Pharm - Disease-Modifying Anti-Rheumatic Drugs

Question 1

what is the first drug of choice for RA pain relief

what can be added for additional relief

Answer 1

NSAIDs

acetominophen

Question 2

MOA and effects glucocorticoids - prednisone

Answer 2

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 3

indications for glucocorticoids like prednisone

Answer 3

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 4

adverse effects glucocorticoids

Answer 4

• cushing’s
• DM
• fluid retention
• menstrual irregularities

many side effects

Question 5

how is “mild” RA classified

Answer 5

5 or less inflamed joints

normal to increased ESR and CRP

no extra-articular dz

no evidence of erosions or cartilage loss on plain radiographs

most pts lack RF or CCP antibodies

Question 6

how is “moderate” RA classified

Answer 6

more than 5 inflamed joints

increased ESR and CRP

positive RF and/or CCP antibodies

evidence of inflammation on plain radiographs

Question 7

MOA methotrexate

Answer 7

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 8

indications methotrexate

Answer 8

drug of first choice for RA

often used in combo w/ other traditional DMARD

Question 9

administration of methotrexate

Answer 9

once per week either orally or injection

Question 10

adverse effects methotrexate

Answer 10

bone marrow suppression

hepatic fibrosis

GI ulceration

pneumonitis

fetal death

Question 11

MOA hydroxychloroquine

Answer 11

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 12

indications hydroxychloroquine

Answer 12

antimalarial

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

Question 13

can hydroxychloroquine be used during pregnancy?

Answer 13

yep

Question 14

half life of hydroxychloroquine

Answer 14

23 days so loading doses are needed to speed up onset

Question 15

adverse effects hydroxychloroquine

Answer 15

retinal damage

Question 16

MOA sulfasalazine

Answer 16

metabolized to sulfapyridine –> active moiety in RA patients

Question 17

indications sulfasalazine

Answer 17

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

Question 18

side effects sulfasalazine

Answer 18

GI side effects

sulfa drug reactions

Question 19

MOA leflunomide

Answer 19

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

Question 20

indications leflunomide

Answer 20

second choice drug for RA

Question 21

half life leflunomide

Answer 21

16.5 days, so loading doses are needed

Question 22

adverse effects leflunomide

Answer 22

diarrhea, respiratory infection, reversible alopecia, rash

stevens johnson syndrmoe

Question 23

should biologic DMARDs be combined?

Answer 23

NEVER

Question 24

what do these suffixes indicate:

• cept
• mab
• ximab
• zumab
• umab

Answer 24

• 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 25

effects of TNF antagonists

Answer 25

reducing RA symptoms and dz progression

Question 26

indications for TNF antagonists

Answer 26

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

Question 27

adverse effects TNF antagonists

Answer 27

developing serious infections including TB

Question 28

list the TNF antagonists

Answer 28

etanercept infliximab adalimumab (Humira)

Question 29

MOA, indications, and administration of etanercept

Answer 29

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

Question 30

MOA, indications, and administration of infliximab

Answer 30

TNF antagonist inflammatory arthritis, IBD IV infusion every 6 weeks

Question 31

MOA, indications, and administration of adalimumab

Answer 31

TNF antagonist RA, psoriatic arthritis, ankylosing spondylitis, crohn's IV infusion every 2 weeks

Question 32

MOA rituximab

Answer 32

antibody targeting CD20

Question 33

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

Answer 33

plasma cells have a resistance to rituximab because they do not have CD20 on their surface

Question 34

indications rituximab

Answer 34

non-hodgkin's lymphoma, chronic lymphocytic leukemia RA pts who have not responded to TNF antagonists positive testing for RF and CCP antibodies predict greater likelihood of responsiveness

Question 35

adverse effects rituximab

Answer 35

infusion related hypersensitivity rxns stevens johnson syndrome hep B reactivation

Question 36

MOA abatacept

Answer 36

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

Question 37

indications abatacept

Answer 37

moderate to severe RA, generally not used until after failure of TNF antagonists

Question 38

adverse effects abatacept

Answer 38

headache, URI, serious infections

Question 39

MOA and effects of tocilizumab

Answer 39

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 40

indications tocilizumab

Answer 40

moderate to severe RA if other DMARDs and TNF antagonists have been ineffective

Question 41

adverse effects tocilizumab

Answer 41

URIs life threatening infections

Question 42

MOA tofacitinib

Answer 42

JAK3 antagonist suppresses production of IL-17 and IFN-y and proliferation of CD4 T cells

Question 43

indications tofacitinib

Answer 43

moderately to severely active RA who had an inadequate response to methotrexate

Question 44

administration of tofacitinib

Answer 44

oral (unusual among the DMARDs) ***

Question 45

adverse effects tofacitinib

Answer 45

serious infections by opportunistic pathogens increased malignancies

Question 46

MOA anakinra

Answer 46

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

Question 47

indications anakinra

Answer 47

moderate to severe RA that has not responded to DMARDs

Question 48

adverse effects anakinra

Answer 48

serious infections hypersensitivity reactions