Transcript NSAIDs

Update guidelines for
the treatment of
chronic musculoskeletal pain
경희대학교
류마티스내과
홍승재
Introduction
• Chronic rheumatic pain
- major and growing burden on today’s aging populations
- prevalence of musculoskeletal pain
: increases with rising age
- back pain and arthritis : most common causes of pain
• Appropriate and up-to-date guidelines
- to optimize care for the large, and growing, population of
patients with chronic musculoskeletal pain
Chronic pain by age and type
30%
3,605 people in
Grampian, Scotland
20%
Arthritis
Back pain
10%
Angina
0%
25-34 35-44 45-54 55-64 65-74 >75
Age group
Elliot et al. Lancet 1999;354:1248–52.
Arthritis is a Leading Cause of Disability
Arthritis
17.5%
16.5%
Back or Spine
7.8%
Heart Trouble, Hardening of the Arteries
Lung or Respiratory
4.7%
Deafness or Hearing
4.4%
Limb/Extremity Stiffness
4.2%
Mental or Emotional
3.7%
Diabetes
3.4%
Blindness or Vision
3.3%
About 39 million physician visits/ yr1
More than 500,000 hospitalizations/ yr1
2.8%
Stroke
0
2
4
6
8
10 12 14 16 18
% All Disabilities
Census data for 1999. CDC. MMWR Morb Mortal Wkly Rep. 2001;50:120-125.
1 CDC, Arthritis Foundation. National Arthritis Action Plan: A Public Health Strategy. 1999.
Preferences for improved health
examined in 1,024 patients with RA
: Pain has highest priority
Pain
Hand and Finger Function
68.6%
44.6%
Walking and Bending
33.3%
Household Tasks
25.1%
Mobility
23.9%
Arm Function
18.5%
Mood
17.3%
Social Activity
13.2%
Self-care
11.9%
Work
n=1,024 RA patients
9.0%
0
20
40
60
Responders (%)
Heiberg et al., Arthritis & Rheum. 2002;47:391-7.
80
Biopsychosocial Model of Pain
PAIN
Biological
Factors
• Disease activity
• Overall physical
condition
• Medication intake
Psychological
Factors
• Pain behavior
• Pain coping
• Self-efficacy
• Helplessness
• Cognitive distortion
• Personality
characteristics
Social
Factors
• Social support
• Marital
adjustment/spousal
responses
• Children: Parental
responses
• Cultural practices
F. Keefe and V. Bonk, Psychosocial Assessment of Pain in Patients in Patients Having Rheumatic Diseases, 1999 Rheumatic
Disease Clinics of North AMERICA. 25, p. 82
Pathogenesis of joint pain in OA
Lancet 2005; 365: 965–73
Pain pathway
1. Transduction
2. Transmission
3. Modulation
4. Perception
Current status of treatment guidelines
• In 2000, American College of Rheumatology (ACR)
• In 2002, American Pain Society (APS)
• In 2003, European League Against Rheumatism (EULAR)
?
• In 2006, Working group on pain management (WGPM)
• In 2008, Osteoarthritis research society international (OARSI)
Current status of treatment guidelines
Pharmacologic therapy for osteoarthritis – ACR 2000 Update
• Oral
Acetaminophen
COX-2-specific inhibitor
Nonselective NSAID plus misoprostol or a proton pump inhibitor**
Nonacetylated salicylate
Other pure analgesics
Tramadol
Opioids
• Intraarticular
Glucocorticoids
Hyaluronan
• Topical
Capsaicin
Methylsalicylate
Arthritis Rheum 2000;43:1905-15
Current status of treatment guidelines
Pharmacologic therapy for osteoarthritis – ACR 2000 Update
Physical Measures – Patient Education
Medications
Arthritis Rheum 2000;43:1905-15
Anti-inflammatory
Analgesics
Intra-articular
NSAID plus PGE2/PPI
COX-2
Non-acetylated salicylate
Paracetamol
Depot steroids
Hyaluronate
Tramadol
Capsaicin
Opioids
Antispasmodics / Antidepressants / Sugars / Anthraquinone / Lipids
Surgery
Current status of treatment guidelines
Pharmacologic therapy for osteoarthritis – APS 2002
Simon LS, American Pain Society (APS), Glenview, IL, pp 179
Current status of treatment guidelines
Pharmacologic therapy for osteoarthritis – APS 2002
Simon LS, American Pain Society (APS), Glenview, IL, pp 179
Current status of treatment guidelines
EULAR recommendations for treating osteoarthritis - EULAR 2003
Non-pharmacological
Pharmacological
Intra-articular
Surgical
Education
Exercise
Insoles
Orthotic devices
Weight loss
Laser, Spa
Telephone
Vitamins/minerals
Pulsed EMF
Ultrasound, TENS
Acupuncture
Nutrients, Herbal remedies
Paracetamol
NSAIDs
Opioid analgesics
Sex hormones
SYSADOA
Psychotropic drugs
Topical NSAID
Topical capsaicin
Corticosteroid
Arthroscopy
Hyaluronic acid
Osteotomy
Tidal irrigation
UKR
TKR
EMF, electromagnetic field therapy; TENS, transcutaneous electrical nerve stimulation; NSAIDs,
non-steroidal anti-inflammatory drugs; SYSADOA, SYmptomatic Slow Acting Drugs for OA
(includes avocado/soybean unsaponifiables (ASU), chondroitin, diacerein and glucosamine);
UKR, unicompartmental knee replacement; TKR, total knee replacement.
Jordan KM, Ann Rheum Dis 2003; 62:1145-55
Current status of treatment guidelines
EULAR recommendations for treating osteoarthritis - EULAR 2003
• Tailor treatment according to:
Knee risk factors (obesity, adverse mechanical factors, physical activity)
General risk factors (age, co-morbidity, polypharmacy)
Level of pain intensity & disability
Sign of inflammation, e.g. effusion
Location & degree of structural damage
• Non-pharmacological treatment
• Paracetamol as first oral analgesic
• Topical applications (e.g., NSAIDs, capsaicin)
• NSAIDs in patients unresponsive to paracetamol.
: GI risk  NSAIDs with gastroprotective agents or COX-2 inhibitors
• Opioids±paracetamol
: NSAIDs, COX-2 inhibitors, are CIx, ineffective, and/or poorly tolerated
• SYmptomatic Slow-Acting Drugs in Osteoarthritis (SYSADOA)
• Flare of knee pain
: intra-articular injection of long-acting corticosteroid
• Joint replacement
: radiographic evidence of knee OA who have refractory pain & disability
Jordan KM, Ann Rheum Dis 2003; 62:1145-55
How to treat arthritis pain
•
•
•
•
•
•
Acetaminophen
NSAIDs
Tropical agents
DMARDs
Hyaluronic acid
Glucocorticosteroids
– Systemic
– Intra-articular
• Opioids
– Tramadol
• Analgesics for neuropathic pain
American Pain Society Guidelines for Osteoarthritis, Rheumatoid Arthritis, and
Chronic Juvenile Arthritis Pain Management
Mode of action of analgesics
Acetaminophen

Inhibition of central Cox-2 / Cox-3 (?)
(Inhibition of PG synthesis)
Opioids

Activation of opioid receptors
Acetaminophen

Interaction with serotoninergic
descending inhibitory pathway
NSAIDs

Inhibition of peripheral and central Cox-1
/ Cox-2 (Inhibition of PG synthesis)
.
Pini LA et al. JPET 1997;280(2):934-40.
Chandrasekharan NV et al. PNAS 2002;99(21):13926-31.
Acetaminophen
 Active metabolite of phenacetin
 Anti-inflammatory activity weak, no antiplatelet effect
NHCOCH3
Action mechanism
 Inhibition of NO synthesis in C fiber
 Inhibition of PG synthesis in CNS level
 May be inhibit the COX-2 variant or COX-3(?)
OH
Dosage and clinical efficacy
 Oral or rectal dose : 500-1000mg q 4-6 hrs up to 4 g/D
 The initial drug of choice to treat the OA (ACR guideline, 2000)
 Trials comparing with NSAIDs in knee OA or hip OA
NSAID treated pts greater improvement in resting and motion pain
(Bradely JD, 1992; Eccles M, 1998; Pincus, 2001)
‘‘Self-synergistic’’ Spinal/Supraspinal
Antinociception Produced by Acetaminophen
J Pharmacol Exp Ther 2000; 295: 291–4
Safety
 At recommended dosage, well tolerated, mild side effects
 not attack gastric mucosa nor affect platelet function
 In alcoholism or liver dis. develop severe hepatotoxicity
 Hepatic necrosis in acute over-dosage
: single dose over 25 g can be fatal
Strategy
 Low toxicity and low cost
 Ix. for mild pain, older pts with risk for peptic ulcer or
cardiovascular disease
 Frequently, combination with tramadol and opioids
 more effective in combination with codeine 60 mg
Dosages of NSAIDs used to OA Pain
Medication
Individual dosage and frequency usual daily dose
FDA Approved use
Acetaminophen
325-650mg(q4h)/650mg-1g(q.i.d.)
RA, OA, AS, JCA, ST
Aspirin
600-1,500mg(q.i.d.)
RA, OA, AS, JCA, ST
Diflunisal
500-750mg(b.i.d.)
RA, OA, AS, JCA, ST
Salsalate
750-1,500mg(b.i.d.)
RA, OA, AS, JCA, ST
Fenoprofen
300-600mg(t.i.d.)
RA, OA
Flurbiprofen
50-100mg(b.i.d.)
RA, OA
Ibuprofen
OTC:200-400mg(q.i.d.)
RA, OA, JCA
Ketoprofen
25-75mg(t.i.d.)
RA, OA
Naproxen
250, 375, 500mg(b.i.d.)
RA, OA, JCA, ST
Diclofenac
50mg(t.i.d.)/75mg(b.i.d.)
RA, OA, AS
Etodolac
200-300mg(b.i.d.~q.i.d.)max1,200mg
OA, pain
Indomethacin
25-50mg(t.i.d. or q.i.d.)
RA, OA, G, AS, JCA
Meclofenamate
50-100mg(t.i.d. or q.i.d.)
RA, OA
Mefenamic acid
250mg(q.i.d.)
RA, OA
Meloxicam
7,5mg OA(q.d.)/15mg RA(q.d.)
OA, RA
Phenylbutazone
100mg(t.i.d. up to 600mg)
Severe arthritis
Piroxicam
10,20mg(q.d.)
RA, OA
COX-2 selective
Celecoxib
100,200mg(q 12hr)/200mg(q.d.)
RA, OA, acute pain
Naphthylakanones
Nabumetone
500mg(b.i.d. up to 1.5g)
RA, OA
Carboxylic acid
derivatives
Propionic acid
derivatives
Acetic acid derivatives
Fenamates
Enolic acid derivatives
NSAIDs: Mechanism of Action
Arachidonic Acid
COX-2
Inducible
COX-1
Constitutive
NSAIDs
Coxibs
TXA2 in platelets
PGI2 in stomach
PGE2 in kidney
Cytokines:
IL-1, TNF
growth factors
LPS
Glucocorticoid
Cytokines:IL-4
PGE2 at inflammatory sites
PGE2 in macrophages
PGE2 in synoviocytes
Crofford et al. Arthritis Rheum 2001;43:4
Adverse reaction in NSAIDs
• Gastrointestinal - Nausea, vomiting, dyspepsia, diarrhea,
constipation, abdominal cramps
• Renal - Glomerulopathy, interstitial nephritis, alterations in renal
plasma blood flow
• Hematologic - Decreased platelet aggregation possibly leading to
bleeding, oozing gums, petechiae
• Central nervous system - Headache, dizziness, confusion,
hallucination, depersonalization reactions
• Hypersensitivity - Asthma, urticaria, rashes
• Respiratory - Bronchospasm, laryngeal edema, shortness of breath
• Cardiovascular – Increased BP, thrombosis(?)
Safety Issue of NSAIDs
 Risk of Death per 1,000,000 (Germany, 1996)
0.82
1-10
110
NSAID > 2 months : 820
NEJM, 1999; 340(24).
Current status
- risk of serious gastrointestinal (GI) complications
: 16,500 deaths each year in arthritis patients in the USA (ARAMIS)
VIGOR trial
Vioxx Gastrointestinal Outcomes Research (VIGOR)
연구 디자인
8,076 RA patients over 50 years of age
Rofecoxib 50 mg qd vs. Naproxen 500 mg bid
Double-blind, randomized, controlled trial
Aspirin taking patients were excluded
심근경색증 발생빈도
심혈관계 사망률
Naproxen vs.
Rofecoxib
0.1 % vs. 0.4 %
Naproxen vs.
Rofecoxib
0.2 % vs. 0.2 %
Cumulative Incidence of the Primary End
Point of a Confirmed Upper G-I Event
among All Randomized Patients.
 해석 ??
Bombardier C, N Engl J Med 2000; 343:1520–28
APPROVe trial
The Adenomatous Polyp Prevention on Vioxx (APPROVe) trial
연구 디자인
2,586 patients with a history of colorectal
adenomas.
1,287 receive 25 mg of rofecoxib daily, and
1,299 receive placebo
Double-blind, randomized, controlled trial
혈전증의 발생 위험도 – 1.92
Cumulative Incidence of the Primary End
Point of a Confirmed cardiovascular
events among All Randomized Patients.
Cardiac events : threefold
Cerebrovascular event : twice
Hazard ratio for CHF, pulmonary edema,
cardiac failure - 4.61
Bresalier RS, N Engl J Med 2005; 352:1092–102
APC trial
APC (Adenoma Prevention with Celebrex) trial
연구 디자인
2,035 patients with history of colorectal
neoplsia
Celecoxib 200 mg or 400 mg bid vs. placebo
Double-blind, randomized, controlled trial
Kaplan-Meier Estimates of the Risk of the
Composite End Point of Death from
Cardiovascular Causes, AMI, Stroke, or
Heart Failure among Patients Who Received
Celecoxib (200 mg Twice Daily or 400 mg
Twice Daily) or Placebo.
Solomon SD, NEJM 2005;352:1071-80
RCT of valdecoxib and parecoxib
Complications of the COX-2 Inhibitors
Parecoxib and Valdecoxib after Cardiac Surgery
연구 디자인
3 randomized groups; 1,671 patients
- 555 ; group given parecoxib and valdecoxib
- 556 ; placebo and valdecoxib
- 560 ; placebo group
혈전증의 발생 위험도
primary end point was the combined
incidence of predefined adverse
events in the following four clinically
relevant categories
Fourfold increase in CV events after
only 10 days of treatment.
Cardiovascular events:
parecoxib and valdecoxib vs. placebo,
2.0 percent vs. 0.5 percent
Nussmeier NA, NEJM 2005;352:1081–91
NSAIDs and CV events
Population-based, nested case-control study of 454 Scandinavian
patients diagnosed with oral cancer between 1975 and 2003, and
454 gender- and age-matched controls
Hazard ratio for CV death in long-term NSAID users compared with non-users
Sudbo J, Lancet 2005;366:1359–66
Oral Opioid Analgesics
Medication
Usual starting oral dose
for moderate to severe pain
Special Consideration
Not recommended because of
adverse side effects common
5-10mg q.i.d. hydrocodone
short-acting opioid
Short-Acting Opioid Agonists
Codeine
Hydrocodone and acetaminophen
Available only in combination with
APAP, aspirin, or ibuprifen
Hydrocodone and ibuprofen
Hydrocodone and aspirin
Hydromorphone
2-3mg q.i.d.
Short-acting opioid
Not recommended because of
potential CNS side effects
Very short-acting opioid
seizures when used for>2days
Morphine
7.5-15mg q.i.d.
short-acting opioid agonist
MS contin
30mg q 12h/30mg q 8h
Meperidine
Oxycodone
5-10mg q.i.d.
short-acting opioid
Long-Acting Opioid Agonist
Oxycodone
Hydrochloride-ER
10-20mg q 12 h
Controlled-release opioid
Adverse Effects of Opioids
Medication
Clinical significant
frequent adverse events
Codeine
Fentanyl,
Transdermal
GI, CNS
R, GI, CV, CNS
Hydrocodone and APAP
Hydrocodone and ibuprofen
Hydrocodone and aspirin
Hydromorphone
Tramadol
CV, CNS
CV, CNS, GI
CV, CNS, R, HY, O
Special Considerations
Not recommended for use
Adverse side effects common even at minimally effective
analgesic doses, constipation, drowsiness and nausea
Should be prescribed and monitored by persons
-> Not recommended for treatment of acute pain, may cause
severe hypoventilation
May have decreased BP, fast heartbeat, increased sweating,
redness or flushing of face, wheezing or troubled breathing;
dizziness
Dizziness and lightheadedness-especially in ambulatory
patients; drowsiness
Should not be used when following conditions present : acute
intoxicaiton with alcohol, hypnotics, centrally-acting
analgesics, opioid
Tramadol
Dose and efficacy
 centrally acting analgesic for moderate to severe pain
 dual effects (weak opioid and nonopioid properties)
- bind to μ,δ, opioid receptors
- inhibition of presynaptic reuptake of noradrenaline and serotonin
 50-100mg q 4-6 hrs, up to 400 mg/day
 efficacy shown in nociceptive pain & neuropathic pain
 Lower back and OA pain, fibromyalgia and diabetic neuropathy

Tramadol taken before sleep
 relieve nocturnal leg cramps effectively
Tramadol
Safety & Strategy




Side effects : nausea, vomiting, somnolence, dizziness
Recommended initial dosing of 25 mg/day
 incremental doses every 3 days, until the desired dose
Seizures
- seizure rate 1/106 use, long-time tramadol users
- Risk pts
: history of seizures, head trauma
: concomitant use of SSRI, TCA antidepressants, opioids
More effective when used with NSAIDs
by reducing the need for drug and adverse effect
Combination therapy
(Raffa RD, J clin phar thera, 2001)
Combined Rationale
Synergy in an Animal Model
– Isobologram of the analgesic effect
Acetylcholine-induced abd. constriction in mice
7
6
Tramadol
(mg/kg, po)
5
The Best Fit 1:8.667
1:3
4
1:1
3
Line of Additivity
1:5. 1:5.7
1:1
9
2
1
1:50
0
1:100
1:400
0
40
80
1:200
1:800
1:1600
120
Acetaminophen (mg/kg, po)
160
200
Analgesic Efficacy of combination
Pharmacokinetic/pharmacodynamic model
4
Pain Relief
probabilities
fd
3
Tramadol/APAP
2
APAP
1
Tramadol
0
0
2
4
6
8
10
Time, h
Relationship between the probability distribution of pain relief scores
to tramadol and APAP plasma concentration time profiles
Mechanisms of Action
* 3 Synergistic Mechanism
 Monoamine reuptake
inhibition(5-TH/NE)
 Opioid receptor binding
 NO production inhibition
Raffa RB, Journal of Clinical Pharmacy and Therapeutics 2001:26
Pharmacologic Management of Pain
in OA and RA
- Recommendation 8~16 8) 진통제와 항염제와 함께 영양공급, 물리치료, 교육, 인지-행동 중
재술을 동시에 시행하는 것이 좋다.
9) 임상의는 약제 선택에 있어서 효과, 부작용, 용량용법, 순응도와
비용을 고려해서 선택해야 함.
10) 경도의 통증에서 1차 선택약? Acetaminophen
Pharmacologic Management of Pain
in OA and RA
- Recommendation 8~16 11) 중증도~중증 통증이나 염증이 동반될 때?
 고혈압과 신장이상이 없을 때 : coxibs
 고혈압과 부종이 있을 때 : 기존의 NSAIDs를 주의하며 사용
 NSAIDs, including both non-selective and COX-2 selective
agents, should be used with caution in patients with CV risk
factors.
 All medications, including selective and non-selective NSAIDs
and acetaminophen have cardiovascular or/and cardiorenal
risks.
Zhang W et al. OARSI recommendations for the management of hip and knee OA,
Part II: OARSI evidence-based, expert consensus guidelines.
Osteoarthritis and Cartilage 2008 (Feb);16:137-62
Pharmacologic Management of Pain
in OA and RA
- Recommendation 8~16 12) 비선택적 NASIDs는 coxibs나 Acetaminophen (4g/d)에 반응이
없을 때만 사용. 이때 위장관 합병증 위험이 있다면 PPI나
misoprostol을 예방적으로 함께 처방.
 PPI or misoprostol 사용시 고려 사항

고용량 misoprostol에 대한 low tolerability

저용량 misoprostol에 대한 low efficacy

PPI의 long-term safety에 대한 우려 (community-acquired pneumonia,
Clostridium difficile-associated diarrhea, hip fracture 등)

GI risk reduction:
Celecoxib > ns-NSAIDs + PPI> ns-NSAIDs + misoprostol
The Relative Efficacies of Gastroprotective Strategies in Chronic Users of NSAIDs.
Gastroenterology 2008 (In Press, Available online 11 January 2008)
Pharmacologic Management of Pain
in OA and RA
- Recommendation 8~16 13) 심혈관계 위험이 있는 환자는 저용량 아스피린 (75 ~ 160mg/day)을
함께 규칙적으로 복용해야 함.
 KFDA 3월 11일자, 아스피린 label 변경
 NSAIDs 및 살리실산과 병용 투여할 경우 출혈을 증가시키거나
신기능을 감소시킬 수 있으므로 병용 투여하지 않는다
 Low-dose aspirin과 병용 투여 가능?
(Based on KFDA approved label): Celecoxib vs. other NSAIDs
Pharmacologic Management of Pain
in OA and RA
- Recommendation 8~16 14) Tramadol은 NSAIDs 단독으로 통증완화가 불충분 할 때
단독 또는 acetaminophen나 NSAIDs와 병용 가능함.
15) Active RA환자는 DMARDs가 일차 선택약이나
acetaminophen 또는 NSAIDs (주로 coxibs)와 병용 가능
16) Opioids는 다른 약제가 불충분하고 환자의 삶의 질이 저하될 때만
사용.
- Morphine, oxycodone, hydrocodone : 단독 또는 항염제와 병용함
- Codeine, propoxyphene : 주의해서 사용
Tramadol/Acetaminophen Tablets as Add-on
for OA Pain in Receiving a COX-2 Drug
Ronald Emkey et al., J Rheumatol. 2004;31:150-6.
The response from
regulatory authorities
FDA and EMEA (European Medicines Agency)
 American and European regulatory authorities (Feb. 2005)
- a class effect of COX-2-selective anti-inflammatory drugs on CV risk
- All prescription NSAIDs
: required to carry a boxed warning, and OTC NSAID labelling changed to
include specific warnings about potential serious GI or CV risks
- all COX-2 inhibitors
: contraindicated in patients with ischaemic heart disease or stroke,
peripheral arterial disease
: should be used with caution in patients with CV risk factors such as
hypertension or diabetes
 Committee on Medicinal Products for Human Use (CHMP)
- “all patients should take the lowest effective dose of non-selective
NSAIDs for the shortest time necessary to control symptoms”.
Development of updated
guidelines from WGPM
WGPM guidelines
WGPM guidelines
•
2 meetings of the WGPM
– 1st meeting December 14, 2004, Taplow, UK
– 2nd meeting June 8, 2005, Vienna, Austria
•
•
•
Discussion of the background and impact of the coxib- and NSAIDrelated safety debate and regulatory decisions on current analgesic
treatment patterns
Development of expert recommendations
– For moderate to severe pain
 Related to osteoarthritis
 Lower-back pain
 Acute sports injury / pain after day-case surgery
Based on review of EBM, expert opinion, and clinical vignettes
General principles for systemic analgesia in
moderate to severe musculoskeletal pain ?
• Multimodal opioid approach recommended
– Paracetamol/tramadol preferred initial option:
• Efficacy
• Safety, tolerability
• NSAID/coxib-sparing effect (particularly long term)
Moderate to severe pain in OA
without risk factors
Moderate to severe pain in OA
with risk factors
Moderate to severe low back pain
Moderate to severe pain following injury
- immediately following injury -
Development of updated
guidelines from OARSI
Osteoarthritis Research Society
International (OARSI) guidelines
Osteoarthritis and Cartilage (2008) 16, 137-162
Methodology
Data from
1966 to
2002
Data from 2002 to
Jan 2006
(2nd source of
data)
Guidelines from
1966 to Oct 2005
(First source of
data)
Cornerstone:
EULAR 2002
Recommendation
Data from
Jan 2006 to
Jun 2008
Current Guideline
built on the basis of
the existing EULAR
2002
Recommendations +
2002-6 data
Current Guideline
plus additional
recommendations
annually
Annual
Review on
OARSI
Website
OARSI recommendation - 13th
SOR: Strength of recommendation: 92% (95% CI 88-99)
OARSI recommendation - 14th
SOR: Strength of recommendation: 93% (95% CI 88-89)
OARSI recommendation - 20th
SOR: Strength of recommendation: 82% (95% CI 74-90)
Relative risk of GI adverse events
associated with NSAIDs and prevention
Relative risks of CV and renal adverse events
associated with COX-2 and NSAIDs
Summary (I)
Pain killer
• Analgesics relieve pain but do not have any effect on inflammation.
– recommended does not respond to nonpharmacologic measures.
– acetaminophen and opioid analgesics.
• Acetaminophen can relieve mild to moderate arthritis pain.
– avoid the serious liver damage and excessive alcohol use
• The pain of sudden, severe arthritis exacerbations may require
treatment with opioid analgesics.
– should be taken for only short periods of time
– most effective when taken together with NSAIDs and APAP
– Multimodal approach recommended from WGPM
Summary (II)
Anti-inflammatory therapy
• NSAIDs relieve pain and reduce inflammation.
• Recommended before analgesics for OA with inflammation and
non-inflammatory OA without adequate pain relief with analgesics
• Be careful the adverse side effects !!
 should take the lowest effective dose and for the shortest time
necessary to control symptoms
• Combination therapy with pain killer is effective and safe as add-on
for musculoskeletal pain
Thank you for your attention !!