Describe Identify Compare Recognize

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2 Goal To educate nurses about the challenges associated with treating chronic pain and the safety and efficacy of alternative therapy options in relation to Opioids.

3 Objectives Describe the challenges associated with pharmacological treatment of chronic pain. Identify non-opioid therapies that can substitute for opioids when it comes to treating chronic pain. Compare and contrast the clinical efficacy and safety profile of alternative therapies for chronic pain management. Recognize the role of the nurse in reducing pain.

4 Pain is subjective

5 What is Pain? Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage Acute Chronic Response to tissue damage that does not last longer than it takes for normal healing to occur Persistent pain that lasts >3 months or past the time of normal tissue healing

6 Chronic Pain One of the highest incidence rates among chronic disease states Ranks high on the list of leading reasons individuals seek healthcare in the U.S. Lowers patient quality of life Associated with high rates of depression and anxiety U.S. Pharmacist March 2017

7 U.S. Pharmacist March 2017 Physiology of Pain Nociceptive- responds to acetaminophen, NSAIDs, and opioids Somatic Visceral Neuropathic- responds to antidepressants and anticonvulsants Nociceptors transmit feeling of pain by A-delta and C fibers A-delta- transmit fast, sharp, well-localized pain signals C fiber- transmit poorly localized, dull, burning type pain signals

8 CDC Website The New York Times, June 2017 The Opioid Epidemic Declared a national health emergency Deaths from prescription opioids have more than quadrupled since 1999 Drug overdoses are now the leading cause of death among Americans under 50 years

9 Overdose Deaths Across the Years The number of overdose deaths reached 64,000 people in Deaths from drug overdoses jumped in nearly every county across the United States. New York Times Jan 19, 2017

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11 Commonly Used Opioids Agent Fentanyl Hydromorphone Morphine Methadone Initial Dose* mcg mg Q3H 1-2 mg Q3H 2-4 mg Q6H mg Q4H 5-10 mg Q4H mg Q4H mg Q8-12H 5 mg Q8H Route IV IM IV IM PO IV IM PO IV IM PO Onset (min) Route of Elimination Renal Renal Renal Renal Oxycodone 5-15 mg Q6H PO Renal Hydrocodone mg daily PO Renal Codeine mg Q4H PO Renal Tramadol mg Q4-6H PO 60 Renal *Recommended initial dose in adult patient with normal renal and hepatic function Birrer KL. PSAP. 2014: ; Lexicomp Website

12 Commonly Used Combination-Opioids Agent Initial Dose* Route Onset (min) Strengths (mg) Max 24 Hour Dose (mg) Hydrocodone- Acetaminophen (APAP) Vicodin Norco Lorcet mg Q4-6H PO /325 5/300 5/ / /325 10/300 10/ mg APAP 60 mg hydrocodone Oxycodone- Acetaminophen Percocet Endocet mg Q6H PO /325 5/ /325 10/ mg APAP 80 mg oxycodone Codeine- Acetaminophen Tylenol #3 Tylenol # mg Q4H PO mg APAP 360 mg codeine

13 Pharmacology of Opioids

14 Lexicomp Website Adverse Effects of Agent Fentanyl Opioids Opioid Related Adverse Drug Events (ORADEs) Hydromorphone Morphine Methadone Oxycodone Hydrocodone Codeine Bradycardia CNS depression Respiratory depression Constipation Sedation Tramadol

15 CDC Guideline for Prescribing Opioids for Chronic Pain, March 2016 Treating Chronic Pain with Opioids No dose ceiling Reassess risks vs. benefits at 50 MME/day* Avoid increasing dose >90 MME/day Chronic use can lead to: Physiologic tolerance Opioid-use disorder DSMV: a problematic pattern of opioid use leading to clinically significant impairment or distress A higher dose is associated with a higher incidence of overdose *Morphine Milligram Equivalents per day (MME/day)

16 harmacy Practice News, January 2017 How to Prevent Medication Diversion in the Workplace Procurement: Person ordering the drug is not receiving/stocking Wasting: Watch for time-related gaps Nurse pulls a larger amount of a controlled substance than indicated and documents the rest as waste Cancellations: Watch for cancelled transactions Nurse can switch out vials of fentanyl with water-filled vials from home, then cancel entire transaction Shift Behaviors: Watch for changes in behavior Going to the restroom frequently Patient reports medication does not relieve pain only during a specific shi

17 Opioid Use Disorder Addiction Tolerance Withdrawal Persistent desire/unsuccessful efforts to cut down Social or occupational activities given up or reduced due to substance abuse Misuse- using other than how prescribed To get high Diversion- selling or trading Aberrant behaviors Early refills Doctor shopping

18 Pharmacy Practice News, January 2017 Becker s Hospital Review, March National Survey on Drug Use and Health by the Substance Abuse and Mental Health Services Administration Opioid Diversion in the Workplace 10-15% of health care workers develop substance addiction 103,000 health care workers abuse drugs each year nurses stole nearly 16,000 pills (mostly oxycodone) due to breakdowns in automated drug cabinet security Hospital fined $2.3 million Technician stole at least 216,000 Norco tablets by manipulating purchases California Board of Pharmacy held PIC liable and revoked his license even though he was unaware of theft

19 Alternative Therapies to Chronic Pain NSAIDs Topical Anticonvulsan t Antidepressan t Misc Ibuprofen Lidocaine Pregabalin Duloxetine Acetaminophen Naproxen Capsaicin Gabapentin Venlafaxine ER Diclofenac Menthol Topiramate Amitriptyline Celecoxib Carbamazepine Nortriptyline Ketoprofen Oxcarbazepine The CDC recommends using non-opioid pharmacologic therapy for chronic pain U.S. Pharmacist March 2017 CDC Guideline for Prescribing Opioids for Chronic Pain, March 2016

20 CDC Guideline for Prescribing Opioids for Chronic Pain, March 2016 Evidence from Guidelines Evidence supports short term efficacy of opioids for reducing pain and improving function in nociceptive and neuropathic pain in RCTs lasting 12 weeks No long-term studies meeting CDC standards that compare effectiveness of opioids to non-opioids for chronic pain Chronic use of opioids may be linked to increased opioid abuse and dependence

21 A Stepwise Approach World Health Organization. Pain Relief. Geneva: WHO, 1986

22 Lexicomp Website Acetaminophen Acetaminophen Tylenol Starting Dose Maximum Dose 650 mg Q4-6H 4000 mg/day Mild-moderate pain Does not exert an anti-inflammatory effect Safety concerns Hepatotoxicity occurs at a total daily dose of >4g Use lower dose in renal insufficiency and history of alcohol abuse

23 Lexicomp Website NSAIDs Starting Dose Ibuprofen Advil 400 mg Q4-6H Naproxen Naprosyn 500 mg/day Diclofenac Voltaren 50 mg TID Celecoxib Celebrex 100 mg BID Ketoprofen Frotek mg Q6-8H Max Dose 3200 mg/day 1000 mg/day 150 mg/day 400 mg/day 300 mg/day Exerts anti-inflammatory effects Safety Concerns Gastrointestinal Can cause gastric bleeding Consider using H2RA or PPI Renal Increases sodium retention, decreases renal blood flow Cardiovascular Can cause heart attack or stroke Consider using naproxen or celecoxib

24 U.S. Pharmacist March 2017 Evidence Supporting NSAID Use Tramadol 50 mg QID versus Celecoxib 200 mg BID Double-blind, double-dummy study Results showed a greater response to celecoxib use Opioids did not show superiority over NSAIDs when used for treating chronic low back pain

25 U.S. Pharmacist March 2017 Topical Products Lidocaine Can be used for neuropathic pain Available as 4% and 5% patches Side effects: redness, irritation, skin edema Apply up to 3 patches in a single application for up to 12 hours per day Capsaicin Can be used for neuropathic pain available as 0.025%, 0.075%, and 0.1% creams Side effects: erythema, burning, stinging, and itching Apply 3-4 times daily Topical NSAIDs relieve pain similar to its oral counterpart with fewer side effects

26 Lexicomp Website Antidepressants Tricyclic Antidepressants (TCAs) FDA-approval in pain management Starting Dose Amitriptyline Elavil 25 mg/day Nortriptyline Pamelor mg/day Maximum Dose 100 mg/day 150 mg/day Advantages Extensive history of use in neuropathy Low cost Beneficial for patients who experience depression or insomnia Disadvantages Not effective in chronic back pain compared to placebo Anticholinergic side effects Safety Concerns Avoid use in patient with history of cardiac arrhythmias

27 Lexicomp Website Antidepressants cont. Serotonin- Norepinephrine Reuptake Inhibitors (SNRIs) FDA-approval in pain management Starting Dose Maximum Dose Duloxetine Cymbalta Diabetic neuropathy Fibromyalgia 30 mg/day 60 mg/day Venlafaxine ER Effexor XR or 75 mg/day 225 mg/day Initiate in patients who experience pain and depression Safety Concerns Concomitant monoamine oxidase inhibitor (MAOI) use Side effects: nausea, dizziness, sexual dysfunction, mood change Caution in hepatic and renal impairment Venlafaxine may cause changes in blood pressure

28 Lexicomp Website Anticonvulsants FDA-approval in pain management Starting Dose Maximum Dose Gabapentin Neurontin Post herpetic neuralgia (PHN) 300 mg/day 3600 mg/day Pregabalin Lyrica PHN Diabetic peripheral neuropathy Fibromyalgia 150 mg/day 600 mg/day Safety concerns Side effects: sedation, weight gain, swelling, changes in mental status Topiramate (Topamax ) Off label indication for diabetic neuropathy Evidence for efficacy much weaker than other anticonvulsants and not recommended

29 Lexicomp Website Anticonvulsants cont FDA-approval in pain management Starting Dose Maximum Dose Carbamazepine Carbatrol Trigeminal Neuralgia 100 mg/day 1200 mg daily Oxcarbazepine Trileptal 300 mg/day 900 mg BID Safety Concerns CYP3A4 inducer Carbamazepine contraindicated in patients taking a MAOI or with bone-marrow suppression Monitor CBC and changes in mood

30 Review of Side Effect Profiles NSAIDs Opioids Topical Acetaminophe n Cardiovascular Gastrointestina l Renal Gabapentin Pregabalin Dizziness Drowsiness Weight gain Swelling Changes in mental status Bradycardia CNS depression Respiratory depression Constipation Sedation Opioid-use disorder Anticonvulsants Carbamazepine Oxcarbazepine Dizziness Nausea Drowsiness Ataxia Steven-Johnson Syndrome Erythema Dryness Numbness Burning Tingling Amitriptyline Nortriptyline Dry mouth Constipation Drowsiness Urinary retention Blurred vision Hepatotoxicity Dizziness Antidepressants Duloxetine Venlafaxine ER Dizziness Nausea Fatigue Constipation Sexual dysfunction

31 Review of Patient Exclusions NSAIDs Opioids Topical Acetaminophe n Ischemic heart disease or Cerebrovascular disease History of ulcers Renal insufficiency Use of anticoagulants Gabapentin Age > 75 years Pregabalin Anticonvulsants Severe renal impairment Age > 65 years Renal/hepatic insufficiency Pulmonary disease Concomitant sedating drugs Carbemazepine Oxcarbazepine Concomitant CYP3A4 substrate drug use Bone marrow Hypersensitivity Amitriptyline Nortriptyline Elderly Recent MI Cardiac arrhythmias Liver failure Alcohol use Antidepressants Duloxetine Venlafaxine ER MAOI use

32 How Nurses Can Play an Effective Role Knowledge of self Knowledge of pain Knowledge of Standard of Care

33 U.S. Pharmacist March 2017 Conclusion Opioids are easy choices for pain, but other options should also be utilized first Chronic use of both NSAIDs and opioids is associated with increased adverse events Weigh risk versus benefit of therapy Look at patient specific factors Location and type of pain Past medical history and lifestyle

34 References James A. Jorgenson, MS, RPh, FASHP, Gregory S. Burger, MS, RPh, FASHP & Maureen E. Burger, RN, MSN, CPHQ, CPPS, FACHE. Drug Diversion in Hospitals: Are You next? Becker's Hospital Review, 18 Mar. 2016, Katz, Josh. Drug Deaths in America Are Rising Faster Than Ever. The New York Times, The New York Times, 5 June 2017, Morbidity and Mortality Weekly Report (MMWR). Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 18 Mar Pharmacy vs. Diversion: Technology, Education Key. Pharmacy Practice News, vol. 44, no. 1, Jan. 2017, pharmacypracticenews.com. Utilizing Non-Opioids for Chronic Pain in the Setting of an Opioid Epidemic. U.S. Pharmacist, Mar. 2017, pp ,

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