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Arthritis > Rheumatoid Arthritis > Flashcards

Rheumatoid Arthritis Flashcards

1
Q

Is RA autoimmune?

A

Yes

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2
Q

Autoantibodies called ______ attack helathy tissue especially in the synovium

A

Rheumatoid factors (RF)

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3
Q

inflammation starts where in the joint?

A

synovial membrane

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4
Q

what is a pannus

A

vascular granulation tissue compoased of inflammatory cells; erodes cartilage and eventually distryos bone; bone losses density and secondary osteoporois occurs

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5
Q

What causes RF?

A

genetic and environmentap factors like age, virus infection, women

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6
Q

MOA of corticosteroids?

A

binds and block PLA2 to stop productino of arachidonic acid; and also crosses nucleus and dec DNA transcription

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7
Q

prednison is high or low protein bound?

A

high

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8
Q

metabolite of prednisone?

A

prednisolone

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9
Q

irreversible side effects of corticosteroids?

A

bone thinning and weakening

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10
Q

rare and non-reversible side effects of corticosteroids

A

softening or destruction of the hip,knee,wrist or foot joing (osteonecrosis)

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11
Q

common and reversible of steroids?

A

swelling, wt gain, inc BP, inc risk of infection, diabetes, mood swings, glaucoma

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12
Q

what are the differences between cox 1 and 2?

A

membrane binding domains and active sites

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13
Q

where is cox 3 expressed?

A

in the heart and the brain

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14
Q

does pCOX1 a/b have any catalytic activity?

A

no

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15
Q

which cox controls the infammatry response and which controls physiologic stimulus?

A

2 and 1 respectively

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16
Q

where does COX reside?

A

endoplasmic reticulum of cells in the cell membranes

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17
Q

where do the 2 chemical reactions occur in COX?

A

two different active sites that are mechanistcially coupled

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18
Q

What med is used to tx patent ductus arteriosus?

A

Indomethacin

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19
Q

What OTC drug is same potenacy as ASA but better tolerated?

A

Ibuprofen

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20
Q

What drug is an inactive prodrug closesly related to indomethacin used for inflammation?

A

Sulindac

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21
Q

Which NSAID is a very powerful anti-inflammatory durg but is limited by toxicity?

A

Phenylbutazone

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22
Q

What drug may also be good for asthmatics as well as inflammation?

A

ketoprofen

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23
Q

Why was COX-2 specific inhibitors thought be good

A

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

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24
Q

For pts with GI toxicity risk use what?

A

classic NSAID + PPI or H2

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25
Q

What is the place in tx of NSAIDs/ steroids and DMARDs?

A

Bridge/bridge/long term disease modifying

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26
Q

how does MTX work?

A

competitive inhibitor of DFHR; interferes with tetrahydrofolate and purines and thus affects immune cells/mucosal cells/ hair follicles

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27
Q

how often is MTX given for RA? Onset of action? Avoid in what populations

A

1/wk; 4-6wks; pregnancy,alcohol, sulfa

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28
Q

SE of MTX

A

malaise/n/rise in liver enzymes/fever

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29
Q

What drug do you supplement with when taking MTX?

A

Folic Acid

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30
Q

Hydroxychloroquine

A

Plaquenil; anti-malarial; in intracellular pH; dec cells ability to degrade and process proteins; onset is 6-12 wks

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31
Q

SE of Hydroxycholorquine

A

rash;n/d/accomodation;ocular/skeletal muscle/heart damage

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32
Q

Sulfasalazine is a combo of what?

A

Salicylic acid and sulfapyridine

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33
Q

What metabolizes sulfasalazine

A

bacteria

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34
Q

SE of sulfasalazine

A

associated with sulfapyridine: malaise,N,Rash,HA,Dz, hypersensitivity reaction

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35
Q

Leflunomide brand name and is it a pro drug?

A

DMARD, ARAVA, inactive prodrug converted to Terifluonomide in the GI tract and liver

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36
Q

What is the MOA of Leflunomide?

A

inhibits Dihydro-orotate dehydrogenase, an importatnt enxme in the de novo synthesis of pyrimidines

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37
Q

Onset of action of Leflunomide?

A

6-8wks

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38
Q

Is Leflunomide Teratogenic or avoid alcohol?

A

Yes

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39
Q

SE of leflunomide

A

D/N/malaise,HTN,alopecia,rash: RARE: liver and bone marrow damage, infection, cancer

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40
Q

What do you do if MTX isnt working by itself?

A

change to SQ MTX or add Leflunomide or add a biologic agent

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41
Q

brand name, category and MoA of Adalimumab

A

Humira/anti-TNF/blocking TNF receptor

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42
Q

Etenercept brand name/MOA

A

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

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43
Q

Which two anti-TNF are directed against TNF

A

infliximab and adalimumab

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44
Q

What anti-TNF is a soluble receptor

A

etanercept

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45
Q

Side effects of TNF-inhibitors

A

infection, TB, inc risk of lymphoma, MS, Seizures, Systemic Lupus Erythematosus

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46
Q

Non-TNF-inhibitors: Anakinra

A

Kineret/anti-IL1 receptor

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47
Q

abnormal lab findings for RF

A

Anti-CCP, RF, CRP, ESR, ANA, LE

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48
Q

which lab is diagnosis tof RA?

A

Anti-ccp, RF

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49
Q

what are diagnostic criteria of RA?

A

morning stiffness lasting for ore tjan 1 hr; swlling in 3 or more joints; swelling in had jooints; syymmmetric joint swelling

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50
Q

Which artritis has osteophytes?

A

Osteoarthritis

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51
Q

WHat is the difference between acute onset, chronic intermittent and chronic progressive RA?

A

acute onset spikes and goes away slowly,

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52
Q

which arthritis involves proximal joint of hand mostly and which involves distal part of hard primarily?

A

Proximal (herburdens) = RA; distal Buchards = OA

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53
Q

vasculitiis

A

small digital infarcts along the nail beds

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54
Q

What is the difference in 1st line tx for OA and RA?

A

analgesics vs. DMARDs

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55
Q

What is the last line for OA vs RA?

A

Intra- articular and opioids vs biologic agents

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56
Q

What do the DMARDs do?

A

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

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57
Q

What are the 5 DMARDs we studied?

A

MTX (Rheumatrex), Sulfasalazine (Azulfidine), Hydroxychloroquine (Plaquenil), Leflunomide (Arava), Minocycline (Minocin)

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58
Q

How often is MTX dosed for RA and how long does it take to work?

A

every week and it takes 4-6 wks to work (7.5mg/wk - 25mg/wk)

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59
Q

How often is Hydroxychloroquine given and how long does it take to work? Does it need to be given adjuctively?

A

doses daily; 2-4 months; Ocular toxicities and its for mild RA so should be given with something else.

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60
Q

Sulfasalazine dose regimen, how long it takes to work, SE and should you need Sun screen?

A

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

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61
Q

what DMARD is best for pregnancy?

A

Hydroxychloroquine

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62
Q

What DMARD do you have to supplement with FOlic Acid

A

MTX

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63
Q

What DMARD is preferred in liver diesase

A

Sulfasalazine

64
Q

What DMARD is contraindicated in pregnacy (cat X)

A

Leflunomide, MTX

65
Q

What is the dose and time to effect and side effects of Leflunomide?

A

daily, 4-8 wks (only MTX is faster); Diarrhea, GI upset, alopecia and inc LFTs; similar efficacy as MTX

66
Q

What two DMARDs cause alopecia?

A

Leflunomide and MTX

67
Q

What is the brand name, dose regimen, onset of action, SE and indication of Minocycline

A

Minocin, daily, 2-3 months, diarrhea, DZ, skin rash, sensitivity to TCN, For Mild RA

68
Q

What are two bridge therapy agents?

A

NSAIDs and Corticosteroids

69
Q

What two organ systems have issues with chronic NSAID use?

A

GI and CV

70
Q

Do you need low or high dose NSAIds for anti-inflammatory effect?

A

high

71
Q

Do you use high or low does Corticosteroids for RA?

A

low dose to minimize side effects

72
Q

does NSAIDs or OCS modify disease activities?

A

OCS may

73
Q

Does corticosteroids inhibit cox 1 or 2?

A

COX-2

74
Q

What are some cons of corticosteroids?

A

Doesnt stop disease progression, tapering has issues still, steroid induced osteopenia and reduce immune function

75
Q

What is the tx flow for RA?

A

DMARDs –> Biologic (combination)

76
Q

What cytokine is the most important to stop in RA?

A

TNF-a

77
Q

What two Anti-TNF biologics can be used as monotherapy?

A

Etanercept (embrel) or Adilumumab (Humira)

78
Q

Which Anti-TNF biologic is a soluble receptor decoy for TNF-a?

A

Embrel

79
Q

What is Golimumab and what is the brand name?

A

Simponi - anti-TNFa for RA

80
Q

What is Certolizumab pegol?

A

Cimzia; anti-TNF for RA

81
Q

What is infliximab?

A

Remicade Anti-TNFa for RA

82
Q

What are the 4 non-TNF biologic agents?

A

Anakinra (Kineret), Abatacept (Orencia), Rituximab (Rituxan), Tocilizumab (Actemra)

83
Q

What is the MOA of Anakinra?

A

Kineret; IL-1R antagonist

84
Q

What is the MOA of abatacept?

A

Orencia; CD-28 co stimulatory blocker; inhibits T cell activation

85
Q

What is the MOA of Rituximab?

A

inhibits CD-20; and causes B-cell depletion

86
Q

What is the MOA of Rituximab?

A

Rituxan; B-cell depletion

87
Q

What is the MOA of Tocilizumab?

A

Actemra; IL-6 receptor inhibitor

88
Q

Which med is a combo of two p75 TNF receptors binding for TNF-a

A

Etanercept

89
Q

What is the onset of action of Etanercept?

A

1-2wks

90
Q

if you discontinue the drug how long will it provide a similar response after stopping therapy?

A

18 months

91
Q

What category for pregnancy is Etanercept?

A

B

92
Q

What are the side effects of Etanercept and are long term side effects like cancer, and infections and autoimmune diseases known?

A

injection site reactions (may go away 3 months of regular dosing); HA, respiratiory infections, HA, rhinitis; long term side effects not known

93
Q

What TNF biologic is also used for Crohn’s disease and RA?

A

infliximab (remicade)

94
Q

What is 2-5 times higher in RA patients than the general population and then 6 times higher when taking infliximab (remicade)

A

lymphomas

95
Q

What was the 1st fully human TNF-a

A

Humira (adalimumab)

96
Q

How often is adalimumab administered?

A

Every 2 wks; every 1 wk to timprove repsone for patients not taking MTX; preg B (no experience in preg pts)

97
Q

Golimumab bran name is ________ and should it be used with or without MTX for RA?

A

Simponi; with MTX

98
Q

How often is Golimumab administered?

A

Every 4 weeks

99
Q

Which med is least frequent administration of the TNFa biologics?

A

Golimumab

100
Q

What is Certolizumab Pegol? Whats it used to tx? What is it used for? Is it monotherpay or combination? how often is it given?

A

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

101
Q

What med targets IL-1 and why?

A

Anakinra (Kineret); because IL-1 is a downstream product of TNF-a and is found in high concentrations is RA joints

102
Q

Is anakinra used in combination or by itself?

A

Used in combination in pts who do not respond adequately to MTX alone

103
Q

Which biologic has the lowest response rate?

A

Anakinra (Kineret)

104
Q

Is it a solulbe decoy receptor or an antibody that acts as on antagonist of IL-1R?

A

Anakinra is an antagonist

105
Q

Abatacept; what is the brand name and what does it target?

A

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

106
Q

When is Abatacept indicated?

A

When pts do not respond to DMARDs or TNF antagonists (mod to severe RA)

107
Q

Can Orencia be used by itself or with DMARDs or other TNF biologics?

A

Yes, Yes, No

108
Q

Why is Orencia (Abatacept) not recommened with the use of anakinra or other TNF antagonists?

A

Due to the risk of infection

109
Q

What is the response rate for Abatacept

A

12-16 wks typically; pts improve for up to 12 months

110
Q

What biologic targets b-cells and the CD-20 receptor and what does it do?

A

Rituximab (Rituxan) it doesnt allow for maturation of B cells

111
Q

When is Rituximab indicated? Can it be given in combination or alone

A

When pts dont have an adequate response to TNF antagonist therapies; alone or in combinate with cyclophosphamide or MTX

112
Q

Which drug has a two dose therapy that is good for 6 months?

A

Rituximab

113
Q

How is Rituximab administered?

A

two iv infusions over 2 wks with or without MTX

114
Q

What should you give along with rituximab to reduce allergic reactions?

A

methlyprednisolone 100 mg IV or rquivalent glucocorticoid is recommened 30 mins prior to each infusion

115
Q

WHat is the brand name of Tocilizumab and what does it target?

A

Actemra; IL-6

116
Q

What is the SE of Actemra?

A

infections; diverticular perforations and hypersensitivity reactions

117
Q

How often do you administer Actemra?

A

every 4 wks IV infusion with final assessment after 3rd infusion; can be used in pts refractoy to DMARDs and anti-TNF

118
Q

When can you use anti-TNF in early RA?

A

when there is HIGH disease activity

119
Q

When can you throw on a biologic typically?

A

When pts arent responsive to MTX monotherapy or 2 DMARDs

120
Q

What are the 5 BBW of biologic agents?

A

Active infections; active TB; fatal infusion reactions; tumor lysis syndrome; severe mucocutaneous reactions

121
Q

pts using ________ are at least 4 times more likely than average americans to get active TB.

A

Infliximab; highest risk during first 3 months; test pts for TB before using infliximab or biologics

122
Q

pts with latent TB and needing anti-TNFa should be given what first for how long?

A

isoliazid for 9 months; safe to start therapy after 1 month of isoizide tx

123
Q

there have een 45 deaths in pts taking etanercept, infliximab and adlimumab due to _________

A

fungal infections (histoplasmosis)

124
Q

Can shingles risk inc when taking anti-TNF? Which meds had a significant association?

A

yes infliximab and adalimumab

125
Q

What is the only oral inhibitor indicated for RA? What do they have to look out for?

A

Janus-associated Kinas (JAK); Tofacitinib (Xelianz); oral 5mg or 10mg BID; look out for infections and elevated cholesterol levels

126
Q

What is a possible thrid line agent?

A

Tofacitnib

127
Q

How often should drug therapy be adjusted?

A

Every 3 months

128
Q

What is the primary target for all pts?

A

remission

129
Q

in order to be in remission what must be the parameters?

A

tender joint count <1

130
Q

how long should someone recieve DMARD therapy?

A

6 months or greater

131
Q

for biologic therpay?

A

6 months or greater

132
Q

poor prognosis includes?

A

funcional limitations, extra-articular disease, pos RF or CCP antibody, bone erosions by radiograph

133
Q

other predicrots for poor RA outcomes

A

older pts, female gender, cig smoking, HAQ score

134
Q

pts who go from low to mederate/high disease activity after 3 months of DMARD monotherapy what do you do?

A

Add MTX/HCQ/LEF

135
Q

pts with moderate/high disease activity after 3 mos of MTX alone or MTX/DMARd combination what do you do

A

add anther non-MTX DMARD or switch to different non-MTX DMARD

136
Q

After trying MTX or DMARD Combination and still moderate to high disease what do you try? Or combination DMARDs

A

anti-TNF biologic

137
Q

When do you switch from one to another biologic?

A

when therapy isnt improving after 6 month

138
Q

Should vaccinations be given to pts before taking DMARD/biologic?

A

yes!

139
Q

What are the 5 BBW of biologic agents?

A

Active infections; active TB; fatal infusion reactions; tumor lysis syndrome; severe mucocutaneous reactions

140
Q

pts using ________ are at least 4 times more likely than average americans to get active TB.

A

Infliximab; highest risk during first 3 months; test pts for TB before using infliximab or biologics

141
Q

pts with latent TB and needing anti-TNFa should be given what first for how long?

A

isoliazid for 9 months; safe to start therapy after 1 month of isoizide tx

142
Q

there have een 45 deaths in pts taking etanercept, infliximab and adlimumab due to _________

A

fungal infections (histoplasmosis)

143
Q

Can shingles risk inc when taking anti-TNF? Which meds had a significant association?

A

yes infliximab and adalimumab

144
Q

What is the only oral inhibitor indicated for RA? What do they have to look out for?

A

Janus-associated Kinas (JAK); Tofacitinib (Xelianz); oral 5mg or 10mg BID; look out for infections and elevated cholesterol levels

145
Q

What is a possible thrid line agent?

A

Tofacitnib

146
Q

How often should drug therapy be adjusted?

A

Every 3 months

147
Q

What is the primary target for all pts?

A

remission

148
Q

in order to be in remission what must be the parameters?

A

tender joint count <1

149
Q

how long should someone recieve DMARD therapy?

A

6 months or greater

150
Q

for biologic therpay?

A

6 months or greater

151
Q

poor prognosis includes?

A

funcional limitations, extra-articular disease, pos RF or CCP antibody, bone erosions by radiograph

152
Q

other predicrots for poor RA outcomes

A

older pts, female gender, cig smoking, HAQ score

153
Q

pts who go from low to mederate/high disease activity after 3 months of DMARD monotherapy what do you do?

A

Add MTX/HCQ/LEF

154
Q

pts with moderate/high disease activity after 3 mos of MTX alone or MTX/DMARd combination what do you do

A

add anther non-MTX DMARD or switch to different non-MTX DMARD

155
Q

After trying MTX or DMARD Combination and still moderate to high disease what do you try? Or combination DMARDs

A

anti-TNF biologic

156
Q

When do you switch from one to another biologic?

A

when therapy isnt improving after 6 month

157
Q

Should vaccinations be given to pts before taking DMARD/biologic?

A

yes!

Arthritis (2 decks)

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