1. Opioids in Chronic Pain Management o Benefits and Risks o Side effects: constipation, sleep disruption, altered mental status, itching, nausea, respiratory depression o Addiction vs. Dependence o Assessing whether medication improves quality of life and participation in life or diminishes them

2. Benefits of Opioids for Pain o Opioids “take the edge off pain” or “make it easier to manage it” o Opioids do not eliminate pain, in therapeutic doses

3. Goals of Opioid Use o In Cancer Pain: Improved Quality of Life o Relief of suffering, even if there is sedation, etc. o In Nonmalignant Pain: Improved Function

5. Timing o Short-acting/Rescue medications: codeine, hydrocodone, oxycodone, morphine Drug level time

6. Problems with Short-acting Medications Drug levelLoaded In pain Time

7. Long-acting narcotics: Drug level Time Fentanyl patches (Duragesic) Methadone MS Contin OxyContin o Need to be dosed on a schedule, not prn

8. Side Effects of Opioids o Nausea and Vomiting o Constipation o Sedation- sleepiness o Respiratory depression o Urinary retention (difficulty peeing) o Dysphoria – depression o Gonadal atrophy o Myoclonus, muscular rigidity o Increase in Pain Sensitivity

9. Opioid-induced Hyperalgesia o Animal studies show that repeated opioid administration... can lead to a progressive and lasting reduction of baseline nociceptive thresholds, resulting in an increase in pain sensitivity. o The decreased baseline nociceptive thresholds lasted as long as 5 days after the cessation of four fentanyl bolus injections

10. Opioid-induced Hyperalgesia o Six chronic low back pain patients were assessed for both opioid tolerance and opioid-induced hyperalgesia using quantitative sensory testing (cold and heat) before and after the institution of oral morphine therapy. o Preliminary results showed hyperalgesia and tolerance with cold but no hyperalgesia with heat or analgesic tolerance to heat pain. o Chu L.F., Clark D.J., Angst M.S.: Opioid tolerance and hyperalgesia in chronic pain patients after one month of oral morphine therapy: a preliminary prospective study. J Pain 7. (1): 43-48.2006

11. Opioid-induced Hyperalgesia o Patients treated intraoperatively with remifentanil reported more postoperative pain than the matched nonopioid controls o Vinik H.R., Igor K.: Rapid development of tolerance to analgesia during remifentanil infusion in humans. Anesth Analg 86. 307-311.1998; Crawford M.W., Hickey C., Zaarour C., et al: Development of acute opioid tolerance during infusion of remifentanil for pediatric scoliosis surgery. Anesth Analg 102. (6): 1662-1667.2006; o Guignard B., Bossard A.E., Coste C., et al: Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requiremnt. Anesthesiology 93. (2): 409-417.2000;

12. Opioid-induced Hyperalgesia o A number of case reports document decreases in pain with stopping opioids o Wilson G.R., Reisfield G.M.: Morphine hyperalgesia: a case report. Am J Hosp Palliat Care 20. (6): 459-461.2003 Mercadante S., Ferrera P., Villari P., et al: Hyperalgesia: an emerging iatrogenic syndrome. J Pain Symptom Manage 26. (2): 769-775.2003; o Heger S., Maier C., Otter K., et al: Morphine induced allodynia in a child with brain tumour. BMJ 319. (7210): 627-629.1999; o Sjogren P., Jensen N.H., Jensen T.S.: Disappearance of morphine-induced hyperalgesia after discontinuing or substituting morphine with opioid agonists. Pain 59. 313-316.1994; o Mechanism may be NMDA receptor-mediated central sensitization o

13. Some Definitions o Tolerance is a state resulting from regular use of opioid(s) in which an increased dose of the substance is needed to produce the desired effect. o Physical dependence is a physiologic state of adaptation to a specific opioid(s) characterized by the emergence of a withdrawal syndrome during abstinence, which may be relieved in total or in part by re- administration of the substance.

14. Definitions o Withdrawal syndrome is a specific constellation of signs and symptoms due to the abrupt cessation of, or reduction in, a regularly administered dose of opioid(s). o Pseudoaddiction – Medication-seeking behaviors that arise as a result of pain being poorly controlled

15. Definitions o Addiction is a disease process involving use of opioid(s) wherein there is a loss of control, compulsive use, and continued use despite adverse social, physical, psychological, occupational, or economic consequences. o Substance abuse is the use of any substance(s) for non-therapeutic purposes; or use of medication for purposes other than those for which it is prescribed.

16. Patients vs. Addicts o Control of medication o Medications increase quality of life o Medications are decreased if side effects occur o Concerned about medical problem o Follow the contract o Medications left over o Med use not controlled o Medications decrease quality of life o Medications continued in the face of side effects o Lack of concern about medical problems o Ignore the contract o Never have medication left; often have stories about drug losses and shortages

17. Addiction in Patients with Chronic Pain o (1) Intense desire for the drug and overwhelming concern about its continued availability (psychological dependence) o (2) Evidence of compulsive drug use o unsanctioned dose escalation o continued dosing despite significant side effects o Use of drug to treat symptoms not targeted by therapy o Unapproved use during period of no symptoms Or – see next slide

18. Addiction in Patients with Chronic Pain o (3) Evidence of one or more of a group of associated behaviors o manipulation of the treating physician or medical system for the purposes of obtaining additional drug (altering prescriptions, for example) o Acquisition of drugs from other medical sources or from a nonmedical source o Drug hoarding or sales o Unapproved use of other drugs (particularly alcohol or other sedatives/hypnotics) during opioid therapy

19. Questions to Ask: o Is the person’s day centered around taking medication? o Does the person take pain medication only on occasion, perhaps three or four pills per week? o Have there been any other chemical (alcohol or drug) abuse problems in the person’s life? o Does the person in pain spend most of the day resting, avoiding activity, or feeling depressed? o Is the pain person able to function (work, household chores, and play) with pain medication in a way that is clearly better than without?

20. Signs Someone Is Being Harmed More Than Helped by Pain Medication o Sleeping too much or having days and nights confused o Decrease in appetite o Inability to concentrate or short attention span o Mood swings (especially irritability) o Lack of involvement with others o Difficulty functioning due to drug effects o Use of drugs to regress rather than to facilitate involvement in life o Lack of attention to appearance and hygiene

21. Addiction Issues with Non-Opioids o Many of the same questions apply when looking at use of o Muscle Relaxants o Cannabis o Other adjunctive medications – Anticonvulsants Etc.

22. Adjunctive Medications o Topical – lidocaine, capsaicin, antiinflammatories, other o Antidepressants o Anticonvulsants o Antiarrhythmic drugs o Ultram

23. Antidepressants for Pain o Work by affecting neurotransmitters o Do not only work for treating pain by improving depression. o Work as well in non-depressed people as in people with depression o Effectiveness for pain does not correlate with effectiveness for depression o Do not work for all types of pain.

24. Stopping or Tapering Opioids o Withdrawal Symptoms o Anxiety/Restlessness o Sweating o Insomnia o Diarrhea o Nausea, vomiting o Yawning, rhinorrhea (runny nose) o Transient increase in pain

25. Treatment of Withdrawal o Each of the symptoms of withdrawal can be treated, and herbal support is also available for opioid withdrawal o Passionflower o Clonidine o Lomotil o Hydroxyzine o Trazodone o Etc.