Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Pharmacotherapy Eric J. Visser Lets review the drug cupboard Paracetamol Does it work? Not sure how paracetamol works? - COX-2, ‘cannabinoid’, serotonin? Mainstay analgesic in most chronic pain protocols Not much good for MSS pain? - exception: older patients? Adverse effects (liver, warfarin; NSAID-like?) Rx for acute LBP - especially as combination drug with NSAID/coxib, tramadol, codeine (NNT 3) Machado GC et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ 2015 Mar 31;350:h1225. doi: 10.1136/bmj.h1225. Tramadol Good for acute & chronic LBP 1/3rd opioid, 1/3rd SSRI (serotonin), 1/3rd SNRI (nor adrenaline) 1st line for acute & chronic LBP (NNT 4) Effective for neuropathic pain (NNT 4) ↓ Respiratory depression & constipation OK with TCAs, SSRIs, SNRIs; ‘sensible doses’; no seizures Accumulates in renal impairment Pro-drug, 11 active metabolites Won’t work in 10% of patients (like codeine, cytochrome P450 2D6) Tapentadol SR Like tramadol without the serotonin ‘Weak’ opioid (S8) & NARI in one molecule -noradrenaline is main pain-inhibiting neurotransmitter 2nd line for chronic pain? Effective in nociceptive & neuropathic pain (NNT 4) ↓ Constipation ↓ Side effects than tramadol? Minimal accumulation in renal impairment OK with TCAs, SSRIs, SNRIs Tapentadol SR 50 mg ~ 10 mg oxycodone po ~ 20 mg morphine po NSAIDs & coxibs Effective (NNT 3) Rapid-acting formulations ARE better Rx acute pain flare-ups (days-fortnight) Do NOT use long-term for chronic pain Renal & gastric risk (NSAIDs) (PPI) Hypertension & cardiovascular risk Naproxen-best cardiovascular risk (MI) Celecoxib-best overall risk profile (gut, bleeding, CVS) Antidepressants & anticonvulsants TCAs: NOT effective for CLBP Duloxetine (SNRI): moderately effective - chronic LBP - neuropathic pain (NNT 4) (radicular leg pain?) Gabapentinoids (pregabalin, gabapentin) Not effective for LBP Radicular leg pain? (noradrenaline effect) Opioids for CLBP? Opioids don’t work well in CLBP (NNT = 8, NNH = 4) (Level I) Adverse effects (tolerance, hyperalgesia, overuse, addiction) Poor risk vs benefit Opioids ‘contraindicated’ in CNSLBP (especially < 60s) Consider in > 60s with spondylosis (more side effects?) Opioid prescribing is always an ongoing therapeutic trial (90 days) 3Ts: tramadol SR, tapentadol SR, transdermal buprenorphine Ceiling dose is ≤ 90 mg oral morphine equivalents/day (no more) Chaparro LE et al. Opioids compared with placebo or other treatments for chronic low back pain: an update of the Cochrane Review. Spine (Phila Pa 1976). 2014 1;39(7):556-63. 8 Transdermal buprenorphine patch Mu partial agonist, kappa antagonist No ceiling effect for analgesia Use it like any other opioid Safer respiratory profile Safer renal profile (no accumulation) Better dose control....only 1 patch per week What about Bob? Above the ceiling dose Bob has ‘’opioid non-responsive pain’’ Taper & cease Opioid rotation - tapentadol (wean morphine slowly-may get withdrawal) - oxycodone/naloxone CR - transdermal buprenorphine patch Radicular (neuropathic) leg pain Analgesics don’t work? (level I) TCAs, opioids & NSAIDs don’t work Pregabalin? Duloxetine? 2nd line, tramadol SR or tapentadol SR 3rd line, transdermal buprenorphine Oral steroids? Natural history; improvement in 3-6 months Pinto RZ et al. Drugs for relief of pain in patients with sciatica: systematic review and meta-analysis. BMJ. 2012 Feb 13;344:e497. doi: 10.1136/bmj.e497. Acute-on-chronic LBP flare-ups Rx as per acute LBP guidelines Comfort measures (heat) Continue baseline analgesia Celecoxib 100-200 mg bd for ≤ 4 days? Paracetamol w/ tramadol IR (or codeine?) prn Short-term IR opioid? (oxycodone) (≤ 4 days) Orphenadrine (?) or baclofen for muscle spasms (avoid diazepam) Four-hour rule for prn analgesia: ≤ 4/24 prn, ≤ 4 x daily, ≤ 4 days Summary An inconvenient truth Pharmacotherapy: part of a multimodal pain Mx approach Not much works for CLBP or radicular leg pain Avoid opioids in CNSLBP (HARM > help) - consider in > 60s with spondylosis; or spondylitis - 3Ts: tramadol, tapentadol, transdermal buprenorphine - opioid ceiling dose = 90 mg oral morphine/eq per day - ‘opioid-non responsive pain’ (taper & cease, opioid rotation) Radicular pain: pregabalin, duloxetine, tramadol, tapentadol? Acute pain: celecoxib, paracetamol-combo prn Start low & go slow (↓ side effects) Thank you Pharmacotherapy for chronic NSLBP Learning objectives Pharmacotherapy must always be part of a multimodal pain Mx approach CLBP is often a ‘mixed’ pain (nociceptive & neuropathic pain elements) Analgesics are NOT that effective for CLBP Analgesics are NOT that effective for radicular leg pain Opioids are (essentially) contraindicated in CNSLBP (especially in < 60s) Exceptions: > 60s with ‘degenerative’ spinal pain (spondylosis), or patient w/ ‘inflammatory spinal pain’ (spondylitis) Preferred opioids, 3Ts: tramadol, tapentadol, transdermal buprenorphine Mx acute-on-chronic LBP flare-ups (multimodal, COX-2, paracetamol-analgesic combo) Avoid benzodiazepines Always titrate medications: ‘’start low and go slow’’ Adverse effects of long-term opioids Classical side effects (respiratory, sedation, dizziness, nausea, constipation) Overuse (chemical-coping, addiction) (+ reward centre, dopamine) Opioid-induced hyperalgesia & tolerance (the pain gets worse) Endocrine changes (testosterone, osteoporosis) Immune modulation (activates glia via Toll-like receptors) Cortical changes on fMRI (cognitive, anxiety, mood, motivation) Increased all cause mortality Poor QoL, social & health outcomes >150mg oral morphine equivalents per day = really bad outcomes Visser MED 200 UNDA pain pharmacology 2015 16