THE MODERN MANAGEMENT OF PAIN IN PALLIATIVE MEDICINE

ASSESSMENT

WHO LADDER Pain NOT controlled STEP 3 STEP 2 Pain NOT controlled STRONG OPIOIDS Initial treatment with immediate release MORPHINE (eg ORAMORPH/SEVREDOL) 5-10mg* every 4 hours orally and as required for breakthrough pain (* a 2.5mg dose may be enough in elderly or patients with renal impairment) WEAK OPIOID/ PARACETAMOL COMBINATION (CO CODAMOL 30/500) 2 qds STEP 1 Breakthrough: immediate release MORPHINE 5mg PRN (eg ORAMORPH/SEVREDOL PARACETAMOL 1 gram 4 times daily + Stimulant & softening laxatives eg CO-DANTHRAMER 2 nocte or DOCUSATE + BISACODYL + Stimulant & softening laxatives eg CO-DANTHRAMER 2 nocte Or DOCUSATE + BISACODYL +/- ANTIEMETIC eg HALOPERIDOL 1.5mg od/ METOCLOPRAMIDE 10mg tds +/- NSAIDs +/- NSAIDs +/- adjuvant medication +/- NSAIDs +/- adjuvant medication +/- adjuvant medication

MORPHINE Morphine strong opioid of choice for moderate/severe pain This recommendation decided by: Availability Familiarity Established effectiveness Simplicity of administration Relative inexpensive cost Not based on proven therapeutic superiority over other options Clinical response to morphine is very variable. Studies have suggested this variability may be related to: Age Renal and hepatic function inducers eg carbamazepine, phenytoin, spironolactone Concomitant medications steroids → reduced opioid availability (the importance of cytochrome CYP3A4) inhibitors eg midazolam, clarithromycin, fluconazole, cyclizine → reduced opioid availability Mechanism of pain Genetic variation

OPIOID SWITCHING (ROTATION) Indications: Unmanageable side effects or toxicity (consider dose reduction or hydration initially) Inadequate analgesia Caution: Individual variability in the response to different opioids in terms of analgesia and side effects Need to monitor for possible morphine withdrawal Fluids may be required if patient is toxic

ALTERNATIVE OPIOIDS Oxycodone (oral, sc) Hydromorphone (oral, sc) Fentanyl (transdermal, buccal) Buprenorphine (transdermal) Alfentanil (sublingual, sc) Methadone (oral, sc)

DOSAGE ADJUSTMENTS FOR PATIENTS WITH RENAL IMPAIRMENT Chronic renal disease classified as: eGFR(ml/min/1.73m2) Mild 60 – 89 Moderate 30 – 59 Severe 15 – 29 Established < 15 Doses can be adjusted in 3 possible ways: By reducing the actual dose By increasing the interval between doses By reducing the dose and increasing the interval between doses

DOSE ADJUSTMENTS Drug Mild Moderate Severe Paracetamol Normal Give 6 hourly Give 8 hourly NSAIDs (diclofenac) 50-100% 50% 25% Codeine 100% 75% 8 hourly 12 hourly Tramadol Avoid Morphine, diamorphine 75-100% Avoid if possible Oxycodone Methadone 50-75% Alfentanil Fentanyl

HEPATIC FAILURE Metabolism to active or inactive metabolites in the liver In encephalopathy reduced metabolism and potential for toxicity increased May need to change to PRN medication

BREAKTHROUGH ANALGESIA Assessment of breakthrough pain, character, aggravating factors etc Analgesia for treatment of pain or prevention of pain If on regular opioid analgesic – breakthrough opioid 1/6th total dose of regular opioid (disputed) 1/6th rule not applicable to use of Fentanyl lozenge and probably methadone

NEUROPATHIC PAIN Occurs in approximately 40% of patients with cancer pain Vast majority of pain mixed Compared with nociceptive pain, patients with neuropathic pain: - obtain less pain relief with single dose of analgesics - are more likely to escalate opioid dose - are likely to have poorer outcome with treatment - often obtain less relief with spinal analgesia There is a lack of evidence for opioids in cancer neuropathic pain (not evidence of lack of effort)

MANAGEMENT OF NEUROPATHIC PAIN Assessment including use of tools, eg LANSS Medication: WHO ladder + opioid switching Amitriptyline Gabapentin or Pregabalin Ketamine + Dexamethasone Methadone Anaesthetic procedures

MODULATION OF OPIOID RECEPTOR MEDIATED EFFECTS ( effectiveness by  efficacy or reducing adverse effects) 2 adrenergic agonists - clonidine – epidural - no studies of oral clonidine or tizanidine NSAIDs NMDA receptor antagonists – Ketamine CCK antagonists Gabapentin or pregabalin NH-1 receptor antagonists Use of 2 opioids eg Fentanyl + morphine Methadone + Fentanyl Methadone + morphine

OTHER APPROACHES Other modalities: external beam XRT unsealed sources eg Sr89 Chemotherapy Other routes: Intranasal – alfentanil, fentanyl, diamorphine, morphine oxycodone Topical – morphine Other drugs: Complementary: Baclofen Acupuncture Bisphosphonates Hypnotherapy