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COMPASS Therapeutic Notes on the Use of Strong Opioids in Chronic Non-Cancer Pain

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COMPASS Therapeutic Notes on the Use of Strong Opioids in Chronic Non-Cancer Pain COMPASS Therapeutic Notes on the use of Strong Opioids in Chronic Non-Cancer Pain Glossary of terms In this issue: Hyperalgesic A paradoxical phenomenon whereby a patient receiving treatment for Page syndrome pain may actually become more sensitive to certain painful stimuli Introduction and background 1 MHRA Medicines and Healthcare products Regulatory Agency Strong opioids in common use 2 Neuropathic pain Pain due to disturbance of the nervous system Less commonly used opioids 4 NNT Number Needed to Treat Adverse effects of opioids 4 Nociceptive pain Pain due to tissue damage; can be either somatic or visceral Opioids in specific conditions 6 RCT Randomised controlled trial Opioids and problem drug use 6 SmPC Summary of Product Characteristics Transdermal opioid patches 7 Pain emanating from muscles, skeleton, skin; pain in the parts of the Somatic pain Practical aspects of prescribing 9 body other than the viscera. Visceral pain Pain relating to any of the large interior organs of the body Successful completion of the assessment questions at the end of this issue will provide you with 2 hours towards your CPD/CME requirements. Further copies of this and any other edition in the COMPASS Therapeutic Notes series, including relevant CPD/CME assessment questions, can be found at: www.centralservicesagency.com/display/compass GPs can complete the multiple choice questions on-line and print off their CPD/CME certificate at: www.medicinesni.com Pharmacists can complete the multiple choice questions on-line and print off their CPD certificate at: www.nicpld.org Introduction and background The use of strong opioids in the Table ONE: Classification of opioids management of cancer pain and Approved name palliative care is widely accepted. The Formulations available use of opioids to treat moderate to (some proprietary names) severe acute pain is also widely Buprenorphine (Temgesic®, Transtec®, BuTrans®) Sublingual, transdermal accepted. The use of opioids to treat Diamorphine Oral, injection ® chronic non-cancer pain, however, Dipipanone (Diconal ) Oral 1-5 ® ® Transdermal, oral remains controversial. Areas of Fentanyl (Durogesic DTrans , Matrifen , 6-8 ® ® ® ® transmucosal, sublingual, uncertainty include: Effentora , Abstral , Actiq , Instanyl ) nasal spray safety and efficacy of opioids in the ® ® long-term Strong Hydromorphone (Palladone , Palladone SR) Oral opioids Methadone Oral, injection propensity for strong opioids to cause Morphine (Oramorph®, Sevredol®, MST Continus®, problems of tolerance, dependence ® ® Oral, rectal, injection MXL , Zomorph ) and addiction Oxycodone (OxyNorm®, OxyContin®) Oral type(s) of chronic conditions that Pentazocine Oral, injection should be treated with strong opioids Pethidine Oral, injection patient selection Tramadol* (Zydol®, Zamadol®) Oral, injection clinical goals. Codeine Oral, injection Weak ® ® The treatment objectives in chronic Dihydrocodeine (DF118 Forte , DHC Continus ) Oral, injection opioids ® non-cancer pain are subtly, but Meptazinol (Meptid ) Oral, injection significantly, different and more Note: oral formulations can be immediate or modified release complex than the goals of opioid * Tramadol can be a weak or strong opioid, depending on dose therapy in the settings of terminal Use of pharmacological options should opioid-sensitive pain. Tramadol is conditions or acute pain. The objective be based on the analgesic ladder considered as either a weak opioid or a of the treatment of chronic pain of non- developed by the World Health strong opioid, depending on the cancer origin includes, when possible, Organisation (WHO). Treatment should administered dose.9 The term weak not only management of painful start at the bottom of the ladder and opioid should not encourage lack of symptoms but an emphasis on ascend in accordance with response to caution in prescribing. maintaining functionality and continued medication in terms of both efficacy and Opioid pharmacology participation in society. These side effects. objectives can be thwarted by the use The term “opioid” refers to all of opioids. compounds that bind to opioid WHO analgesic ladder for chronic receptors. The term “opiate” can be Chronic pain can be treated with a nociceptive pain: used to describe those opioids derived variety of non-pharmacological and Step 1 = non-opioid + adjuvant from the opium poppy; these include pharmacological measures. Non- Step 2 = weak opioid + non-opioid + morphine and codeine. Opioids include pharmacological options include: adjuvant semi-synthetic opiates, i.e. drugs that physiotherapy, Step 3 = strong opioid + non-opioid are synthesised from naturally heat or cold pack application, + adjuvant. occurring opiates (e.g. diamorphine graduated exercise programmes, (Adjuvants include corticosteroids, from morphine; oxycodone from transcutaneous electrical nerve antidepressants and anticonvulsants) thebaine), as well as synthetic opioids stimulation (TENS), and such as methadone and fentanyl. cognitive behavioural therapy. How are opioids classified? It is acknowledged that these Opioids are classified as either strong Opioid receptors are widely distributed interventions may be difficult to obtain or weak (see Table ONE). Strong in the body. When an opioid binds to in the primary care setting and this may opioids differ from weak opioids in opioid receptors, analgesia may be be the reason why, for many patients, having a much broader dose range and accompanied by any of a diverse array the only available option is drug a proportionately greater effect can be of side-effects related to the activation treatment. achieved by increasing the dose in of receptors involved in other functions. These may have an effect on peristalsis COMPASS Therapeutic Notes on the Use of Strong Opioids in Non-cancer Pain January 2011 1 (leading to constipation), may cause Table TWO: Effects of stimulation of mu, kappa, and delta receptors itch, or have an effect in the CNS (leading to miosis, drowsiness, or Receptor type Effects of stimulation Analgesia (mainly at supraspinal sites), respiratory depression, respiratory depression). Activation of Mu other CNS pathways by opioids may miosis, reduced gastrointestinal motility Analgesia (mainly in the spinal cord), less intense miosis and also produce mood effects, either Kappa dysphoria or euphoria. See Table respiratory depression, dysphoria TWO. Delta Uncertain, probably analgesia Although several types of opioid (e.g. naltrexone, naloxone); they can What is meant by “chronic pain”? receptors exist (e.g. mu, kappa and reverse the effects of mu opioid Chronic pain is defined by the delta), opioid drugs largely produce agonists. Those opioids with a low International Association for the Study their analgesic effects via activation of activity at opioid receptors are called of Pain as “pain that persists beyond partial opioid agonists (e.g. normal tissue healing time, which is the mu opioid receptors; thus, opioids 12 used for pain are often described as buprenorphine) – increases in dose of assumed to be three months”. A study “mu agonists”. Mu drugs that have the these agents will only increase effects conducted in a community in the ability to fully activate opioid receptors up to a ceiling point, after which dose greater London area to quantify the increases produce no additional prevalence of chronic pain found that are referred to as opioid agonists or full 10,11 mu agonists (e.g. morphine, oxycodone effects. 46.5% of the general population reported chronic pain; low back and methadone). Those opioids that How is pain classified? problems and arthritis were the leading occupy but do not activate receptors See Figure ONE. causes.13 are referred to as opioid antagonists Figure ONE: Pain Classification Strong opioids in common use: Morphine, diamorphine, oxycodone, fentanyl and tramadol Table THREE gives approximate 14 equivalent doses of various opioids. Table THREE: The approximate potency of various opioids Morphine Opioid Route Equivalent 24 hour dose The drug most often associated with Morphine Oral 30 milligrams potent analgesia within the general Codeine Oral 240 milligrams population is morphine. Morphine tends Hydromorphone Oral 6 milligrams to be the standard against which other Oxycodone Oral 10-15 milligrams analgesics are compared. Alternative Methadone Oral 30 milligrams opioids have not demonstrated Fentanyl Transdermal 12 micrograms/hour advantages that would make them Buprenorphine Transdermal 20-35 micrograms/hour preferable as first-line drugs for Tramadol Oral 120 milligrams moderate to severe pain. Morphine Note: This is only a guide. Since there is considerable interpatient variation in the dosage and response can vary widely response to these drugs it is essential to titrate the dose.15 in the adult population. Older people may require smaller doses due to receptor sensitivity and impaired renal Table FOUR: Common drug interactions with opioids function, whereas the very anxious individual in pain may require a larger- Opioid Interacts with: Effect 14 Domperidone, than-expected dose. Sedation, Antagonism of GI effect dizziness, nausea and constipation can metoclopramide be problematic (discussed in detail All CNS depressants Enhanced depressant effect later). These are especially common in Anticonvulsants Increased opioid metabolism the frail or elderly, and when using Cimetidine Reduced opioid metabolism large doses. Euphoria, dysphoria and Methadone Phenytoin, Rifampicin Faster elimination of opioid Increased bioavailability
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