Practical Considerations in Analgesic Selection for Chronic Noncancer Pain
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Primary Care Pain Management in Pennsylvania: Optimizing Treatment, Minimizing Risk PRACTICAL CONSIDERATIONS IN ANALGESIC SELECTION FOR CHRONIC NONCANCER PAIN MARY LYNN MCPHERSON, PHARMD, MA, BCPS, CPE UNIVERSITY OF MARYLAND SCHOOL OF PHARMACY . LEARNING OBJECTIVES 1. Given an actual or simulated patient with chronic noncancer pain, demonstrate consideration of patient- and drug-related variables in selecting opioid analgesics. 2. Demonstrate competence in basic opioid conversion calculations and opioid dosage titration. 3. Given an actual or simulated patient with chronic noncancer pain, recommend appropriate coanalgesic. WHAT IS PAIN? ¡ “Total” Pain (Dame Cicely Saunders) ¡ Physical (due to disease or treatments) ¡ Psychological (anger, fear of suffering, depression, past experience of illness) ¡ Social (loss of role, status, job; financial concerns, worries about future/ family, dependency) ¡ Spiritual (anger, loss of faith, finding meaning, fear of the unknown ¡ An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (IASP). ¡ “Pain is whatever the person experiencing it says it is” (McCaffery). www.iasp-pain.org/AM/Template.cfm?Sec8on=Home&Template=/CM/ContentDisplay.cfm&ContentID=8705 PATHOGENESIS OF PAIN Pain Nocicep8ve Neuropathic Central or Visceral Somac Peripheral Type of pain How patient’s describe it Analgesics Nociceptive • May be sharp or dull, often aching in nature Responds well to somatic pain • Familiar pain (e.g., toothache) primary analgesics • May be exacerbated by movement (incident pain) such as NSAIDs • Well localized and consistent with underlying lesion and opioids • Examples include metastatic bone pain, postsurgical pain, musculoskeletal pain, arthritis pain Nociceptive • Arises from distention of a hollow organ Responds well to visceral pain • Usually poorly localized, deep, squeezing and crampy primary analgesics • Often associated with autonomic sensations such as nausea, such as opioids, vomiting, diaphoresis possibly non- • May be referred (heart pain to shoulder or jaw; gallbladder opioids. pain to scapula; pancreas pain to back) • Examples include pancreatic cancer, intestinal obstruction, intraperitoneal metastasis Neuropathic • Patient struggle to describe it; it’s unfamiliar Adjuvant agents pain • They use words such as burning, electrical, numb such as • Innocuous stimuli may bring on pain (allodynia) anticonvulsants, • Patients may complain of paroxysms of electrical sensation antidepressants (lancinating or lightning pains) are primary • Examples include trigeminal neuralgia, postherpetic intervention. neuralgia, painful diabetic neuropathy WHO Pain Relief Ladder (1996) hKp://www.who.int/cancer/palliave/painladder/en/ • Non-opioid Analgesics • Adjuvant Analgesics • Opioid Analgesics ACETAMINOPHEN ¡ Other names – Tylenol, APAP, Paracetamol ¡ APAP (N-acetyl-para-aminophenol) ¡ Analgesic, antipyretic ¡ Widely available in US ¡ Legend prescription combinations – 228 ¡ OTC monotherapy and combinations – > 60 ¡ 31,580 individual NDC codes for mono and combo prescription and OTC products ¡ 28 billion doses purchased yearly in US ¡ Single ingredient OTC 8 billion doses ¡ Combination OTC 9.7 billion doses ¡ Acetaminophen / opioid combos 11 billion doses Retrieved from National Drug Code Directory database: (http://www.fda.gov/Drugs/InformationOnDrugs/ucm142438.htm) IMS Health, IMS National Sales Perspectives™, Year 2005, Extracted 9/06. ACETAMINOPHEN MECHANISM OF ACTION ¡ Active metabolite of phenacetin ¡ Not clearly understood; centrally active ¡ Weak COX-1 and COX-2 inhibitor ¡ Equivalent to ASA as an analgesic and antipyretic agent ¡ Lacks anti-inflammatory properties ¡ Does not affect uric acid levels ¡ Does not inhibit platelet function ¡ Role in therapy ¡ Minimal role in OA of knees; no role in low back pain Smith HS. Poten8al analgesic mechanisms of acetaminophen. Pain Physician; 2009;12:269-280. ¡ Hepatotoxicity ¡ Skin reactions ¡ Drug-Drug interactions ¡ Age-related metabolic changes ¡ Pregnancy ¡ Asthma LET’S PUT YOU TO WORK! ¡ Mr. Smith is a 74 year old man who presents in your pharmacy requesting assistance purchasing a product for his newly diagnosed osteoarthritis of the knees. ¡ His physician suggested he start acetaminophen. ¡ During the conversation it comes up that Mr. Smith drinks 3-4 beers per day, and occasionally has a shot of whiskey for good luck (once or twice a week), and he has liver impairment. ¡ Under what circumstances would you be comfortable recommending acetaminophen for this patient? A. If he stops the whiskey shots once or twice a week B. If he reduces the beer consumption to no more than 2 a day C. If he “pinky swears” he will never drink alcohol again D. You would not recommend acetaminophen at this time NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) AGENTS • Diclofenac* ¡ Meloxicam • Indomethacin ¡ Fenoprofen Analgesic Antipyretic • Sulindac ¡ Flurbiprofen Anti-inflammatory • Tolmetin ¡ Ibuprofen *** Antiplatelet • Celecoxib ** ¡ Ketoprofen • Meclofenamate ¡ Naproxen • Mefenamic acid ¡ Oxaprozin • Nambumetone ¡ Etodolac • Piroxicam ¡ Ketorolac *** www.online.factsandcomparisons.com *Available as topical; **COX-2 selective; ***Available as injectable NSAID TOXICITY ¡ Gastrointestinal ¡ Perforation, ulcers, bleeding ¡ Cardiovascular/cerebrovascular ¡ MI, heart failure, CVA ¡ Renal adverse effects ¡ Decreased GFR, progression of CKD ¡ Other adverse effects • Non-opioid Analgesics • Adjuvant Analgesics • Opioid Analgesics WHO’S UP FOR AN ADJUVANT ANALGESIC? Adjuvant hKp://www.who.int/cancer/palliave/painladder/en/ WHAT IS AN ADJUVANT? ¡ What is an adjuvant? ¡ “Serving to help or assist; auxiliary.” ¡ “Serving to aid or contribute.” ¡ What is an adjuvant analgesic? ¡ “Drugs with a primary indication other than pain that have analgesic properties in some painful conditions.” ¡ “Medications whose primary indication is the treatment of a medical condition, with secondary effects of analgesia.” ¡ Also referred to as “co-analgesics” www.ask.com; www.merriam-webster.com; hKp://theoncologist.alphamedpress.org/content/9/5/571.full Am J Hospice Pall Med 2012:29(1):70-79 ADJUVANT ANALGESICS • Mul,purpose Analgesics • An8depressants, CCS, NSAIDs, α-2 adrenergic agonists, neurolep8cs • Adjuvants for Neuropathic Pain • An8convulsants, Na+ channel blockers, NMDA antagonists, cannabinoids • Topical Analgesics • Capsaicin, local anesthe8cs, NSAIDs • Adjuvants for Bone Pain • CCS, NSAIDs, calcitonin/bisphosphonates, Radiopharmaceu8cals • Other • Adjuvants for bowel obstruc8on, musculoskeletal pain Portenoy, Ahmed. hKp://www.futuremedicine.com/doi/abs/10.2217/ebo.11.340 HOLD THE PHONE! ¡ Which of the following antidepressants is LEAST likely to provide pain relief? A. Nortriptyline B. Duloxetine (Cymbalta) C. Sertraline (Zoloft) D. Venlafaxine (Effexor) PRINCIPLES OF ADJUVANT ANALGESIC USE ¡ Assess complaint of pain, determine relationship to underlying disease, consider comorbidities ¡ Depression? ¡ Avoid initiating several adjuvant analgesics concurrently ¡ Initiate treatment with low doses and titrate gradually according to analgesic response and adverse effect ¡ Select adjuvant analgesics based on knowledge of pharmacology, evidence base, interaction with other drugs, and potential adverse effects Portenoy, Ahmed. hKp://www.futuremedicine.com/doi/abs/10.2217/ebo.11.340 PRINCIPLES OF ADJUVANT ANALGESIC USE ¡ General principles of adjuvant analgesic use: ¡ Multiple pathways of pain transmission provide multiple targets of pain relief ¡ Use specific adjuvant for specific condition ¡ Titrate only one drug at a time ¡ May take several days-weeks to notice improvement in pain ¡ Adjuvants usually do not provide full pain relief ¡ Educate patients about trial-and-error nature of adjuvant use ¡ Select rational combinations of analgesics/adjuvant analgesics Portenoy, Ahmed. hKp://www.futuremedicine.com/doi/abs/10.2217/ebo.11.340 • Non-opioid Analgesics • Adjuvant Analgesics • Opioid Analgesics WHO LET THE OPIOIDS OUT? Opioids hKp://www.who.int/cancer/palliave/painladder/en/ OPIOID CATEGORIES Category Examples Phenanthrenes • Morphine • Codeine • Hydromorphone • Levorphanol • Oxycodone • Hydrocodone • Oxymorphone • Buprenorphine • Nalbuphine • Butorphanol Benzomorphans • Pentazocine Phenylpiperidines • Fentanyl, alfentanil, sufentanil • Meperidine Diphenylheptanes • Methadone • (Propoxyphene) – off market Pain Physician 2008;11:S133-S153. ATYPICAL OPIOIDS ¡ Tramadol and Tapentadol ¡ Indicated for the management of moderate to severe acute or chronic pain ¡ Tramadol: Weak mu opioid agonist, increases serotonin and norepinephrine levels ¡ Tapentadol: Mu opioid agonist and primarily inhibits reuptake of norepinephrine OPIOID INDICATIONS AND USES ¡ Analgesia ¡ Moderate to severe pain ¡ Anesthesia ¡ Cough ¡ Detoxification ¡ Diarrhea ¡ Dyspnea OPIOIDS FOR PAIN MANAGEMENT ¡ Are all painful conditions amenable to opioid treatment? ¡ Consider benefits and burdens of therapy ¡ If an opioid is appropriate, should it be monotherapy? Which opioid? When should an adjuvant be used? ¡ If an opioid is appropriate, should a tamper-resistant formulation be used? ¡ If the patient doesn’t respond to the first opioid, or has an adverse outcome, should we switch to a different opioid? ¡ Are there special considerations when switching to methadone? ¡ What is the role for adjuvant analgesics? ORAL MORPHINE FOR CANCER PAIN ¡ Effectiveness of oral morphine in treating moderate to severe cancer pain. ¡ 62 studies with 4241 participants