Cancer and Non cancer Pain: Opioiphile or Opioiphobe? Eastern - PDF document

10/24/2012 Nothing to Disclose Cancer and Non ‐ cancer Pain: Opioiphile or Opioiphobe? Eastern Medicaid Pharmacy Administrator Association (EMPPA) Mary Lynn McPherson, Pharm.D., BCPS, CPE Hospice and Palliative Care Consultant Pharmacist Professor and Vice Chair Department of Pharmacy Practice and Science University of Maryland School of Pharmacy 1 2 Learning Objectives Opioid Therapy for Cancer Pain 1. Define treatment differences between cancer Mary Lynn McPherson, PharmD, BCPS, CPE and non ‐ cancer pain for the 2010 decade. Professor and Vice Chair University of Maryland School of Pharmacy 2. Describe the role of opioid therapy in cancer mmcphers@rx.umaryland.edu and non ‐ cancer pain management. 3. Explain strategies to screen for, and limit drug abuse and diversion. 3 4 http://www.lifeinitaly.com/garden/tuscan ‐ poppies.asp Learning Objectives Prevalence of Cancer • At the conclusion of this session, the • Cancer is a leading cause of death worldwide, participant will be able to: accounting for 7.6 million deaths (around 13% – Select the opioid best suited to individual cancer of all deaths) in 2008 patients and their pain condition on the basis of • Deaths from cancer worldwide are projected pharmacodynamic and pharmacokinetic to continue rising, with an estimated 13.1 considerations, receptor activity, and adjunctive million deaths in 2030 analgesics used in combination therapies. • Risk factors: high body mass index, low fruit and vegetable intake, lack of physical activity, tobacco use, alcohol use. http://www.who.int/mediacentre/factsheets/fs297/en/ 5 6 1

10/24/2012 Pain in Cancer Management of Cancer Pain • Cancer patients who experience pain and • Pharmacologic and non ‐ require treatment with analgesic drugs: pharmacologic – 33% of cancer patients in active therapy interventions – 66 ‐ 100% of advanced cancer patients • Patient, family, – Pain generally worsens as disease progresses caregiver education • Pain may be acute and/or chronic • Ongoing evaluation and modification of the • Various pathologies (disease, treatments) treatment plan – Bone metastases (breast, prostate, lung, etc.) • WHO 3 ‐ step ladder • Cancer pain is undertreated ‐ up to 80% http://www.who.int/cancer/palliative/painladder/en/ Foley KM. Palliative Medicine 2011;25(5):398 ‐ 401. 7 8 Which Opioid? Opioid Effectiveness in Cancer Pain • Eenie ‐ Meenie Miney Mo’phine: • Opioids are considered the gold standard for Why morphine isn’t ALWAYS the answer to treatment of moderate to severe cancer pain cancer pain.” • Literature search 1996 ‐ 2010 – Observational studies for chronic cancer pain treated with opioids – 18 studies reviewed; 7 met inclusion criteria • Result was a 1C/strong recommendation with benefits clearly outweighing risks and burdens Colson J et al. Pain Physician 2011;14:E85 ‐ 102. 9 10 http://www.greekmyths ‐ greekmythology.com/morpheus ‐ the ‐ god ‐ of ‐ dreams/ First Line Opioids Considerations in Opioid Selection? • Patient ‐ related variables • Morphine • Assessment information about patient’s pain complaint • Oxycodone • Specific information about the patient’s pre ‐ existing conditions that may alter the expected dosing and effects • Hydromorphone (both therapeutic and toxic) prior to selection of pharmacotherapy • Methadone • Agent/Drug ‐ related variables • Buprenorphine • Characteristic properties of a medication that affects it use in a given situation, including pharmacodynamic and • Fentanyl pharmacokinetic parameters, dosage formulations or routes of administration, adverse effects, and costs (cost of medication, administration and monitoring). Pain Pract 2008;8:287 ‐ 313 University of Maryland School of Pharmacy 11 12 2

10/24/2012 Patient Related Variables Chemical Classes of Opioids • History of opioid ‐ use Chemical Class Examples Phenanthrenes Morphine, codeine, hydromorphone, – Opioid ‐ naïve or tolerant levorphanol, oxycodone, hydrocodone, – Opioids that gave positive response in the past oxymorphone, buprenorphine, • History of opioid allergy or intolerance nalbuphine, butorphanol Benzomorphans Pentazocine – Differentiate between opioid adverse effects and Phenylpiperidines Fentanyl, alfentanil, sufentanil, allergy meperidine • Codeine “allergy”; opioid ‐ induced sedation/delirium Diphenyheptanes Methadone, (propoxyphene) • Opioid ‐ induced pruritus vs. true allergic reaction Other Tramadol, tapentadol Laird B et al. Eur J Cancer 2008;44:1078 ‐ 82. 13 14 Patient Related Variables Opioids in Renal Failure • Age, race, body habitus Not Use with caution Safest option recommended • Health care beliefs Morphine Hydromorphone Fentanyl – Regarding the management of pain and addiction Codeine Oxycodone Methadone – Beliefs regarding specific opioids Meperidine Oxymorphone • Renal and hepatic function (Propoxyphene) – Morphine, hydromorphone, oxycodone – caution with patients and chronic kidney disease – All opioids – caution with hepatic impairment Johnson SJ. www.Pain ‐ Topics.org 15 16 Patient Related Variables Agent/Drug ‐ Related Variables • History of substance abuse • Defined as those properties of any agent which are characteristic of that agent and – Patient effect its use in a given situation: – Home environment – Mechanism of action • Ability to manipulate or tolerate dosage – Available dosage forms, bioavailability of various formulations formulations, distribution in the body, onset, – Transdermal, transmucosal peak, duration of action, serum half ‐ life, method – Ability to swallow solid dosage formulations of elimination from the body • Febrile, pregnant, breast ‐ feeding – Side effects and toxicities • Financial resources – Cost (drug, administration, monitoring) University of Maryland School of Pharmacy 17 18 3

10/24/2012 First Line Opioids Morphine • Mu agonist; kappa agonist (negligible activity) • Morphine • Metabolized in liver to active metabolites • Oxycodone – Morphine ‐ 3 ‐ glucuronide (neurotoxicity) • Hydromorphone – Morphine ‐ 6 ‐ glucuronide (analgesia) • Methadone – Accumulates in renal impairment • Buprenorphine – Increased BAB with hepatic impairment • Fentanyl • LA and SA tablets, capsules, oral solution/intensol • Rectal suppositories, injectable formulation Pain Pract 2008;8:287 ‐ 313 19 20 Hydromorphone Fentanyl • Mu opioid agonist • Mu agonist; kappa agonist (negligible activity) • Metabolized by the liver to inactive metabolites • Metabolized in the liver to active metabolites – Despite this, consider dosage adjustment in continuous – Hydromorphone ‐ 3 ‐ glucuronide infusion or transdermal fentanyl with severe renal impairment – Accumulates in renal impairment (neurotoxicity) – Avoid TDF in severe hepatic disease – Increased BAB with hepatic impairment • 100 times the potency of morphine • LA and SA tablets, oral solution • Transmucosal formulations (OTFC, effervescent tablet, sublingual tablet, sublingual spray, mucosal • Rectal suppositories, injectable formulation film, intranasal spray) • Transdermal, transmucosal, parenteral 21 22 Buprenorphine Oycodone • Partial agonist at the mu opioid receptor, antagonist at • Mu opioid agonist the kappa receptor • Metabolized in liver to noroxycodone via 3A4 • Metabolized to norbuprenorphine (weak mu agonist) – 3x affinity for mu receptor but poor CNS penetration and buprenorphine ‐ 3 ‐ glucuronide • No dosage adjust needed in renal impairment/failure • Also metabolized to oxymorphone via 2D6 or mild to moderate hepatic impairment • Caution with renal disease and hepatic disease • 75 times more potent than morphine • SA and LA tablets, capsules, oral • Approximately equipotent with fentanyl solution/intensol • SL tablets (with and without naloxone) • Often in combination with acetaminophen • Transdermal patch, parenteral 23 24 4

10/24/2012 Methadone Rational Polypharmacy Analgesia • Mu opioid agonist, NMDA receptor antagonist • Metabolized to inactive metabolites – No dosage adjustment with renal impairment; caution with ESRD – Prolonged half life with hepatic impairment • Tablets, oral solution/intensol, parenteral • Caution with switching from other opioids – Do not adjust dose before 4 ‐ 7 days 25 26 Beydoun A, Backonja MM. J Pain Symptom Manage 2003;25:S18 ‐ S30 . Reasons to combine analgesics (Opioid + Nonopioid) 1. To prolong analgesic duration 2. To enhance or optimize analgesic efficacy 3. To diminish or minimize adverse effects 4. To diminish opioid effects that are not beneficial 5. To reduce opioid tolerance/opioid ‐ induced hyperalgesia 6. To combat dependency/addiction/cravings Smith HS. Pain Physician 208;11:201 ‐ 214. 27 28 Opioid/Nonopioid Combination Tx Conclusion • Opioids and… • Opioid analgesics are effective in treating cancer pain – Norepinephrine transporter modulators – Anti ‐ inflammatory agents • Opioids should be selected for individual – Calcium channel alpha ‐ 2 ‐ delta ligands patients based on patient ‐ and opioid ‐ specific – Local anesthetics variables – Alpha ‐ 2 adrenergic agonists Design ‐ A ‐ • Practitioners need to be skilled at opioid – Calcium channel blockers Drug? conversion calculations – Cannabinoids • Consider rational opioid combination – GABA B agonists Dexa ‐ methadone ‐ S analgesic regimens – Glial inhibitors Smith HS. Pain Physician 208;11:201 ‐ 214. 29 30 5