THE PRINCIPLES OF PAIN MANAGEMENT

Transcription

1 THE PRINCIPLES OF PAIN MANAGEMENT Judith Paice, PhD RN Northwestern University Chicago, IL

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3 AAHPM Intensive Board Review Course Principles of Pain Management Judith A. Paice, RN PhD FAAN Northwestern University, Feinberg School of Medicine, Chicago, IL Disclosure Information Judith A Paice, RN PhD FAAN Has no relevant financial relationships to disclose. Principles of Pain Management Assessment Pharmacologic management Nonopioids Opioids Adjuvant analgesics Others Non pharmacologic management Emerging controversies Preventing diversion Care of people with addictive disease

4 Case A 52 year old man presents with a history of lung cancer. He reports severe pain. He is currently taking hydrocodone/apap 5/500 mg 2 every 4 hours (12 per day) without relief. How do we assess pain? How do we treat this pain? How do we balance relief and safety? Case (cont d) He describes pain over the healed thoracotomy incision site; this pain is tingling and worsened when touched. He has throbbing pain in low back with radiation down right leg (he has a documented vertebral body metastases). He wakes often in pain. What type of pain(s) does he have? What are the pharmacologic options? What are non pharmacologic options? Question 1 What is the best next step in modifying the pharmacologic treatment plan? 1. Increase the hydrocodone/apap to 2 every 3 hours. 2 Add gabapentin 2. Add gabapentin 3. Add methadone 20 mg q 8 hours 4. Add morphine ER 30 mg 1 every 12 hours

5 Quality of Pain: Treatment Type of pain Somatic (nociceptive) Neuropathic Visceral Pharmacologic interventions Non opioids Acetaminophen NSAIDs Opioids Opioids (may require higher doses) Adjuvant analgesics Antiepileptics Antidepressants Corticosteroids Local anesthetics NMDA antagonists Opioids Corticosteroids Adjuvant analgesics? Case (con t) He is started on morphine er 30 mg q 12 and morphine ir 15 mg; he takes approximately 4/day. He is also taking gabapentin 300 mg tid and has been started on dexamethasone 4 mg q day. He does well on this regimen but reports breakthrough pain when he stands. What is your next step? What other drugs might be helpful? What about non drug therapy? Question 2 What is the best next step in modifying the pharmacologic treatment plan to treat breakthrough pain? 1 Instruct him to take morphine ir 15 mg approximately 1. Instruct him to take morphine ir 15 mg approximately min before standing 2. Change the morphine ir 15 mg to Roxanol 3. Change to fentanyl patch 4. Change to hydromorphone

6 Case (con t) He was doing well on the previous regimen, but calls to inform you he ran out of medications. He had gotten a one month supply 10 days ago. What questions might you ask? What is your next step? Prevention Relief of pain Improved function Safety Prevent diversion? Goals of Treatment Non opioids Therapeutic Advances in Pain Acetaminophen NSAIDs Opioids Adjuvants Adjuvants Anticancer therapies

7 Acetaminophen Acetaminophen or paracetamol N acetyl para aminophenol Analgesic Antipyretic Does not have peripheral antiinflammatory effect Paice J, Ferrell B. CA: Cancer J Clin 2011:61: Acetaminophen Safety Acetaminophen overdose leading cause of acute liver failure in US 78,000 ED visits/year 16.7% accidental to obtain pain control Only 31% knew acetaminophen active ingredient in Tylenol King J, Am J Prev Med 40: , 2011 Budnitz D, et al. Am J Prev Med 40: , 2011 Acetaminophen Is 4000 mg safe? No long term safety and efficacy studies RCT of novel hydrocodone/acetaminophen agent: placebo, 4 gm apap alone, hydro/4 gm apap 14 day trial; healthy adults Serum alanine aminotransferase (ALT) increased in those receiving apap, not placebo group Watkins P, et al. JAMA 296; 87 93, 2006

8 Acetaminophen January 13, 2011: FDA asked manufacturers to limit acetaminophen to 325 mg/tablet or dosing unit Two years to comply Add box warning regarding risk of liver toxicity NSAIDs Analgesic, antipyretic, anti inflammatory Mechanism of action inhibition of prostaglandin synthesis Toxicities include Gastric ulceration (PPIs prevent) Renal failure Platelet aggregation abnormalities Myocardial infarction/stroke Schlansky B, Hwang JH. J Gastroenterol 2009; 44: NSAIDs Highly protein bound potential drug drug interactions Warfarin Methotrexate Digoxin Cyclosporine Oral antidiabetic agents Sulfonamide-containing drugs NCI PDQ

9 NSAIDs Systematic review of cancer pain; 42 trials, 3084 patients NSAIDs appear to be more effective than placebo for cancer pain No clear evidence to support superior safety or efficacy of one NSAID compared with another Trials of combinations of an NSAID with an opioid have disclosed either no significant difference, or at most a slight but statistically significant advantage, compared with either single entity. McNicol E, et al. J Clin Oncol 2004;22: Therapeutic Advances in Pain Non opioids Opioids Adjuvants Anticancer therapies Opioids Buprenorphine* Codeine Fentanyl* Hydrocodone Hydromorphone* Methadone* Morphine* Oxycodone* Oxymorphone* Tapentadol* Tramadol* * Long acting version available Paice J, Ferrell B. CA: Cancer J Clin 2011:61:

10 Used WHO three step ladder as framework Step 1: mild pain Step 2: moderate pain Step 3: severe pain Lancet Oncol 2012; 13: e58 68 Which Opioid Do We Use First? The data show no important differences between morphine, oxycodone, and hydromorphone given by the oral route and permit a weak recommendation that any one of these three drugs can be used as the first choice step III opioid for moderate to severe cancer pain. Lancet Oncol 2012; 13: e58 68 Opioid Titration Few studies Open label, 62 pts: iv morphine faster control than oral, same adverse effects The data permit a weak recommendation that immediaterelease and slow release oral formulations of morphine, oxycodone, and hydromorphone can be used for dose titration. The titration schedules for both types of formulation should be supplemented with oral immediate release opioids given as needed. Lancet Oncol 2012; 13: e58 68

11 Initiating Short Acting Opioids: Naïve Patients Oral Pain 4 NCCN Clinical Practice Guidelines in Oncology: Adult Cancer Pain Initiating Short Acting Opioids: Naïve Patients Parenteral Pain 4 NCCN Clinical Practice Guidelines in Oncology: Adult Cancer Pain Titration: Opioid Tolerant Patients Oral Pain 4 NCCN Clinical Practice Guidelines in Oncology: Adult Cancer Pain

12 Titration: Opioid Tolerant Patients Parenteral Pain 4 NCCN Clinical Practice Guidelines in Oncology: Adult Cancer Pain Opioid Switching Reasons for opioid switching or rotation Intolerable adverse effects Poor analgesic response despite aggressive titration Drug drug interactions Need dfor different route Change in clinical status (e.g., malabsorption) Financial or drug availability considerations Fine P, Portenoy RK. JPSM 2009;38: Opioid Switching Step 1 Calculate the equianalgesic dose Dose reduce by 25 50% Step 2 Consider additional increase or decrease of 15 30% based upon medical and psychosocial characteristics Consider adverse effects, risk of withdrawal Frequently reassess and titrate Rescue dose 5 15% of 24 hour dose Fine P, Portenoy RK. JPSM 2009;38:418 25

13 Opioid Switching The data permit a weak recommendation that patients receiving step III opioids who do not achieve adequate analgesia and have side effects that are severe, unmanageable, or both, might benefit from switching to an alternative opioid. Lancet Oncol 2012; 13: e58 68 Opioid Switching From Use of opioid analgesics in the treatment of cancer pain: evidence based recommendations from the EAPC, by A Caraceni, G Hanks, S Kaasa, et al., 2012, Lancet Oncol, 13(2), e58 e by Elsevier. Used with permission. NCCN Clinical Practice Guidelines in Oncology: Adult Cancer Pain

14 Routes of Administration Oral Transdermal Passive Iontophoretic Sublingual Buccal Rectal/stomal Vaginal Nasal Inhalational Subcutaneous Intramuscular Intravenous Epidural Intrathecal Intraventricular Intraarticular Paice J, Ferrell B. CA: Cancer J Clin 2011:61: Routes of Administration Topical Topical delivery dependent upon lipid solubility of drug (fentanyl lipophilic morphine hydrophilic) Bioavailability of topical morphine Healthy volunteers: topical morphine 10 mg or 3 mg SQ Serumlevelsof morphine after topical deliverbelow level of detection Bioavailability of topical methadone Patients: oral methadone, topical, placebo Serum levels after topical same as placebo Paice J, et al. JPSM 2008;35: Sylvester RK, et al. JPSM 2011;41: Alternate Routes of Opioid Administration The data permit three strong recommendations: the subcutaneous route is simple and effective for the administration of morphine, and hydromorphone, and it should be the first choice alternative route for patients unable to receive opioids by oral or transdermal routes; intravenous infusion should be considered when subcutaneous administration is contraindicated (eg, because of peripheral oedema, coagulation disorders, poor peripheral circulation, and need for high volumes and doses); and intravenous administration should be used for opioid titration when rapid pain control is needed. Lancet Oncol 2012; 13: e58 68

15 From Transdermal fentanyl in cachectic cancer patients, by T Heiskanen, S Matzke, S Haakana, M Gergov, E Vuori, E Kalso, 2009, Pain, 144(1), by Elsevier. Used with permission of the International Association for the Study of Pain (IASP ). Opioids: Fentanyl First synthesized in 1960 Approximately 100 X more potent than morphine Lipid soluble Fentanyl for breakthrough pain Transmucosal fentanyl citrate (Actiq) Fentanyl buccal tablet (Fentora) Fentanyl sublingual tablets (Abstral) Fentanyl buccal soluble film (Onsolis) Fentanyl nasal spray (Lazanda) Paice J, Ferrell B. CA: Cancer J Clin 2011:61:

16 Risk Evaluation and Mitigation Strategies (REMS) To ensure benefit of drug outweighs risk FDA Recently approved single REMS for transmucosal immediate release fentanyl based (TIRF) products (Dec, 2011) Prescribers must enroll in TIRF REMS Access Program View educational program, complete knowledge assessment, then enroll Re-enroll every 2 years Not applicable to inpatient, hospice or LTC Opioids in Renal Dysfunction The data permit a weak recommendation that in patients with severe impairments of renal function (glomerular filtration rate <30 ml/min) opioids should be used with caution. The opioid of first choice should be fentanyl or buprenorphine administered subcutaneously or intravenously at low starting doses and with subsequent careful titration. Alternative strategies, for instance reductions in dose or frequency of administration of morphine, might be adequate short term strategies. Lancet Oncol 2012; 13: e58 68 Methadone: Historical Perspectives Developed in 1937 in Germany Shortage of opioids during war Introduced into US in 1947 Dolophine Beganbeing used for methadone maintenance treatment (MMT) Death rate increasing Illicit use in excessive doses Use with other sedating drugs (e.g. benzos) either illicit or prescribed Accumulation during first few days of treatment

17 Methadone: Pharmacodynamics Opioid Agonist: mu receptor, some delta receptor binding NMDA (N methyl D asparate) receptor antagonist Inhibits reuptake of norepinephrine & serotonin Ferrari A, et al: Pharm Research 50: , 2004 Methadone: Indications for Use Cost Morphine allergy Neuropathic pain Opioid adverse effects Pain refractory to other opioids Uncontrolled pain Toombs JD, Krall LA. Am Fam Physician 2005;71: Parsons HA, et al. Cancer 2010;116: Methadone: Routes of Administration Oral Tablets Dispersible tablets Liquid Rectal Intravenous Subcutaneously Epidural Intrathecal Not topical** Ferrari A, et al: Pharm Research 50: , 2004 Sylvester RK, et al. J Pain Symptom Manage 2011

18 Methadone Lipophilic: absorption primarily through stomach Metabolism: hepatic No known active metabolites Elimination: fecal Rapid distribution phase 2 3 hours, followed by slow elimination phase: Extended Half life: from 12 hours up to 190 hours Large inter individual variability in pharmacokinetics Ferrari A, et al: Pharm Research 50: , 2004 Methadone: Cancer Pain Cochrane review 2004: methadone is effective in relieving cancer pain Nicholson AB. Methadone for cancer pain. Cochrane Database of Systematic Reviews 2004 Study investigated methadone vs. morphine as first line agent, morphine still gold standard Bruera, et al.j Clin Oncol 2004; 22: Cherny N. Palliat Med 2011; 25: Issues in Methadone Use QT prolongation P450 interactions Long and variable half life 3-5 hours duration of analgesia when started 8-12 hours after repeated dosing Repeated dosing may take 5-7 days to stabilize Kornick, et al. Pain 2003;105; 499 Krantz, et al. Ann Intern Med 2002:137;501 Reddy S, et al. J Pall Med 2010:13; resources/index.php

19 Inducers That May Decrease Methadone Effects Abacavir Amprenavir Barbiturates Carbamazepine Cocaine Dexamethasone Efavirenz Ethanol (chronic use) Fusidic Acid Heroin Lopinavir+Ritonavir Nelfinavir Nevirapine Phenytoin Rifampin Spironolactone St. John s wort Tobacco Urinary acidifiers Leavitt (2005) Addiction Treatment Forum 3 rd Ed. Inhibitors That May Increase Methadone Effects Cimetidine Ciprofloxacin Delavirdine Diazepam Diltiazem Disulfiram Ethanol (acute use) Fluconazole Grapefruit Haloperidol Leavitt (2005) Addiction Treatment Forum 3 rd Ed. Methadone Ketoconazole Macrolides (erythromycin, clarithromycin) Metronidazole Omprazole SSRI(fluoxetine, paroxetine, nefazodone, sertraline) Urinary alkalinizers Verapamil Methadone Start low 10 mg or less per day in divided doses (q 8) Regardless if patient is naïve or tolerant Provide breakthrough medications Increase no more than 25 50% weekly Caution when combining with benzodiazepines especially at night Caution in patients with sleep apnea, respiratory infection

20 Methadone Methadone has a complex pharmacokinetic profile with an unpredictably long half life. The data permit a weak recommendation that it can be used as a step III opioid of first or later choice for moderate to severe cancer pain. It should be used only by experienced professionals. Lancet Oncol 2012; 13: e58 68 Opioid Abuse, Addiction and Diversion Increasing deaths from opioids Preventing diversion Identifying abuse Care of the person with addictive disease Okie S. NEJM 2010; 363:

21 Where Do People Get the Drugs 55% Obtained free from friend or relative 17.3% Prescribed by one doctor 11.4% Bought from friend or relative 4.8% Took from friend or relative without asking 4.4% Bought from dealer 7.1% Other sources Sources of Diversion Thefts from pharmacies, drug distribution centers Thefts from medicine cabinets Internet Smuggling Prescriptions from pill doctors 57

22 Prevent Diversion Educate patients/families regarding safe medication practices Don t leave medications out Lock boxes Safe disposal Take back programs pharmacies, police departments Mix drug in wet coffee grounds or kitty litter until dissolved, then dispose in garbage do not flush down toilet Pain and Substance Abuse Perform a thorough assessment Pain Addiction history Set realistic goals Treat concomitant psychiatric disorders Differentiate abuse behaviors from undertreatment Use interdisciplinary approach Whitcomb et al. Current Pain Headache Reports 2002;6: Addiction and Pain: Assessment Loss of control of drug use (no partially filled med bottles; will not bring in bottles) Adverse life consequences Use despite harm (legal, work, social, family) Indications of drug seeking behavior (reports lost/stolen t l meds, requests for high street h tvalue meds) d) Drug taking reliability (frequently takes extra doses, does not use meds as prescribed) End of Life Physician Education Resource Center

23 Addiction and Pain: Assessment Abuse of other drugs (current/past abuse of prescription or street drugs) Contact with drug culture (family or friends with substance abuse disorder) Cooperationwith treatment plan (does not follow up with referrals, or use of non drug treatments) End of Life Physician Education Resource Center Differential Diagnosis of Aberrant Drug Taking Behavior Addiction Pseudo addiction (inadequate analgesia) Other psychiatric disorders Chemical coping Mood ddisoders d (anxiety, depression) Encephalopathy Borderline personality disorder Inability to follow a treatment plan (low literacy) Criminal Intent Passik SD, Kirsh KL, and Portenoy RK. Pain and Addictive Disease. In: von Roenn JH, Paice JA, Preodor ME, editors. Current Diagnosis and Treatment of Pain. New York: Lange Medical Books, 2006: 78. Pain Management Guidelines for Patients with Addiction Team approach with case conferences Set realistic goals with pain and addiction Treat tdepression and comorbid psychiatric problems If possible, treat the cause of the pain Try nondrug methods Maximize nonopioids and adjuvants Choose long acting opioids when possible Minimize i i short acting ti PRN doses if possible Avoid parenteral route Consider tolerance patients with abuse history usually require higher doses 63

24 4 A s Analgesia 0 10 or percent relief (0 100%) Activities of daily living Function Adverse effects Constipation, hypogonadism, sleep disordered breathing, cognitive changes Aberrant drug related behavior Pill counts, prescription monitoring programs, urine drug screening, agreements Passik SD, Kirsh KL, and Portenoy RK. Pain and Addictive Disease. In: von Roenn JH, Paice JA, Preodor ME, editors. Current Diagnosis and Treatment of Pain. New York: Lange Medical Books, 2006: Dispensing Issues One provider One pharmacy Limit the amount of medication given at any one time Weekly or 2 3 day prescriptions Utilize prescription monitoring programs Utilize pill counts Assess for independent dose escalation and shortages Passik SD, Kirsh KL, and Portenoy RK. Pain and Addictive Disease. In: von Roenn JH, Paice JA, Preodor ME, editors. Current Diagnosis and Treatment of Pain. New York: Lange Medical Books, 2006: 78. Care of Person with Addictive Disease Strategies to prevent or identify diversion Agreements Urine toxicology Weak evidence to support in chronic pain; no trials in palliative care (systematic review) Starrels JL, et al. Ann Intern Med 2010:152:

25 Therapeutic Advances in Pain Non opioids Opioids Adjuvants Corticosteroids Antiepilepsy drugs Antidepressants Local anesthetics NMDA receptor antagonists Cannabinoids Never doubt that a small group of thoughtful, committed citizens can change the world. Indeed, it is the only thing that ever has. Margaret Mead