1. August 2009 Agony of Pain Ethical and Rational Approach to Pain Management

2. Disclosure of Conflicts  I have no financial interests or significant relationships that constitute a conflict of interest related to this presentation in any of the following categories: Equity holdings (mutual funds and pension funds excluded) Board membership, consulting services or fees, honoraria, speakers fees, gifts or other compensation paid by any for-profit entity for speaking, attending meetings or serving on an advisory board. August 2009

3. Objectives  Recognize the multiple manifestations of pain.  Describe the differences between Tolerance, Physical Dependence, Psychological Dependence, and Addiction; and describe the approach towards patients with each of these phenomena.  Convert single parenteral doses of meperidine, morphine, hydromorphone, and fentanyl to any of the alternates. (Dose equivalence)  List 4 reasons that physicians under-prescribe opioids.  List 4 patient behaviors that alert the physician to opioid misuse or addiction. August 2009

4. Cancer Pain Impairs Quality of life

5. August 2009 What is Pain?  Pain is an unpleasant sensation and experience that in the acute state we commonly associate with or describe in terms of tissue damage.  Chronic pain frequently resembles an emotional state more than a sensation

6. August 2009 Clinical Picture of Chronic Pain Pain Control Constipation Nausea/Vomiting Anxiety Insomnia Depression

7. August 2009 Current View of Pain Perception

8. August 2009 Long-term changes that can be measured in patients suffering from persistent pain. New pain fibers recruited and stronger signals.

9. Inadequate Pain Control Russell Portnoy: “more than 40% of cancer patients are under treated” for their pain.

10. August 2009 WHO Guidelines  By following the WHO Guidelines cancer pain can be controlled 70-90% of the time

11. August 2009 Reasons that physicians do not use adequate pain medications (1)  Failure to ask about or evaluate pain  Disbelief of patient report of pain  Fear that patient will become “addicted”

12. August 2009 Reasons that physicians do not use adequate pain medications (2)  Lack of knowledge about how to use opioids safely and effectively Fear of respiratory depression  (Sedation usually precedes) Fear of accelerating death  Belief that some suffering is necessary  Fear of regulatory sanctions

13. August 2009 Other factors that are associated with under treatment of pain  Minority or lower S-E status  Women  Elderly  Dementia  No family advocate (e.g. in nursing home)  History of substance abuse  Lack of availability  Cultural differences

14. August 2009 Elderly & Pain Control  Nursing home study showed that in the last 3 months of life 70% of patients had severe or moderate pain  ¼ of elderly cancer patients received no analgesic for daily pain  Patients over 85 are 50% less likely to receive any analgesia than patients 65-74

15. August 2009 Patient reluctance to take pain medications  Fear of the medications/misconceptions Fear of addiction, getting “hooked Wanting to save narcotics for when pain gets bad  Denial of the pain/disease process  Stoicism  Desire to be liked by the physician  Concerns about distracting the physician from the disease  Non-compliance

16. August 2009 Pain in Cancer and Sickle Cell Anemia  Pain associated with malignancy or sickle cell disease is a constant reminder  the person’s condition (limited life span)  imagined fate (worsening pain, shortness of breath, painful death)

17. August 2009 Why Clock Watching? Inadequate Scheduled Dose

18. August 2009 The E.R.A. of Effective Pain Control 1.Evaluate the pain problem 2.Remove or reduce the physical source of the pain 3.Alleviate the symptoms

19. August 2009 Evaluation and Treatment Planning for Pain in Cancer (1)  What is the background of patient and pain problem? Nature of primary underlying disease Physical condition and performance status of the patient, including co-morbid diseases Psychological, emotional, social situation of patient Prior history of alcohol or drug use, misuse or abuse

20. August 2009 Evaluation and Treatment Planning for Pain in Cancer (2)  Characteristics of the pain - requires thorough assessment Quality, Severity Onset, duration, frequency Exacerbating and alleviating factors Impact on function (work, sleep, eating, relationships)  What is the availability and practicality of potential methods of pain relief?

21. August 2009 Evaluation and Treatment Planning for Pain in Cancer (3)  Steps in pain management Set Goals Plan Initial Analgesic Therapy Discuss Re-evaluation and Adjustment  How soon Consider Issues of tolerance, toxicity Make Adjustments for prior history of alcohol or drug abuse, which may increase dose requirements  Evaluation and treatment of other medical and psychological problems

22. August 2009 Self Report Method of Pain Measurement  Procedures Verbal description of the pain  Pain score (0-10)  Visual analog scale Functional assessment of activity  Value Recognizes subjective nature of pain perception Observer’s bias not interjected Simple quantification  Limitations Influenced by psychological state and “drug-seeking” behavior as well as nociceptive or neuropathic stimuli

23. August 2009 Signs of Pain  Agitated or irritable behaviors  Depressed mood  Loss of interest and decreased overall activity level  Decreased Mobility  Disturbed sleep  Reduced appetite These may differ in chronic and acute pain

24. August 2009 Clinical Mechanisms of Pain Stimulation of peripheral pain receptors or damage to afferent fibers  Compression, stretching, invasion or chemical irritation of receptor, nerve, root, or plexus Inflammation, infection, necrosis, or other tissue damage Obstruction of a viscous Occlusion of a vessel with engorgement or ischemia Infiltration and tumefaction of tissue invested by capsule, fascia, or periosteum Inflammation of nerves and vessels  Spontaneous activity in nerves damaged by disease or treatment

25. August 2009 Removal or Reduction of the Physical Source of the Pain  Surgery - Bypass or removal of obstructing lesion; fracture fixation; bypass arterial obstruction  Radiation Therapy - Shrink regional obstructing, infiltrating, stretching, or pressing tumor.  Chemotherapy - Reduce tumor burden systemically (e.g. lymphoma)  Antibiotics, corticosteroids - Decrease inflammation and cytokine production  Cytokine inhibitors - Anti-tumor necrosis factor alpha antibodies (infliximab) - mediation of immune function

26. August 2009 Alleviation of Symptoms Reduce Peripheral Reception Block Conduction of Impulses Interfere with perception and affective responses Steroids, NSAID’s, antipyretics Local anesthetics, CNS opioids,  2 adrenergic agonists Opioids, ? Adjuvants (TCA’s, anti-convulsants, SSRI’s, SNRI’s steroids)

27. August 2009 Pain Types and Selection of Analgesic Agents Somatic Visceral Neuropathic NSAID’s, anti-pyretics, corticosteroids. Opioids Tricyclic anti-depressants, SSRI’s,selective serotonin and norepinephrine reuptake inhibitors (SNRI’s) Anti-convulsants

28. August 2009 Principles of Analgesic Administration  Avoid parenteral route when possible  Administer majority of daily dose on a scheduled, not PRN basis  Give at a sufficient dose and short enough interval to prevent pain from becoming moderate or severe (< 5/10 on pain scale) >5/10 affects quality of life.

29. August 2009 PRN vs. Scheduled Doses Toxic level Effective Control Pain Toxic level Effective Control Pain Poor Control Good Control

30. August 2009 Desirable Characteristics of Analgesics for Patients with Chronic Pain  Effective by the oral or trans-dermal route  Moderate to long duration of action (4-12 hours)  Minimum of adverse side effects at effective doses

31. August 2009 Starting Doses of Strong Opioid Analgesics DrugOralParenteral Morphine5-15 mg q 3-4 hr 3-5 mg q 3-4 hr Dilaudid1-4 mg q 3-4 hr0.5 - 1.5 mg q 3-4 hr Oxycodone5-10 mg q 3-4 hrN/A Fentanyl, transdermal: 25 micrograms/hr (Difficult to titrate) DrugOralParenteral Morphine5-15 mg q 3-4 hr 3-5 mg q 3-4 hr Dilaudid1-4 mg q 3-4 hr0.5 - 1.5 mg q 3-4 hr Oxycodone5-10 mg q 3-4 hrN/A Fentanyl, transdermal: 25 micrograms/hr (Difficult to titrate)

32. August 2009 Converting Parenteral to Long Acting Oral Narcotics Determine 24 hour dose of IV morphine E.g., Total 24 hour dose IV morphine = 80 mg Calculate oral equivalent 80mg x 3 = 240 mg oral morphine Start with 50% of calculated dose 120 mg MS-Contin (60 q 12 h) or 80 mg Oxy-Contin (40 q 12 h)

33. August 2009 Quick and Dirty Dose Equivalence * Not good for chronic pain

34. August 2009 Methadone - Effective Long-Acting Oral Opioid for Chronic Pain in Cancer Use short acting opioid for break- through pain Estimated methadone per day (mg) = (oral morphine per day (mg)  15) + 15 W Plonk, J Palliat Med 8:478,2005

35. August 2009 Opioid Side Effects  Direct CNS or PNS - Sedation, euphoria, delirium (hallucinations), respiratory depression myoclonus (All dose related)  GI - Nausea, vomiting, constipation  GU - Urgency, difficulty voiding, SIADH  Cutaneous - Itching  Dependence - Physical, psychological  Tolerance

36. August 2009 Tolerance  The requirement for larger doses to obtain the effects observed with the original dose  A physiological phenomenon Not a sign of weakness, moral turpitude, psychological dependence, or addiction

37. August 2009 Physical Dependence  An altered physiologic state produced by the repeated administration of the drug which necessitates the continued administration of the drug to prevent an abstinence or withdrawal syndrome.

38. August 2009 Psychological Dependence  The effects produced by the drug or the conditions associated with its use are necessary to maintain an optimal state of well being. (Perceived) May lead to compulsive drug use or abuse.

39. August 2009 Addiction  A behavioral pattern of compulsive drug use characterized by overwhelming involvement with the use of the drug, the securing of its supply, and a high tendency to relapse after withdrawal. Function of patient is impaired.  Occurs RARELY in patients with cancer pain. (< 1/1000)

40. August 2009 Pseudoaddiction  Phenomenon seen in a patient who seeks additional medications appropriately or inappropriately because of significant undertreatment of their pain  An iatrogenic syndrome that may mimic behaviors usually associated with addiction, and which is caused by the under medication of pain

41. August 2009  Drug use impairs rather than improves patient function (Reduced occupational, social, and recreational activities.), medical condition,and quality of life  Drugs obtained from more than one physician or pharmacy after being asked to use only one  Frequent “losses” of drug  Frequent occasions where greater opioid use than was intended  Selling prescription drugs  Forging prescriptions  Stealing drugs  Injecting oral agents Characteristics of Drug Abuse Predictive of Addiction in Patients Receiving Opioids for Pain

42. August 2009 Approaches to Pain Management of Patient with Substance Abuse Problems  Physician must set parameters for opioid use more closely than for other patients  Open discussion with patient about issues of concerns Avoid “blaming”, but don’t gloss over magnitude of problem Let patient know that you can work together, but there will be tight control

43. August 2009 Alternative Methods to Control Abuse in Patient with History of or Current Substance Abuse Problems  Written Contract that explicitly delineates the intention of the physician to help, the obligations of the patient who wishes the help, and the consequences of failure to fulfill the obligations.  Less formal understanding reached between the physician and patient

44. August 2009 Possible Consequences of Failure to Meet Obligations  Severing physician-patient relationship  Discontinuation of ordering any opioids  Notification of legal authorities, pharmacies, other medical facilities  Closer control of opioid availability by decreasing interval for new prescription.

45. August 2009 Dependence Issues  Habituation abuse rarely a clinical problem 7/24,000 among patients with no history of addiction  Tolerance can be overcome by increasing the dose  Physical dependence effectively managed by tapering dose as the pain abates  Psychological dependence and pseudo-addiction minimized by giving sufficient doses at regular intervals

46. August 2009 Special Populations  Substance abuse history  Active addict  Person who injures self to get medication  Geriatric  Cognitively impaired (Difficult to assess)  Dying

47. August 2009 Additional Cancer Pain Control Methods Useful in Selected Situations Transdermal narcotics (Fentanyl) Sub-lingual morphine, fentanyl “lollipops” Transcutaneous electrical nerve stimulation Epidural or sub-arachnoid opioids Continuous infusion narcotic Patient controlled analgesia (PCA) pumps Biofeedback Nerve, ganglion, plexus block Transdermal narcotics (Fentanyl) Sub-lingual morphine, fentanyl “lollipops” Transcutaneous electrical nerve stimulation Epidural or sub-arachnoid opioids Continuous infusion narcotic Patient controlled analgesia (PCA) pumps Biofeedback Nerve, ganglion, plexus block

48. August 2009 Rational Approach to Cancer Pain Management - Summary  Pain impairs quality of life  Most cancer pain can be controlled through careful assessment, planning, and informed therapy  Physical and psychological side effects are real issues, but can be minimized  The knowledgeable and compassionate physician and nurse are key to effective care.

49. Thank You

50. August 2009

51. Converting Parenteral to Long Acting Oral Narcotics: Day 1 give 50% of IV Dose Calculate 24 hour dose of IV morphine - 24 hours @ 1 mg/h = 24 mg - 28 doses by PCA demand button @ 2 mg/dose = 56 mg Total 24 hour dose IV morphine = 80 mg Oral equivalent = 80 x 3 = 240 mg Start with 50% = 120 mg MS-Contin (60 q 12 h) or 80 mg Oxy-Contin (40 q 12 h)

52. August 2009 Pain Construct (from E. Bruera)

53. August 2009 US 30 mg

54. August 2009 (Meperidine)