical guideline 173: neuropathic pain - pharmacological management. Retrieved at: http://www.nice.org.uk/guidance/cg173. Accessed
20 Nov 2014.3. Rosenquist E. Overview of the treatment of chronic pain. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.4. Feldman EL, McCulloch DK. Treatment of diabetic neuropathy. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.
FibromyalgiaWidespread musculoskeletal pain, believed to be due to amplified pain signals and altered brain processes, accompanied by fatigue, sleep, memory and mood issues.
• Acetaminophen • TCAs: amitriptyline, nortriptyline, desipramine• SNRIs: venlafaxine, duloxetine*, milnacipran*• Cyclobenzaprine
First line
• AEDs: gabapentin, pregabalin*• Selective Serotonin Reuptake Inhibitors (SSRIs): fluoxetine, paroxetine• Tramadol
Second line
• Opioids• NSAIDs
Not recommended
1. Ablin J, Fitzcharles MA, Buskila D, et al. Treatment of fibromyalgia syndrome: recommendations of recent evidence-based interdisciplinary guidelines with special emphasis on complementary and alternative therapies. Evid Based Complement Alternat Med. 2013; 2013:485272
2. Goldenberg DL. Initial treatment of fibromyalgia in adults. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.3. Goldenberg DL.Treatment of fibromyalgia in adults not responsive to initial therapies. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24
2014.
Somatic PainA throbbing, stabbing like pain
• Acetaminophen• NSAIDs
First line
• AEDs: gabapentin, carbamazepine• TCAs: amitriptyline
Second line
• Skeletal muscle relaxants: cyclobenzaprine, benzodiazepines• Opioids for SHORT-TERM use for flare-ups
Third line
1. Walsh, Nicolas E. MD, Peter Brooks, MBBS, J. Mieke Hazes, MD<, PhD, et al. Standards of Care for Acute and Chronic Musculoskeletal Pain: The Bone and Joint Decade (2000-2010). Arch Phys Med Rehabil. 2008;89:1830-1845.
2. Chou R. Subacute and chronic low back pain: pharmacologic and noninterventional treatment. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.
3. Anderson BC, Isaac Z, Devine J. Treatment of neck pain. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.4. Drugs for pain. The Medical Letter. 2013;11:31-42.
Opioids
Chemical Classes of Opioids
Phenanthrenes Phenylpiperidines Diphenylheptanes
Natural Codeine Morphine
Semisynthetic Hydrocodone Hydromorphone Oxycodone Oxymorphone
Synthetic Fentanyl Meperidine
Synthetic Methadone
Baumann TJ, Strickland JM, Herndon CM. Pain Management. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill; 2011:539-541.
True Drug Allergy vs Intolerance
“An immune-mediated allergic reaction, usually due to production of antibodies to the medication, that results in hives, wheezing, swelling of the tongue/lips/face and/or anaphylaxis”
Pichler WJ. Drug allergy: classification and clinical features. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.
Adverse Drug Reactions
VA/DoD Clinical Practice Guidelines for Management of Opioid Therapy for Chronic Pain. Available at http://vaww.sites.Irn.va.gov/pain/opioids. Accessed 24 Sept 2014.
Managing Opioid Side Effects
Side Effect Recommendations Tolerance
Constipation• Senna 8.6mg po daily• Docusate 100mg po once or twice daily
NO
Dry mouth• Increase fluid intake• Artificial saliva
Yes
Nausea/vomiting
• Ondansetron 4mg po q8hrs prn• Prochlorperazine 5mg po QID prn
Yes
Pruritus • Diphenhydramine 25mg po q4hrs prn Yes
Sedation• Dose adjustment• Opioid rotation
Yes
Respiratory depression
• Naloxone kits• Avoid polypharmacy (benzodiazepines)
NO
Rosenquist E. Overview of the treatment of chronic pain. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.VA/DoD Clinical Practice Guidelines for Management of Opioid Therapy for Chronic Pain. Available at http://vaww.sites.Irn.va.gov/pain/opioids. Accessed 24 Sept 2014.
Identifying High-Risk Patients
Comorbid conditions○ Sleep apnea or sleep disorder diagnosis○ Kidney dysfunction
Concurrent medications○ Benzodiazepines, antihistamines, sedatives or
other CNS depressants Lifestyle choices
○ Smoking, history of alcohol or drug dependence/abuse
Extremes of age
VA/DoD Clinical Practice Guidelines for Management of Opioid Therapy for Chronic Pain. Available at http://vaww.sites.Irn.va.gov/pain/opioids. Accessed 24 Sept 2014.
Special Considerations Drug metabolism: liver enzyme (CYP2D6)
polymorphisms Codeine: Black Box Warning
○ Fast metabolizers - more side effects
○ Slow metabolizers/DDIs - less effective
Electrocardiogram changes Methadone: Black Box Warning
○ QTc prolongation
VA/DoD Clinical Practice Guidelines for Management of Opioid Therapy for Chronic Pain. Available at http://vaww.sites.Irn.va.gov/pain/opioids. Accessed 24 Sept 2014.
Opioid AnalgesiaWarnings Chronic pulmonary
disease Central sleep apnea
Obstructive sleep apnea
(OSA) not on CPAP
Risk for suicide or
unstable psychiatric
disorder
Receiving treatment for
substance use disorder
(SUD)
Contraindications Severe respiratory
instability
Acute psychiatric
instability
Active diversion and/or
SUD not in remission or
in treatment
Paralytic ileus
True allergy
VA/DoD Clinical Practice Guidelines for Management of Opioid Therapy for Chronic Pain. Available at http://vaww.sites.Irn.va.gov/pain/opioids. Accessed 24 Sept 2014.
Risks with Long-Term Use
Changes in sleep architecture
Respiratory depression
Endocrine changes
Immunosuppression
Opioid-induced hyperalgesia
Rosenquist E. Overview of the treatment of chronic pain. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.VA/DoD Clinical Practice Guidelines for Management of Opioid Therapy for Chronic Pain. Available at http://vaww.sites.Irn.va.gov/pain/opioids. Accessed 24 Sept 2014.
Treatment of PainNon-pharmacologic
Rosenquist E. Overview of the treatment of chronic pain. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.
Acupuncture
Chiropractic manipulation
Heat and cold
Massage
Physical therapy
Opioid Safety Initiative
What is it?Action plan to improve patient safety and
quality of pain management specific to opioid therapy
Focus on prescriber education and trainingAligned with national private and public
initiatives to reduce the number of patients on high dose opioids, overdoses, and death
Midboe, A. “Patient Safety Center of Inquiry: Promoting Patient Safety through Improved Tools for Opioid Prescribing.” Presentation for Patient Safety Awareness Week. March 06, 2013.Accessed online July 15, 2014.
Opioid Prescribing Related Changes
Hydrocodone/acetaminophen Schedule II
Tramadol Schedule IV
Naloxone Kits available from FHCC, Departments of Public Health, and retail pharmacies
Opioid Safety Initiative
GoalsIdentify veterans at immediate, short term,
and long term risk of harms associated with high dose opioid therapy
Develop individualized clinical action plan to mitigate risks
Educate opioid prescribers regarding appropriate use and benefits of urine drug screening
Midboe, A. “Patient Safety Center of Inquiry: Promoting Patient Safety through Improved Tools for Opioid Prescribing.” Presentation for Patient Safety Awareness Week. March 06, 2013.Accessed online July 15, 2014
Opioid Safety Initiative
MeasuresUrine toxicology screen in the past yearConcurrent opioid (including tramadol) and
benzodiazepine usersGreater than 400mg morphine (or equivalent)
daily Future: patients on an opioid and with active
SUD not in treatment
Midboe, A. “Patient Safety Center of Inquiry: Promoting Patient Safety through Improved Tools for Opioid Prescribing.” Presentation for Patient Safety Awareness Week. March 06, 2013.Accessed online July 15, 2014
Patient Provider Agreement
Patient-Provider Partnership Agreement. Packard Health A Community Partnership for Care. http://www.packardhealth.org/patient/provideragreement Published 2014. Accessed November 1, 2014.
Urine Drug Monitoring Methods
Enzyme-Multiplied Immunoassay (EMIT)
Gas Chromatography-Mass Spectrometry (GC-MS)
Initial testing Confirmatory testing
Qualitative Quantitative
Contains specific antibodies against drugs and their metabolites
Breaks down drug molecules into ionized fragments and identifies substances based on mass-to-charge ratio
Rapid, inexpensive, widely available Time consuming, expensive
↑ sensitivity, ↓ specificity ↑ sensitivity, ↑ specificity
1. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;2012. 2. Standbridge JB, et al. Am Fam Physician. 2010;81(5):635-640.3. Moeller KE, et al. Mayo Clin Proc. 2008;83(1):66-76.
Labs at FHCC Urine Drug Screen (EMIT; Urine Tox Quick Order)
○ Opiates○ Benzodiazepines○ Amphetamines○ Cocaine○ Cannabinoids○ Phencyclidine (PCP)
Results in 24 hours Confirmatory Test (GC-MS)
Automatic send out to Hines VA if EMIT positive for opioids and amphetamines
Results in 48-72 hours
Opioid Metabolism
Oxycodone
Hydrocodone
Codeine Morphine
Hydromorphone
Oxymorphone
CYP2D6
< 15% < 5%
Heroin
6-MAM
1. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;2012.2. Moeller KE, et al. Mayo Clin Proc. 2008;83(1):66-76.
Use and DetectionMarijuanametabolites
Single Use 2-8 days
Chronic Use 20-30 days
Cocaine hours BEG 2-4 days
Opioidmetabolites
Heroin 40 minutes
6-MAM 4-12 hours
Codeine/Morphine2-3 days
Oxycodone 2-4 days
Methadone 3-6 days
AmphetamineAmphetamine
1-2 daysMethamphetamine
3-4 days
BenzodiazepineShort-acting
3 daysLong-acting
30 days
BarbiturateShort-acting
1 dayLong-acting
21 days
Alcohol 7-12 hoursEthyl glucuronide
≥ 72 hours
1. Tenore PL. Journal of Addictive Diseases. 2010;29:436-448.2. Standbridge JB, et al. Am Fam Physician. 2010;81(5):635-640.3. Moeller KE, et al. Mayo Clin Proc. 2008;83(1):66-76.4. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;2012.5. Drug Testing: A White Paper of the American Society of Addiction Medicine. 2013.
False Positives Alcohol
OTC cough products Mouth wash
Marijuana Dronabinol Efavirenz PPIs
Cocaine Topical anesthetic
BZD Sertraline ≥ 100mg
Barbiturates Ibuprofen Naproxen
Opioids Poppy seeds Fluoroquinolones Rifampin Verapamil Trazodone
Amphetamines Highly cross reactive with
many medications Amiodarone SSRIs MAOIs TCAs Pseudoephedrine
1. Reisfield GM, et al. Annals of Clinical & Laboratory Science. 2007;37(4):301-314.2. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;2012.3. Tenore PL. of Addictive Diseases. 2010;29:436-448.4. Vincent EC, et al. J Fam Pract. 2006;55(10):893-897. 5. Moeller KE, et al. Mayo Clin Proc. 2008;83(1):66-76.6. Brahm NC, et al. Am J Health-Sys Pharm. 2010;67(16):1344-1350. 7. Vincent EC, et al. J Fam Pract. 2006;55(10):893-897.
False Negatives
OpioidsRapid CYP 2D6 metabolizers
BZDsClonazepamLorazepam
HeroinUsually undetectable; short half life6-MAM metabolite detected for 4-6 hours
1. Reisfield GM, et al. Annals of Clinical & Laboratory Science. 2007;37(4):301-314.
2. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;20123. Tenore PL. Journal of Addictive Diseases. 2010;29:436-44.
Frequency of Monitoring
Interagency Guideline on Opioid Dosing for Chronic Non-cancer Pain: An educational aid to improve care and safety with opioid therapy 2010 Update.
Limitations of Monitoring Results do not indicate
Length of time exposed to a medication Amounts of a specific drug in the patient’s system Frequency of use True for urine drug screens: use of multiple medications in
the same family Positive results
Reflect use over a few days Do not indicate overall adherence or if the patient is taking
more or less than prescribed. Negative results
Assay not sensitive to the medication a patient is taking Do not indicate lack of use1. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;2012.
2. Moeller KE, et al. Mayo Clin Proc. 2008;83(1):66-76.
Patient Case AD is a 56 year old male with PMH
significant for lumbar spinal stenosis, chronic back pain with sciatica, TIIDM with moderate peripheral neuropathy, and HTN. Pt presents for urine drug test follow up. He’s been managed on the pain regimen below for the past 30 days:Morphine 45mg sustained acting PO BID Morphine 15mg immediate release PO TID PRN Gabapentin 300mg PO TID
UDS Screen
UDS Confirmation
Opioid Metabolism
Oxycodone
Hydrocodone
Codeine Morphine
Hydromorphone
Oxymorphone
CYP2D6
< 15% < 5%
Heroin
6-MAM
1. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;2012.2. Moeller KE, et al. Mayo Clin Proc. 2008;83(1):66-76.
Patient Case
Pt states he was seen in emergency department for back pain prior to UDS
He was given 1mg hydromorphone (Dilaudid)
Does this explain the (+) hydrocodone?
Questions?