drugs for rheumatoid arthritis and other rheum diseases

Question 1

NSAIDs major risk include (3)

Answer 1

1. Gi bleed
2. HTN and renal failure
3. coronary vascular disease

Question 2

NSAIDs facts to consider

1. older adults
2. testing
3. higher CV risk

Answer 2

1. older adults- use a proton pump inhibitors
2. testing kidney function and blood pressure
3. avoiding them with higher CV risk

Question 3

NSAIDs is used as a first line therapy in RA

Answer 3

NOPE!!! not a drug modifying disease only used to treat symptomatic pain relief

Question 4

which drug induces osteoporosis and thus increase risk of fracture

Answer 4

glucocorticoid

Question 5

glucocorticoids increase infection?

Answer 5

yep, it is an immunosupressor

Question 6

General principles of DMARDs:

1. How fast do they work?
2. infection risk?
3. effect on would healing
4. follow up needed?
5. teratogenic?
6. risk of malignancies?

Answer 6

1. Slowly
2. increased risk of infection
3. probably no effect on wound healing
4. regular clinical and laboratory follow-up
5. yep a lot of them are teratogenic
6. lymphoma is seen but it is might be confounding and it is really high disease activity that is the culprit

Question 7

methotrexate in RA vs malignancies

Answer 7

much lower dose used in RA

Question 8

first line therapy for RA

Answer 8

Methotrexate

** often used for peripheral inflammatory arthritis associated with SLE and other diseases

Question 9

Methotrexate:

1. MOA
2. Side effects
3. Monitor
4. supplementation

Answer 9

1. Binds to dihydrofolate reductase blocking purine synthesis but not sure how it works in RA
2. side effects: liver damage, bone marrow suppression, pulm. fibrosis and highly teratogenic
3. liver function tests and blood counts but also the occasional creatinine due to kidney clearance
4. Folic acids which helps to limit side effects

Question 10

do we need to abstain from alcohol with methotrexate?

Answer 10

yep

Question 11

Often used as first line therapy when MTX is contraindicated (e.g. alcohol use) or not tolerated

Answer 11

leflunomide (LEF) and sulfasalazine (SSZ)

Question 12

Mechanisms of action:

1. LEF (leflunomide)
2. SSZ (sulfasalazine)

Answer 12

1. LEF: probably inhibits pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase
2. SSZ: not clear

Question 13

side effects difference between LEF and SSZ

Answer 13

LEF has the same side effects as methotrexate but SSZ does not have liver SE but can cause bone marrow suppression

Question 14

is often used in combination with MTX and/or HCQ (‘triple therapy’)

Answer 14

SSZ

Question 15

First line therapy for non-organ- and non-life-threatening manifestations of SLE
almost all those with SLE should be on HCQ
Often used for RA and other arthritides, especially in combination with other DMARDs

Answer 15

hydroxychloroquine

Question 16

hydroxychloroquine MOA

Answer 16

poorly understood was originally developed as an antimalarial

Question 17

hydroxychloroquine side effects

Answer 17

pretty safe!!! SE is to the eye, leading some retinopathy issues and it is irreversible but it is a cumulative effect

Question 18

hydroxychloroquine can be used during pregnancy

Answer 18

yes!!!!!!

Question 19

2nd line or maintenance therapy for many non-life-threatening manifestations of SLE, vasculitides, and others
occasionally used for RA

Answer 19

azathioprine (AZA),

Question 20

used for organ- and life-threatening manifestations of SLE, vasculitides, and other autoimmune diseases

Answer 20

mycophenolate (MMF), and cyclophosphamide (CYC)

*** they are heavy hitters, only really used with increased risk of multiorgan failure

Question 21

Mechanisms of action pair azathioprine (AZA), mycophenolate (MMF), and cyclophosphamide (CYC) :

1. antagonizes purine metabolism, inhibiting DNA synthesis
2. inhibits inosine monophosphate dehydrogenase, inhibiting guanosine nucleotide synthesis, thus inhibiting DNA synthesis
3. cross-links DNA strands by alkylation, inhibiting DNA synthesis

Answer 21

1. AZA: antagonizes purine metabolism, inhibiting DNA synthesis
2. MMF: inhibits inosine monophosphate dehydrogenase, inhibiting guanosine nucleotide synthesis, thus inhibiting DNA synthesis
3. CYC: cross-links DNA strands by alkylation, inhibiting DNA synthesis

Question 22

Side effects: azathioprine (AZA), mycophenolate (MMF), and cyclophosphamide (CYC)

Answer 22

bone marrow suppression and risk of infection AZA«< MMF

Question 23

which other drug besides hydroxychloroquine can be used during pregnancy?

Answer 23

AZA

Question 24

Biologic agents

Answer 24

made in biologic system often are monoclonal ab

Question 25

Biologic agents are given how?

Answer 25

need to be injected or infused

Question 26

why are biologics not a first line therapy if they are generally as effective as MTX?

Answer 26

expensive

Question 27

biologics are used in combination with each other

Answer 27

noppe!!!

Question 28

Soluble TNF receptor fusion protein

Answer 28

etanercept - it is a distractor

Question 29

TNF antagonists *****TNF, despite its name (Tumor Necrosis Factor), is a ubiquitous cytokine involved in the regulation of the immune response

Answer 29

binds/blocks soluble or cell surface TNF or TNF-receptor

Question 30

TNF antagonist compared to gcs how immunosuppressive is it?

Answer 30

less immunosuppressive than medium/high dose GCs

Question 31

major side effect of TNF antagonist

Answer 31

reactivation of latent TB

Question 32

MAb targeting the interleukin-6 (IL-6) receptor. IL-6 is a ubiquitous cytokine in inflammatory processes

Answer 32

tocilizumab:

Question 33

fusion protein targeting CD80/CD86, thus blocking interaction with CTLA4, a costimulatory signal required for full T cell activation

Answer 33

abatacept:

Question 34

MAb targeting CD20, a B-cell antigen | kills/depletes B-cells and pre-B cells

Answer 34

rituximab

Question 35

rituximab depletes B-cells, but NOT plasma cells

Answer 35

yep!! therefore there is still ab production

Question 36

side effect of rituximab (2)

Answer 36

1. infusion reaction | 2. PML

Question 37

targets IL-1 approved for RA but not used much as it is not very effective seems to be very effective for ‘autoinflammatory’ diseases such as Familial Mediterranean Fever, the systemic form of JIA, and adult onset Still’s disease

Answer 37

anakinra

Question 38

targets BLyS approved for minor symptoms of SLE despite FDA approval, its efficacy is not clear

Answer 38

belimumab

Question 39

targets RANK-Ligand | approved for osteoporosis

Answer 39

denosumab

Question 40

targets IL-12 and IL-23 | approved for psoriasis and psoriatic arthritis

Answer 40

ustekinumab

Question 41

targets the JAK/STAT pathway | first new oral approved to treat RA

Answer 41

tofacitinib

Question 42

inhibits phosphodiesterase 4 | recently approved to treat psoriatic arthritis

Answer 42

apremilast

Question 43

principles of RA management 1. start time of treatment 2. Screening 3. treat initially with 4. disease not controlled 5. goal of treatment 6. maintenance

Answer 43

1. start early- prolonged treatment with NSAIDs/GCs alone is not adequate 2. screen for hep B/C and TB if starting a biologic. vaccinate if possible 3. treat initially with MTX 4. switch after 3-6 month trial 5. goal of treatment is to lower disease activity or clinical remission 6. continue appropriate vaccinations