Pharm - Disease-Modifying Anti-Rheumatic Drugs COPY

Question 1

MOA and effects glucocorticoids - prednisone

Answer 1

binds to glucocorticoid receptor which complexes with NF-kB and AP-1 transcription factors –> indirect mechanism for immunosuppression reduces activity of immune system via suppression of IL-1,2,3,4,5,6,8 and IFN-y suppresses neutrophil migration decreases eosinophils in the blood and tissue

Question 2

indications for glucocorticoids like prednisone

Answer 2

added to a regimen for RA for a short period to rapidly minimized disease activity while awaiting clinical response to a slower-acting disease-modifying anti-rheumatic drug (DMARD) **effective for up to 6 months

Question 3

MOA methotrexate

Answer 3

polyglutamation –> MTX-glu –> accumulates in cells over weeks –> blocks thymidylate synthase and 5-aminoimidazole-4-carboxamide ribodnucleotide (AICAR) transformylase –> accumulation of AICAR –> adenosine efflux –> binds to purinergic GPCRs –> ANTI-INFLAMMATORY EFFECTS

Question 4

indications methotrexate

Answer 4

drug of first choice for RA often used in combo w/ other traditional DMARD

Question 5

adverse effects methotrexate

Answer 5

bone marrow suppression hepatic fibrosis GI ulceration pneumonitis fetal death

Question 6

MOA hydroxychloroquine

Answer 6

accumulates in lysosomes and then protonated –> increases pH of lysosome from 4 to 6 –> limits association of peptides with class II MHC –> slows dz progression

Question 7

indications hydroxychloroquine

Answer 7

antimalarial can be first choice for mild RA with lack of poor prognostic features

often combined with methotrexate ± sulfasalazine in an attempt to control more severe rheumatoid arthritis

Question 8

can hydroxychloroquine be used during pregnancy?

Answer 8

yep

Question 9

half life of hydroxychloroquine

Answer 9

23 days so loading doses are needed to speed up onset

Question 10

adverse effects hydroxychloroquine

Answer 10

retinal damage

Question 11

MOA sulfasalazine

Answer 11

metabolized to sulfapyridine –> active moiety in RA patients

Question 12

indications sulfasalazine

Answer 12

RA - used alone or in combo with hydroxychloroquine and/or methotrexate (triple therapy)

Question 13

side effects sulfasalazine

Answer 13

GI side effects sulfa drug reactions

Question 14

MOA leflunomide

Answer 14

inhibition of mitochondrial enzyme dihydroorotate dehydrogenase to block the synthesis of the pyrmidine rUMP –> inhibits T cell proliferation

Question 15

indications leflunomide

Answer 15

second choice drug for RA

used in combination with methotrexate, sufasalazine or hydroxychloroquine

Question 16

half life leflunomide

Answer 16

16.5 days, so loading doses are needed

Question 17

adverse effects leflunomide

Answer 17

diarrhea, respiratory infection, reversible alopecia, rash stevens johnson syndrmoe

Question 18

should biologic DMARDs be combined?

Answer 18

NEVER

Question 19

what do these suffixes indicate: - cept - mab - ximab - zumab - umab

Answer 19

• cept: fusion of receptor to Fc portion of human IgG1
• mab: monoclonal antibody
• ximab: chimeric monoclonal antibody
• zumab: humanized monoclonal antibody
• umab: human monoclonal antibody

Question 20

effects of TNF antagonists

Answer 20

 highly effective at reducing rheumatoid arthritis symptoms and disease progression

indicated for moderate to severe rheumatoid arthritis, generally after traditional DMARDs have proven to be ineffective

often used in combination with methotrexate

Question 21

indications for TNF antagonists

Answer 21

moderate to severe RA, generally after traditional DMARDs have been proven to be ineffective often used in combo with methotrexate

Question 22

adverse effects TNF antagonists

Answer 22

developing serious infections including TB

severe allergic reactions

Question 23

list the TNF antagonists

Answer 23

etanercept infliximab adalimumab (Humira)

Question 24

MOA, indications, and administration of etanercept

Answer 24

TNF antagonist a number of forms of inflammatory arthritis including RA, psoriatic arthritis, ankylosing spondylitis 1 or 2 x weekly SC

Question 25

MOA, indications, and administration of infliximab

Answer 25

TNF antagonist inflammatory arthritis, IBD **IV infusion every 6 weeks**

Question 26

MOA, indications, and administration of adalimumab

Answer 26

TNF antagonist RA, psoriatic arthritis, ankylosing spondylitis, crohn's ## Footnote **subcutaneous infusion every 2 weeks**

Question 27

MOA rituximab

Answer 27

antibody targeting CD20

Question 28

when taking rituximab, how do immunoglobulin levels stay in the normal range despite targeting CD20

Answer 28

plasma cells have a resistance to rituximab because they do not have CD20 on their surface overall immunoglobulin levels usually remain within the normal range, despite profound B cell lymphopenia that persists for months following a single course of treatment  levels of autoantibodies with the potential for roles in disease pathophysiology are affected by B cell depletion

Question 29

indications rituximab

Answer 29

non-hodgkin's lymphoma, chronic lymphocytic leukemia RA pts who have not responded to TNF antagonists ## Footnote **positive testing for RF and CCP antibodies predict greater likelihood of responsiveness** **indicated in combination with methotrexate for patients with rheumatoid arthritis​**

Question 30

adverse effects rituximab

Answer 30

**infusion related hypersensitivity rxns** stevens johnson syndrome hep B reactivation

Question 31

MOA abatacept

Answer 31

compromises CTLA-4 and Fc portion of IgG1 ## Footnote **prevents CD28 from binding to CD80/CD86**

Question 32

indications abatacept

Answer 32

**moderate to severe RA**, generally not used until after failure of TNF antagonists ## Footnote **can be used in combination with nonbiological DMARDs (e.g., methotrexate)**

Question 33

adverse effects abatacept

Answer 33

generally well tolerated **can increase the risk of serious infections**, most often pneumonia, cellulitis, bronchitis, diverticulitis, pyelonephritis and urinary tract infections

Question 34

MOA and effects of tocilizumab

Answer 34

**humanized anti-human IL-6 receptor** antibody can't activate JAK kinases and RAS mediated signaling limits hepatic acute phase response and activation of T and B cells

Question 35

indications tocilizumab

Answer 35

moderate to severe RA if other DMARDs and TNF antagonists have been ineffective ## Footnote **can be used with or without methotrexate**

Question 36

adverse effects tocilizumab

Answer 36

**URIs, life threatening infections**

Question 37

MOA tofacitinib

Answer 37

**JAK3 antagonist suppresses production of IL-17 and IFN-y and proliferation of CD4 T cells** **used with or without methotrexate**

Question 38

indications tofacitinib

Answer 38

moderately to severely active RA who had an inadequate response to methotrexate ## Footnote **considered less efficacious than other biologic DMARDs, so a late choice**

Question 39

administration of tofacitinib

Answer 39

**oral** (unusual among the DMARDs) \*\*\*

Question 40

adverse effects tofacitinib

Answer 40

serious infections by opportunistic pathogens increased malignancies

Question 41

MOA anakinra

Answer 41

IL-1 receptor antagonist blocks pro-inflammatory activity of IL-1

Question 42

indications anakinra

Answer 42

moderate to severe RA that has not responded to DMARDs

Question 43

adverse effects anakinra

Answer 43

**serious infections, hypersensitivity reactions**