Pain and Analgesics

1. Pain and Analgesics Dr Ian Coombes, Judith Coombes, Dr Lisa Nissan University of Queensland Schools of Medicine and Pharmacy Safe Medication Practice Unit, Queensland Health The University of Queensland

2. Outline What is pain Pain assessment Principles of Pain Management Drug therapies Neuropathic Pain and adjuvant therapy Role of the Pharmacist / other health professionals

3. You have been asked to recommend a patient’s analgesia including medication choice dose and duration… What patient factors do you need to consider?

4. What is Pain? A signaling system : mechanical and nerve Unpleasant sensory & emotional experience – IASP A perception : unlike taste or hearing cannot define independent of person experiencing it Only know 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. Acute pain (e.g. sprain, surgery) • 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 +++

7. Acute vs Chronic Acute Pain Passive patient Short term planning “hands-on” Tx Rest PRN Tx (inc. Meds) Resume usual life Chronic Pain Active patient Long term planning “hands-off” Tx Activity Regular Tx (inc.Meds) Retraining, readjustment

8. Examples of acute pain Acute post operative pain Sprains and strains Sports injuries Period pain Headaches Toothache / dental

9. Types of chronic pain Chronic back or neck pain Total body pain Chronic daily headaches Musculoskeletal pain Include: OA,RA, polymyalgia Painful diabetic neuropathy (PDN) Post-herpetic neuralgia (PHN) Phantom limb pain

10. Cancer Pain – 4 sources Malignancy E.g. infiltration of tumor, fractures Treatment Pain E.g. radiotherapy, mucositis Debility E.g. bed sores Unrelated E.g. history of underlying lower back pain

11. Types of pain mechanical inflammatory neuropathic

12. Two Main categories Nociceptive Pain Pain due to stimulation of superficial or deep tissue pain receptors as a result of injury or inflammation Neuropathic Pain Pain due to dysfunction or primary lesion in the central or peripheral nervous system

14. Patient Assessment Goal to individualise analgesic therapy Assess patient characteristics:

15. Assessment • Pain History (LINDOCARRF) • Location • Intensity • Nature • Duration • Onset, Offset • Concomitants • Aggravating • Relieving • Radiating • Frequency

16. 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”

21. Principles of Analgesic Prescribing • Analgesic Ladder • Adjuvants - • TCA • Anti-convulsants • Anti-arrhythmic 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

22. Analgesic, antipyretic, Act centrally (PGs) Not useful as an anti-inflammatory FewSE if taken at therapeutic doses Onset of effect 30 - 60 min Dosing: 500 –1000mg QID Max 4g for adult Paracetamol

23. Paracetamol Should be 1st line therapy minor, non-inflammatory pain 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: 1g QID, or for example in people with OA ALTERNATE Extended release: 1330mg TDS

24. Paracetamol Dosing in Children - Often under dosed! Appropriate: 15mg/kg Q4H MAX 60mg/kg (community) 15mg/kg Q4H MAX 90mg/kg (hospital) Can use in Combination with Ibuprofen Careful with other OTC products Esp. cough and cold medications “cumulative paracetamol”

25. Side-effects major risk: is poisoning with overdose Paracetamol can damage the liver (mainly OD) Risk of toxicity  - dehydrated, malnourished, alcohol (chronic) Common: N/V, dizziness, sedation Less common: headache, skin rash *NOTE: paracetamol & NSAID can be used together

26. 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

27. COXib Withdrawal 2004 Vioxx® withdrawn 2004  CV risk MOA CV risk COX-2 is the main source of the prostacyclin PGI2 PGI2 acts in opposition to thromboxane TXA2 generated by COX-1 PGI2 = anti-clotting (anti-thrombotic) TXA2 = pro-clotting (pro-thrombotic) Therefore, inhibiting COX-2   PGI2 synthesis  “pro-thrombotic” effect (TXA2)  risk of MI, stroke

28. Non-Steroidal Anti-inflammatory Drugs (NSAID) Analgesic, antipyretic Antiinflammatory - several days dosing must dose constantly at least several days prnnot significant anti-inflammatory action Onset of action / effect 30 – 60 min difference in half-life and SE NOTE: elderly patients should not be on NSAID's with long half-lives can be even more prolonged in elderly

29. NSAIDs- Adverse Effects

30. NSAIDs- Adverse Effects

31. 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!

32. Where do Opioids Act?

33. How do Opioids Act?    G-protein G-proteins 2nd messenger systems • Interact with specific cell-surface receptors in • CNS and PNS • other tissues (GIT, immune cells, other tissues)

34. Pharmacological Effects of Opioid Agonists • Desired Action – analgesia • Unwanted actions • Analgesic tolerance • physical dependence • Respiratory depression • Nausea, vomiting sedation Tolerance often develops

35. Other unwanted effects • Constipation • inhibition of GIT motility • slowing of oral-caecal transit times • Never forget laxatives • Endocrine effects • may alter male sex hormones in chronic dosing • Must monitor in chronic therapy • Neuro-excitatory SE • e.g. myoclonus, allodynia, seizures • very high doses No tolerance

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

37. What are Opioids? • Step 2 / 3 - Moderate to severe pain • Definite role in cancer + non-cancer pain • Mu, Kappa, Delta receptors • Many available • Typical SE profile • Nausea, Drowsiness, Respiratory Depression • Constipation, Sweating, Itch • Caution in hepatic and renal impairment

38. Opioids – what to do? • Assess requirements – calculate dose • Conversion table as a guide (if on other opioids) • Can start on one Short Acting opioid and titrate • Conversion to SR / CR preparation when possible • Adding it up ….. • If currently on multiple Tx - Use conversion table • E.g. convert all to oral morphine equivalent

39. Opioids – what to do? ****** • Start low go slow ….. • When converting between opioids • Reduce calculated total daily dose ~20-30% • Breakthrough (incident pain – esp. in cancer) • Calculate as: 1/6th – 1/12th of TDD • Or ~ 50% of the dose just given (if e.g. Q4H)

40. Oral Morphine equivalent * 100mg tramadol ~ 60mg codeine ~ 10mg oral morphine

41. Reference: AMH

42. Regular vs PRN Analgesia • regular analgesia is better in setting of continuous 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 • prn dose = 1/6 →1/12 total regular daily dose

43. Tramadol (Tramal) Centrally acting analgesic with a dual MOA 1st - opioid effects similar to morphine (mu) Active Metabolite M1 M1 - 6x tramadol as analgesic, 200x binding 2nd - inhibit re-uptake ofNA / 5-HT descending pain inhibitory pathway Hepatic Metab. Via CYP 2D6 (P450) similar to codeine

44.  doses in renal and hepatic impairment 50 – 100mg 4-6 hrs (Max 400mg) or SR equiv. Interactions: SSRI, TCA, carbamazepine, MAOI, warfarin ( INR) Can cause serotonin syndrome by itself! Start low – go slow ……. Short term use only! Start on IR then (switch to SR if appropriate)

45. More serious ADR’s with tramadol • Australian Adverse Drug Reactions Bulletin - Volume 22, Number 1, February 2003 NNT > / = 50% relief 3.5 (2.4 to 5.9) NNH = 7.7 (4.6 to 20)

46. 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

47. Neuropathic Pain • Can be due to a central or peripheral component • Opioids not particularly effective • Post Herpetic Neuralgia: acute herpes zoster • Phantom Limb Pain • Postoperative Pain • Diabetic neuropathy • May be lancinating (shooting, stabbing) • non-lancinating (dull, aching) • burning (dysesthesia)

48. TREATMENTS FOR NEUROPATHIC PAIN Antidepressants Anticonvulsants Opioids Topical agents Eg. CBZ Gabapentin pregabalin Eg. Tramadol oxycodone Eg. Lidocaine patch Capsaicin Eg. Amitriptyline Desipramine paroxetine

50. Things to think about when reviewing Prescriptions • Regular dosing of pain medications • Dosage form issues • Crushing, breaking SR/CR • Appropriate level of breakthrough medication • Managing SE • Importance of laxative use • Increasing needs ? More breakthrough • Interactions ….. Watch OTC / complementary