Exam 4 Osteo and Rheumatoid arthritis Flashcards
What is the cause of osteoarthritis?
Degenerative changes in cartilage and the associated bone
What joints are most commonly affected by osteoarthritis?
Distal interphalangeal joint, hips, knees
What patients are at a higher risk of getting OA?
Females, older patients, obesity, repetitive stress, major joint trauma, heredity, congenital/anatomical defects, muscle weakness
Are Herberden’s and Bouchard’s nodes characteristic of OA or RA?
Osteoarthritis
Which is associated with systemic symptoms: OA or RA?
RA
Which has asymmetric involvement: OA or RA?
OA
What arthritis symptoms could be similar to tendinitis or strain?
Pain, worse with activity, inflammation, weight bearing joint instability, crepitus
How long does morning stiffness last in osteoarthritis? Rheumatoid arthritis?
OA: under an hour. RA: over an hour
Which arthritis develops osteophytes?
OA
Which arthritis develops pannus?
RA
Which arthritis has an elevated ESR?
RA
Which arthritis can develop at any age?
RA
Which arthritis has absent or mild inflammation?
OA
What non-pharmacologic first steps can we take in OA?
Psychological support, education, rest/activity balance, weight loss, heat/ice, physical and occupational therapy
What step 2 options are available for OA?
Acetaminophen, topicals (menthol/camphor/oil of wintergreen, capsaicin cream, diclofenac), and glucosamine/chondroitin
How is acetaminophen used?
500mg q4-6h (nmt 6/24 hours) (scheduled)
MAX: 3g/day
2-4 week trial
What patients are at highest risk for hepatotoxicity?
Pts with heavy EtOH intake, pre-existing liver disease, elevated liver enzymes
How do menthol, camphor, and oil of wintergreen work to relieve OA?
Counter-irritant, applied sparingly multiple times per day. Avoid eye contact! More prn use.
How does capsaicin cream work to relieve OA?
Capsaicin depletes substance p, applied sparingly to joint several times daily (2-4).
Can cause burning, stinging, redness
How does diclofenac work to relieve OA?
Local inhibition of COX-2 enzymes. Do not give in combination with systemic NSAIDS
Gel: apply to joint QID, MAX 16g daily
Solution: 10 drops to each joint QID
ADE: burning, stinging, pain, garlic smell/taste from solution vehicle
How does glucosamine/chondroitin work to relieve OA?
It stimulates proteoglycan synthesis from articular cartilage.
Given 500mg/400mg tab PO TID, stick to one herbal product.
Slow onset – >4 weeks (3 month trial)
ADE: gas, gloating, cramping, nausea, increased insulin resistance (concern for DM, HTN, HLD)
What step 3 agents can we use to treat OA?
NSAIDS at analgesic dose, COX-2 selective inhibitors, and NSAID/protective combo products
How long should you try NSAIDS?
1-2 week trial for pain, 2-4 week trial if inflammation present
Try different NSAIDs before moving up a step
What ADEs are we concerned about with NSAIDS?
GI upset, GI ulcers, bleeding, renal dysfunction, increased BP
What patients are at high risk for NSAID ADRs and therefore should receive a selective COX-2 inhibitor or NSAID/protective combo product?
Pts with h/o GI bleed, PUD, on anticoagulant/antiplatelet or glucocorticoid therapy, elderly (>65)
Pts with CHF, HTN, renal dysfunction, dehydration greater risk nephrotoxicity.
What should you monitor with NSAID therapy?
BP, edema/weight gain, BUN/SCr, Hgb/Hct, signs of dehydration
What combination products can we give give in step 3?
NSAID + PPI (naproxen + esomeprazole, Vimovo) and NSAID (diclofenac) + misoprostol (Arthrotec)
What pros and cons are associated with selective COX-2 inhibitors?
Pro: lower incidence of GI bleeds and other GI SEs
Cons: increased cost, risk of CV disease
Same impact on kidneys and INR as other NSAIDs
What options do we have once we reach step 4 with a patient with OA?
Opioid analgesics, tramadol, IA corticosteroid injections, and hyaluronadate injections
What options do we have at step 5 in OA?
Joint resurfacing surgery/joint replacement
What should you always monitor in OA patients, regardless of pharmacotherapy?
Pain, joint stability/function, risk of fall, ROM, X-rays, degree of disability, weight, ADRs from medications, compliance with non-PCOL, QOL issues
How are opioid analgesics used in OA?
PRN for breakthrough pain – start dosing low and go slow
Can also schedule a long acting and use short acting prn
Closely watch total APAP dose!
ADE: nausea, somnolence, constipation, dizziness, drug seeking behavior
How does tramadol work to relieve OA pain?
It blocks the mu receptor, inhibiting norepinephrine and serotonin.
Dosed 25-50mg q 4-6 hours MAX 400mg/day
ADE: nausea, vomiting, dizziness, constipation
How often can IA corticosteroid injections be used?
NMT q4-6 months in isolated joints (temporary or if cant do opioids or surgery)
Peak pain relief in 7-10 days
How do hyaluronate injections help with OA?
They temporarily increase the viscosity of the joint.
Injected once weekly x 3-5 weeks into joint
Max benefit in 8-12 weeks. Dont use over years
What patients are more likely to get rheumatoid arthritis?
Women and those with an HLA genetic predisposition to it.
What causes rheumatoid arthritis?
Chronic autoimmune disease characterized by inflammatory cell infiltration into joints, cytokine release, and pannus formation (inflammed proliferating synovium that invades cartilage and bone, eroding them)
What are the “prodrome” nonspecific symptoms of RA?
Fatigue, weakness, joint pain, low grade fever, loss of appetite, stiffness and muscle ache leading to joint swelling
What score must a patient have from what four categories to be diagnosed with RA?
A score of 6 or more from any of joint involvement (more and smaller is more points), serology (RF or ACPA), symptom duration (greater or less than 6 weeks), and acute phase reactants (ESR or CRP).
What joints are most common in RA?
Hands, wrists, and feet.
Elbows, shoulder, hip, knees, and ankles may also be affected.
There are seven categories of extra-articular manifestations that can present in RA (outside joint and not prodromal). Name them.
Rheumatoid nodules, vasculitis, pulmonary, ocular, cardiac, Felty’s, and other (lymphadenopathy and renal disease [thrombocytosis, anemia] perhaps associated with treatment)
Where are rheumatoid nodules usually located? What type of RA are they usually found in?
Located on pressure points, commonly on hands, elbows, and forearms. 20% of patients are affected, more commonly in erosive disease. Do not require intervention if asymptomatic and no interference with ADL.
What is vasculitis?
Inflammation of small, superficials that is associated with stasis ulcers and infarction, which can lead to necrosis. Depends on disease duration.
What pulmonary extra-articular manifestations can be seen in RA?
Pleural effusions, pulmonary fibrosis, nodules, in rare cases even interstitial pneumonitis.
What ocular extra-articular manifestations can be seen in RA?
Inflammation of the sclera, episclera, and cornea, nodules on the sclera, and Keratoconjunctivitis sicca (itchy dry eyes + inflammation)
Sjorgens syndrome = KS + RA
What cardiac extra-articular manifestations can be seen in RA?
Increased risk of CV mortality, pericarditis, conduction abnormalities, and rarely myocarditis
What is Felty’s?
Splenomegaly as result of chronic inflammation, and neutropenia
What does ESR measure and what is it useful for?
Measures erythrocyte sedimentation rate or non-specific amount of inflammation so is elevated (>20) in RA. Can help diagnose but even better for measuring treatment success.
What does CRP measure and how can we use it?
Measures non-specific inflammation markers from liver and is useful for diagnois and more importantly serial monitoring for treatment success assessment.
What does RF measure and how do we use it?
It looks for antibodies specific for IgM and is positive in 60-70% of RA patients. Great for diagnosis because specific.
What does Anti-CCP or ACPA measure and what does it mean if a patient is positive for it?
ACPA measures anti-citrullinated protein antibody. It is highly specific and present earlier in the disease. A positive value is a predictive value for erosive disease and a marker of poor prognosis.
What does ANA measure?
Anti-nuclear antibodies, suggesting autoimmune disease. More indicative of SLE, so usually done in initial workup to differentiate between that and RA.
How would the fluid from joint aspiration of a RA patient appear?
Turbid with increased WBC and normal to low glucose.
How does RA appear on X-ray?
With joint space narrowing and bone erosion.
What two types of factors do we consider when determining if a patient has poor RA prognosis?
Social factors (socioeconomic status, lack of formal eucation, psychosocial stress, high HAQ scores (questionnaire about ADL, social impact)) and physical factors (extra-articular manifestations, elevated CRP and EST, high titers of RF, elevated ACPA, erosions on X-ray, duration of disease, and swelling of >20 joints)
What non-pharmacological treatments do we recommend for RA patients?
Education, emotional/support groups, rest, splints/prosthetics, PT and OT, weight reduction, heat, surgery for some extra-articular manifestations
True or false: NSAIDs used as monotherapy at analgesic doses can alter RA disease progression and prevent joint destruction
False–NSAIDs are effective at reducing pain, swelling, and stiffness, but do not alter disease progression/destruction and should only be used in combo with DMARDs. When used for acute therapy, they should be used at anti-inflammatory doses, not analgesic doses.
What NSAID is contraindicated in a patient with a sulfa allergy?
Celecoxib (Celebrex)
100-200mg PO BID
What DMARD provides the most predictable benefit and best long-term outcome?
Methotrexate (Rheumatrex)
How does methotrexate (MTX) work to improve RA?
It inhibits dihydrofolic acid reductase, inhibiting neutrophil adhesion and chemotaxis
How is MTX dosed?
7.5mg per WEEK PO as 2.5mg tablets or IM. Up to 20mg weekly dose in one day.
Onset: 1-2 months
What ADEs are associated with MTX and how do we monitor them?
Myelosuppression (monitor CBC with Plt q1-2 mos),
GI (N/V/D, stomatitis/mucositis),
Hepatic (cirrhosis, hepatitis, fibrosis–monitor LFTs q1-2mos)
Pulmonary (pneumonitis, fibrosis–baseline CXR)
Dermatologic (rash, urticaria, alopecia)
Teratogenic (wait one cycle on BCP before starting, 3 mos off before considering conception)
Also monitor SCr
In what patients is MTX contraindicated?
Pregnant/nursing mothers, chronic liver disease (caution EtOH abuse), immunodeficiency, pre-existing blood dyscrasias, pleural/peritoneal effusion, CrCl
What prodrug DMARD inhibits cell cycle progression by inhibiting de novo pyrimidine synthesis and tyrosine kinase and is better tolerated than MTX?
Leflunomide (Arava)
How is leflunomide dosed?
Loading dose of 100mg PO x 3 days then 20mg daily. (Can decrease to 10mg if SE problems)
Onset: 1 month.
Half life of 14-16 days (hepatobiliary)
What adverse effects are associated with leflunomide?
Diarrhea, rash, alopecia, increased LFTs, teratogenic (males and females both reliable contraception–can use cholestyrimine to decrease half life to wash out if want conception)
Baseline CBC and LFTs then monthly LFTs, especially if taking with methotrexate.
What prodrug DMARD inhibits IL-1 and should not be used in patients with a sulfa allergy?
Sulfasalazine (SSZ) (Sulfazine)
How is sulfasalazine dosed?
500mg PO BID
Onset 1-2 months
What adverse effects are associated with SSZ?
GI (N/V/D, anorexia), dermatologic (rash, urticaria, photosensitivity), hematologic (leukopenia, thrombocytopenia, rarely hemolytic and aplastic anemia)
What should you monitor for SSZ?
CBC w/ plt baseline, then weekly for a month, then every three months
What non-traditional DMARD has lower efficacy and works by modifying cytokine infiltration into the joint?
Hydroxychloroquine (Plaquenil)
How is hydroxychloroquine (HCQ) dosed?
200mg tablet PO BID
Onset: 2-4 months (D/C if no change in 6 mos)
What adverse effects are associated with HCQ?
No myelosuppression, hepatic, or renal toxicity!
However, retinal toxicity, esp >70yo, cumulative dose >800g, GI (N/V/D-take with food), dermatologic (rash, alopecia, increased skin pigment)
Monitor: baseline vision exam and every 6-12 mos
How are corticosteroids used for RA?
As burst therapy in flares, bridge therapy when waiting for DMARD onset, long-term/low dose for advanced/difficult cases.
10-25mg IA but try
What warnings come with the TNF neutralizers?
Risk of infection, especially tb/opportunistics, do NOT use with anakinra, demyelinating disorders, malignancies, CHF, no concurrent live vaccine administration.
What adverse effects come with TNF neutralizers?
HA, rash, infection risk, injection site rxn, CHF exacerbations, malignancy risk, risk of demyelinating disease.
How does etanercept (Enbrel) function to treat RA?
It is a dimeric protein with two soluble TNF receptors fused to the IgG1 molecule, so it binds and inhibits TNF so that it cannot interact with receptors.
How is etanercept dosed?
50mg SC once a week, AFTER negative TB skin test
How is infliximab (Remicade) dosed and used?
Used in combination with MTX after TB test.
A chimeric antibody that binds and inhibits TNF.
Dosed 3 mg/kg IV at 0, 2, 6, and then q8 weeks
Can increase to 10mg/kg or as often as q4 weeks but not greater than 5mg/kg in CHF Class III and IV
What patients should receive adalimumab (Humira)?
TB negative patients who have inadequate response to one or more DMARDs, alone or in combination with MTX
What is adalimumab (Humira) and how is it dosed?
It is a recombinant human IgG1 antibody, binds to TNF-a and blocks interaction
Dosed 40mg SC every other week. Can increase to weekly if not taking MTX.
How is golimumab (Simponi) used clinically?
In patients with moderate to severe RA, in combination with MTX. Human monoclonal antibody specific for TNF alpha (soluble and transmembrane)
How is golimumab dosed?
50mg SC once a month
MONITOR: CBC with Plt, LFTs (unique)
How is certolizumab pegol (Cimzia) used?
In TB negative RA patients with mild to moderate disease. Can be used alone or in combination with non-BRM DMARDs. PEGylated anti-TNF therapy.
Binds and neutralizes TNF-a.
How is certolizumab pegol dosed?
400mg (2 injections of 200mg) SC at 0, 2, 4 weeks then 200mg q2 weeks or 400 q4 weeks
What is the only IL-1 receptor antagonist BRM?
Anakinra (Kineret)
In what circumstances is anakinra used?
Moderate to severe RA in pts who have failed one or more DMARDs, alone or in combination with DMARDs (besides TNF antagonists)
How is anakinra dosed?
100mg SC every day. If CrCl
What adverse events are associated with anakinra?
Injection site reactions, HA, N/V, flu-like symptoms, HS to e coli-derived proteins, increased risk of infection, decreased neutrophils (monitor baseline, monthly x3 mos, quarterly up to 1 year)
What biologic T cell costimulation modulator can we use for RA?
Abatacept (Orencia)
How is abatacept used clinically?
For moderate to severe RA in patients with inadequate response to one or more DMARDS, as monotherapy or in combination with other DMARDs (not TNF antagonists or anakinra)
How is abatacept dosed?
Dosed IV over 30 min at 0, 2, and 4 weeks then q4 weeks
100kg = 1g
What adverse effects and precautions are associated with abatacept?
HA, nausea, RTI, nasopharingitis, infusion reactions, serious infection, malignancy, caution in pts with COPD
No monitoring required
What is the only available biologic IL-6 receptor inhibitor?
Tocilizumab (Actrema)
When should tocilizumab be used?
In patients with moderate to severe RA after inadequate response to other DMARDS, alone or in combination.
How is tocilizumab dosed?
4mg/kg IV infusion over 1 hour every 4 weeks. Can increase to 8mg/kg but doses >800mg not recommended.
What precautions and side effects are associated with tocilizumab?
Contraindicated with liver toxicity, thrombocytopenia, and neutropenia.
ADE: serious infection, hepatotoxiicty (monitor LFTs), thrombocytopenia (monitor plt), neutropenia (monitor neutrophils), infusion reactions, intestinal perforations, and lipid abnormalities (monitor lipid profile)
Monitoring should occur every 4-8 weeks except lipid abnormalities q6 mos after initial 2.
How is rituximab used for RA and how is it dosed?
Used for moderate to severe RA in pts with inadequate response to one or more TNF antagonists, in combo with MTX
Dosed as two 1g infusions IV separated by 2 weeks. Then retreat at 6mo intervals. Give with methylprednisolone 100mg IV 30 minutes before infusion along with APAP and diphenhydramine.
What adverse effects are associated with rituximab?
Infusion reactions, tumor lysis syndrome, mucocutaneous reactions, viral infection, hypersensitivity, renal toxicity, bowel obstruction, Hep B reactivation, cardiac arrhythmia.
Monitor: CBC w/ plt, SCr, vital signs during infusion (q6mos)
What janus kinase inhibitor can we use in RA?
Tofacitinib (Xeljanz)
How is tofacitinib used clinically?
In moderate to severe RA after inadequate response to MTX, alone or in combination with DMARDs but not other BRMs, azathioprine, or cyclosporine
How is tofacitinib dosed?
5mg orally twice daily
What adverse effects are associated with tofacitinib?
CYP interactions, do not use if hepatic impairment, risk of infection, risk of malignancy, RTI, HA, diarrhea, nasopharyngitis
Do NOT use if Hgb
What benefits are associated with combination therapy?
Decreased dosages minimize side effects of individual drugs, more effective in treating resistance, dramatically alter disease progression through multiple mechanism approach
Often MTX + HCQ, SSZ, leflunomide, or BRM
What approach do we take with all patients?
Early, aggressive treatment with DMARDs within 3 mos of diagnosis.
What two things were missing from the 2008 ACR guidelines?
How to switch agents/when to add agents and diagnostic criteria
