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Pain and Analgesics

Pain and Analgesics. Nimali Peters and Dr Lisa Nissan 2010 Adapted by Bhabitha Santhakumaran 2019. Outline. What is pain Types of pain Pain assessment Principles of pain management Drug therapies Neuropathic pain and adjuvant therapy Pain management of osteoarthritis

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Pain and Analgesics

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  1. Pain and Analgesics Nimali Peters and Dr Lisa Nissan 2010 Adapted by BhabithaSanthakumaran2019

  2. Outline What is pain Types of pain Pain assessment Principles of pain management Drug therapies Neuropathic pain and adjuvant therapy Pain management of osteoarthritis Role of the pharmacist / other health professionals

  3. What is Pain? The International Association for the Study of Pain (IASP) definition - An unpleasant sensory and emotional experience associated with actual or potential tissue damage • Analgesia - alters patient perception of pain • Analgesia - aims to reduce experience of pain, cannot eliminate

  4. What is Pain? Vital part of the nervous system because it warns of potential and actual injury A signaling system : mechanical and nerve Unpleasant sensory & emotional experience – IASP A perception : unlike taste or hearing cannot define independent of the person experiencing it Only know if in pain by statements & actions Pain is what the patient says “hurts”

  5. Psychological Factors Sex Age Cognitive Level Previous Pain Family Learning Culture Noxious Stimulus, Tissue Damage Pain Sensation Situational Factors Expectation Control Relevance Emotional Factors Fear Stress Anxiety Frustration

  6. Two main pain categories Nociceptive Pain Stimulation of superficial or deep tissue pain receptors as a result of injury or inflammation nociceptive pain can be subdivided into somatic (superficial and deep) and visceral, according to the origin of the nociceptive stimulus Neuropathic Pain Dysfunction or primary lesion in the central or peripheral nervous system arises as a direct consequence of a lesion or disease affecting the somatosensory nervous system

  7. Acute pain (e.g. sprain, surgery) • of limited duration • related specifically to an event or trauma • bodies’ natural “healing” process Palliative Care components of both e.g. incident pain, disease progression Chronic pain • pain persists beyond time of healing • often no specific pathology identified •  changes in the CNS •  development of NP • complex interplay physical+psychological • Often - sleep disturbances, fatigue, depression, social withdrawal, and self-esteem issues +++

  8. Recurrent/Breakthrough pain: leaves and returns

  9. Comprehensive Pain Assessment Goal = to individualise analgesic therapy Assess patient characteristics –

  10. Assessment – use a BPI (Brief Pain Inventory) tool • Pain History (LINDOCARRF) • Location • Intensity • Nature • Duration • Onset, Offset • Concomitants • Aggravating • Relieving • Radiating • Frequency

  11. Pain Scales Pain severity usually subjectively measured: • categorical scales (none→ worst ever) • numbered scales or • visual analogue scales Scales used to monitor patient response to interventions • find the scale that works best for the patient • assess subjective pain score with other pain indicators • functional pain scales – less subjective

  12. Verbal Rating Scale:On a scale of 1-10 ….. How would you rate your pain?Sometimes add – “where 10 is the worst ever and zero is no pain”

  13. Principles of Analgesic Prescribing • Analgesic Ladder • Adjuvants - • TCA • Anti-convulsants STEP 3 • NSAID • Non-opioid (paracetamol) • Strong Opioid (morphine, oxycodone) • Adjuvant Medication STEP 2 STEP 1 • NSAID • Non-opioid (paracetamol) • Weak Opioid (codeine, tramadol) • Adjuvant Medication • NSAID • Non-opioid (paracetamol) • Adjuvant Medication

  14. Empirical Pain Management • Analgesic ladder NOT always appropriate • Empirical therapy sometimes more appropriate • palliative care • e.g. metastatic bone pain – initiate opiate, don’t escalate from paracetamol! • Previous response to analgesics assists determining initial dose • The right dose gives pain relief for as long as necessary with minimal side effects

  15. Analgesic, antipyretic, acts centrally (role PG’s) Not useful as anti-inflammatory Fewside effects if taken at therapeutic doses Onset of effect 30 - 60 min Dosing – 500mg & 665mg SR tablets: 500 –1000mg QID Max 4G in 24 hours (? ‘day’) for adult Paracetamol

  16. Paracetamol (continued) Should be 1st line therapy As effective as aspirin/NSAID in relieving acute pain Similar antipyretic actions to aspirin, NSAID No. 1 choice mild to moderate pain in children May be given chronically: for example in OA

  17. Paracetamol (continued) Dosing in Children - often underdosed! Appropriate: 15mg/kg Q4H Max 60mg/kg (community) 15mg/kg Q4H Max 90mg/kg (hospital) Can use in combination with Ibuprofen Careful when given with other products containing paracetamol “cumulative paracetamol”

  18. Paracetamol - side-effects Major risk: poisoning with overdose Risk of toxicity  - if dehydrated, malnourished, alcohol (chronic) Common: N/V, dizziness, sedation Less common: headache, skin rash *Note: paracetamol & NSAID used together

  19. How do they work? - NSAID v COX2 Arachidonic acid Maintenance Induced COX-1 COX-2 NSAIDs Coxibs thromboxane / prostaglandins prostaglandins Primarily mediate inflammation, pain & fever Primarily support platelet function Primarily protect GI mucosa

  20. NSAID Analgesic, antipyretic Antiinflammatory - several days dosing dose regularly for several days at least PRN -not significant anti-inflammatory action Onset of action / effect 30 – 60 min Difference across class in half-life and SE Note: elderly patients should not be on NSAIDs with long half-lives – T1/2 can be further prolonged

  21. NSAIDs- Adverse Effects

  22. NSAIDs – Caution! • Major cause of ADEs and hospital admissions • use lowest effective dose for shortest possible time • use paracetamol as alternative or to reduce NSAID dose • COX-2 inhibitors • similar adverse effects to non-selective • increase risk of thrombotic events (stroke; MI)! • little difference in efficacy between NSAIDs • avoid aspirin < 18 yrs in viral illness, Reye’s syndrome • elderly - increased risk of adverse effects • Continue only if effective. Avoid if possible!

  23. Opioids - Mechanism of action • Opioid analgesics mimic endogenous opioids by • activating opioid receptors in the central and peripheral nervous systems to produce analgesia, respiratory depression, sedation and constipation. • They reduce transmission of the pain impulse by • acting pre- and post-synaptically in the spinal cord, and by modulating the descending inhibitory pathways from the brain.

  24. Where do Opioids Act?

  25. Opioid Analgesia Potent pain-relieving agents, commonly used in moderate - severe pain *Differ in: • affinity for receptors, speed of onset, duration of action • route of administration – oral, IV, IM, sub-cut, transdermal, intrathecal. • IM = unpredictable absorption – avoid! • sub-cut - more constant blood level

  26. Codeine • weak opioid, metabolised to morphine • only provides analgesia for up to four hours • saturable > 30mg  ↑ dose no additional effect • no therapeutic benefit in 6-10% Caucasians (nearly no CYP2D6 expressed) • side effects NOT dose limited

  27. Morphine – the gold standard • cleared renally   dose if CrCl < 30 mL/min • 70% metabolised (oral bioavailability = ⅓ of parenteral) • Active metabolites (Morphine 6&3 glucuronides) can accumulate in renal impairment • M6G (15%) - more potent analgesic than morphine • M3G (55%) - may antagonise analgesic effects of morphine & M6G

  28. Fentanyl • very potent (~ 40 x morphine), synthetic opioid • infusion; IV; sub-cut; transdermal patch • rapid onset IV • short duration of action (30-60 mins IV) • hepatic metabolism (inactive metabolite) • more lipophilic than morphine

  29. Fentanyl PATCH

  30. Morphine equivalent to Fentanyl patches (BNF)

  31. Opioids – Adverse Effects • respiratory depression • sedation • nausea and vomiting • confusion • hypotension; bradycardia • pruritus • constipation / ∆ gut motility • urinary retention

  32. Opioids – Precautions • hypotension, shock • concomitant CNS depression • impaired respiration /↓ respiratory reserve • elderly • hepatic impairment • renal impairment • epilepsy/recognised seizure risk • biliary colic or surgery • phaeochromocytoma

  33. Tramadol • Chemically non-opioid, but acts centrally • low affinity for mu opioid receptors (70% analgesia) • blocks NA and 5HT reuptake (30% analgesia) • Common side effects as for opioids • Significant interactions • SSRIs – major risk of serotonergic syndrome • warfarin -  bleeding risk • CYP450: 2D6; 3A4 • Caution in elderly/renal impairment (active metabolite) • Potential for dependence and tolerance • NOT RECOMMENDED - USE WITH CAUTION!

  34. Case Study 1 • Mr. GP is a 35 y.o. male admitted for fracture of femur. Dr wants to start the patient on oral morphine. • What formulation should be used initially (e.g. sustained release tablets or mixture)? • How should their doses be titrated to achieve optimal pain relief?

  35. How should doses be titrated to achieve optimal pain relief? Initial dose depends on previous opioid exposure: If no prior opioid exposure (including codeine) commence with: • Elderly patient: Morphine 2-5mg Q4h po • Younger, larger patient: Morphine 5-10mg Q4h po • Use the liquid formulation e.g. Morphine HCl 10mg/ml • Titrate doses to effect, and when stable calculate 24-hour morphine requirement for maintenance dosing.

  36. Initial Dose If patient taken other opioids: See AMH Analgesia - Opioid Comparative Information Table: • Calculate total dose required in 24 hours and convert to the equivalent dose of morphine • Give 1/6 of this total daily dose Q4h.

  37. Breakthrough pain • Breakthrough doses used when regular dosing not adequate for entire dosing interval • 50% to 100% of 4-hourly dose • In elderly or in renal impairment, use lower dose • Take prn but not more than every 30 minutes • Take normal dose of opioid at the regular time, not 4 hours after the breakthrough dose

  38. Breakthough tx – subsequent doses Determining the dose for next day – 2 options: • OPTION 1: Using immediate release formulation • Add morphine doses for the previous 24hrs (regular plus breakthrough doses) • Divide the total amount by 6 to give four hourly doses (q4h) • OPTION 2: Change to sustained release formulation

  39. OPTION 2:Change to sustained release formulation • Add morphine doses for previous 24hrs (regular + breakthrough doses) • Halve dose to calculate sustained release dose (MS Contin) give q12hours • Order breakthrough of 1/12 to 1/6 of total daily dose • Give first dose of SR preparation with last dose of immediate-release morphine • Ensure laxatives given when tx started e.g. Coloxyl & Senna, Lactulose, Durolax NOT when constipated

  40. Case Study 2 • Mrs Herath is a 65 y.o female recently diagnosed with breast cancer • Currently takes morphine liquid 10mg/ml: 1ml q4h regularly • Dr orders - change to long acting morphine formulation and asks you for advice. • What would you recommend?

  41. Case: Step 1: Convert 24-hour dose of oral liquid to equivalent dose of controlled release product for maintenance tx • Total liquid morphine/24 hours =60mg (10mg q4h x 6) Step 2: Oral controlled release tablet: Total daily dose of oral liquid, give HALF total daily dose every 12 hours • Dose of CR morphine = 30mg q12h • Liquid morphine should be taken as needed for breakthrough pain, = 1/6 – 1/12 of the total daily dose (i.e. 5-10mg q2-4h prn).

  42. Change in Opioid • If adverse effects of morphine eg delirium intolerable, switch to alternative opioid - may reduce refractory ADR • When changing opioids - start at half the equi-analgesic dose, as may be incomplete cross-tolerance b/w opioids • Monitor closely, titrate dose based on assessment of pain • Add breakthrough doses of opioid if required - to establish adequate analgesia

  43. Opioid comparative informationWhen changing opioid, start at 50% of the approximate equi-analgesic dose; then titrate according to response

  44. Case Study 3: Mr. Herath • Mr. Herath is terminally ill with prostate cancer. • His pain is well controlled on Morphine Sustained Release, 90mg every 12 hours. • Mr. Herath develops swallowing difficulties so his Dr wants to prescribe a transdermal Fentanyl patch • Convert Morphine dose to appropriate Fentanyl dose • Calculate the hourly dose of the Fentanyl patch.

  45. Mr Herath - • Step 1: Calculate total dose oral Morphine over 24 hours 2 x 90 mg = 180 mg • Step 2: Convert to equivalent dose of Fentanyl patch • Step 3: BNF: Morphine oral 180mg daily = Fentanyl 50mcg/hr patch • AMH, when changing opioids: • Start at 50% of the approximate equi-analgesic dose as may be incomplete cross-tolerance between opioids • Start Mr Herath on Fentanyl 25mcg/hr patch

  46. Regular vs PRN Analgesia • regular analgesia best in chronic or persistent pain • PRN only if pain intermittent and unpredictable • in most settings, pain is predictable • problems with using only PRN analgesia • dose prescribed by Dr/administered by nurse • patients don’t ask for medication • inadequate or infrequent dosing → unrelieved pain • keeping up with pain is easier than catching up with pain

  47. What is Neuropathic Pain? Pain or abnormal sensations due to a dysfunction of, or damage to, a nerve or group of nerves • primarily peripheral nerves, although pain due to CNS damage (“central pain”) may share these characteristics

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