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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
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Outline What is pain Pain assessment Principles of Pain Management
Drug therapies Neuropathic Pain and adjuvant therapy Role of the Pharmacist / other health professionals
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What patient factors do you need to consider?
You have been asked to recommend a patient’s analgesia including medication choice dose and duration… What patient factors do you need to consider? Prompt students to answer - What is the relevance to them as junior prescribers? You have the knowledge and want to show importance of recalling that knowledge in clinical situation Safe Medication Practice Unit 3
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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”
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Psychological Factors
Noxious Stimulus, Tissue Damage Pain Sensation Psychological Factors Sex Age Cognitive Level Previous Pain Family Learning Culture Situational Factors Expectation Control Relevance Emotional Factors Fear Stress Anxiety Frustration
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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 +++
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Acute vs Chronic Acute Pain Chronic 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
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Examples of acute pain Acute post operative pain Sprains and strains
Sports injuries Period pain Headaches Toothache / dental
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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
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Cancer Pain – 4 sources Malignancy Treatment Pain Debility Unrelated
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
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Types of pain mechanical inflammatory neuropathic
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Two Main categories Nociceptive Pain Neuropathic 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
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Goal to individualise analgesic therapy
Patient Assessment Goal to individualise analgesic therapy Assess patient characteristics: indication for analgesia age, sex, weight culture vital signs allergies/ADRs opioid tolerance respiratory status renal/hepatic function other medical co-morbidities mental state other Rx availability of oral/rectal routes In adults, age rather than weight is a better predictor of opioid requirements (although there is large inter-patient variation) Need to evaluate current analgesia (if applicable) - what patient was prescribed and what they are actually taking. Look for other sources of analgesia e.g. PCA, site perfusion devices etc. Titrate analgesia to patients needs – wide variability in patient response to pain (“emotional” experience) respiratory status (sleep apnoea, chronic lung disease) other Rx (e.g. antidepressants; analgesics; benzos) Safe Medication Practice Unit 14
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Assessment Pain History (LINDOCARRF) Location Intensity Nature
Duration Onset, Offset Concomitants Aggravating Relieving Radiating Frequency
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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”
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Principles of Analgesic Prescribing
Analgesic Ladder Adjuvants - TCA Anti-convulsants Anti-arrhythmic STEP 3 STEP 2 NSAID Non-opioid (paracetamol) Strong Opioid (morphine, oxycodone) Adjuvant Medication STEP 1 NSAID Non-opioid (paracetamol) Weak Opioid (codeine, tramadol) Adjuvant Medication NSAID Non-opioid (paracetamol) Adjuvant Medication
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Paracetamol Analgesic, antipyretic, Act centrally (PGs)
Not useful as an anti-inflammatory Few SE if taken at therapeutic doses Onset of effect min Dosing: 500 –1000mg QID Max 4g for adult
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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 23
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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”
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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
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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
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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
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Non-Steroidal Anti-inflammatory Drugs (NSAID)
Analgesic, antipyretic Anti inflammatory - several days dosing must dose constantly at least several days prn not 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
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NSAIDs- Adverse Effects
Side effects Cautions hypersensitivity/allergy GI (GORD/PUD) platelet inhibition sodium retention, oedema renal toxicity hepatic toxicity Platelet inhibition, but remember – COX-2 inhibitors INCREASE the risk of thrombotic events! GI bleeding/ulceration – risk NOT reduced by use of enteric coated or rectal dosage forms. Use a proton pump inhibitor to minimise risk of GORD/PUD Safe Medication Practice Unit 29
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NSAIDs- Adverse Effects
Side effects Cautions hypersensitivity/allergy asthma GI (GORD/PUD) GI bleeding/ulceration platelet inhibition coagulation disorders warfarin therapy sodium retention, oedema hypertension cardiac failure ACEI/ARA/diuretics renal toxicity renal impairment gentamicin therapy hepatic toxicity hepatic impairment Platelet inhibition, but remember – COX-2 inhibitors INCREASE the risk of thrombotic events! GI bleeding/ulceration – risk NOT reduced by use of enteric coated or rectal dosage forms. Use a proton pump inhibitor to minimise risk of GORD/PUD Safe Medication Practice Unit 30
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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! Little difference in efficacy between NSAIDs (choice depends on individual response and tolerance) children - no aspirin < 2 y.o. and avoid < 18 y.o. in viral illness (Reye’s syndrome) elderly - increased risk of adverse effects (esp. in heart failure, GI ulceration; renal impairment) Safe Medication Practice Unit 31
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Where do Opioids Act?
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How do Opioids Act? CNS and PNS
Interact with specific cell-surface receptors in CNS and PNS other tissues (GIT, immune cells, other tissues) 2nd messenger systems G-proteins G-protein
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Pharmacological Effects of Opioid Agonists
Desired Action – analgesia Unwanted actions Analgesic tolerance physical dependence Respiratory depression Nausea, vomiting sedation Tolerance often develops
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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
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Opioids – Precautions hypotension, shock concomitant CNS depression
impaired respiration /↓ respiratory reserve elderly hepatic impairment renal impairment epilepsy/recognised seizure risk biliary colic or surgery hypotension, shock —reduced blood volume increases hypotensive risk. impaired respiration/↓ respiratory reserve – respiratory depression. elderly; infants ≤ 12 months hypoxia; hypercapnia; cor pulmonale acute/severe asthma; COPD avoid opiates during acute asthma attack — opioids depress respiration and cough reflex and dry secretions elderly (increased risk of cognitive impairment and falls) - ↓ dose phaeochromocytoma - pressor response 2o to histamine release (no histamine release with fentanyl) hepatic impairment - severe hepatic disease may precipitate coma (↓ dose) renal impairment - active/toxic metabolites accumulate (↓ dose/use fentanyl or oxycodone) epilepsy/recognised seizure risk - increased risk of seizure head injury; metabolic disorders; EtOH/drug withdrawal; CNS infections; CNS depressants (eg. hypnotics) (CNS depression) biliary colic or surgery (spasm of sphincter of Oddi) Safe Medication Practice Unit 36 12
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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
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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
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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)
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Oral Morphine equivalent
DRUG DOSE x CONVERSION FACTOR Pethidine (oral) Pethidine (IV) x 0.125 x 0.4 Methadone x 1.5 Oxycodone Buprenorphine x 50 Codeine x 0.16 Dextropropoxyphene x 0.1 Morphine (IV) Morphine (oral) x 3 x 1 Oral Morphine equivalent * 100mg tramadol ~ 60mg codeine ~ 10mg oral morphine
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Adjust dose in renal impairment
Drug / action Duration of action Active metabolites Adjust dose in renal impairment Codeine (A) 3-4 Morphine Yes Dextropropoxyphene (A) 4-6 Nordextropropoxyphene (toxic) Fentanyl (A) 0.5-2 (iv) No no Hydromorphone 2-4 hydromorphone-3-glucuronide (H3G - toxic) yes Methadone (A) Variable (>24hr) Morphine (A) 2-3 CR/SR 12-24 morphine-6-glucuronide (M6G), morphine-3-glucuronide (M3G – toxic) Oxycodone (A) oxymorphone Pethidine (A) 2–3 norpethidine (CNS +++) yes; contraindicated Tramadol (A) 3–6 desmethyl tramadol Buprenorphine (partial agonist) 6–8 norbuprenorphine Reference: AMH
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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 In acute pain setting, regular is preferred over just PRN. PRN prescribing is for when pain is possible but not predictable. In most post-op settings, pain is predictable. Regular analgesia should be given and then PRN analgesics can be used to manage breakthrough pain. A vicious cycle can occur if doctors don’t initially prescribing enough or adjust doses to individual patient needs: nurses give lower dose (if range prescribed) and less frequently, because PRN is translated as “when requested by patient”. patients don’t ask for medication because they don’t want to bother busy staff, so try to hold out. patients not regularly assessed for pain delays in administering analgesia promote anxiety in the patient and emotion is a part of the pain experience. Unfounded fears of giving too much/overdose or causing addiction. Evaluate PRN analgesic use and assess whether regular analgesia should be increased. Safe Medication Practice Unit 42 5
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Tramadol (Tramal) 1st - opioid effects similar to morphine (mu)
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 of NA / 5-HT descending pain inhibitory pathway Hepatic Metab. Via CYP 2D6 (P450) similar to codeine
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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)
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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) 45
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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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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)
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TREATMENTS FOR NEUROPATHIC PAIN
Antidepressants Anticonvulsants Opioids Topical agents Eg. CBZ Gabapentin pregabalin Eg. Tramadol oxycodone Eg. Lidocaine patch Capsaicin Eg. Amitriptyline Desipramine paroxetine
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Inflammatory e.g. rheumatoid arthritis
DRUGS PAIN TYPE Nociceptive e.g. fracture Neuropathic eg neuralgia Inflammatory e.g. rheumatoid arthritis Paracetamol Effective when taken regularly at max. dose Less effective Effective, but not anti-inflammatory Opioids Effective May be effective (agent + dose) (depends on dose) NSAIDs Not effective TCAs, parenteral, local anaesthetics antiepileptic Rarely used (clonidine may be effective as adjunct) Rarely used (may be effective as adjunct) Adapted from Table 3-1, Australian Medicines Handbook Adapted from Table 3-1, Australian Medicines Handbook Different pharmacological groups of analgesics effective for different types of pain. Again, must take people through this in question and answer format. Safe Medication Practice Unit 49
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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
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Monitoring – making it work
Frequent assessment is essential Important to maintain communication with Doctor, patients, carers Nursing staff and pharmacist …… Monitor for response to therapy Include increase in need Change in pain “type” or “origin” Change in severity ADR / SE Esp. laxatives with opioids
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Key Messages individualise analgesic therapy
choose analgesics judiciously use multimodal analgesia regular pain monitoring is critical to outcomes regularly review and revise analgesic doses adjust regular dose according to breakthrough usage anticipate and manage analgesic-associated adverse events avoid NSAIDs – major cause of morbidity/mortality! avoid tramadol, dextropropoxyphene, pethidine
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Questions?
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