a.    HIP + at least two of the following

                                          i.    ESR (Erythrocyte sedimentation rate)  < 20 mm/h

                                         ii.    Femoral or acetabular osteophytes on radiography

                                        iii.    Joint space narrowing on radiography (occurs over  a progression)

b.    Knee pain + osteophytes and radiographs AND at least one of the following

                                          i.    Age > 50 years

                                         ii.    Morning stiffness lasting 30 minutes or less

                                        iii.    Crepitus on motion

a.    Patient education

b.    Social support

c.    Exercise--aerobic, muscle strengthening

d.    Weight loss--1-2lbs/wk

e.    Physical therapy

f.     Occupational therapy

g.    Heat/Cold packs--cold reduces inflammation, heat may decrease stiffness

h.    Surgery--knee/hip replacement

assistive devices--canes, crutches, walkers

appropriate footwear--lateral-wedge insoles

a.    Indications

                                          i.    Analgesic

                                         ii.    *NOT Anti-Inflammatory

                                        iii.    Helps with bone pain and dulls the pain sensation

                                       iv.    Numbs what the PGs are doing (increasing the pain sensation)

                                          i.    > 12 years

1.    General 325-

a.    Tylenol Arthritis: 650mg (1-2 tabs PO Q8-12h prn)

2.    *MDD = 400mg

                                         ii.    Hepatotoxicity at doses > 4000mg/day

1.    >2g/day in select patient populations

a.    Preexisting liver disease

b.    Concomitant use of hepatotoxic medications

c.    Poor nutrition

d.    Consumption of > 3 alcohol beverages/day

                                          i.    Side effects = uncommon

1.    Rare

a.    Nephropathy

b.    Blood dyscrasias/anemia

                                         ii.    No effect on

1.    Uric acid excretion

2.    Prothrombin synthesis

3.    Platelet aggregation

                                        iii.    Caution

1.    Alcohol consumption

2.    Potential INR increases with doses > 2275mg/week

                                          i.    Do NOT exceed 4000 mg in 24 hours

1.    Check all OTC and Rx labels for APAP

                                         ii.    With or without food

                                        iii.    Do NOT consume alcohol

Topical Therapy:

a.    Rubefacients—cause vasodilation and also act as counterirritant

                                          i.    Modest, short-term efficacy

                                         ii.    More for acute than chronic

                                        iii.    Vasodilation of peripheral vasculature

1.    Increase blood flow (redness)

                                       iv.    Methyl salicylate/ trolamine salicylate

1.    Mechanism unknown

2.    Hypothesized as PG inhibition

o   Trolamine salicylate does not have much evidence supporting it.  Methyl salicylate is preferred over trolamine

o   A 2 fold mechanism to help treat

Topical Therapy:

a.    Capsaicin à OTC

                                          i.    Source—hot peppers

                                         ii.    MOA: Depletes substance P from sensory neurons

1.    Reduces pain signaling, not inflammation

2.    Sensitizes the area and stops substance P production.  This takes time, usually 2-4 weeks for full effect.  In the beginning use the 0.25% and as that sensitivity starts to go away you can use 0.75%

                                        iii.    Strength: 0.025%

                                       iv.    May take 2-4 weeks for full effect

                                        v.    Monotherapy for mild OA

                                       vi.    Adjunctive therapy for moderate to severe OA

a.    Diclofenac sodium (Voltaren 1%)—for knees, hands, and wrists; not for hip

                                          i.    Dose

1.    Lower extremity = 4g QID (MDD per joint = 16g)

2.    Upper extremity = 2g QID (MDD per joint =8g)

3.    Total MDD = 32g

                                         ii.    Do not wash area for at least 1 hour

                                        iii.    Avoid exposure to sunlight

                                       iv.    Avoid covering for at least 10 mins

b.    Solaraze 3% à actinic keratoses;not for arthritis; do not confuse with Voltaren«

c.    PENNSAID—only for knee arthritis. 1.5% solution.  Applied 40 drops to the area«

glucosamine sulfate (GS)

• moa
• efficacy
• dosing
• SEs
• monitoring

a.    Source—chitin from shellfish or synthetic

b.    Use: arthritis

c.    MOA

                                          i.    Stops and reverses progression of OA

1.    Inhibits proteoglycan destruction

2.    Stimulates proteoglycan synthesis

3.    Stimulates growth of cartilage

                                         ii.    Trying to put the cushioning back into the joint

d.    Potential affect from sulfate component

                                          i.    Stabilizes connective tissue matrix

e.    Well tolerated and safe

f.     Efficacy

                                          i.    Onset/Duration

1.    At least 6-8weeks for full effectsàuse in combination with other agents for faster relief

2.    Effects last longer than NSAIDs—approximately 6 months

3.    D/C if no benefit seen after 6 months

                                         ii.    Dosing

1.    1500mg/day in three separate doses

g.    Side effects

                                          i.    GI Upset

1.    Cramping

2.    Bloating

                                         ii.    Take with food to minimize SEs

h.    Not recommended in shellfish allergies

i.      Consult MD for use in pregnancy

j.      Regularly check cholesterol, blood glucose (in diabetics)

a.    Derived from shark and cow cartilage

b.    MOA: protects cartilage against degradation

                                          i.    Inhibits degradation enzyme

c.    Dose: 400mg TID (MDD = 1200mg)

d.    Onset of Action: ~ 1 month

e.    ADR: nausea à otherwise well tolerated

f.     DDI: warfarin à may have increased INR and bleeding complications so counsel and monitor

g.    Also promotes synthesis of other components to help the joint

a.    Can be used alone or in combination

b.    Not for immediate relief

                                          i.    Use for at least a month for efficacy eval

c.    More beneficial in moderate to severe knee OA

d.    GIAT trial: overall patients didn’t have benefit unless used in combination for mod to severe knee OA

e.    Not much positive results from clinical trials but well tolerated

a.    MOA: blockage of prostaglandin synthesis by inhibiting cyclooxygenase enzymes

a.    Dose: see chart  95-2 (Dipiro pg 1527—be familiar with names)

                                          i.    Nonselective

1.    Ibuprofen

a.    1200-3200mg/day in 3-4 divided doses (MDD = 3200mg)

2.    Naproxen Sodium

a.    275-550mg twice a day (MDD = 1375mg)

                                         ii.    Selective COX2-inhibitor

1.    Celecoxib

a.    100mg BID or 200mg daily (MDD = 200mg)

b.    Less CV risk compared to Vioxx

a.    CI: hx of asthma, hypersensitivity to aspirin or other NSAIDs, perioperative pain for CABG surgery patients

a.    ADR:  GI issues (nausea, dyspepsia, anorexia, abdominal pain, flatulence and diarrhea)

b.    Caution; increased risk of renal dysfunction

                                          i.    Have PGs in kidney that promote renal blood flow à so NSAIDs cant worsen kidney function à monitor for Cr

a.    DDI: Li, warfarin, oral hypoglycemic, high dose methotrexate, ACEI’s, beta blockers, diuretics, aspirin

a.    Risk Factors for NSAID-Induced Ulcers

                                          i.    Definite risk factors

1.    Age > 65

2.    Previous ulcer disease or GI bleeding

3.    Use of multiple NSAIDs or high dosage

4.    Concomitant oral corticosteroid therapy

5.    Concomitant anticoagulant therapy

6.    Duration of therapy (risk is higher in first three months of treatment)

                                         ii.    Possible risk factors

1.    Female gender

2.    Smoking

3.    Alcohol consumption

4.    Helicobacter pylori Infection

a.    Prevention of NSAID-Induced Ulcers

                                          i.    Take with food or milk

                                         ii.    For patients at increased risk for ulcers

1.    Misoprostol (Cytotec) 200 mcg QID with food

a.    Limitations: abortifacient properties, diarrhea, abdominal cramps

2.    Proton Pump Inhibitors

3.    Sucralfate or H2 blockers—not effective

                                        iii.    Use Cox2 Inhibitor (Celecoxib)

Intra-articular corticosteroid injections

• MOA
• Indication
• Dose
• ADR

a.    Methylprednisolone or triamcinolone

b.    MOA: anti-inflammatory

c.    Indication;  alternative agent for pain relief

                                          i.    Often used with aspiration for joint effusion

d.    Dose: based on size of joint

                                          i.    No more than 3 or 4 injections/year à due to SEs

e.    ADR: hyperglycemia, edema, á BP, dyspepsia, infection, break down of cartilage/bone with long term use—systemic CST not recommended in OA due to ADRs

Hyaluronate Injections

• available products
• MOA
• Dosing frequency
• ADR

a.    Available products:

                                          i.    Hyalgan: 20mg sodium hayluronate/2mL

                                         ii.    Supartz: 25mg sodium hayluronate/2.5mL

                                        iii.    Synvisc 16mg hylan polymers/2mL

                                       iv.    Orthovisc 30mg hyaluronan/2mL

                                        v.    Euflexxa 20mg sodium hyaluronate/2mL

b.    MOA: synovial fluid replacement

c.    Indication: OA of the knees only if unresponsive to other less $$$ therapies

d.    Dosing Frequency

                                          i.    Hyalgan/Supartz: 5 weekly injections

                                         ii.    Synvis/Orthovis/Euflexxa: 3 weekly injections

                                        iii.    Synvisc-One: 1 injection

e.    ADR: acute joint swelling, rash, pruritis

a.    Tramadol (100mg/dayà200mg/day)

b.    Opioid Analgesics

c.    Disease Modifying Drugs(DMARDS)

                                          i.    Used more in RA patients

d.    Doxycycline