step by step approach in patient with low back pain...diclofenac: mekanisme kerja perifer dan...
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Step by Step Approach in Patient with Low Back Pain
Dr. dr. Rizaldy Pinzon, MKes, SpS
RS Bethesda/ FK UKDW Yogyakarta
Email: [email protected]
Curiculum vitae
• S1 : FK UGM
• S2 : FK UGM
• Spesialis FK UGM
• S3 : FK UGM
• Pengajar S2 UGM dan FK UKDW Yogyakarta
• Dokter spesialis saraf RS Bethesda Yogyakarta
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Transduction: convert stimuli (thermal, mechanic, chemical) into electrical activity at peripheral sensory of nociceptor nerve.
Conduction: conduct action potential from peripheral terminal axon to terminal nociceptor at CNS.
Transmission: transfer among synapse & modulate inputs among neuron.
Modulation: inhibit & facilitate from brain which modulate nociceptive transmission at spinals.
Perception: impulse is ‘translated’ at higher structures (CNS)
Mechanism of Pain
COX, cyclooxygenase; PG, prostaglandin; TxA2, thromboxane A2. *Red text indicates involvement in inflammation.1McLain et al. Spine J 2005;5:191-201; 2Funk CD. Science 2001;294:1871-5; 3Miller SB. Semin Arthritis Rheum 2006;36:37-49; 4Khanapure et al. Curr Top Med Chem 2007;7:311-40.
Cell membrane phospholipids
Phospholipases
Arachidonic acid
5-Lipoxygenase
Leukotrienes
Prostaglandin G2 (PGG2)
Prostaglandin H2 (PGH2)
*Vasodilation,inhibits platelet aggregation
*Vasodilation, increased vascular permeability,hyperalgesia
*Vasoconstriction promotes platelet aggregation
Tissue injury Disc injuryNerve injury
BradykininInterlukin-1Serotonin,
Norepinephrine
COX-1 COX-2
Inflammation and pain
*VasoconstrictionIncrease vascular permeability
Effects
Prostacyclin (PGI2)
Prostaglandin D2(PGD2)
Prostaglandin E2 (PGE2)
ThromboxaneA2 (TXA2)
Mediators
Types of injury
Mediators of Inflammation and Pain1-4
Cyclooxygenase
Mechanism of Pain
HIV, human immunodeficiency virus; IBS, inflammatory bowel syndrome.1Melnikova I. Nat Rev Drug Discov 2010;9:589-90.
Pain
Acute Chronic
Nociceptive NeuropathicVisceral Mixed
Osteoarthritis
Rheumatoid arthritis
Central Peripheral
Internal organ involvement
IBS
Lower back
Cancer
Fibromyalgia
Post-stroke Diabetic neuropathy
Injury
Post-operative pain
Spinal cord injury
MigraineHIV-related
neuropathic pain
Post-herpetic neuralgia
Gout
Ankylosing spondylitis
Dysmenorrhea
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Lower Back
Types of Pain
• Pain lasting <30 days1
• Sudden onset• Severe in intensity• Pain plus anxiety
Acute Pain
• Arises as a result of tissue injury that stimulates nociceptors and generally disappears when the injury heals1
• Treatment includes NSAIDs (mainstay of therapy), opioids, and local anesthetic analgesics3
Chronic Pain
• Pain lasting >3 months1
• Persists although the original cause is not clearly present2
• May be the result of inadequately treated acute pain2
• May recur due to the presence of noxious stimuli or repeated exacerbation of injury1
• Affects lifestyle, attitudes, and behavior2
• Treatment includes acetaminophen, NSAIDs, selective COX-2 inhibitors, opioids3
NSAIDs, non-steroidal anti-inflammatory drugs; COX-2, cyclooxygenase-2.1WHO guidelines on the pharmacological treatment of persisting pain in children with mental illnesses. 2012; 2Thomas
MA. Oschner J 2003;5:15-21; 2http://www.npcnow.org/system/files/research/download/Pain-Current-Understanding-of-
Assessment-Management-and-Treatments.pdf. Accessed July 15, 2015; 3Breivik H et al. Br J Anaesth 2008;101:17-24.
Acute vs Chronic Pain
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Classification of Pain
Step by step approach
Classification of lower back pain, by duration3:
Acute: Lasts <4 weeks
Sub-acute: Lasts 4-12 weeksChronic: Lasts > 12 weeks
A debilitating, recurrent, and highly prevalent condition1
- Lifetime prevalence, 84%- 1-year prevalence, 50%- Point prevalence, 25%
Incidence peaks in the third decade of life2
Prevalence increases until age 60-65 years, and then gradually declines2
Mixed pain is common
1Morlion B. Nat Rev Neurol 2013;9:462-73; 2Golob A and Wipf JE. Med Clin N Am 2014;98:405-28;3Chou R. Ann Intern Med 2014;ITC1-16.
Low Back Pain: Epidemiology
McCarberg, 2010; Swarm et al, 2004
Etiology
Mechanic non-specific:
• Lumbar strain/sprain, • Ligament strain• Lumbago • Facet joint syndrome,
sacroiliac syndrome, • Myofascial syndrome
Non-mechanic potential:
• Neoplasm, • Infections, • Arthritis.
Nerve compression, visceral organs disorders (referred pain)
Kasus
• Ibu Wati, 44 tahun, nyeri punggung bawah tidak menjalar ketungkai,karakteristik: kemeng/pegal, nyeri intensitas ringan-sedang, NPS: 3-4, memberat bila membungkuk, nyeri bertambah saat bekerja, membaik bila istirahat, sejak 2 minggu lalu, tidak memberat
• Tidak ada riwayat trauma yang signifikan
• Tidak ada kelemahan anggota gerak
• Apa yang harus saya tanyakan ?
• Apakah saya harus menyingkirkan penyakit yang serius ?
Esesmen nyeri pada LBP
Pain Scales
Valid and reliable assessment of pain is essential for effective pain management1
0-10 Numeric Pain Intensity Scale2 Visual Analog Scale2
0No pain
10Highest imaginable
pain
Verbal Pain Intensity Scale2
Due to variability in purpose, content, method of administration, respondent and administrative burden, and evidence to support the psychometric properties of each measure, no single pain measure can be
recommended for use in all situations3
1Breivik H et al. Br J Anaesth 2008;101:17-24; 2Hague M and Shenker N. Best Pract Res Clin Rheum 2015; [Epub ahead
of print]; 3Hawker GA et al. Arthritis Care Res 2011;63:S240-52.. 17
Faces Pain Scale2
Assessment of Pain: intensitas nyeri
Penyebab
KasusBu Wati: nyeri akut, non spesifik, ringan-sedang, red flags (-)
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Benefits and Risks of Pharmaceutical Therapy in pain management
Paracetamol – risk but no evidence of benefit1-3
• No good evidence of efficacy in any chronic pain condition• Increased risk of liver damage compared with NSAIDs
NSAIDs – risk, with evidence of benefits4-9
• Largest known risk with traditional NSAIDs is gastrointestinal• Cardiovascular risk is modestly elevated in RCTs, but not in longitudinal studies• Other risks include renal failure; therefore, NSAIDs should be avoided in patients with low eGFR• 49-59% of patients on NSAIDs have moderate pain improvement• 39-44% of patients on NSAIDs have substantial benefit
Opioids – risk, but doubtful evidence of benefit10-13
• Tramadol has marginal benefits and side-effects may be limiting in OA• NSAIDs and coxibs have lower rates of significant harm than opioids in large matched cohorts• No trials of traditional opioids have shown benefits in chronic non-cancer pain• Drop-out rates can be high, up to 65% in 12-week studies
eGFR, estimated glomerular filtration rate; NSAIDs, non-steroidal anti-inflammatory drugs; OA, osteoarthritis; RCTs, randomized controlled trials.1Towheed TE et al. Cochrane Database Syst Rev 2006;CD004257; 2Machado GC et al. BMJ 2015;350:h1225; 3Moore RA et al. Eur J Pain 2014; [Epub ahead of print]; 4Moore RA. BMC Musculoskel Dis 2007;8:73; 5Rodriguez LAG et al. Arthritis Res Ther 2001;3:98-101; 6Coxib and traditional NSAID Trialists’ (CNT) Collaboration.Lancet 2013;382:769-79; 7Mangoni AA et al. Br J Clin Pharmacol 2010;69:689-700; 8Gutthann SP et al. Arch Intern Med1996;156:2433-9; 9Moore RA et al. Ann Rheum Dis 2010;69:374-9; 10Cepeda MS et al. Cochrane Database Syst Rev 2006;CD005522; 11Solomon DH et al. Arch Int Med 2010;70:1968-78; 12Moore RA et al. Pain 2013;154:S77-86; 13Lange B et al. Adv Ther 2010;27:381-99.
Drug treatment choices
2121
Inadequate Pain Management
The present analysis was conducted on the data from 1305 patients. The median duration of CNCP was 24 (interquartile range [IQR], 39) months. The mean pain level on the BS-11 scale was 6.0 (SD 1.9), with the majority of patients reporting moderate (44.4%) or severe pain (44.9%) at the time of the survey. The most common causes of pain were arthritis (33.3%) and poor posture(27.6%).
Patients who experienced any common AE weremore likely to find their pain treatments inadequate than those who did not (32.4%). p < 0.0001
employed were also more likely to find their treatment inadequate compared with those who were unemployed (31.7%). p = 0.007
Effective chronic pain management aims torestore function and reduce pain intensity
Substantial number of patients who receiving pain treatment still reported having moderate-to-severe pain, 20% of patients did not receive analgesic treatment despitemoderate-to-severe pain
Cheung Chi Way et al. SN Comprehensive Clinical Medicine. 2019;1:442–450
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Pharmacological
COX-2, cyclooxygenase-2; CLBP, chronic low back pain; LBP, low back pain; NSAIDs, non-steroidal anti-inflammatory drugs.Morlion B. Nat Rev Neurol 2013;9:462-73.
• Paracetamol: First-line therapy for acute LBP and CLBP
• NSAIDs: Non-selective (aspirin) and selective COX-2 inhibitors- Oral NSAIDs as first-line therapy for CLBP
• Opioids• Antidepressants: Duloxetine• Anticonvulsants: Gabapentin
and pregabalinMuscle relaxants: Benzodiazepines
Intervention Pain Management
• Epidural steroid injections• Facet joint interventions
Spine Surgery
• Spinal decompression surgery
• Spinal fusion surgery• Disc arthroplasty
Treatment Low Back Pain
Diclofenac: mekanisme kerja perifer dan sentral
Van der gaag WH, Roelofs PD, Enthoven WT, Van tulder MW, Koes BW. Non-steroidal anti-inflammatory drugs for acute low back pain. Cochrane Database Syst Rev. 2020;4:CD013581.
• 1 in 14 reduction in pain intensity
• 1 in 12 reduction in disability
• 1 in 13 global improvement
• NNT: jumlah pasien yang harusmendapat terapi untukmendapatkan pengurangan nyeri> 50% pada 1 pasien
• NNT kecil: semakin efektif
Selectivity of NSAIDs to COX2/COX1
• The ideal NSAID is more selective for COX-2 than COX-1, and achieves levels of COX-2 inhibition required to achieve pain relief while minimizing the harm
• Low-dose NSAIDs with short half-lives and dosing intervals of up to 8 hours could permit the recovery of vasoprotective COX-2 dependent prostaglandins
Diclofenac : preferentially COX2 inhibitor
Impact Selectivity of NSAIDs COX2/COX1
• Favour NSAIDs with favourable
tissue distribution and short
plasma half-lives
• Each patient’s clinical
background, including
gastrointestinal and
cardiovascular risk factors,
should be taken into account
when selecting appropriate
NSAIDs.
Diclofenac dan ibuprofen waktu paruh pendek
Methods: We enrolled lumbar facet syndrome patients treated at Srinagarind Hospital. Enrolled patients were randomly assigned
to receive 100 mg/day oral diclofenac, an 80 mg injection of methylprednisolone into each symptomatic facet joint, or both.
Endpoints were the Oswestry disability index (ODI) and visual analogue scale (VAS) before treatment, and at four and 12 weeks
after treatment.
Results: Of the 99 patients, the mean age was 46.4 years and 48 were men. The initial ODI (mean ±SD) for the diclofenac,
methylprednisolone and combined treatment was 45.1± 9.3, 42.9± 15.6, and 42.2± 11.5, respectively.
Lumbar facet joint syndrome is thought to be an important cause of low back pain. The prevalence of this condition ranges between 15 and 40 %.
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Diclofenac Effective Reducing Pain in Lumbar Facet Syndrome Patients
This prospective randomized trial is to determine the effectiveness of treating lumbar facet syndrome with oral diclofenac, methylprednisolone facet joint injection or both. We enrolledlumbar facet syndrome patients, were randomly assigned to receive 100 mg/day oral diclofenac, an 80 mg injection of methylprednisolone into each symptomatic facet joint, or both.Endpoints were the Oswestry disability index (ODI) and visual analogue scale (VAS) before treatment, and at four and 12 weeks after treatment.
Sae-Jung S., Jirarattanaphochai K. International Orthopedics (SICOT) (2016) 40:1091–1098.
12 weeks4 weeksInitial visit
Lumbar Facet Syndrome cause of Low Back Pain
Lumbar Facet Syndrome cause of Low Back Pain
Sae-Jung S., Jirarattanaphochai K. International Orthopedics (SICOT) (2016) 40:1091–1098.
Diclofenac effective improve Oswestry disability index (ODI) in lumbar facet syndrome patients
12 weeks4 weeksInitial visit
This prospective randomized trial is to determine the effectiveness of treating lumbar facet syndrome with oral diclofenac, methylprednisolone facet jointinjection or both. We enrolled lumbar facet syndrome patients, were randomly assigned to receive 100 mg/day oral diclofenac, an 80 mg injection ofmethylprednisolone into each symptomatic facet joint, or both. Endpoints were the Oswestry disability index (ODI) and visual analogue scale (VAS) beforetreatment, and at four and 12 weeks after treatment.
Oral diclofenac alone or methylprednisolone facet injection alone can relieve facet joint inflammation, resulting in pain reduction.
The combination of oral diclofenac and methylprednisolone facet injection produces a better result (which showed significantly better function and pain relief results) than each treatment alone.
Background: Low back pain is an important medical problem in Western industrialised countries. NSAIDs are one of the main options
for symptomatic pain relief in the early management of this painful condition.
Methods: A randomised, double-blind, parallel, active controlled, multicenter study that included 370 outpatients with acute low back
pain was conducted to compare the analgesic efficacy of dexketoprofen 50mg twice daily versus diclofenac 75mg twice daily
administered intramuscularly for 2 days.
Results: The median change in the RDQ was –6 points for both groups (p = 0.69), showing an overall improvement on the disability
scale. No significant differences between groups were observed regarding the percentage of patients needing rescue medication or in
the mean values of pain after repeated doses (SAPID0-last).
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Diclofenac Injection effective reducing pain in acute Low Back Pain
Acute Low Back Pain
A randomised, double-blind, parallel, active controlled, multicenter study that included 370 outpatients with acute low back pain was conducted to compare the
analgesic efficacy of dexketoprofen 50mg twice daily versus diclofenac 75mg twice daily administered intramuscularly for 2 days. Efficacy outcomes were
assessment of pain intensity (PI) measured on a visual analogue scale, total PI scores from baseline to 6 hours after the first-dose administration (primary efficacy
endpoint; SAPID0-6), score on a physical disability scale using the Roland Disability Questionnaire (RDQ), and use of rescue medication. Tolerability and safety were
also assessed as secondary variables.
Zippel H and Wagenitz A. Clin Drug Invest. 2007;27(8):533-543.
Acute episodes of low back pain lasting <3 months (90% of cases) are usually benign and self- limiting (90% of people recover within 6 weeks), although 2–7% of subjects develop chronic pain.
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Background: The vascular and gastrointestinal eff ects of non-steroidal anti-infl ammatory drugs (NSAIDs), including selective COX-2
inhibitors (coxibs) and traditional non-steroidal anti-infl ammatory drugs (tNSAIDs), are not well characterised, particularly in patients at
increased risk of vascular disease. We aimed to provide such information through meta-analyses of randomised trials.
Methods: We undertook meta-analyses of 280 trials of NSAIDs versus placebo (124 513 participants, 68 342 personyears) and 474
trials of one NSAID versus another NSAID (229 296 participants, 165 456 person-years).
Results: The proportional effects on major vascular events were independent of baseline characteristics, including vascular risk. Heart
failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications (coxibs 1·81, 1·17–
2·81, p=0·0070; diclofenac 1·89, 1·16–3·09, p=0·0106; ibuprofen 3·97, 2·22–7·10, p<0·0001; and naproxen 4·22, 2·71–6·56, <0·0001).
• Meta-analysis of individual subjects are taken from NSAID RCts of 4 weeks or longer duration.
• CV risks were also evaluated. For full reference please refer to doi :0.1016/S0140-6736913)60900-9.
Diclofenac has equal GI risk compared to Coxibs and lower compared to ibuprofen and naproxen.
• Meta-analysis of individual subjects are taken from NSAID RCts of 4 weeks or longer duration.
• CV risks were also evaluated. For full reference please refer to doi :0.1016/S0140-6736913)60900-9.
Comparative ratio to Placebo (95%CI)
Coxib and traditional NSAID Trialists' (CNT) Collaboration, Lancet. 2013;382(9894):769-779.
Favors therapy Favors placeboFavors therapy Favors placebo
Favors therapy Favors placebo Favors therapy Favors placebo
Gastrointestinal Risk
Meta-analysis from 280 NSAID studies vs. placebo and 474 NSAID vs other NSAID. Meta-analyses included are RCTs, duration of at least 4 weeks. Data analysis were done using three methods: trial identifications, feasibility evaluation, prespecified analysis, and statistical analysis. Almost all of the studies (~99%) involves coxibs or high-dose NSAIDs (diclofenac 150 mg/day, ibuprofen 2400 mg/day, or naproxen 1000 mg/day).
Kesimpulan
• Nyeri punggung bawah umum terjadi
• Proporsi terbesar adalah nyeri non spesifik
• NSAID adalah pilihan terapi farmaka utama
• Perhatikan 3 M:
• Multi disciplinary
• Multi mechanistic analgesia
• Multi modal analgesia
• Diclofenac adalah salah satu pilihan NSAID utama dengan profilefektivitas dan keamanan yang baik