1. 1 Opioid Selection for Acute and Chronic Pain Control J K Lilly MD MS Appalachian Pain Therapy Institute Charleston, WV

2. 2 Objectives  Identify the difference between acute and chronic pain treatment in opioid- naive verses opioid-tolerant patients.  Identify medications appropriate for treatment of each type of pain.  Know the Equianalgesic Doses of IV Morphine, Dilaudid and Fentanyl & convert to oral doses (enterohepatic=1.3).  Know about Iatrogenic Abstinence Syndrome  Realistically apply the Visual Analog Pain Score to evaluating response to opioids.  Differentiate Addiction Disorder from Chronic Pain and Chronic Pain Behavior

3. 3 Equianalgesic Dosing Pure Opioids DrugPO DoseIM Dose & 1/2 life Morphine 130-6010 (=) Hydrocodone 130-60n/a (=) Oxycodone 1.315-3020 (=) Methadone20 acute (1.3) 2-4 chronic (8-12) 10 (++) Fentanyl 100400 mcg0.1 (+) Levorphanol 152-42-4 (+) Hydromorphone “Dilaudid” 5 4-81.5 (=)

4. 4 Equianalgesic Dosing Weak Opioids and Mixed Agonists Drug POIM & ½ Life Meperidine 0.1 Codiene 0.5 Propoxyphene 0.15 Buprenorphine 10 Nalbuphine 1 Butorphanol ~25 Pentazocine 0.15 300 60-120 450 n/a (30) n/a 325 100-200 (=) 130-160 (=) n/a (+).32-.96 (+) 10 (=) 5 (=) 30-60 (=/+)

5. 5 Equianalgesic Dosing  Consider the example of switching from Methadone 10 tid to Oxycodone-SR  First, determine the Morphine equivalent dose to current drug,  Then, estimate dose of new drug from the Morphine equianalgesic dose i.e. Methadone → Morphine → Oxycodone 30 mg/d x 8 = 240 mg/d x.66= 160mg/day

6. 6 Equianalgesic Dosing  Convert from Fentanyl 50 mcg/hr patch plus Percocet 10/650 up to tid for recurrent pain plus IV Demerol 25 mg up to once per shift for “bad” pain to IV Morphine infusion dose (real example) Fent 50 x24hr=1200 mcg/day x100= 120mg MS; Oxycod 30 x1.3= ~ 40mg MS; Demerol 75 = 75x.1= ~8-10mg MS => 120+~40+~10= ~180mg MS equivalent dose/day or IV-infusion hourly dose of 6.6 mg/hr

7. 7 Acute Pain Control Plan  Acute Pain: physical discomfort, short duration (hours to weeks), usually severe, usually associated with disease, birthing process or injury  Opioid-Naïve (narcotic celibacy)  Opioid-Tolerant (taking the equivalent of >25 mg/ day of Oxycodone or equivalent dose of any sustained release opioid preparation)  Visual Analog Pain Score (0-10) only advisory!

8. 8 Chronic Pain Control Plan  Pain lasting longer than six months  Persists disproportionately beyond the initial cause  May not respond in the same way as acute pain to techniques and medications  Cause may not be resolvable!  May require combined treatment modalities  Long Term Opioid Therapy (LTOT) may be the final therapeutic (last/ best) alternative  Chronic Pain Syndrome and its attendant behavior ARE NOT equivalent to Addiction Disorder

9. 9 Opioid -Naive With PCA (preferred)  Continuous (controversial)- MS 2mg/hr or second line drug in equianalgesic dose (0.2 mg/ hr HM, 20 mcg/ hr Fentanyl)  Demand Bolus - MS 1 mg or equianalgesic dose  Lockout – 10-15 minutes  Rescue – RN administered intermittent rescue ~ twice the dose of PCA bolus q 1 hr prn until reviewed  Review & adjust orders q 12 hrs  Continuous Oximetry

10. 10 Opioid -Naive Without PCA (but IV)  First Line: Morphine 2mg IV q 5 min prn ‘til comfortable or AE  Second Line:  Hydromorphone 0.2 mg IV q 5 min prn or Fentanyl 20 mcg IV q 5 min prn, (1st if creatanine >2.5) Meperidine not recommended!!  Review orders q 12 hrs  Continuous Oximetry  Convert to Oral ASAP  Avoid 3 rd & 4 th Line Agents

11. 11 Opioid Tolerant (taking opioid equivalent to >25 mg Oxycodone/ 24 hrs ) With PCA (preferred) Continuous Infusion = PCA Background – baseline 24 hr opioid dose X.3 per day, ( ie. MS Contin 60mg q12h = 120 x.3 = 40mg/24hrs, or 2.5mg/ hr infusion – round-up to 3mg/ hr) PCA Demand- 50-100% of hourly rate, Lockout – q10-15 min Review adjust at least q 12h, titrate systematically Continuous Oximetry

12. 12 Opioid Tolerant (taking opioid equivalent to >25 mg Oxycodone/ 24 hrs ) Without PCA 10-20% of 24 hr dose q 1-3 hrs prn “basal dose” RN administered IV “Rescue Doses” @ 2x the “basal dose” Continuous Oximetry Adjust doses q 12h

13. 13 Pain Taxonomy  Acute Pain- tissue injury, distention or inflammation  Episodic Pain- related to activity recurrent, breakthrough, incident  Chronic Pain- constant and unremitting waxes & wanes but seldom subsides

14. 14 Episodic Pain  Short acting opioids indicated  Oral route preferred  Usually treated Schedule III (+APAP or IB)  Exertion/ Activity related

15. 15 Constant Pain  Sustained Response (SR) oral agents indicated  Consider Immediate Response (IR) agents for rescue doses – start at ~10% of 24 hr dose of long acting agent q4-8 hrs prn  SR formulations are designed for q 12 hr dosing but mean effective dose may be shorter duration (q 8-10 hr)  Use coanalagesics and anticipate adverse effects  Addiction risk is 3% or less (large studies)

16. 16 Analgesic Selection  Mu (  ) Opioid Receptor Agonists – most familiar to clinicians as to effects and side- effects; best for initiating opioid therapy for moderate to severe pain (VAPS 5-10/10).  Morphine, Hydromorphone, Oxycodone, Hydrocodone, Fentanyl, Codeine, Hydrocodeine, Levorphanol, Methadone, Meperidine..

17. 17 Analgesic Selection  Agonist/ Antagonists & Partial Agonists – Primarily activate the Kappa (  ) receptor and antagonize or partially occupy the Mu receptor (  antagonists), analgesic ceiling effect, risk iatrogenic abstinence syndrome when given with  agonist tolerant patients, watch out in ER! no proven advantage in avoiding abuse.  Pentazocine, Butorphanol, Nalbuphine and the “partial agonists” Buprenorphine and Dezocine (VAPS 4-7/10)

18. 18 3 rd & 4 th Line Analgesic Agents  Limited Proven Analgesic Efficacy  Adverse Effects  Drug-to-Drug Interaction  Toxic Metabolites  Organ-limited Elimination

19. 19 3 rd & 4 th Line Analgesic Agents  Propoxyphene equianalgesic to Extra Strength Tylenol in blind studies (VAPS 1-3/10 = mild) norpropoxyphene-cardio & neurotoxic  Tramadol weak  agonist but primarily active on spinal adrenergic receptors similar to tricyclics (VAPS 4-5/10 = moderate)  Meperidine short acting (450-90 mins), metabolites accumulate within 48 hrs, side-effects common normeperidine- cardio & neurotoxic  Codiene effective pain relief but many side-effects at analgesic doses  Hydrocodiene isn’t routinely monitored on UDS  NSAIDs, APAP and AEDs, TCAD are “co-analgesics”

20. 20 Dosing for Relief  Around-The-Clock (ATC) dosing is associated with more consistent relief  PRN-dosing is associated with more unpredictability and side-effects  Optimal analgesic dosing varies widely among patients; review regularly; titrate systematically  Anticipate side effects; most subside with time  For some, NO dose of opioid will sufficiently relieve ALL of their pain...aim for TOLERABLE pain levels (VPA3-4/10), improved functionality and controlled side effect  Transition quickly from IV to PO (enterohepatic)

21. 21 Opioids and Addiction Physical Dependence  Physiologic occurrence usually within 3 days of initiating therapy;  Pharmacological property characterized by withdrawal syndrome after abrupt discontinuation;  Abstinence symptoms usually lacking or attenuated with “wean to discontinue” orders  NOT synonymous with tolerance or addiction!

22. 22 Opioids and Addiction Tolerance  Spectrum of acquired physiologic responses to therapy  Pharmacological property of the class drug; With chronic use, larger dose may be needed for same effect  Countered with drug rotations, furloughs, tolerance inhibitors, prescriptive boundaries  NOT synonymous with physical dependence or addiction!

23. 23 Opioids and Addiction Pseudo-addiction  Usually attributable to provider practice pattern, ergo iatrogenic  Unrealistic expectation by prescriber  Misconceived safety concern by providers  Patient motivation: ”relief, not rush”  NOT synonymous with physical dependence, tolerance or addiction!

24. 24 Opioids and Addiction Addiction  Psychological and physiologic state ( 0.3% of chronic pain suffers) characterized by obsessive pursuit of access to medication- regardless of consequences, for psychological effects  Not a pharmacological property of a given drug  NOT synonymous with tolerance or physical dependence!

25. 25 Plan if Addiction is Recognized -Be Humane - Intervene and Wean to withdrawal -Evaluation, treatment and extended recovery care by addiction professionals is optimal -Know community and regional resources for treatment & extended recovery care when initiating LTOT -Prescribing opioids to treat addiction (Methadone Clinics) is advisable only for specially certified addiction medicine and psychiatry physicians -Buprenorphine Addiction Treatment (Subtex) requires additional training and additional DEA certification…too new to assess.

26. 26 Opioid Therapy Current Clinical Guidelines  Pain relief is defined as a primary care (PCP) function  Remain reasonable, rational, responsible and available  Examine thoroughly and review regularly  Utilize LTOT Informed Consent to Treat and Opiate Access Agreement  Document & define providers & pharmacy  Require patient to notify all providers of Opiate Access Agreement participation  Monitor compliance (pill counts, UDS, etc.) and response to therapy (functional assessments, charts, diaries, surveys, etc.),  Review OAA violation consequences regularly  Match the tool to the problem-SR opioid for continual pain, IR for recurrent pain; pick analgesics sensibly

27. 27 Opioid Therapy Current Clinical Guidelines (cont.)  Consult and co-manage appropriately, require formal behavioral assessment periodically  Stipulate that verified non-clinical information may be considered when deciding whether to continue LTOT  Beware of 90 day prescription “Prescription Drug Benefit Requirements” -cost saving scheme that may be technically illegal for opioids; i.e.. unmonitored and unlicensed warehousing of Class II & III medications in homes not supported by law or regulation  Recognize that LTOT may be the therapy of last resort

28. 28 Opioid Options on the Near Horizon  Lipid-Based Sustained Release Opioid & Local Anesthetic Vehicles  Vanilloid and Cannabinoid Receptor Agonists  New Spinally-infused Drugs  Abuse-resistant Opioid Preparations  Co-analgesic Use of Anti-seizure Drugs  Deep-Brain and Motor Cortex Stimulation

29. 29 Thanks! I Enjoyed your attention!

30. 30 Opioid Selection for Acute and Chronic Pain Control Thanks for you’re your questions!! It’s time to head home.