Professional Documents
Culture Documents
IN THE MANAGEMENT OF
PAIN AND INFLAMMATION
Musculoskeletal
pain
Malignancy
Chronic infection
Burden of Arthritis:
Escalating Prevalence
59.4
60
Arthritis prevalence
50
Million
40
Arthritis causing
activity limitation
37.9
30
20
10
0
11.6
7.0
1990
2020*
Year
*Projected
Lawrence et al. Arthritis Rheum. 1998;41:778799.
Barriers to Treatment of
Chronic Pain
Patient reluctance to report pain
Physician reluctance to prescribe opioid
therapy
Patient reluctance to take opioid analgesics
Ineffectiveness of simple analgesics in reducing
inflammation, swelling, and stiffness
Complications of NSAIDs and opioids
significant burden on health care resources
major factor in the hospitalization and premature
death of patients with arthritis
Mechanism of Action of
Anti-inflammatory Agents
Arachidonic
acid
COX-1
COX-2
NSAIDs
Prostaglandins/
thromboxane
Primarily support
platelet function
Primarily protect
gastroduodenal
mucosa
COXIBS
Prostaglandins
Primarily mediate
inflammation, pain,
and fever
C99000DT000- III.2
Central
Inflammatory
stimulus
COX-2
Prostaglandins
PGE2
COX-2
Adapted from Smith CJ et al. Proc Natl Acad Sci USA. 1998;95:13313-8.
Fatigue
Bone-on-bone
condition
Muscle
strength and
endurance
Chronic
inflammation
Activities of
daily living
Depression
Multimodal Management
of OA and RA
Nonpharmacologic
Pharmacologic
Exercise/Weight loss
Physical therapy
Other
Analgesics
Anti-inflammatory agents
DMARDs/DMOADs
Surgical
Osteotomy
Arthroplasty
Nonpharmacologic
Therapy for Arthritis
Patient education
Weight loss (if overweight)
Aerobic and muscle-strengthening
exercise training
Physical/occupational therapy, rangeof-motion exercises
Joint protection, assistive devices
ACR Subcommittee on RA Guidelines. Arthritis Rheum. 2002;46:328-46.
ACR Subcommittee on OA Guidelines. Arthritis Rheum. 2000;43:1905-15.
RA
Analgesics
NSAIDs
DMARDs
nonselective
COX-2 specific
inhibitors
Intra-articular
glucocorticoids
Intra-articular
hyaluronic acid
NSAIDs
nonselective
COX-2 specific
inhibitors
Local or low-dose
systemic steroids
ACR Subcommittee on RA Guidelines. Arthritis Rheum. 2002;46:328-46.
Creamer P et al. Lancet. 1997;350:503-8.
Hochberg MC et al. Arthritis Rheum. 1995;38:1535-40.
ACR Subcommittee on OA Guidelines. Arthritis Rheum. 2000;43:1905-
Goals of OA Treatment
No known cure for OA
Individualized treatment can
reduce pain
maintain and/or improve joint mobility
limit functional impairment
ACR 2000
Osteoarthritis Guidelines
Nonpharmacologic measures (ie, patient education, weight loss,
exercise, physical therapy [PT])
Pharmacologic therapy
mild-to-moderate joint pain
acetaminophen
topical agents (ie, methylsalicylate or capsaicin as adjunct or alone)
moderate-to-severe joint pain
joint aspiration in addition to other agents depending on upper
gastrointestinal (UGI) and renal risks
intra-articular injections (glucocorticoids or hyaluronic acid)
COX-2 specific inhibitors
nonselective NSAIDs
tramadol
opioids
ACR Subcommittee on OA Guidelines. Arthritis Rheum. 2000;43:1905-15.
ACR 2000
Osteoarthritis Guidelines
Nonpharmacologic measures
Acetaminophen
Mild-to-moderate joint pain
Topical agents
Methylsalicylate or
capsaicin
for those who do not want
systemic therapy
Anti-inflammatory therapy
Nonselective NSAID
(with misoprostol
or proton pump inhibitor in at-risk
patients)
Tramadol
Opioids
ACR Subcommittee on OA Guidelines. Arthritis Rheum. 2000;43:1905-15.
Nonselective NSAID
plus misoprostol or PPI in high-risk patients
(even with low-dosage nonselective NSAID)
Nonacetylated salicylates
Pure analgesics
(tramadol or opioids)
ACR Subcommittee on OA Guidelines. Arthritis Rheum. 2000;43:1905-15.
Yes
Moderate-to-severe pain
Inflammation
Plus, as needed:
Nonpharmacologic
interventions
Yes
Glucosamine
Continued pain?
Adjunctives
Conduct GI risk
factor analysis
High risk
Nonselective NSAID
+ PPI or misoprostol
Intra-articular
hyaluronic acid
Continued pain?
Tramadol
Yes
Surgical intervention
Dose 50%75% in
patients with impaired
renal or hepatic
function or history of
EtOH abuse
Continued pain?
Monitor for
efficacy
and
adverse
events
Yes
Avoid nonselective
NSAIDs for patients
requiring long-term,
daily analgesia
No
Continued pain?
Yes
Fixed-dose APAP/opioid
or NSAID/opioid
combinations
American Geriatrics Society. J Am Geriatr Soc. 2002;50:S205-S224.
Optimizing Treatment
Medical Concerns
Optimizing Treatment
Practical Concerns
Cost of therapy
Compliance (dosing frequency)
Convenience of dosage form (oral vs
topical vs injectable)
Patient preference
ACR 2002
Rheumatoid Arthritis Guidelines
Establish diagnosis of rheumatoid arthritis early
Document baseline disease activity and damage
Estimate prognosis
Initiate therapy
Provide patient education
Start DMARD(s) within 3 months
Consider NSAID
Consider local or low-dose systemic steroids
Provide physical therapy/occupational therapy
Periodically assess disease activity
ACR Subcommittee on RA Guidelines. Arthritis Rheum. 2002;46:328-46.
NSAIDs
Most inhibitors affect both COX isoenzymes with near equal potency
flurbiprofen, ibuprofen, mefenamic acid, docosahexaenoic
acid,diclofenac
More potent COX-1 inhibitors
piroxicam, indomethacin, sulindac sulfide
COX-2 selective
nabumetone, meloxicam, etodolac, nimesulide
COX-2 specific
celecoxib, rofecoxib
COX-1 Selectivity
Diclofenac
Diclofenac
Ibuprofen
Ibuprofen
Sulindac
Indomethacin
Indomethacin
Piroxicam
Piroxicam
10
Sulindac
0
10
100
1000
NSAID-Induced
Upper GI Bleeds and Perforations
3.1
Nabumetone
Ibuprofen
4.3
Indomethacin
4.4
5.6
Mefenamic Acid
6.5
Ketoprofen
6.7
Naproxen
7.8
Diclofenac
15.9
Piroxicam
10
15
20
Specificity
an in vivo concept
clinically relevant
inhibition of COX-2
without inhibition
of COX-1
NSAID-INDUCED GI COMPLICATIONS
Incidence by number of risk factors
Mean incidence Rate over 6 months
Incidence Rate
10
9.24%
4.32%
5
1.95%
0.38%
0
0.87%
1
2
3
4
Number of Risk Factors
Risk Factors: age > 65, history of PUD, history of
GI bleed, cardiovascular disease
Silverstein FE et al. Ann Intern Med 1995
Opioid analgesics
oxycodone, codeine, morphine
Pharmacotherapy for RA
DMARDs
Hydroxychloroquine Injectable gold
Sulfasalazine
Cyclosporine
Methotrexate
Azathioprine
Leflunomide
Etanercept
Infliximab
ACR Subcommittee on RA Guidelines. Arthritis Rheum. 2002;46:328-46.
Overview of DMARDs
Agent
Patients Who
Discontinue Owing
to Toxicity (%)
38
Sulfasalazine
2030
Methotrexate
1035
Overview of DMARDs
Agent
Patients Who
Discontinue Owing
to Toxicity (%)
Injectable gold
Dermatitis, stomatitis,
thrombocytopenia, proteinuria/
nephrotic syndrome,
pneumonitis
Cyclosporine
1530
Azathioprine
1530
30
Overview of DMARDs
Agent
Infliximab
Leflunomide
Etanercept
Pharmacotherapy in RA
Glucocorticoids
Advantages
treat flares
minimize/control
disease activity
Disadvantages
greater toxicity
with higher doses,
longer duration
discontinuation
difficult
Progress in Treatment of
Arthritis:
Optimal Drugs = Effectiveness
Efficacy
Safety
Tolerability