NSAIDs and DMARDs - Sweatman Flashcards Preview

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Flashcards in NSAIDs and DMARDs - Sweatman Deck (59):
1

How do NSAIDs exert their analgesic effect?

Prevent release of inflammatory cytokines that act on nociceptors to cause pain

2

How do NSAIDs cause gastric ulcers?

Blocking PGE2 synthesis causes decreased mucous production and bicarbonate release and increases proton secretion
Decreases the protective effect of PGE2 on mucosal lining

3

What are some of the risk factors of adverse GI events with NSAID use?

1) Older age
2) Male
3) Use of maximum dose
4) Excessive alcohol use
5) Heavy smoking
6) Prolonged NSAID use

4

Which NSAID has the highest and lowest relative risk of adverse GI events?

Diclofenac has lowest, ibuprofen and naproxen have highest

5

Why are older patients at risk for increased CV risk with NSAID use?

Old people take low-dose prophylactic aspirin which irreversibly inhibits platelets --> giving NSAIDs will block the action of aspirin, this increasing risk for MI

6

All NSAIDs fuck up your liver. Which one is the worst?

Sulindac

7

Why is renal toxicity a concern with NSAID use?

Blocks PGI2 & PGE2, which are needed to control renal perfusion during abnormal conditions

8

What should you monitor in patients chronically on NSAIDs?

LFTs and CBCs --> hepatotoxicity and blood dyscrasias may occur

9

Why is salicylate poisoning a big concern with aspirin use?

Cerebral and pulmonary edema can kill the patient --> must decontaminate/provide support

10

What is the biggest concern in giving NSAIDs to old ass people?

GI bleeds and peptic ulcers

11

Why is acetaminophen the "special kid" of the NSAIDs?

Doesn't have anti-inflammatory effects, only analgesia
GI problems are very rare, but overdose is a bigger problem

12

What are the bullshit NSAIDs we're expected to memorize, not learn?

1) Acetaminophen
2) Aspirin
3) Diclofenac
4) Ibuprofen
5) Indomethacin
6) Ketoprofen
7) Ketorolac
8) Naproxen
9) Piroxicam
10) Sulindac
11) Celecoxib

13

What is the first line treatment of rheumatoid arthritis?

Methotrexate + NSAID + corticosteroids

14

What DMARD is used in milder cases of rheumatoid arthritis other than methotrexate?

Hydroxychloroquine --> fewer side effects

15

By what mechanism does methotrexate induce immunosuppression?

Increased adenosine inhibits lymphocyte proliferation --> suppresses secretion of IL-1, INF-gamma, and TNF

16

What unique metabolism does methotrexate undergo?

Polyglutamation keeps the drug intracellularly

17

What is the biggest adverse effect/concern with methotrexate administration?

Bone marrow suppression

18

What does methotrexate do to the lungs?

Interstitial pneumonitis and pulmonary fibrosis --> must monitor pt lung function

19

What is the mechanism of action of sulfasalazine?

Metabolized to sulfapyridine and mesalamine by bacteria in colon --> mesalamine inhibits prostaglandin and leukotriene production

20

What major allergy should you be careful of with sulfasalazine?

Sulfa allergy --> previous bad reaction to salicylate or sulfonamide drugs

21

What is the mechanism of action of leflunomide?

Inhibits dihydroorotate dehydrogenase --> blocks de novo pyrimidine synthesis in T and B cells

Also produces a uricosuric effect from metabolite

22

What are some of the cautions associated with leflunomide use?

Elevated LFT's --> don't drink booze with it
Category X drug
Can't be used in patients with immune suppression or infections

23

What is the mechanism of action of hydroxychloroquine?

Increases intracellular vacuole pH --> antigenic peptides aren't digested and MHC II proteins aren't properly assembled --> CD4+ cells not stimulated

24

What are the major toxicities associated with hydroxychloroquine?

1) Concentrates in liver --> hepatotoxicity
2) Blood dyscrasia and CNS toxicity
3) Can cause corneal opacities, keratopathy, or retinopathy --> DO NOT USE IN OCULAR DISEASES

25

What are the monitoring parameters for methotrexate?

1) CBCs with differential
2) LFTs
3) Serum creatinine/BUN
4) Serum uric acid
5) Pregnancy testing (category X)

26

What are the monitoring parameters for sulfasalazine?

1) CBCs with differential
2) LFTs
3) Serum creatinine/BUN
4) Urinalysis --> assess renal function regularly

27

What are the monitoring parameters for leflunomide?

1) CBCs with differential
2) LFTs
3) Pregnancy test (category X)
4) Serum electrolytes - causes diarrhea, hypokalemia, hypocalcemia

28

What are the monitoring parameters for hydroxychloroquine?

1) CBCs
2) Opthalmologic exam

29

Which non-biogical DMARDs do you have to check CBC on?

All of them: methotrexate, sulfasalazine, leflunomide, hydroxycholorquine

30

Which non-biological DMARDs do you have to to check LFTs on?

Methotrexate, sulfasalazine, leflunomide --> all except hydroxycholoroquine

31

Which non-biological DMARDs do you have to check serum creatinine/BUN?

Methotrexate and sulfasalazine?

32

Why do you have to give an opthalmalogic exam with hydroxycholorquine?

Can cause corneal opacity, keratopathy, and retinopathy --> pts slowly lose vision

33

What are the beneficial effects of giving corticosteroids?

NF-kb expression decreased --> decreased production of TNF-a, IL-1, IL-5

34

What are the major bad effects of giving corticosteroids chronically?

Increased RANK-L and MCF expression --> glucocorticoid induced osteoporosis --> initial increase in respiration and then decreased formation

35

What should be given with glucocorticoids to prevent osteoporosis?

Bisphosphonates, VitD, Ca2+

36

RA patients are at 2x greater risk for CV events. Why?

Chronic inflammatory condition and drugs used to treat (especially glucocorticoids-->obesity, accelerated atherosclerosis)

37

What steroids are best for intra-articular injection?

The less water soluble ones --> Triamcinolone, methylprednisone, betamethasone --> stay in joint space

38

What should you monitor in a patient on chronic glucocorticoid therapy?

1) Blood sugar
2) Bone mass
3) Glaucoma
4) Edema

39

What are the biological DMARDs (there are 9)?

1) Abatacept --> CTLA4/IgG1 Fc fusion protein
2) Adalimumab --> TNF-a antibody
3) Anakinra -->IL-1 receptor antagonist
4) Certolizumab -->TNF-a antibody Fab fragment
5) Etanercept --> TNF receptor linked to IgG
6) Golimumab --> TNF-a antibody
7) Infliximab --> IgG1k against TNF-a
8) Rituximab --> IgG1k against CD20
9) Toclizumab --> IL-6 receptor antibody

40

What is the mechanism of action of abatacept?

Binds CD80 and CD86 --> prevents T cell co-stimulatory signal

41

What is the mechanism of action of adalimumab?

Binds TNF-a preventing interaction with p55 and p75 cell receptors

42

What is the mechanism of action of anakinra?

Competitively inhibits IL-1a and IL-1b binding to IL-1 type 1 receptor

43

What is the mechanism of action of certolizumab?

TNF-a antibody that neutralizes membrane-bound and soluble TNF-a

44

What is the mechanism of action of etanercept?

Soluble TNF-a receptor/antibody fusion protein

Binds to and inactivates circulating TNF --> does not affect production or serum levels

45

What is the mechanism of action of golimumab?

Binds and neutralizes soluble and membrane-bound TNF-a

46

What is the mechanism of action of infliximab?

Binds and neutralizes soluble and membrane-bound TNF-a

47

What is the mechanism of action of rituximab?

Binds CD20 and recruit immune cells to induce B cell apoptosis

48

What is the mechanism of action of toclizumab?

Binds soluble and membrane-bound IL-6 receptors to inhibit signaling

49

What is the biggest side effect/problem associated with using the biological DMARDs?

Immunosuppression --> increased susceptibility to bacterial, fungal, and parasitic infection
May have increased likelihood of malignancy

50

Which biological DMARDs are associated with CHF or hypotension/angina/dysrhythmia?

1) Rituximab
2) Adalimumab
3) Infliximab
4) Golimumab

51

Which biological DMARDs are associated with causing a lupus-like syndrome (arthralgia, myalgia, fatigue, skin rash)?

1) Adalimumab
2) Certolizumab
3) Etanercept
4) Infliximab

52

Which biological DMARD is associated with Steven-Johnson syndrome?

Rituximab

53

Why must women taking rituximab be on contraception?

Can cross placenta and deplete B-cells in fetus

54

Which biological DMARDs are associated with blood dycrasias?

1) Anakinra
2) Certolizumab
3) Rituximab
4) Tocilizumab

55

Which biological DMARDs should you monitor LFT for?

1) Golimumab
2) Infliximab
3) Tocilizumab

56

Which biological DMARD should you get a serum lipid profile for?

Toclizumab

57

Which drugs should you counsel the patient to rotate the site of injection?

1) Abatacept
2) Adalimumab
3) Anakinra
4) Certolizumab
5) Etanercept
6) Golimumab

58

Which biological DMARD is approved for use in psoriatic arthritis and plaque psoriasis?

Apremilast --> orally active PDE4 inhibitor that reduces pro-inflammatory mediators

59

What are major adverse effects you should watch for in patients taking apremilast?

Weight loss and depression