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
Role of the pharmacist / other health professionals 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 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 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 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 Acute pain (e.g. sprain, surgery) of limited duration related specifically to an event or trauma bodies natural healing process Palliative Care 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 selfesteem issues +++ components of both e.g. incident pain, disease progression Acute Pain Chronic Pain
Acute post 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 operative pain Sprains and strains Sports injuries Period pain Headaches Toothache / dental Neuropathic Pain
Pain Scales Pain severity usually subjectively measured: 1. categorical scales (none worst ever) 2. numbered scales or 3. 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 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 Principles of Analgesic Prescribing Analgesic Ladder Adjuvants - STEP 3 TCA
Medication Adjuvant Medication NSAID Empirical Pain Management Analgesic ladder NOT always appropriate Empirical therapy sometimes more appropriate - palliative care e.g. metastatic bone pain initiate opiate,
dont 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 Paracetamol Analgesic, antipyretic, acts centrally (role PGs) Not useful as anti-inflammatory Few side 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 (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 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 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: together paracetamol & NSAID used How do they work? - NSAID v COX2
support platelet function Coxibs prostaglandins Primarily protect GI mucosa Primarily mediate inflammation, pain & fever NSAID
Analgesic, antipyretic Anti inflammatory - 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 NSAIDs- Adverse Effects Side effects
Cautions hypersensitivity/allergy - asthma GI (GORD/PUD) - GI bleeding/ulceration platelet inhibition - coagulation disorders
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, Reyes syndrome elderly - increased risk of adverse effects Continue only if effective. Avoid if possible! 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. Where do Opioids Act? Brain Opioids
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 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 Morphine the gold standard cleared renally dose if CrCl < 30 mL/min 70% metabolised (oral bioavailability = 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
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 Fentanyl PATCH Morphine equivalent to Fentanyl patches (BNF) Morphine oral (24 hours dose)
- 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! 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? 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 24hour morphine requirement for maintenance dosing. 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. 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
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 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 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? 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). 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
Opioid comparative information When changing opioid, start at 50% of the approximate equianalgesic dose; then titrate according to response Drug Approximate dose equivalent to 10 mg IM/SC morphine codeine 120130 mg SC/IM; 200 mg oral
fentanyl 100150 mcg SC morphine 30 mg oral tramadol 100120 mg IM/IV; 150 mg oral 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. 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 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 dont ask for medication inadequate or infrequent dosing unrelieved pain
keeping up with pain is easier than catching up with pain 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 Neuropathic Pain Can be due to central or peripheral component
Opioids not particularly effective May be lancinating (shooting, stabbing) non-lancinating (dull, aching) burning (dysesthesia) TREATMENTS FOR NEUROPATHIC PAIN Antidepressants Anticonvulsants Opioids Eg.
agents Eg. Lidocaine patch Capsaicin Miss Claire Davies 47yo woman Weight 55kg PC: Appendicitis (perforated) HPC: Vomiting for 2 days, abdominal pain, fever for 24hours Pain relief: Morphine CR 20mg BD, Ibuprofen 400mg tds for 3 days
Time for discharge Lets discuss discharge analgesics Are the medications prescribed appropriate? What extra medications should be considered? What else do we need to know for discharge? Role of the Pharmacist When reviewing Prescriptions think about.. Regular dosing of pain medications more effective
than prn or intermittent Dosage formulations crushing, breaking scored SR/ CR Provision of breakthrough medication Managing SE for eg recommend laxatives at outset of tx Interactions .. aware of OTC / complementary or traditional ayurvedic medicines Monitoring Frequent re-assessment is essential Important to maintain communication with other HCPs patients, carers Nursing staff & pharmacist to monitor response to tx
Communicate if increased analgesic need Change in pain type or origin Change in pain severity ADR /SEs 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
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