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Flashcards in Rheumatoid Arthritis Deck (117):
1

Rheumatoid Arthritis (RA) afflicts -- adults in the US

2.0 million

2

RA afflicts ~X:X women than men characterized by daily joint pain

3:1

3

most patients with RA also experience some degree of

depression
anxiety
feelings of helplessness

4

RA can interfere with routine

daily activities

5

what is RA

an inflammatory disease causing pain, swelling, stiffness, and loss of function in joints

6

how long does RA last for

few months and disappear w/o causing any noticeable damage

7

are there various degrees of RA

yes, some patients have mild or moderate forms of the disease with period of worsening symptoms (flares) and period they feel better (remission)

8

describe the severe form of RA

-diseaseis active most of the time, lasts for many years or a lifetime, leading to serious joint damage, disability

9

in RA, what happens to the synovium of a joint

-it becomes inflamed causing warmth, redness, swelling and pain
-as the disease progresses, the inflamed synovium invades and damages the cartilage and bone of the joint

10

in RA what happens to the surrounding muscle

muscles, ligaments and tendons become weakened

11

what effects does RA have on bones

can cause more generalized bone loss that may lead to osteoporosis

12

what type of disease is RA

autoimmune disease
-a person's immune system attacks joint tissues for unknown reasons
-WBC travel to the synovium causing inflammation, characterized by typical symptoms of RA

13

RA effects in other parts of the body

-anemia
-neck pain
-dry eyes and mouth
-rarely ppl have inflammation of the blood vessels, the lining of the lungs, or the sac enclosing the heart

14

causes of RA

1. genetic factors
2. environmental factors
3. hormonal factors
4. state of the immune system

15

genetic factors causing RA

-some genes, involved in the immune system, are associated with a tendency to develop RA

16

environmental factors causing RA

appears that some viral or bacterial infections may trigger the disease process in people genetically susceptible to RA

17

hormonal factors causing RA

women are more likely to develop RA than men, pregnancy may improve the disease and RA may flare after a pregnancy

18

how can the state of the immune system cause RA

interleukin 12 and tumor necrosis factor-alpha may contribute to RA development

19

how can RA be diagnosed

-difficult to diagnose in its early stages
-no single test for the disease, symptoms and their severity differ form person to person

20

how can laboratory test diagnose RA

-Rheumatoid factor, antibody present in the blood of most people with RA: not all people with RA test positive for rheumatoid factor, especially early in the disease
-some people test positive for R factor, yet never develop the disease
-WBC count, C-reactive protein

21

clinical features of RA

-tender, warm, swollen joints
-symmetrical pattern of the affected joints
-joint inflammation often affecting the wrist and finger joints closest to the hand
-joint inflammation sometimes affecting other joints (eg. neck, shoulder, elbow, hips, knees, ankles, feet)
-fatigue, occasional fevers, a general sense of not feeling well
-pain and stiffness lasting for more than 30 mins in the morning or after a long rest

22

how long do RA symptoms last for

many years

23

what are the 2 primary objectives of treating inflammatory diseases

1. relief of pain
2. relief of inflammation

24

what drugs are used to treat RA

1. NSAIDs
2. Glucocortiocids

25

properties of NSAIDs

-have antinociceptive and anti-inflammatory properties

26

NSAIDs are useful in treating

acute and chronic pain

27

properties of glucocorticoids

-have significant anti-inflammatory properties
-useful for the treatment of acute RA episodes

28

glucocorticoids have limited use as

chronic administration associated with serious toxicity

29

function of disease-modifying antirheumatic drugs (DMARDs)

slowing and stopping the tissue damage process

30

function of DMARDs in treating RA

-slow rate of RA associated bone damage
* acts upon basic aspects of the immune response

31

what is the downfall of DMARDs

have significant side effects

32

most RA patients are treated with

-salicylates and other related agents having anti-inflammatory, analgesic and antipyretic effects

33

pain intensity of RA is related to what

the severity of the inflammation

34

what may be more effective in reducing or preventing joint damage

-treating RA with more powerful drugs and the use of drug combinations instead of one medication alone

35

NSAIDs are effective in treating

-RA
-seronegative sponduloarthropathies (eg. psoriasis arthritis)
-osteoarthritis
-localized musculoskeletal syndromes
-gout

36

look at the COX-1 and COX-2 inhibitors slide 12

look at the COX-1 and COX-2 inhibitors slide 12

37

aspirin and select NSAIDs all have

-antipyretic, analgesic & anti-inflammatory properties

38

anti-inflammatory activity mediated mainly through the inhibition of

prostaglandin synthesis

39

when are NSAIDs found in the synovial fluid

after repeated dosing

40

what are the anti-inflammatory effects of aspirin

-nonselective
-irreversible COX-1 and COX-2 inhibitor

41

what are the analgesic effects of aspirin

decreases mild to moderate intensity pain due to its anti-inflammatory effects and its probably inhibition of pain stimuli at a subcortical site

42

antipyretic effects of aspirin reduces fever though

COX inhibition in the CNS as well as blocking release of interleukin-1 from macrophages

43

aspirin also inhibits aggregation of

platelets

44

see brand names of aspirin slide 15

see brand names of aspirin slide 15

45

see combinations of aspiring slide 16 + 17

see combinations of aspiring slide 16 + 17

46

other possible NSAIDS mechanism of actin include

-inhibition of chemotaxis
-down regulation of interleukin-1 production
-decreased production of free radicals and superoxide
-interference with calcium mediated-mediated intracellular events

47

cylooxigenase-2 selective inhibitors (COXIBS) were developed to

inhibit prostalgandin synthesis by COX-2 isoenzyme induced at sites of inflammation, without affecting the constitutively active housekeeping COX-1 isoenzyme found in the GI tract, kidneys and platelets

48

COXIBS bind to and block the active site of

COX-2 enzyme much more effectively than that of COX-1

49

COX-2 inhibitors do not have a significant effect on

-platelet aggregation, which is mediated by the COX-1 enzyme
-do not offer aspirin cardioprotective effects

50

where is COX-2 is constitutively active

kidneys

51

COX-2 inhibitors produce -- toxicities

renal toxicities similar to traditional NSAIDs

52

why do COX-2 inhibitors have a limited use

-bc have a higher incidence of cardiovascular thrombotic effects resulting from the use of COX-2 inhibitors

53

glucocorticoids are used in --% of RA patients

60-70%

54

function of glucocorticoids in RA patients

rapid and dramatic effects, capable of slowing the appearance of new bone erosions

55

prolonged use of glucocorticoids results in

serious toxic effects

56

what is the primary function of NSAIDs

-offer mainly symptomatic relief
-have little effect on the progression of bone and cartilage destruction

57

DMARDs are used to

arrest or slow RA progression by modifying the disease itself

58

DMARDs are -- acting

slow acting and their beneficial effects may take 6 weeks to 6 months to become evident

59

name 4 DMARDs

1. methotrexate
2. cyclosporine
3. Azathioprine
4. Sulfasalazine

60

what DMARDs is the choice in RA treatment

methotrexate

61

mechanism of action of methotrexate

-inhibits aminoimidazolecarboxamide (AICAR) ribnucleotide transformylase and thymidalate synthetase thus decreasing polymorphonuclear chemotaxis
-decreasing lymphocyte and macrophage function

62

how is methotrexate absorbed

-from GI, hydroxulated, and both parent drug and metabolite intracellularly polyglutamated where they remain for prolong periods

63

what is the plasma half life of methotrexate

6-9 hr which may go up to 24 hrs in some patients

64

methotrexate decreases the rate of appearance of

new erosions, and is effective to treat juvenile chronic arthritis

65

methotrexate also used to treat

-psoriatic arthritis
-psoriasis
-systemic lupus erythematosus

66

what are the side effects of methotrexate

nausea and mucosal ulcers are the common toxicities
-may cause cirrhosis

67

-reports of "hypersensitivity" lung reaction or RA is characterized by

-shortness of breath, as well as pseudolymphomatus rxn

68

what supplement is recommended to reduce GI and liver side effects of methotrexate

folic acid

69

what are contraindications for using methotrexate

pregnancy

70

mechanism of action of cyclosporine

inhibits synthesis of interleukin 1 and 2 receptors through gene transcription regulation

71

cyclosporine results in decreased

-macrophage T-cell interaction and T cell responsiveness
-affects T-cell dependent B cell function

72

why is cyclosporine involved in a # of drug interactions

-incomplete GI absorption
-metabolized by the liver P450 CYP3A

73

what drugs can cyclosporine interact with

potassium-sparing diuretics

74

FDA approved cyclosporine for the treatment of

RA; shown to delay new bony erosions

75

cyclosporine use is limited by

serious toxicity including nephro- and liver effects, hypertension, hirsutism, etc.

76

what is Azathioprine

a prodrug that is converted to its active metabolite 6-thioguanine

77

mechanism of action of Azathioprine

inhibits inosinic acid synthesis, as well as B and T cell function

78

FDA approved Azathioprine for use in the treatment of

RA

79

what are serious adverse effects of Azathioprine

-bone marrow suppression
-GI alterations

80

metabolism to 6-thioguanine is

bimodal
-slower metabolizers accumulate azthioprine, are at high risk of developing symptoms of myelosuppression

81

sulfasalazine is effective in treating

RA and juvenile chronic arthritis

82

sulfasalazine is metabolized by

bacteria in the bowel to sulfapyridine and 5-aminosalicylic acid which appears to be active agent in the treatment of RA

83

mechanism of action of sulfasalazine

-modify various immune response in RA patients (decreases production of IgA and IgM rheumatoid factors

84

what are the serious side effects of sulfasalazine

GI alterations
neutropenia

85

what are the tissue necrosis factor-alpha (TNF-A) Blocking Agents

Adalimumab
Infliximab
Etanercept
Leflunomide

86

what is Adalimumab

-recombinant human anti-TNF monoclonal antibody

87

what is infliximab

similar to adalimunab

88

etanercept interacts with

TNF-a mediated process

89

leflunomide interacts with

TNF-a mediated processes

90

cytokines play a critcal role in the immune response and in

RA

91

what factor appears to play a crucial role in the etiology of the inflammatory process

TNF-a

92

what does TNF-a modulate

cellular functions by activating specific TNFR1 and 2 membrane bound receptors

93

administration of soluble TNF receptors may combine with

soluble TNF, this inhibiting its effect

94

monoclonal aniTNF antibody inhibits

T cell and macrophage function

95

see diagrams 33-34

see diagrams 33-34

96

in RA where are cytokines expressed

in the joints of patients

97

what are cytokines

are a category of signalling proteins and glycoproteins that, like hormones and neurotransmitters are used extensively in cellular communication

98

what is Adalimumab

fully human IgG1 anti-TNF monoclonal Ab

99

Adalimumab is FDA approved to treat

RA, psoriatic arthritis and ankylosing spondylitis

100

Adalimumab given subcutaneous forms a complex with

soluble TNF preventing its interaction with p55 and p75 cell surface receptors, thus down-regulating macrophage and T cell function

101

methotrexate decreases the clearance of Adalimumab by

?40%

102

function of Adalimumab

decreases ne bone erosion formation rate when used either as monotherapy or in combination with other DMARDS

103

what are the adverse effects of Adalimumab

-increases the risk of macrophage-dependent infection (including TB and other opportunistic infections)
-vasculitis
-leukopenias
-evaluate for TB

104

what is infliximab

chimeric IgG1 monoclonal Ab, binds to soluble and possibly membrane bound TNF-a

105

mechanism of action of infliximab

similar to Adalimumab

106

infliximab used to treat

RA
inflammatory diseases

107

what combination simprove drug effectiveness of Infliximab

- methotrexate, DMARDS

108

use of Infliximab is limited by

toxic side effects

109

contraindications of using Infliximab

latent or active tuberculosis
-this drug is a potent macrophage inhibitor, may activate latent TB

110

Etanercept is used for

1. surgery
2. joint replacement
3. tendon reconstruction
4. synovectomy

111

purpose of surgery

-reduce pain
-improve the affected joint's function and patients ability to perform daily activities

112

purpose joint replacement

-most frequently performed surgery for RA
-artificial joints not always permanent and may have to be replaced
-important for young ppl

113

purpose of tendon reconstruction

used most frequently on the hands, reconstructs the damaged tendon by attaching an intact tendon to it
-can help to restore hand function

114

function of synovectomy

-the inflamed synovial tissue is actually removed

115

routine monitoring and ongoing care monitors

-the course of the disease
-determines the effectiveness and any negative effects of medications, and changes therapies as needed

116

what are alternative and complementary therapies for treating RA

-special diets
-vitamin supplements

117

see health behaviour change slide 42

see health behaviour change slide 42