Musculoskeletal Disorders in the Elderly Flashcards
Rheumatoid Arthritis in the Elderly
– > 50% RF negative
– “Milder” disease
– Fewer joints and large joints more predominant
– Abrupt onset
– Morning stiffness is greater in the elderly
DMARD Considerations in the Elderly: What are the drug options?
- Methotrexate
- Cyclosporine
- Cyclophosphamide
- Sulfasalazine
- Azathioprine
- Hydroxychloroquine
DMARD Considerations in the Elderly: Methotrexate
- decreased elimination associated with age related decline in renal function
- increased ADRs as a result
- Folic acid supplement is especially important in the elderly to minimize side effects
- Weekly total doses should never exceed 20 mg
- MTX 7.5 mg weekly with 5 mg folic acid weekly
DMARD Considerations in the Elderly: Cyclosporine
decreased elimination
DMARD Considerations in the Elderly: Cyclophosphamide
Overall incidence of infectious and noninfectious complications is not higher in the elderly but mortality from these side effects is increased
DMARD Considerations in the Elderly: Sulfasalazine
- Older patients should be prescribed enteric coated tablets as they are more prone to GI side effects.
- Elimination half-life is greater.
DMARD Considerations in the Elderly: Azathioprine
No age related difference in efficacy or tolerability
DMARD Considerations in the Elderly: Hydroxychloroquine
- Decrease dose in severe renal impairment.
- Elderly are more prone to retinopathy.
Biologic DMARDs in the Elderly: What are the drug options?
- Leflunomide (Arava*)
- Etanercept (Enbrel*)
- Infliximab (Remicade*)
- Adalimumab (Humira*)
- Anakinra (Kineret*)
- Abatacept (Orencia*)
- Tofacitinib (Xeljanz*)
Using Biologic DMARDs in the Elderly
Due to risk of infections and/or malignancies (esp. with TNF antagonists and abatacept) older people may be predisposed to an increased risk of these effects
Leflunomide (Arava*)
inhibits pyrimidine synthesis – anti-inflammatory effect
Etanercept (Enbrel*)
TNF Antagonist
Infliximab (Remicade*)
TNF Antagonist
Aadalimumab (Humira*)
TNF Antagonist
Anakinra (Kineret*)
IL-1 anatagonist
Abatacept (Orencia*)
Selective T-cell costimulation blocker
Tofacitinib (Xeljanz*)
JAK inhibitor
NSAIDs in the Elderly with RA
– Increased risk of GI ulceration and bleed in the elderly.
– Due to prostaglandin inhibition greater likelihood of salt and water retention and thus worsening of CHF or HTN.
Steroids in the Elderly with RA
– Use low doses: Prednisone ≤ 10 mg per day and taper over 3 months
– Increased risk of osteoporosis and due to mineralocorticoid effects may worsen HTN or CHF
– Cataracts, glucose intolerance
What happens when you use NSAIDs and steroids together?
additive GI risks
Epidemiology of osteoarthritis (OA) in the elderly
- 12% of adults have symptomatic OA
- Prevalence rises sharply with advancing age
- After age 75, > 80% of people have OA pathology
- After age 65, female:male ratio of knee OA ranges from 1.5:1 to 2:1
Pathophysiology of Osteoarthritis
- Characterized by loss of articular cartilage in synovial joint: Exposed bone thickens and is remodeled, Osteophytes form
- These changes along with thickening of joint capsule, weakening muscles and chronic synovitis limit movement
- Loss of cartilage is a two step process: Mechanical wear, Abnormal enzyme activity
- Imbalance between cartilage synthesis and degradation resulting in loss of cartilage, eburnation (thinning of cartilage) and pain
Describe a joint with mild Osteoarthritis
- osteophytes “spurs”
- mildly thickened inflamed synovium
- thickened, stretched capsule
- roughened thinning cartilage
Describe a joint with severe Osteoarthritis
- thickened, crunched-up bone with no covering cartilage
- inflamed synovium
- tight, thickened capsule
- light remaining cartilage
- bone deformity
Risk Factors for Osteoarthritis
- Aging
- Obesity
- Quadriceps muscle weakness
- Joint overuse/injury
- Genetic susceptibility
- Developmental abnormalities
Goals of Osteoarthritis Therapy
- Relieve pain / inflammation
- Enhance QOL and functional independence
- Retard disease progression
- Control comorbidity
- Minimize risks of therapy
Pharmacological Management of Osteoarthritis
• Cornerstone - Oral analgesics - Topical NSAIDs and capsaicin - Intra-articular corticosteroids • Other - MSM: Methylsulfonylmethane - Glucosamine / Chondroitin
Intra-articular corticosteroids
- benefit only for a short period of time
- cannot inject a particular join more than 3 times with a steroid before being concerned about effects of that steroid on that joint and bone
Pharmacological Management of Osteoarthritis: APAP
• Analgesic with some anti-inflammatory effect
• Dose: Up to 3 grams per day
• Toxicity:
- Hepatoxicity: Dose and duration related, Pre-existing liver disease and/or concomitant chronic alcohol use increases risk
- Renal: Rare, > 365 doses/year – RR = 2.1 (ESRD)
Pharmacological Management of Osteoarthritis: NSAIDs
- Aspirin and Non-acetylated salicylates (Salsalate, Diflunisal, Choline salicylate)
- Antipyretics, analgesic, antiinflammatory
- Toxicity - GI
- Acid / base disorders
- None are more effective than aspirin
- Side-effect profile, kinetics and cost determine preference of one agent over another
Kinetics of NSAIDs
- Kinetic considerations: First order to zero order
- Poor correlation between serum levels and analgesic effects
- Piroxicam (Feldene), meloxicam (Mobic) - qd dosing
- Naproxen (Naprosyn), sulindac (Clinoril), celecoxib (Celebrex*), - bid dosing
- Ketoprofen (Orudis) and naproxen (Naprosyn) are highly protein bound - risk of drug interactions
Recommendations for NSAID Monitoring
• Baseline
– CBC and differential, platelet count, creatinine, ALT, AST
• Systematic review
– Dark/black stool, dyspepsia, N/V, abdominal pain, edema, shortness of breath
– CBC, LFTs, creatinine
– NSAID induced nephropathy
Toxicities of NSAIDs
- Dyspepsia > 10%
- Gastric or duodenal ulceration: 1 - 10%
- Gastrointestinal bleeding: 1- 2%
- Renal toxicity: 5% (Sodium and water retention, Analgesic nephropathy, Interstitial nephritis)
- CNS < 1% (Aseptic Meningitis)
- Cardovascular: Increased risk of thromboembolic events with COX-2 selective agents, (rofecoxib are valdecoxib are now off the market)
NSAID Toxicities of Importance in the Elderly
- Risk of serious gastrointestinal toxicity is 2.5 to 5.5 times greater in the elderly
- Complications of salt and water retention can worsen hypertension and CHF
Relative GI Toxicity of NSAIDs
• Dyspepsia, diarrhea, abdominal pain – 25 to 28 % with COX-2 Inhibitor – 31% with Non-specific NSAIDS • Ulceration, bleeding, perforation – Celecoxib (Celebrex*) vs. Other NSAIDs – 12 month: 0.4% vs. 1.27%
Risk Factors for Serious Upper GI Complications Associated with NSAIDs
- Older age
- Hx of PUD, upper GI bleeding
- Arthritis related disability
- High-dose NSAID or multiple NSAID
- Concurrent steroid use
- Prior GI side effects
Recommendations for Decreasing Risk of NSAID Toxicity: Dyspepsia
- Take dose with at least 8 ounces of water
* Take with food or antacids
Recommendations for Decreasing Risk of NSAID Toxicity: Reduction ulceration and bleeding risk
In patients with history of PUD or GI bleeding or complications from NSAIDs
– Co-administration of misoprostol or a PPI
– Use minimally effective doses, monitor duration of use (No more than 10 consecutive days)
– Cox-2 inhibitor (?)
Recommendations for Decreasing Risk of NSAID Toxicity: Other CV Risk
– sulindac (Clinoril*) appears to have least effect on renal blood flow
– Monitor use, avoid prolonged use
Pharmacological Management of Osteoarthritis: Glucosamine / Chondroitin
- Remains a mixed message regarding effects on pain, functionality and disease progression
- Purity of preparations appears to be important
- Results of a NIH sponsored multi-center long term trial suggested only modest benefit in patients with severe OA of the knee
- Safe
- Can take a while to take effect
- Very modest effects
Principles of Managing Chronic Pain
• Break the pain cycle
• Monitor for effectiveness of analgesic regimen
– Measure degree of pain relief using a visual analog scale
– Measure duration of relief
• Educate about realistic expectation of analgesics
Non-Pharmacological Management of Osteoarthritis
- Weight reduction
- Education
- Assistive devices/orthotics
- Thermal modalities
- Hydrotherapy
- Magnetic therapy
- Muscle strengthening and ROM exercises
- Social support
Other Therapies for the Management of Osteoarthritis
- Hyaluronic Acid injections (knee)
- Surgery (joint replacement therapy)
What is the concern with join replacement therapy?
don’t know how long the joints hold up
What are the different types of gout?
- Acute gouty arthritis
- Uric acid nephrolithiasis
- Gouty nephropathy
- Tophaceous gout
Acute gouty arthritis
Intense pain, erythema, warmth, swelling, fever
Pharmacotherapy of Acute Gouty Arthritis: What are the durgs?
- NSAIDs
- Corticosteroids
Pharmacotherapy of Acute Gouty Arthritis: NSAIDs
- Indomethacin
- Naproxen
- Sulindac
- Ibuprofen
- Colchicine
Indomethacin
75 mg initially followed by 50mg every 6 hours for 2 days, then 50 mg every 8 hours for 1 to 2 days. May be more problematic in the elderly
Naproxen
500 mg BID
Colchicine
– Oral (Colcrys, Mitigare): 1.2 mg initially followed by 0.6 mg in 1 hour
– Authorized generic now available
– Delayed onset and GI toxicity limit its usefulness
– Older people more likely to experience GI side effects and bone marrow suppression: need to use lower doses or possibly avoid especially if CrCl < 30 ml/min.
– Cost is an issue with all products.
Pharmacotherapy of Acute Gouty Arthritis: Corticosteroids
– Intrarticular triamcinolone - 20 to 40 mg
– Oral prednisone - 30 to 60 mg/day for 3 to 5 days then taper over 10 to 14 days (along with colchicine)
Prophylactic Therapy for Gout: What are the drugs?
- Uricosuric
- Xanthine Oxidase Inhibitors
- Uric Acid Transporter 1 inhibitor
- Pegloticase (Krystexxa*) Urate Oxidase
What is the goal uric acid level?
< 6 mg/dl
Pegloticase (Krystexxa*) Urate Oxidase
- IV q 2 weeks
- for completeness of information; just know there are these out there
Prophylactic Therapy for Gout: Uricosuric
- enhances secretion of uric acid at the kidney level
- Probenecid
Prophylactic Therapy for Gout: Xanthine Oxidase Inhibitors
- Allopurinol
- Febuxostat (Uloric*)
- Co-administer low dose colchicine (?)
Prophylactic Therapy for Gout: Uric Acid Transporter 1 inhibitor
Lesinurad (Zurampic*)
Probenecid
do not use if CrCl < 30mL/min
Allopurinol
- 300 mg/day
- Reduce dose in renal insufficiency
Febuxostat (Uloric*)
40 to 80 mg/day
Lesinurad (Zurampic*)
- Use with a xanthine oxidase inhibitors
- for completeness of information; just know there are these out there
