Rheumatoid Arthritis Flashcards
Is RA autoimmune?
Yes
Autoantibodies called ______ attack helathy tissue especially in the synovium
Rheumatoid factors (RF)
inflammation starts where in the joint?
synovial membrane
what is a pannus
vascular granulation tissue compoased of inflammatory cells; erodes cartilage and eventually distryos bone; bone losses density and secondary osteoporois occurs
What causes RF?
genetic and environmentap factors like age, virus infection, women
MOA of corticosteroids?
binds and block PLA2 to stop productino of arachidonic acid; and also crosses nucleus and dec DNA transcription
prednison is high or low protein bound?
high
metabolite of prednisone?
prednisolone
irreversible side effects of corticosteroids?
bone thinning and weakening
rare and non-reversible side effects of corticosteroids
softening or destruction of the hip,knee,wrist or foot joing (osteonecrosis)
common and reversible of steroids?
swelling, wt gain, inc BP, inc risk of infection, diabetes, mood swings, glaucoma
what are the differences between cox 1 and 2?
membrane binding domains and active sites
where is cox 3 expressed?
in the heart and the brain
does pCOX1 a/b have any catalytic activity?
no
which cox controls the infammatry response and which controls physiologic stimulus?
2 and 1 respectively
where does COX reside?
endoplasmic reticulum of cells in the cell membranes
where do the 2 chemical reactions occur in COX?
two different active sites that are mechanistcially coupled
What med is used to tx patent ductus arteriosus?
Indomethacin
What OTC drug is same potenacy as ASA but better tolerated?
Ibuprofen
What drug is an inactive prodrug closesly related to indomethacin used for inflammation?
Sulindac
Which NSAID is a very powerful anti-inflammatory durg but is limited by toxicity?
Phenylbutazone
What drug may also be good for asthmatics as well as inflammation?
ketoprofen
Why was COX-2 specific inhibitors thought be good
because it avoided inhibiting the normal physiological effects of COX1 like GI maintenence inhibiton but it lead to a potential risk of MI and ischemic stroke
For pts with GI toxicity risk use what?
classic NSAID + PPI or H2
What is the place in tx of NSAIDs/ steroids and DMARDs?
Bridge/bridge/long term disease modifying
how does MTX work?
competitive inhibitor of DFHR; interferes with tetrahydrofolate and purines and thus affects immune cells/mucosal cells/ hair follicles
how often is MTX given for RA? Onset of action? Avoid in what populations
1/wk; 4-6wks; pregnancy,alcohol, sulfa
SE of MTX
malaise/n/rise in liver enzymes/fever
What drug do you supplement with when taking MTX?
Folic Acid
Hydroxychloroquine
Plaquenil; anti-malarial; in intracellular pH; dec cells ability to degrade and process proteins; onset is 6-12 wks
SE of Hydroxycholorquine
rash;n/d/accomodation;ocular/skeletal muscle/heart damage
Sulfasalazine is a combo of what?
Salicylic acid and sulfapyridine
What metabolizes sulfasalazine
bacteria
SE of sulfasalazine
associated with sulfapyridine: malaise,N,Rash,HA,Dz, hypersensitivity reaction
Leflunomide brand name and is it a pro drug?
DMARD, ARAVA, inactive prodrug converted to Terifluonomide in the GI tract and liver
What is the MOA of Leflunomide?
inhibits Dihydro-orotate dehydrogenase, an importatnt enxme in the de novo synthesis of pyrimidines
Onset of action of Leflunomide?
6-8wks
Is Leflunomide Teratogenic or avoid alcohol?
Yes
SE of leflunomide
D/N/malaise,HTN,alopecia,rash: RARE: liver and bone marrow damage, infection, cancer
What do you do if MTX isnt working by itself?
change to SQ MTX or add Leflunomide or add a biologic agent
brand name, category and MoA of Adalimumab
Humira/anti-TNF/blocking TNF receptor
Etenercept brand name/MOA
Embrel; fusion of soluble TNF receptor 2 to Fc component of human IgG; functioning decoy receptor that binds to TNF and blocks it from binding to the TNF receptor
Which two anti-TNF are directed against TNF
infliximab and adalimumab
What anti-TNF is a soluble receptor
etanercept
Side effects of TNF-inhibitors
infection, TB, inc risk of lymphoma, MS, Seizures, Systemic Lupus Erythematosus
Non-TNF-inhibitors: Anakinra
Kineret/anti-IL1 receptor
abnormal lab findings for RF
Anti-CCP, RF, CRP, ESR, ANA, LE
which lab is diagnosis tof RA?
Anti-ccp, RF
what are diagnostic criteria of RA?
morning stiffness lasting for ore tjan 1 hr; swlling in 3 or more joints; swelling in had jooints; syymmmetric joint swelling
Which artritis has osteophytes?
Osteoarthritis
WHat is the difference between acute onset, chronic intermittent and chronic progressive RA?
acute onset spikes and goes away slowly,
which arthritis involves proximal joint of hand mostly and which involves distal part of hard primarily?
Proximal (herburdens) = RA; distal Buchards = OA
vasculitiis
small digital infarcts along the nail beds
What is the difference in 1st line tx for OA and RA?
analgesics vs. DMARDs
What is the last line for OA vs RA?
Intra- articular and opioids vs biologic agents
What do the DMARDs do?
They slow down disease progression and joint erosins but can take up to 4-8 wks to start working; they also improve functional disablitiy and dec pain
What are the 5 DMARDs we studied?
MTX (Rheumatrex), Sulfasalazine (Azulfidine), Hydroxychloroquine (Plaquenil), Leflunomide (Arava), Minocycline (Minocin)
How often is MTX dosed for RA and how long does it take to work?
every week and it takes 4-6 wks to work (7.5mg/wk - 25mg/wk)
How often is Hydroxychloroquine given and how long does it take to work? Does it need to be given adjuctively?
doses daily; 2-4 months; Ocular toxicities and its for mild RA so should be given with something else.
Sulfasalazine dose regimen, how long it takes to work, SE and should you need Sun screen?
dosed daily; 6-12 weeks to work; GI and inc LFT (preferred over MTX for liver disease); may have allergy to sulfa and must use sunscreen BUT less effective than MTX
what DMARD is best for pregnancy?
Hydroxychloroquine
What DMARD do you have to supplement with FOlic Acid
MTX
What DMARD is preferred in liver diesase
Sulfasalazine
What DMARD is contraindicated in pregnacy (cat X)
Leflunomide, MTX
What is the dose and time to effect and side effects of Leflunomide?
daily, 4-8 wks (only MTX is faster); Diarrhea, GI upset, alopecia and inc LFTs; similar efficacy as MTX
What two DMARDs cause alopecia?
Leflunomide and MTX
What is the brand name, dose regimen, onset of action, SE and indication of Minocycline
Minocin, daily, 2-3 months, diarrhea, DZ, skin rash, sensitivity to TCN, For Mild RA
What are two bridge therapy agents?
NSAIDs and Corticosteroids
What two organ systems have issues with chronic NSAID use?
GI and CV
Do you need low or high dose NSAIds for anti-inflammatory effect?
high
Do you use high or low does Corticosteroids for RA?
low dose to minimize side effects
does NSAIDs or OCS modify disease activities?
OCS may
Does corticosteroids inhibit cox 1 or 2?
COX-2
What are some cons of corticosteroids?
Doesnt stop disease progression, tapering has issues still, steroid induced osteopenia and reduce immune function
What is the tx flow for RA?
DMARDs –> Biologic (combination)
What cytokine is the most important to stop in RA?
TNF-a
What two Anti-TNF biologics can be used as monotherapy?
Etanercept (embrel) or Adilumumab (Humira)
Which Anti-TNF biologic is a soluble receptor decoy for TNF-a?
Embrel
What is Golimumab and what is the brand name?
Simponi - anti-TNFa for RA
What is Certolizumab pegol?
Cimzia; anti-TNF for RA
What is infliximab?
Remicade Anti-TNFa for RA
What are the 4 non-TNF biologic agents?
Anakinra (Kineret), Abatacept (Orencia), Rituximab (Rituxan), Tocilizumab (Actemra)
What is the MOA of Anakinra?
Kineret; IL-1R antagonist
What is the MOA of abatacept?
Orencia; CD-28 co stimulatory blocker; inhibits T cell activation
What is the MOA of Rituximab?
inhibits CD-20; and causes B-cell depletion
What is the MOA of Rituximab?
Rituxan; B-cell depletion
What is the MOA of Tocilizumab?
Actemra; IL-6 receptor inhibitor
Which med is a combo of two p75 TNF receptors binding for TNF-a
Etanercept
What is the onset of action of Etanercept?
1-2wks
if you discontinue the drug how long will it provide a similar response after stopping therapy?
18 months
What category for pregnancy is Etanercept?
B
What are the side effects of Etanercept and are long term side effects like cancer, and infections and autoimmune diseases known?
injection site reactions (may go away 3 months of regular dosing); HA, respiratiory infections, HA, rhinitis; long term side effects not known
What TNF biologic is also used for Crohn’s disease and RA?
infliximab (remicade)
What is 2-5 times higher in RA patients than the general population and then 6 times higher when taking infliximab (remicade)
lymphomas
What was the 1st fully human TNF-a
Humira (adalimumab)
How often is adalimumab administered?
Every 2 wks; every 1 wk to timprove repsone for patients not taking MTX; preg B (no experience in preg pts)
Golimumab bran name is ________ and should it be used with or without MTX for RA?
Simponi; with MTX
How often is Golimumab administered?
Every 4 weeks
Which med is least frequent administration of the TNFa biologics?
Golimumab
What is Certolizumab Pegol? Whats it used to tx? What is it used for? Is it monotherpay or combination? how often is it given?
anti-TNFa med; used to tx RA; for moderatie to severe RA; can be used in combination or as monotherapy with MTX; doses every 2 wks
What med targets IL-1 and why?
Anakinra (Kineret); because IL-1 is a downstream product of TNF-a and is found in high concentrations is RA joints
Is anakinra used in combination or by itself?
Used in combination in pts who do not respond adequately to MTX alone
Which biologic has the lowest response rate?
Anakinra (Kineret)
Is it a solulbe decoy receptor or an antibody that acts as on antagonist of IL-1R?
Anakinra is an antagonist
Abatacept; what is the brand name and what does it target?
Orencia; it targets the activation of naive T-cells to activated T-cells by binding to CD80 and CD86 which prevents the binding of CD 28 and thus activation of T cells
When is Abatacept indicated?
When pts do not respond to DMARDs or TNF antagonists (mod to severe RA)
Can Orencia be used by itself or with DMARDs or other TNF biologics?
Yes, Yes, No
Why is Orencia (Abatacept) not recommened with the use of anakinra or other TNF antagonists?
Due to the risk of infection
What is the response rate for Abatacept
12-16 wks typically; pts improve for up to 12 months
What biologic targets b-cells and the CD-20 receptor and what does it do?
Rituximab (Rituxan) it doesnt allow for maturation of B cells
When is Rituximab indicated? Can it be given in combination or alone
When pts dont have an adequate response to TNF antagonist therapies; alone or in combinate with cyclophosphamide or MTX
Which drug has a two dose therapy that is good for 6 months?
Rituximab
How is Rituximab administered?
two iv infusions over 2 wks with or without MTX
What should you give along with rituximab to reduce allergic reactions?
methlyprednisolone 100 mg IV or rquivalent glucocorticoid is recommened 30 mins prior to each infusion
WHat is the brand name of Tocilizumab and what does it target?
Actemra; IL-6
What is the SE of Actemra?
infections; diverticular perforations and hypersensitivity reactions
How often do you administer Actemra?
every 4 wks IV infusion with final assessment after 3rd infusion; can be used in pts refractoy to DMARDs and anti-TNF
When can you use anti-TNF in early RA?
when there is HIGH disease activity
When can you throw on a biologic typically?
When pts arent responsive to MTX monotherapy or 2 DMARDs
What are the 5 BBW of biologic agents?
Active infections; active TB; fatal infusion reactions; tumor lysis syndrome; severe mucocutaneous reactions
pts using ________ are at least 4 times more likely than average americans to get active TB.
Infliximab; highest risk during first 3 months; test pts for TB before using infliximab or biologics
pts with latent TB and needing anti-TNFa should be given what first for how long?
isoliazid for 9 months; safe to start therapy after 1 month of isoizide tx
there have een 45 deaths in pts taking etanercept, infliximab and adlimumab due to _________
fungal infections (histoplasmosis)
Can shingles risk inc when taking anti-TNF? Which meds had a significant association?
yes infliximab and adalimumab
What is the only oral inhibitor indicated for RA? What do they have to look out for?
Janus-associated Kinas (JAK); Tofacitinib (Xelianz); oral 5mg or 10mg BID; look out for infections and elevated cholesterol levels
What is a possible thrid line agent?
Tofacitnib
How often should drug therapy be adjusted?
Every 3 months
What is the primary target for all pts?
remission
in order to be in remission what must be the parameters?
tender joint count <1
how long should someone recieve DMARD therapy?
6 months or greater
for biologic therpay?
6 months or greater
poor prognosis includes?
funcional limitations, extra-articular disease, pos RF or CCP antibody, bone erosions by radiograph
other predicrots for poor RA outcomes
older pts, female gender, cig smoking, HAQ score
pts who go from low to mederate/high disease activity after 3 months of DMARD monotherapy what do you do?
Add MTX/HCQ/LEF
pts with moderate/high disease activity after 3 mos of MTX alone or MTX/DMARd combination what do you do
add anther non-MTX DMARD or switch to different non-MTX DMARD
After trying MTX or DMARD Combination and still moderate to high disease what do you try? Or combination DMARDs
anti-TNF biologic
When do you switch from one to another biologic?
when therapy isnt improving after 6 month
Should vaccinations be given to pts before taking DMARD/biologic?
yes!
What are the 5 BBW of biologic agents?
Active infections; active TB; fatal infusion reactions; tumor lysis syndrome; severe mucocutaneous reactions
pts using ________ are at least 4 times more likely than average americans to get active TB.
Infliximab; highest risk during first 3 months; test pts for TB before using infliximab or biologics
pts with latent TB and needing anti-TNFa should be given what first for how long?
isoliazid for 9 months; safe to start therapy after 1 month of isoizide tx
there have een 45 deaths in pts taking etanercept, infliximab and adlimumab due to _________
fungal infections (histoplasmosis)
Can shingles risk inc when taking anti-TNF? Which meds had a significant association?
yes infliximab and adalimumab
What is the only oral inhibitor indicated for RA? What do they have to look out for?
Janus-associated Kinas (JAK); Tofacitinib (Xelianz); oral 5mg or 10mg BID; look out for infections and elevated cholesterol levels
What is a possible thrid line agent?
Tofacitnib
How often should drug therapy be adjusted?
Every 3 months
What is the primary target for all pts?
remission
in order to be in remission what must be the parameters?
tender joint count <1
how long should someone recieve DMARD therapy?
6 months or greater
for biologic therpay?
6 months or greater
poor prognosis includes?
funcional limitations, extra-articular disease, pos RF or CCP antibody, bone erosions by radiograph
other predicrots for poor RA outcomes
older pts, female gender, cig smoking, HAQ score
pts who go from low to mederate/high disease activity after 3 months of DMARD monotherapy what do you do?
Add MTX/HCQ/LEF
pts with moderate/high disease activity after 3 mos of MTX alone or MTX/DMARd combination what do you do
add anther non-MTX DMARD or switch to different non-MTX DMARD
After trying MTX or DMARD Combination and still moderate to high disease what do you try? Or combination DMARDs
anti-TNF biologic
When do you switch from one to another biologic?
when therapy isnt improving after 6 month
Should vaccinations be given to pts before taking DMARD/biologic?
yes!
