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rheumatoid arthritis
n/a
115
Pharmacology
Post-Graduate
03/27/2012

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Cards

Term
what is rheumatoid arthritis?
Definition
it is an autoimmune d/s with systemic inflamation, symmetrical joints involvement, an extraarticlar involement
Term
what extraarticular involvment is typical for RA?
Definition
Rheumatoid nodules
Vasculitis
Eyes
Neurological
Cardiopulmonary
Lymphadenopathy
Splenomegaly
Term
what is a specific marker fot RA?
Definition
anticyclic citrulinated peptide (ACP)
if not present - no RA
Term
what are the signs of RA?
Definition
Joint pain/stiffness,Joint deformity (progression, Tenderness
Onset = > 30 mins and lasts all day,
Warmth/swelling in joints,SYMMETRICAL
Rheumatoid nodules, Rheumatoid Factor (60-70%)
Anticyclic citrullinated peptide (ACP),
Increased ESR and CRP (inflammation),
Normocytic, normochromic anemia
Thrombocytosis, Progressive (weeks to months),Cycle,,Prodromal, mental
Term
what markers are not diagnostic, but present in RA?
Definition
rheumatoid factor, ESR, CRP
Term
what are prodromal signs of RA?
Definition
Joint Pain, Fatigue, Weakness, Low-grade fever, Loss of appetite
Term
what joints are mostly affected?
Definition
small - hands, feet
Term
How joints nodules in RA are different fron OA?
Definition
they are soft when palpate
Term
what are complictions of RA?
Definition
small joints deformities, pain, vasculatis, pulmonary fibrosis, sjogren's syndrome, felty's syndrome
Term
what is sjogren's syndrome?
Definition
decreased tears production
Term
what is felty's syndrome?
Definition
splenomegaly and neutropenia
Term
what is a typical age for RA onset?
Definition
30-40 years
Term
what is a gender prevalence of RA?
Definition
W 3x M (in 15-45: W 6x M)
Term
True/false
RA des not have a genetic component?
Definition
False
Term
What is pathophysiology of RA?
Definition
Autoimmune,Inflammation of synovial tissue,Invades cartilage – bone surface,Erosions,Destruction, reumatoid factor,
Term
What is pannus?
Definition
Inflammation of synovial tissue
Term
what does presense of rheumatoid factor indicate?
Definition
more sevre disease
Term
True/false
Number that patient gets during diagnosis will never change
Definition
False.
RA is a progressive disease, numbers may change
Term
what are RA treament goals?
Definition
Slow progression
Prevent or control joint damage
Prevent loss of function
Decrease pain
Term
True/ false
RA can be cured
Definition
False
Term
which factors help to determine therapy?
Definition
how long
how active disease is
prognostic factors
Term
what factors indicate poor prognosis for RA?
Definition
High tender and swollen joint counts, Radiographic erosions,Elevated RF,Elevated anti-CCP antibodies,
Elevated ESR, Elevated CRP,Age
Female,Genetics,Tobacco use
Worsening physical function
Term
what nonpharmacologic options we havefor RA?
Definition
Education,Physical Therapy,Occupational Therapy,Rest, Weight reduction,Surgery
Term
What is a mainstay treatment for RA?
Definition
DMARDS: non-biologic
biologic
Term
What in RA? adjunctive treatment is used for
Definition
to manage flares
Term
When pharmacologic treatment should be started in RA?
Definition
within 3 months of diagnosis
Term
true/false
All DMARDS have same effect
Definition
false
all DMARDs have different effect
Term
what are non-biologic DMARDS?
Definition
methotrexate (rheumatrex)
leflunomide (Arava)
hydroxichloroquine
minicycline
sulfasalazine
gold, azzathioprine, D-penicilamine, cyclosporine, cyclophosphamide
Term
what are biologic DMARDS?
Definition
anti-TNF alfa: etanercept, infliximab, adalimumab
TNF alfa: abatacept, rituximab, anakinra, tocilizumab,
Term
what other agents are used for RA?
Definition
NSAIDs, CCSs
Term
what is a golden standard for RA?
Definition
methotrexate (Rheumatrex)- MTX
Term
What is MOA of MTX?
Definition
Inhibits cytokines, purines, stimulates adenosine
ANTI-INFLAMMATION
Term
Why TX is a treatment of choice for RA?
Definition
It is cheap and effective
Term
How long does it take for MTX to show the effect?
Definition
3-6 weeks, continue to improve for up to 12 weeks
Term
In what dosage forms MTX is available?
Definition
PO, IM, SC
Term
What is typical for MTX kinetics?
Definition
70% orally bioavailable
Protein bound
Excreted 80% unchanged
Term
What are SE of MTX?
Definition
N/V/D
Thrombocytopenia
Leukopenia
Pulmonary Fibrosis and pneumonitis – rare
Term
With presense of what SE pt should D/C MTX?
Definition
Pulmonary Fibrosis and pneumonitis,
LFT > 2x ULN
Term
When biopsy should be done before starting MTX?
Definition
Alcoholics
Hep B or C
Recurring high LFTs
Term
When biopsi should be done after starting MTX?
Definition
anormal LFTs
Term
Folic acid should not be added to the regimen with MTX because it diminish activity of MTX
true/false
Definition
false. FA does not diminish activity of MTX
Term
what drugs are pregnancy category X?
Definition
MTX, leflunomde
Term
What drug does not determined pregnancy category?
Definition
hydroxychloroquine
Term
what drugs can be used in all disease durations and severities?
Definition
MTX, leflunomide,
sulfasalazine
Term
How MTX can be dosed?
Definition
7.5 mg PO once wekly
or
2.5 mg PO Q 12 H TIW
Term
What is max weekly PO dose of MTX?
Definition
20 mg
Term
Can MTX be used for longer than 2 years?
Definition
Yes, but there is safety data only for 2 years.
Term
Can IM/SC decrease GI MTX SE?
Definition
Yes
Term
What is MOA of leflunomide?
Definition
Inhibits pyrimidine – Decreased lymphocyte proliferation
ANTI-INFLAMMATION
Term
What is an onset of action of leflunomide?
Definition
1 month
Term
How quickly steady state can be achieved with leflunomide without of loading dose?
Definition
Months
Term
What are SEs of leflunimide?
Definition
Dose related
N/V/D
Alopecia
Bone marrow depression
Term
What should be monitored when pt is taking leflunomde?
Definition
CBC monthly x 6 months, then q 6-8 weeks
LFT monthly X 3 months, then quaterly
Term
When leflunomide should be stopped?
Definition
LFTs >2x UNL
Term
What is a C/I for leflunomide?
Definition
liver disease
Term
How to dose leflunomide?
Definition
LD 100 mg PO daily x 3 days
MD 20 mg PO QD
Term
Can MD of leflunomide be adjusted?
Definition
Yes, if SE, by 10 mg/d
Term
Can we forego LD?
Definition
Yes, if worry about toxicity.
Term
What is a purpose of LD?
Definition
to decrease time to steady state
Term
How to care of leflunomide toxicty?
Definition
1. stop leflunomide
2. start cholestiramine 8 mg PO TID x 11 days
3. check leflunomde level 2 tests 14 days apart
4. add more cholestiramine if needed

can use activated charcoal 50 GM Q6 h x 24 h
Term
How does cholestiramine work?
Definition
It gets adsorbed to the drug and gets eliminated with feces.
Term
What is an onset of action of hydroxychloroquine?
Definition
6+ weeks
Term
what is considred a treatment failure for hydroxychloroquine?
Definition
6 months no relieve
Term
What is specil about kinetics of hydroxychloroquine?
Definition
Large Vd
Term
What are SE of hydroxychloroquine?
Definition
N/V/D – Take with food
Ocular – Monitor regularly
Term
When hydroxychloroquine can be used?
Definition
No poor prognostic features
Low disease activity
Duration <= 24 months
Term
What is a dose of hydroxychloroquine?
Definition
400-600 mg PO daily
can reduce after clinical response to 200-400 mg PO QD
Term
How does Minocycline work in RA?
Definition
Inhibits collagenase activity in synovial tissue
Inhibits protein synthesis in immune cells
Term
Minocycline - Kinetics
Definition
highly protein bound
Term
What are minocyclines SE?
Definition
GI
Thrush
liver damage
Photosensitivity (hyperpigmentation)
Term
Pt should use sunscreen whle taking minocycline?
Definition
false, sunscreen does not work, pt should avoid being on sun
Term
hat dose of minocyclne can be used in RA?
Definition
100 mg PO BID
Term
When minocycline can be used?
Definition
No poor prognostic features
Low disease activity
Duration < 6 months
Term
What agent is a prodrug?
Definition
sulfasalazine
Term
What is an active part of sulfasalazine?
Definition
Sulfapyradine is responsible for effect
Term
what is 5-ASA can be used for?
Definition
Chron disease, it stays in the gut
Term
when should one expect to see the respond to sulfasalazine?
Definition
in 4-12 weeks
Term
how shold one take Fe supplement while on sulfasalazine therapy?
Definition
need to separate by 4 hrs
Term
What are SE of sulfasalazine?
Definition
N/V/D/anorexia
Rash
Urticaria
Serum sickness
Hypersensitivity – contraindication
Yellow-orange skin and urine
Term
What dosage form of sulfasalazine is preffered for RA?
Definition
enteric coted
Term
When sulfasalazine can be indicated?
Definition
No poor prognostic features
All disease durations
All disease activities
Term
How to dose sulfasalazine?
Definition
0.5 – 1 gm PO daily x 1 week
Increase daily dose by 500 mg q week until 2 gm TDD (3 gm max)
Can titrate more slowly or divide dose to minimize AE
Term
What is a max dose for sulfasalazine?
Definition
3 GM
Term
what drugs can be used as monotherapy?
Definition
sulfasalazine, methotrexate, minocycline, hydroxychloroquine, leflunomide
Term
What agents are used for bridging
Definition
NSAIDs ad CCSs
Term
In What dosage forms CCSs are available for RA?
Definition
PO, IM, IV, Intraarticular
Term
What CCS is used for RA?
Definition
cortisone
Term
When intraarticular injection of CCS can be used?
Definition
It is reserved for bad cases
Small number of joints is involved
Less systemic effects
q 3 months
Not to exceed more than 2-3 times per year per joint
Term
What agents are reserved for treatment failure?
Definition
Biologics
Term
Biologic agents can be used with non-biologic
True.false
Definition
True, usually methotrexate
Term
What should be checked before start biologics?
Definition
presense of TB infection
Term
True/false
Biologics are less effective than non-biologics in RA treatment
Definition
False, they are as effective as non-biologics.
Term
Available in injection form
Definition
Etanercept (Enbrel), Infliximab (Remicade), Adalimumab (Humira), cortisone, methotrexate
Term
What are indicators for TNF alfa agents?
Definition
1. Early RA + high disease activity + poor prognosis + cost not an issue;
2. Intermediate or long standing RA + failed MTX monotherapy + moderate disease activity + poor prognosis;
3. Intermediate or long standing RA + failed MTX monotherapy + high disease activity;
4. Failed 2 or more non-biologic agents + moderate disease activity
Term
What is MOA of abatacept (Orencia)?
Definition
Binds receptors on antigen-presenting cells
Inhibits T-cells
Term
dosing of abatacept (Orencia)
Definition
Weight based

>100 kg – 1000 mg IV over 30 mins q 2 weeks at weeks 0, 2, and 4, then 1000 mg IV over 30 minutes q 4 weeks starting week 8

60 – 100 kg – 750 mg

<60 kg – 500 mg
Term
when abatacept (Orencia) is recommended?
Definition
Failure of MTX in combo with other DMARDs or sequential admin of other non-biologic DMARDs + moderate disease activity + poor prognosis
Term
What drugs are chimerics?
Definition
rituximab (Rituxan)
infliximab (Remicade)
Term
what is a cause of prolonged effect of rituximab (Rituxan)?
Definition
It binds to peripheral B cells permanently and depletes them
Term
true/false
intermittent therapy is possible with rituximab (Rituxan)
Definition
true
Term
What are SE of rituximab (Rituxan)?
Definition
infusion reaction (highest with first infuson), hematologic
Term
How to minimize infusion reaction with rituximab (Rituxan)?
Definition
Methylprednisolone 100 mg 30 minutes prior to infusion
also
Acetaminophen and antihistamines
Term
What monitoring should be done with rituximab (Rituxan)?
Definition
CBC q 2 and 4 months
Term
what is an indication for rituximab (Rituxan)?
Definition
Failed MTX in combination or failed sequential non-biologic DMARDs + High disease activity + poor prognosis
Term
dosing for rituximab (Rituxan)
Definition
1000 mg IV day 1 and 15
Administer subsequent courses based on clinical symptoms
Don’t give sooner than q 16 weeks
not set interval
Term
what is a last line TNF alfa agent?
Definition
anakinra (Kineret)
Term
dosing for anakinra (Kineret)
Definition
100 mg SC daily (timing is important)
Term
what is a SE of anakinra (Kineret)?
Definition
Injection site reaction
Term
true/false
anakinra must be combined with TNF infibitors
Definition
false
anakinra (Kineret) can't be combined with TNF inhibitors
Term
what are indications for tocilizumab (Actemra)?
Definition
Moderate to severe disease activity
Failed TNF inhibitor
Term
what is MOA of tocilizumab (Acterma)?
Definition
blocks IL-6
Term
what are SE of tocilizumab (Actemra)?
Definition
Can increase LFTs, LDL, HTN, GI perforations
Term
dosing for tocilizumab (Actemra)
Definition
4 mg/kg IV over 1 hour q 4 weeks
Titrate to 8 mg/kg
Do not infuse more than 800 mg at a time
Term
C/I for tocilizumab (Actemra) initiation
Definition
Absolute neutrophile count <2000, Platelets <100,000 or LFT >1.5x UNL
Term
what agent has weight based dosing?
Definition
Abatacept (Orencia)
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