Rheumatoid Arthritis Flashcards
1
Q
Rheumatoid Arthritis (RA) afflicts – adults in the US
A
2.0 million
2
Q
RA afflicts ~X:X women than men characterized by daily joint pain
A
3:1
3
Q
most patients with RA also experience some degree of
A
depression
anxiety
feelings of helplessness
4
Q
RA can interfere with routine
A
daily activities
5
Q
what is RA
A
an inflammatory disease causing pain, swelling, stiffness, and loss of function in joints
6
Q
how long does RA last for
A
few months and disappear w/o causing any noticeable damage
7
Q
are there various degrees of RA
A
yes, some patients have mild or moderate forms of the disease with period of worsening symptoms (flares) and period they feel better (remission)
8
Q
describe the severe form of RA
A
-diseaseis active most of the time, lasts for many years or a lifetime, leading to serious joint damage, disability
9
Q
in RA, what happens to the synovium of a joint
A
- 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
Q
in RA what happens to the surrounding muscle
A
muscles, ligaments and tendons become weakened
11
Q
what effects does RA have on bones
A
can cause more generalized bone loss that may lead to osteoporosis
12
Q
what type of disease is RA
A
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
Q
RA effects in other parts of the body
A
- 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
Q
causes of RA
A
- genetic factors
- environmental factors
- hormonal factors
- state of the immune system
15
Q
genetic factors causing RA
A
-some genes, involved in the immune system, are associated with a tendency to develop RA
16
Q
environmental factors causing RA
A
appears that some viral or bacterial infections may trigger the disease process in people genetically susceptible to RA
17
Q
hormonal factors causing RA
A
women are more likely to develop RA than men, pregnancy may improve the disease and RA may flare after a pregnancy
18
Q
how can the state of the immune system cause RA
A
interleukin 12 and tumor necrosis factor-alpha may contribute to RA development
19
Q
how can RA be diagnosed
A
- difficult to diagnose in its early stages
- no single test for the disease, symptoms and their severity differ form person to person
20
Q
how can laboratory test diagnose RA
A
- 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
Q
clinical features of RA
A
- 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
Q
how long do RA symptoms last for
A
many years
23
Q
what are the 2 primary objectives of treating inflammatory diseases
A
- relief of pain
2. relief of inflammation
24
Q
what drugs are used to treat RA
A
- 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
