Transcript Chronic Low Back Pain

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.
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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
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