pc6 3.2.1 rheumatoid arthritis pharmacology

joint and synovium, but can cause problems in organs

RA effects what

women (gout is men)

is RA more common in women or men

HLA-DR4-HLA-DR1 antigens in MHC region on t lymphocytes

what genetic polymorphisms are associated with RA

smoking, pulmonary disease, infectious agents, periodontal disease, occupational hazards

what environmental factors are associated with RA

synovial and other connective tissue

RA patho:

the immune system is not able to differentiate self from non self tissue, it attacks ___

cell proliferation, inflammation, and destruction of tissues and fluids

RA patho:

the immune cascade dysregulation is multifactorial resulting in what

no

is the initial cause of the RA pathway known

proinflammatory cytokines and cell surface receptors CD28 and CD80/60

RA patho:

activation of T cell lymphocytes is done by what

tissue destruction, blood flow, leukocytes into synovial tissue, stimulate b cells

RA patho:

T cell lymphocytes induces production of cytotoxins and cytokines promote what

produce proinflammatory cytokines, stimulate osteoclasts, produce immunoglobines that activate the complement system

RA patho:

what do b cell lymphocytes do

TNF and IL

what proinflammatory cytokines do b cell lymphocytes produce

TNF, IL-1, IL-6, JAK

RA patho:

cytokines stimulate further migration causing inflammation from what pathways

joint pain, stiffness, fatigue, weakness, low grade fever, loss of appetite, tenderness/warmth/soft and swelling of joints

what symptoms are associated with RA

over 6 weeks and at least over 30 minutes

joint pain with RA is at what duration

morning, disease activity

duration of RA stiffness is correlated with what

proliferation of soft tissues or fluid accumulation

why do RA joints feel soft and spongy

symmetrical

is RA joint involvement asymmetrical or symmetrical

hands, wrists, feet

in RA what joints are most frequently affected

elbows, shoulders, hips, knees, ankyle

in RA what joints are less frequently affected

rheumatoid nodules, vasculitis, pulmonary complications, ocular manifestations, increased CV mortality, felty syndrome

what extra articular involvement does RA have

rheumatoid nodules

what are subcutaneous collections of palisading macrophages surrounded by lymphocytes and fibroblasts

vasculitis

what is caused by inflammation of arterial walls leading to narrowing and tissue ischemia and infart

pulmonary fibrosis, nodule formation

what kind of pulmonary complications are associated with RA

fetly syndrome

what is increased susceptibility to infection

dry eye, uvelitis, scleritis, cataracts, glaucoma, peripheral ulcerative keratitis, retinal vascular occlusion

how does arthritis affect the eye

none! not one single test can

which test can be used to make RA dx

RF , anti-CCP, ESR, CRP, hematological tests, joint fluid aspiration, joint radiographs

what lab tests are used to dx RA

IgM

rheumatoid factor is an antibody specific for what

no, not detectable in all patients

is RF reliable for disease activity

anticyclic citrullinated peptide

anti-CCP antibody tests for what

yes

does anti CCP antibody test have similar sensitivity to RF test

no, its more specific

does anti CCP antibody test have similar specificity to RF test

potentially very early in progression maybe even before symptoms

when is anti-CCP antibody detectable

worse

does positive anti-CCP antibody have a better or worse RA prognosis

no, general inflammation marker

are ESR and CRP specific to RA

CRP

what is produced in the liver in response to cytokines

synovitis of at least one joint with no other explanation

who are candidates for RA diagnositic criteria

6 or higher, but not all patients with RA will score a 6 or higher at first

what score is diagnostic for RA

joint involvement, serology, acute phase reactants, durations of symptoms

what categories are there within the RA dx criteria

treat to target approach

what involves frequent monitoring of disease activity and tx modification to reach a predefined target

remission, low disease activity

what is the target in, treat to target approach

no

do pharmacologic agents reverse RA joint damage

shorter

are patients with longer or shorter disease progression more likely to respond to tx

always

when should nonpharm interventions be considered in RA

rest, ot/pt therapy, exercise, assistive devices, weight loss, surgery, massage tx, ice, hot compress

what nonpharm options are there for RA

synthetic, biologic

what two categories of DMARDS are there

conventional, targeted specific

what subcategory is there of synthetic DMARDs

TNF inhibitors, non TNF inhibitors

what subcategory is there of biologic DMARDs

MTX, leflunomide, sulfasalazine, HCQ

conventional DMARDS (csDMARDs) include what

methotrexate/trexall

what is the DMARD of choice for most pts unless CI

inhibits dihydrofloate reductase, inhibits DNA synthesis, repair, and cellular replication

moa of methotrexate/trexall

folic acid

what must methotrexate be given with

folic acid deficiency, infection, pulmonary complications, GI problems, hematologic changes, hepatic toxicities

methotrexate AE

either

is MTX/trexall used as monotx or in combinations

PO, subQ

what dosage forms does methotrexate come in

MTX/trexall

what has a dosage range for 7.5-20mg

over 20mg

at was dose does methotrexate have increased toxicity

3-6 weeks

when does clinical benefit of methotrexate/trexall kick in

alcoholism, anemia, thrombocytopenia, immunodeficiency, preexisting hematologic disorders

CI of methotrexate/trexall

bone marrow suppression, hepatic disease, pregnancy

methotrexate/trexall black box warning

CBC w/diff, LFTs, renal function

what lab tests are done before and after methotrexate/trexall

2 to 4 weeks

for the first 3 months of methotrexate therapy how often is monitoring done

8 to 12 weeks

for the third to sixth month of methotrexate therapy how often is monitoring done

12 weeks

after 6 months of methotrexate therapy how often is monitoring done

inhibits pyrimidine synthesis

MOA of leflunomide

either

can leflunomide be used as monotherapy or in combo

leflunomide

what has a maintenance dose of 20 daily but can be decreased to 10mg if not tolerated

PO

what dosage form does leflunomide come in

low risk hepatotoxicity, myelosuppression

when is the loading dose of 100mg x 3 done in leflunomide tx

cholestyramine

due to its long half life, what is given if rapid elimination of leflunomide needed

pregnancy, toxicity

when would you need a leflunomide washout

bp, cbc w/diff, LFTs, renal function

lab tests for leflunomide

diarrhea, elevated liver enzymes, alopecia, elevated BP, rash

AE of leflunomide

3x ULN

what ALT result indicates leflunomide should be discontinued

pregnant, nursing mothers, severe hepatic impairment

leflunomide should be avoided in whom

yes

dose leflunomide have the same monitoring schedule as MTX

unknown, maybe immunomodulating, anti inflammatory, prodrug with 5-ASA and sulfapyridine

MOA of sulfasalazine

either

is sulfasalazine used as monotherapy or in combination

sulfasalazine

what has a starting dose of 500-100mg PO daily

then increased by 500 weekly to 2g in 2-3 daily doses

PO

what dosage forms does sulfasalazine come in

4-12 weeks

when is clinical benefits seen in sulfasalazine tx

12 weeks

sulfasalazine can be titrated up to 3g if insufficient response after how much time

sulonfamide allergy, salicylate allergy, GI, urinary obstruction

CI of sulfasalazine

renal impairment, pregnant, nursing

sulfasalazine should be used in caution with what pts

CBC w/diff, LFTs, renal function

baseline monitoring of sulfasalazine

diarrhea, n/v, anorexia-which limits use, urine/skin discoloration

AE of sulfasalazine

yes, but still can use in pregnant and nursing

does sulfasalazine cross the placenta into breast milk

yes

does sulfasalazine have the same monitoring schedule as leflunomide and MTX

plaquenil

brand name of hydroxychloroquine

maybe anti inflammatory, interfere with antigen processing in macrophages

moa of hydroxychloroquine/plaquenil

hydroxychloroquine/plaquenil

what is the DOC in low disease ra activity

both

is hydroxychloroquine/plaquenil used as monotherapy or in combo

PO

what dosage forms does hydroxychloroquine/plaquenil come in

hydroxychloroquine/plaquenil

what has a dosage form of 400-600mg daily in single or divided doses

yes

does hydroxychloroquine/plaquenil have a delayed clinical benefit

n/v ,diarrhea, irreversible rentinal damage

common AE of hydroxychloroquine/plaquenil

take with food, split into two doses

how can you reduce hydroxychloroquine/plaquenil G Iside effects

annually

due to the risk of irreversible rentinal damage, how often should eye exams be done in hydroxychloroquine/plaquenil use if risk factors present

every 5 years

due to the risk of irreversible rentinal damage, how often should eye exams be done in hydroxychloroquine/plaquenil use if risk factors NOT present

low body weight, renal/hepatitic impairment, doses over 6.5 mg/kg, history of ocular disease

risk factors for hydroxychloroquin/plaquenil irreversible retinal damage