PAIN MANAGEMENT STRATEGIES: ALTERNATIVES TO OPIOIDS

Transcription

1 PAIN MANAGEMENT STRATEGIES: ALTERNATIVES TO OPIOIDS SATURDAY/2:00-3:00PM ACPE UAN: L01-P 0.1 CEU/1.0 hr Activity Type: Knowledge-Based Learning Objectives for Pharmacists: Upon completion of this CPE activity participants should be able to: 1. Discuss the concerns with opioid use and abuse. 2. Recommend alternative therapies to opioids for optimal pain management. 3. Describe the limitations with medications used to treat pain. Speaker: John Swegle, PharmD, BCPS, BCACP John received his Bachelor of Science from Drake University in 1992 and his PharmD degree from the University of Iowa in After completion of a pharmacy residency in Family Medicine in 1997, John joined the faculty at the University of Iowa College of Pharmacy and the Mercy Family Medicine Residency Program in Mason City. He currently is a Clinical Associate Professor with the University of Iowa and clinical pharmacist with the Mercy Family Medicine Residency Program. In addition, he works with Hospice of North Iowa serving as a consultant pharmacist and as a faculty member for the Mercy Medical Center North Iowa Palliative Medicine Fellowship. Speaker Disclosure: John Swegle reports no actual or potential conflicts of interest in relation to this CPE activity. Off-label use of medications will be discussed during this presentation.

2 Pain Management Strategies: Alternatives to Opioids John Swegle, PharmD, BCPS, BCACP Clinical Associate Professor University of Iowa College of Pharmacy Clinical Pharmacist Mercy Family Medicine Residency Disclosure John Swegle reports no actual or potential conflicts of interest associated with this presentation 1

3 Learning Objectives Upon successful completion of this activity, participants should be able to: Discuss the concerns with opioid use and abuse Recommend alternative therapies to opioids for optimal pain management Describe the limitations with medications used to treat pain Pre-Assessment Questions Which one of the following is NOT a concerning adverse effects with NSAIDs A. Myocardial infarction B. Renal impairment C. Dyspepsia D. Gastrointestinal bleed 2

4 Pre-Assessment Questions Which of the following are considered first-line treatment options for neuropathic pain? A. Nortriptyline B. Duloxetine C. Gabapentin D. Topical lidocaine E. All of the above Pre-Assessment Questions Which one of the following side effects can be problematic using tricyclic antidepressants? A. Weight loss B. Diarrhea C. Dry mouth D. Urinary frequency 3

5 Pre-Assessment Questions True/False: Gabapentin is an ideal choice for all pain types? A. True B. False Non-opioid Pain Management Things that make you wonder 4

6 We Might Have Been Fooled Letter to the Editor -..the incidence of narcotic addiction in 39,946 hospitalized medical patients there were only four cases of reasonably well documented addiction in patients who had no history of addiction. - We conclude that despite widespread use of narcotic drugs in hospitals, the development of addiction is rare in medical patients with no history of addiction. - Jane Porter Hershel Jick, M.D. Boston Collaborative Drug Surveillance Program Boston University Medical Center, Waltham, MA N Engl J Med 1980;302:123 5

7 We Might Have Been Fooled We conclude that opioid maintenance therapy can be safe, salutary and more humane alternative to the options of surgery or no treatment in those patients with intractable non-malignant pain and no history of drug abuse - Based on 38 patients - No toxicity reported Pain 1986;25: Fast Forward A Few Years 1996 Pain as the 5 th vital sign - Introduced by American Pain Society - Targeted assessment and treatment of pain Was being overlooked 2001 The Joint Commission - Pain Management Standards Grew the idea of pain as the 5 th vital sign In the 2000 s - Opioid use increases Providers felt pressure to treat and aggressive marketing expanded the use of opioids 6

8 The Present Overdoses Addiction Opioid Use Disorder Addiction treatment programs Opioid shortages Reduction in production CDC guidelines What Do We Do? What is the best way to manage pain? How does one approach pain? It is a partnership - Goals need to align with everyone involved Patient/family, healthcare team, standards of care, governing bodies (i.e. Boards, DEA, etc) Pain is not just a score on a 0-10 scale - What does the patient hope to accomplish Sleep? Perform activities? Other? Crit Care Nurs Clin North Am 2017;29: Nurs Clin N Am 2017;52:e1-17 7

9 Understanding Pain Pain is the cognitive, emotional, and behavioral response to nociception Intensity of pain varies - Accounted for by stress, distress, and less effective coping strategies The intensity of the pain and psychosocial factors are linked J Bone Joint Surg 2017;99:e113(1-10) Solutions to Effective Pain Management Must be comprehensive - Just taking a pill will not solve the problem The best pain reliever is self-efficacy in response to nociception Alleviate distress - Optimize functioning of the human mind Cognitive behavioral therapy Resilience of the patient J Bone Joint Surg 2017;99:e113(1-10) 8

10 WHO Ladder Step 1 Non-Opioid: Acetaminophen, NSAID, +/- adjuvants Step 2 Mild opioid with or without nonopioid Step 3 Strong opioid with or without non-opioid Selection of Medications Can be disease specific - Back pain vs. gout vs. herniated disc Can be patient specific - Age, comorbidities, location, duration, etc Can be drug specific - Topical, systemic, injectable, oral Can be other factors involved - Costs, social factors, patient location 9

11 Acetaminophen You know about this one Often preferred for mild/moderate pain - In many combination products Pharmacology - Central inhibition of prostaglandins Relatively safe but not without risks Risks with Acetaminophen Hepatotoxicity - Big one everyone knows about Dosing matters - Generally limit to 3000 mg per day Less in those with history of alcohol abuse, renal/hepatic dysfunction Watch combination products - Often will have more than one option that contains acetaminophen Am J Geriatr Pharmacother 2012;10:

12 IV Acetaminophen (Ofirmev ) Dosing is similar to other formulations - Avoidance of first-pass effect thus thought to have less risk for hepatotoxicity Mostly used in emergency department or postoperatively - Efficacy has been questioned due to methodologic flaws Not unusual Acad Emerg Med 2016;23: NSAIDs Pharmacology - Antipyretic - Analgesic - Anti-inflammatory Mechanism of action - Central and peripheral inhibition of cyclooxygenase (COX) Leads to inhibition of prostaglandins Recent Results Cancer Res 2013;191:

13 NSAIDs Salicylic Acid Derivatives Aspirin Choline magnesium trisalicylate Salsalate Diflunisal Acetic Acids Diclofenac Ketorolac Sulindac Etodolac Indomethacin Proprionic acids Ibuprofen Ketoprofen Naproxen Oxicams Meloxicam Piroxicam Naphthalakanones Nabumetone NSAIDs Salicylic Acid Derivatives Aspirin Choline magnesium trisalicylate Salsalate Diflunisal Acetic Acids Diclofenac Ketorolac Sulindac Etodolac Indomethacin Proprionic acids Ibuprofen Ketoprofen Naproxen Oxicams Meloxicam Piroxicam Naphthalakanones Nabumetone 12

14 Choosing an NSAID Interpatient variability in response All are considered equally effective Selection based on - Doses per day - Cost/insurance coverage - Previous exposure - Toxicity Risks with NSAIDs Gastrointestinal toxicity Cardiovascular Renal Sodium/fluid retention - Aggravate hypertension/heart failure Bleeding Tinnitus Am J Gastroenterol 2009;104: World J Gastroenterol 2012;18:

15 As an Aside IV Ketorolac Available as 15, 30, and 60 mg vials for IV/IM use Likely has a ceiling dose - Studies have shown doses exceeding 10 mg fail to provide additional benefit - Most studies were from emergency departments in patients presenting with abdominal, flank, or musculoskeletal pain - Limitations to the studies do exist Generally speaking, probably no need to give more than 15 mg in the acute setting Ann Emerg Med 2017;70: Neuropathic Pain Classes generally considered first-line for treating neuropathic pain - Tricyclic antidepressants - Selective serotonin/norepinephrine reuptake inhibitors (SNRI s) - Calcium channel 2- ligand Classes generally considered second-line - Topical lidocaine - Opioids - Tramadol - Others Pain Ther 2017;6:S35-S42 Pain Res Manag 2014;19:

16 Antidepressants Depression and pain - Often co-exist estimated 75-80% of patients with depression have persistent pain conditions - Persistent pain has been associated with increased risk for depression Primary mechanism of action - Low levels of serotonin and/or norepinephrine lead to increased levels of pain - Suppress central pain sensitization through inhibition of norepinephrine and serotonin reuptake - Antagonism of peripheral sodium channels and spinal NMDA receptors J Clin Pharmacol 2012;52:6-17 Anesth Analg 2017;125: Tricyclic Antidepressants Most recommend using secondary amines - Nortriptyline or desipramine Tertiary amines considered alternatives if secondary amines unavailable - Amitriptyline, imipramine, doxepin Advantages - Inexpensive - Available - Once-daily administration - Improvement of sleep/depression Pain. 2007;132:237 15

17 Tricyclic Antidepressants Dosing - Initiate with mg HS - Increase by mg daily every 3-7 days as tolerated - Maximum dose of ~150 mg daily - In general, titrate until pain is controlled or side effects limit further titration Adequate trial considered to be 6-8 weeks J Clin Pharmacol 2012;52:6-17 Tricyclic Antidepressants Disadvantages - Adverse effects (more common with tertiary amines): Sedation, weight gain, orthostatic hypotension Anticholinergic effects: dry mouth, constipation, blurred vision, urinary retention - Precautions: Cardiac disease (conduction disorders, arrhythmias) Suggestion to obtain EKG in those over 40 years of age Elderly (minimize amitriptyline) Risk of suicidal ideation Pain. 2007;132:237 16

18 Tricyclic Antidepressants Efficacy has been shown in various types of pain - Chronic low back pain, fibromyalgia, postherpetic neuralgia, diabetic neuropathy Number needed to treat - Diabetic neuropathy Postherpetic neuralgia 2.8 to 3 Good class to keep in mind Pain Res Manage 2014;19: Am Fam Physician 2017;96: Serotonin/Norepinephrine Reuptake Inhibitors Duloxetine (Cymbalta ) Venlafaxine (Effexor ) Milnacipran (Savella ) 17

19 Duloxetine Dosing - Initiate with 30 mg daily - May increase to 60 mg daily after after one week - Maximum is 60 mg twice daily Doses higher than 60 mg per day have shown inconsistent benefit - Adequate trial considered 4 weeks Adverse effects - Nausea may be problematic at 23% Reduced if initiate with 30 mg per day - Headache, dry mouth, somnolence, insomnia, constipation, hyperhidrosis Semin Neurol 2010;30: Venlafaxine No approved indications for pain Studies showing positive outcomes not as large as with duloxetine Less balanced throughout the dosing scheme - Low doses more SSRI effect - Higher doses more SNRI effect Listed as a treatment that should not be used by NICE guidelines 18

20 Calcium Channel 2- Ligands Calcium channel blocking anticonvulsants - Gabapentin (Neurontin ) and pregabalin (Lyrica ) Mechanism of action - Structurally similar to GABA but do not bind to GABA receptors - Binds to 2-delta subunit of voltage-dependent calcium channels - Leads to reduction of calcium influx into neurons - Thought to decrease release of excitatory neurotransmitters glutamate and substance P Many studied in diabetic neuropathy and postherpetic neuralgia Curr Opin Neurobiol 2010;5: Biochem Soc Trans 2010;38: Gabapentin Can be effective but losing favor Dosing titration and kinetics are a limitation Ideal dose varies - Likely target is mg per day Some have suggested lower ( mg/day) Adverse effects - Somnolence, dizziness often dose-limiting May give bulk of dose at night - Ataxia, cognitive/memory problems, peripheral edema Relatively inexpensive Pain Ther 2017;6:S35-S42 19

21 Pregabalin Derivative of gabapentin with same mechanism of action - More linear absorption aiding in dosing scheme Absorption not saturated Higher degree of efficacy in clinical studies - More predictable/meaningful results from dose increases - Broader indications Post-herpetic neuralgia Diabetic peripheral neuropathy Fibromyalgia Epilepsy Res 2007;73: Pain Ther 2017;6:S35-S42 Pregabalin Dosing - Initiate with 50 mg three times daily or 75 mg twice daily Suggested to initiate with 75 mg once daily at bedtime in elderly - Increase to 300 mg daily after 3-7 days then by 150 mg/day every 3-7 days - Maximum of 600 mg daily however suggested dose is 300 mg per day - Adequate trial is 4 weeks Pain. 2007;132:237 Pain Ther 2017;6:S35-S42 20

22 Pregabalin Adverse effects - Mainly CNS Dizziness, incoordination, ataxia, tremor, confusion, asthenia, fatigue Euphoria reports of anxiolytic effects from clinical trials thus schedule V Other: peripheral edema, dry mouth, constipation Expert Opin Drug Saf 2012;11: Epilepsia 2011;52: Other Anticonvulsants Carbamazepine - Trigeminal neuralgia drug of choice - Not recommended for anything other neuropathic pain Lamotrigine - Variable results for neuropathic pain - Dosing scheme is limiting factor Pain Res Manage 2014;19:

23 Topical Agents Advantages: - Able to minimize systemic absorption - Flexibility with regard to applying product directly to area of pain Disadvantages - Need to ensure vehicle will allow penetration - May be short-lived response - Some take time to work whereas others have rapid onset - Must consider area wishing to cover Topical Agents Lidocaine - Considered 4 th line in some guidelines Most practical for localized peripheral neuropathy - Lidocaine patch 5% (Lidoderm ) Only should be used on intact skin Patches may be cut to desired size Application Use up to 3 patches at one time applied for 12 hours per 24 hour period - Lidocaine 3.6% with menthol 1.25% Over-the-counter; considered non-inferior to prescription - Viscous lidocaine An option however duration of effect is less Curr Med Res Opin 2012;28: Pain Res Manag 2014;19:

24 Topical Agents Capsacian cream (Zostrix ) - Strengths: 0.025% and 0.075% (HP) - Derived from red chili peppers Lowers level of substance P from nerve endings - Must be applied 3-4 times per day Not meant to be used PRN Burning sensation during initial use - Overall efficacy is marginal at best Difficult to blind the burning in trials Topical Agents Capsaicin patch (Qutenza ) - Strength: 8% - Prescription product indicated for neuropathic pain associated with postherpetic neuralgia - Provider applied Left in place for 60 minutes then removed Touted as providing relief for 3 months - Very expensive Br J Anaesth 2011;107:

25 Ketamine Derivative of phencyclidine - Derived in 1962 due to need for less hallucinogenic agent for anesthesia Unique properties - Hypnotic, analgesic, and amnestic effects - Produced a dissociative anesthesia disconnecting people from their environment - Historically used for pediatric procedures and in veterinary medicine Acta Pharmacologica Sinica 2016;37: Clin Pharmacokinet 2016;55: Ketamine Mechanism of action - NMDA receptor antagonist Blunt the effects of glutamate - Reduce pain transmission/modulation Involved in wind-up pain and opioid hyperalgesia - Other mechanisms thought to be involved Lower doses than used for anesthesia - Oral: mg every 8 hours - IV: mg/kg single dose (also able to give as infusion) J Anaesthesiol Clin Pharmacol 2016;32:

26 Ketamine Advantages - Minimal effects on respiratory drive May cause transient apnea if rapidly infused - Safer to use in those with hemodynamic instability - Opioid sparing Downsides - Secretions - Long term safety and efficacy is unclear Linked to cystitis, cognitive disturbances, euphoria Acta Pharmacologica Sinica 2016;37: Clin Pharmacokinet 2016;55: Lidocaine Infusions Class IB anti-arrhythmic - Sodium channel blocker Targets neuropathic pain - Postulated to work through peripheral, spinal, and supraspinal mechanisms Block neuronal function in active or depolarized neurons Infusions can provide acute relief of pain - Usually within an hour of administration - Dosing is low J Suppot Oncol 2004;2:90-94 Curr Pain Headache Rep 2007;11:

27 Lidocaine Infusions Side effects depend on level - Target level is 3-4 mcg/ml Lightheadedness, numbness around the tongue/mouth, dizziness Has been used short term and for longer durations May serve as test dose for response to oral options - Mexiletine J Suppot Oncol 2004;2:90-94 Curr Pain Headache Rep 2007;11:20-24 Cannabinoids A talk for another day..it s complicated Iowa cannabis 26

28 Other Treatments of Interest Skeletal muscle relaxants - Carisoprodol, tizanidine, cyclobenzaprine - Majority of studies were in acute pain settings and not chronic Low back pain Myofascial pain Fibromyalgia Anesth Analg 2017;125: Other Treatments of Interest -2 agonists - Dexmedetomidine Central antinociceptive activity making it attractive as adjunctive therapy May have opioid sparing effect in various settings - Clonidine Less selective than dexmedetomidine Less pronounced opioid-sparing effect as well More options for administration oral, transdermal, IV Anesth Analg 2017;125:

29 Other Treatments of Interest NMDA receptor antagonists - Amantadine Theorized to decrease postoperative central sensitization, opioid tolerance, and opioid-induced hyperalgesia Data is mixed - Dextromethorphan Primarily has been used to reduce opioid consumption Anesth Analg 2017;125: Corticosteroids Sympatholytic agents Radiopharmaceuticals Calcitonin GABA agonists Benzodiazepines Bisphosphonates Mexiletine Even More Options 28

30 Nonpharmacologic Physical strategies Cryotherapy TENS Massage Yoga Healing touch Acupuncture Aromatherapy Cognitive/mental strategies Cognitive-behavioral therapy Meditation Guided imagery Mindfulness-based stress reduction Music therapy Pet therapy J Bone Joint Surg 2017;99:e113(1-10) Take Home Points Look at the big picture - Patient goals, motivation, support, other types of pain beyond physiologic One size does not fit all - Cannot expect one medication to treat all types of pain If something doesn t work, try something else - Look outside the box 29

31 Post-Assessment Questions Which one of the following is NOT a concerning adverse effects with NSAIDs A. Myocardial infarction B. Renal impairment C. Dyspepsia D. Gastrointestinal bleed Post-Assessment Questions Which of the following are considered first-line treatment options for neuropathic pain? A. Nortriptyline B. Duloxetine C. Gabapentin D. Topical lidocaine E. All of the above 30

32 Post-Assessment Questions Which one of the following side effects can be problematic using tricyclic antidepressants? A. Weight loss B. Diarrhea C. Dry mouth D. Urinary frequency Post-Assessment Questions True/False: Gabapentin is an ideal choice for all pain types? A. True B. False 31

33 Questions? 32