KIN 429 Midterm 2 Flashcards
1
Q
Mechanism and outcomes of nitrogen containing bisphoshphonates
A
Inhibit pyrophosphate synthase which in involved in intracellular signaling. Leads to osteoclast inactivation and decreased bone turnover
2
Q
Mechanism and outcomes of Denosumab
A
RANKL inhibitor; inhibits OC formation, function and survival
3
Q
Mechanism and outcomes of selective estrogen receptor modulators
A
Binds to estrogen receptors with the same affinity as estradiol; estrogen agonists in some tissue (bone and lipids) and antogonistic in others (uterus and breast); leads to increased osteoblast and osteocyte survival and osteoclast apoptosis
4
Q
Mechanism and outcomes of teriparatide
A
Fragment of PTH molecule, so it acts like PTH. Continuous exposure to elevated PTH enhances osteoclast formation and bone loss, intermittent exposure to PTH will activate osteoblasts more than osteoclasts
5
Q
Mechanism and outcomes of hormone replacement therapy
A
Replacing estrogen, however, WHI suggested that risk outweighs benefits
6
Q
Names of nitrogen containing bisphosphonates
A
Fosamax, Actonel, Aclasta
7
Q
Names of Denosumab drug
A
Prolia
8
Q
Type of drug Evista is
A
Selective estrogen receptor modulator
9
Q
Name of teriparatide drug
A
Forteo
10
Q
Relation of PTHrP in cancer and bone health
A
Tumor produces PTHrP, leading to increased osteoclastic bone resoprtion, increased renal tubular resorption of calcium
11
Q
What ways does cancer treatment increase bone loss?
A
Aromatase inhibitors and other drugs; ovarian function (surgery, radiation, drugs), chemotherapy (toxic effect on osteoblasts, can affect gonadal steroid production)
12
Q
Symbiotic relationship between tumor growth and bone breakdown
A
Tumor secretes PTHrP, which increases RANKL, which activates osteoclasts, which secrete transforming growth factor beata, which stimulates tumor growth
13
Q
Some cancers related to bone
A
osteosarcoma, chondrosarcoma, Ewing sarcoma, giant cell myeloma, chordoma, fibrosarcoma, lymphoma, multiple myelmoa, bone metastases
14
Q
What is multiple myeloma?
A
A cancer of the plasma cells which reside in the bone marrow and can cause bone lesions and kidney dysfunction
15
Q
What is metastasis?
A
A process where tumor cells spread to other places in the body, transported by the lymphatic circulation or in the blood, implanted away from original site of tumor in other places/organs
16
Q
8-% of bone metastases occur from what 3 cancers?
A
prostate, breast, and lung
17
Q
Osteolytic bone metastases
A
Increased bone resorption with little bone formation; most common in lung, renal, and breast cancer patients; skeletal destruction mediated by osteoclasts rather than tumor cells
18
Q
Osteoblastic bone metastases
A
Increased bone formation, but poor quality. Most commonly seen in prostate cancer patients. Prostate tumor cells produce factors that stimulate osteoblast activity to produce abnormal bone; may be release of growth factors that may further stimulate tumor cell growth
19
Q
Consequences of bone metastases in cancer
A
pain, hypercalemia (increased bone resoprtion), fractures, cancer not curable, longer time living with cancer –> skeletal manifestations influence quality of life
20
Q
Cancer therapeutic strategies to treat bone metastases
A
radiation therapy, bisphosphonates, denosumab
21
Q
Potential adverse adverse effects of bisphosphonates
A
Osteonecrosis of the jaw
22
Q
Exercise considerations for indivduals with cancer
A
fall risk (neuropathy), fracture risk (secondary bone loss, metastases, post-menopausal), fatigue, immune suppression, pain, weakness
23
Q
Denosumab for bone metastases in cancer
A
Delays time to developing first skeletal-related event, and reduces risk of multiple events in those with malignancies involving bone. Comparable efficacy to bisphosphonates. Inhibits RANKL binding to RANK
24
Q
Bisphosphonates for bone metastases in cancer
A
Effective in controlling bone pain, hypercalemia and preventing skeletal-related events by 50%. Osteolytics lesions do not heal with bisphosphonates treatment. Osteonecorsis of the jaw a potential adverse effect.
25
Synarthroses?
Fixed joints; adjoining cranial plates separated by fibrous tissue, provide for growth
26
Amphiarthroses?
Bones bound by flexible fibrocartilage, permits modest motion (pubic symphysis and intervertebral discs)
27
Diarthroses?
synocvial joints, moveable joints, surrounded by synovial membrane and fluid
28
Classifications of joints according to shape
ball and socket (hip and shoulder), hinge (interphalangeal, knee), saddle (first carpometacarpal), plane (patellofemoral), pivot (proximal and distal radioulnar joints)
29
Components of a synovial joint
muscles, articular cartilage, menisci, ligaments, joint capsule, synovial lining, synovial fluid, burase
30
What is cartilage?
A dense connective tissue composed of solid phase (ECM), an electrolyte fluid, and relatively few cells.
31
Major ECM constituents of cartilage
large proteoglycans, noncollagenous proteins, small proteoglycans, collagen
32
What is 90% of the dry weight in cartilage?
Type II collagen and aggecran (large proteoglycans). Type II collagen forms a network that entraps proteoglyans.
33
What are attached to proteoglycans in cartilage?
Glycosaminoglycan side chains (GAG) side chains that bind water (70% of water)
34
What are the GAG sidechains made up of?
Chondroitin sulfate and keratin sulfate
35
What is hyaluronic acid?
Matrix component that binds proteoglycans together
36
What is aggrecan?
large keratin sulfate/chondroitin sulfate proteoglycan, provides a hydrated space filling gel contributes to cartilage strength
37
Types of cartilage
hyaline, elastic, fibrocartilage
38
Hyaline cartilage is found where
Synovial joints, fewer fibres
39
Elastic cartilage is found where
Nose, external ear, more fibres (elastic), cells tightly packed
40
Fibrocartilage is found where
menisci in the knee
41
Characteristics of fibrocartilage
Transitional state between true cartilage and fibrous connective tissue; collagenous fibers, minimal matrix; cells are embedded in the matrix between the fibers, but still in lacunae.
42
What does articular cartilage in synovial joints do?
Acts to reduce friction and abosrob shock; prevents bone on bone contact
43
How is cartilage in synovial joints nourished?
Avascular, so it is nourished by diffusion from vasculature of bone and synovial fluid
44
What surround articular cartilage?
Joint capsule
45
What is the synovium, and what does it do?
A soft tissue that lines the non-cartlaginous surfaces within joint cavities; expands and contracts during movement; secretes synovial fluid and is supported by microvessels immediately below lining cells at joint space surface --> nutrients for synovium and avascular cartilage
46
What are the components of synovial fluid?
Hyaluronan and lubricin
47
What does synovial fluid do?
Reduces friction between cartilage and other tissues in joint, lubricates and cushion. Enables exchange of nutrients with articualr cartilage
48
Where is synovial fluid found within a joint?
Fluid forms a thin layer at the surface of cartilage but also seeps into the cartilage
49
What is hydrodynamic lubrication?
Load induced compression forces fluid out of cartilage laterally and to surface, creating a protective, aqueous layer
50
What is boundary layer lubrication?
Lubricin binds to articular cartilage, retains a protective layer of water molecules, providing a slippery coating
51
What is squeeze film lubrication?
load applied --> synovial fluid pressurized, moves out and possibly into cartilage --> ncreased viscosity in fluid -->trapped fluid supports load and reduces friction
52
What is fibromyalgia?
A widespread, musculoskeletal pain accompanied by fatigue, sleep, memory, and mood issues. Chronic widespread pain disorder commonly associated with comorbid coiditions, including fatigue and nonrestorative sleep.
53
Causes of fibromyalgia?
Cause is not clear--genetics and environment (stress) may contribute. Centralized pain--sentral nervous system origin. Disturbances in autonomic and stress response systems. Abnormal processing of pain by CNS --> volume control set to high (levels of NT that facilitate pain transmission). Psychiatric conditions can co-exist, may have some origin such as early life trauma/stress
54
Manifestation of fibromyalgia
Diffuse, chronic pain throughout body, sensory, hyper-responsivenss. Migraine headache. Chronic fatigue, sleep disturbance. Irritable bowel syndrome. Depression. Restless leg syndrome. Temrpomandibular joint syndrome. Myofascial pain syndrome. Fibro "fog" -- memory and mood difficulties
55
Modifiable risk factors for fibromyalgia
poor sleep, obesity, physical inactivity, poor job or life satisfaction, catastrophizing
56
Potential therapies for fibromyalgia
improve sleep patterns, weight loss, activity and exercise, stress reduction, cognitive behavioral therapy
57
Considerations for exercise prescription in fibromyalgia
Limit overuse of small muscle groups (i.e. overhead exercises), minimize eccentric portion, Strategies to increase adherence: self-monitoring, group exercise, action planning/coping planning
58
What is OA?
deterioration and loss of articular cartilage, thickening of the subchondral bone, bony outgrowths at joint margins, mild, chronic synovial inflammation
59
Mechanical risk factors for OA
low quadriceps strength, increased body weight (due to inflammatory environment), occupation, injury (ACL rupture, especially with meniscus tear, other disorders), anatomic abnormalities (genum varum or valgus, congenital hip sublumxation, acetabular displasia)
60
Metabolic risk factors for OA
obesity (adipokines ---> proinflammatory), systemic inflammation may predispose people to OA, metabolic syndrome (advanced glycosylated end products (AGEs accumulation, oxidative stress. Hypertension (leads to subchondral ischaemia)
61
Symptoms of OA
pain, stiffness around joint, limited function. pain typically worsens with activity, lessens at night. Pain at rest or at night a feature of severe disease. Duration of morning stiffness shorter (<30 min). Pain and stiffness worse in damp, cool, rainy weather
62
Signs of OA
bony enlargement, tender at joint margins and at attachment of joint capsule and tendons, pain or limitation of motion related to osteophyte formation, joint surface incongruity, muscle spasm, and contracture. Joint instability: peri-articular muscle weakness or abnormal propriorecption. Joint locking out during ROM (loose bodies or fragments). Creptius. Local inflammation. Joint malalignment 50% of knee OA: varus common
63
Heberden's Nodes
Enlarged end joints of finger (distal interphlangeal joints)
64
Bouchard's nodes
Enlarged middle joints of finger (proximal interphalageal joints)
65
Turnover in normal cartilage
Matrix undergoes turnover via chondrocyte activity: production of enzymes (matrix metallopeoteinases, others) to degrade catilage. Synthesis of new collagen and proteoglycans, growth factors and MMP inhibitors (tissue inhibitor of metalloproteinases). Normal cartilage = low levels of synthesis and degradation --> cartilage volume maintained
66
What happens with aging in NORMAL cartilage?
Glycosaminoglycans become shorter. Changes in [keratin sulfates]. Decrease in chondrocytes and capacity of proteogylcans to retain water --> altered biomechanical properties. Stress fractures of collagen network --> fissurse
67
What happens to cartilage in OA
Mediators of cartilage destruction in OA include MMPs and pro-inflammatory cytokines (e.g. IL-1) ---> degrading enzymes over-expressed relative to capacity to repair = net degradation ---> loss of collagen and proteoglycans, decreased number of chondrocytes, decreased cartilage volume, fibrillation, erosion and cracking in superficial cartilage layer ---> progress to deeper layers ---> eventually large erosions
68
Characteristics of early osteoarthritis
Areas of chondrocyte loss and increased proliferation and synthesis of matrix. Increased cytokine synthesis, prostaglandins, free radicals ---> activation of chondrocytes ---> increased synthesis of MMP and decreased TIMP. Microcracks in cartilage ---> deep fissures and pitting. Subchondral bone demineralization with microfractures. edema
69
Characteristics of late osteoarthritis
Decreased chondrocyte proliferation. Chondrocyte apoptosis. Fissures cause fragments of cartilage to detach. Exposed subchondral bone. Osteophyte formation. Sclerosis of subchondral bone (bone thickening). Persistent synthesis of proteinases and cytokines.
70
Are the changes in cartilage associated with aging the same as OA?
NO!!!
71
What are the two main mechanisms of drug treatment for OA?
control symptoms and disease modifying/specific to the disease
72
What are the three type of treatment for OA that control symptoms?
Analgesics, NSAIDs, glucocorticoids
73
Are analgesics anti-inflammatory, and do they slow the disease progression for oA?
NO
74
What do analgesics do, and what are some examples?
Medicines that relieve pain. Over the counter medicins like Aspirin and Tylenol (acteaminophen)
75
What COX enzyme is responsible for prostaglandins expressed in inflamed tissues?
COX2
76
What COX enzyme is responsible for prostaglandins expressed in GI mucosa, kidneys, platelets, and vascular endothlelium?
COX1
77
How do NSAIDs work?
inhibit one or both of COX enzymes. Effective for treating swelling, pain, and stiffness --> symptom control. No effect on disease course or joint damage
78
What are the problems associated with using NSAIDs?
GI toxicity an issue, especially in older patient
79
What are the adverse effects of using COX-2 specific inhibitor?
May reduce GI toxcity, but there are other adverse reactions (allergy, renal failure, CV). Can use a proton pump inhibitor to reduce gastric acid secretion
80
Why are corticosteroids used in arthritis?
Potent suppressor of inflammtion. Effective for managing pain and functional limitations in active inflammatory joint disease. Not adequate as sole therapy. Can be taken orally or injected into joint. Can't be taken long term
81
Conditional recommendations for NOT using in knee OA?
Chondroitin sulfate, glucosamine, topical capsaicin. No recommendations for hyaluronic acid
82
No recommendations for knee OA?
Participation in balance exercises, either alone or in combinations with strengthening exercises, wearing laterally wedged insoles, receiving manual therapy alone, wearing knee braces, using laterally directed patellar taping
83
Strong recommendations for non pharmacological treatment for hip OA
CV or RT land-based exercise, aquatic exercise, weight loss
84
Intra-articular injections of GC are conditionally recommended for what types of OA
knee and hip
85
Topical NSAIDs are conditionally recommended for what type of OA
knee and hand only
86
topical capsaicin is a conditional recommendation for what type of OA
hand OA only
87
Oral therapy (acetaminophen, NSAIds, Tramadol) is conditionally recommended for what type of OA
all of them
88
Conditional recommendations for non-pharmacological treatment of hand OA
evaluating ADL performance, provide assistive devices as needed, provide instruction in joint protection, instruction in use of thermal modalities for relief of pain and stiffness, provide splints for patients with trapexiometacarpal joint OA
89
Conditional recommendation for NOT using intrac-articular therapies for hand oA
k;f
90
Strong recommendations for non-pharmacological treatment of knee OA
CV or RT land based exercise, aquatic exercise, weight loss
91
Conditional recommendations for non-pharmacological treatment of knee OA
self management programs, manual therapy with supervised exercise, pyschosocial interventions, medially directed patellar taping, medial wedge insole (lateral compartment OA), laterally wedged insoles (medial OA), instructions in use of thermal agents, walking aids as needed, tai chi
92
Conditional recommendations for non pharmacological treatment of hip OA
self management programs, manual therapy, thermal therapy in combo with supervised exercise, pyschosocial interventions, instruction in use of thermal agents, walking aids as needed.
93
Summary of exercise in knee OA
decreased knee pain by 1 point on a scale of 0 to 20. Increased knee function by 3 points on a scale of 0 to 68
94
Summary of exercise in hip OA
may reduce pain slightly, may not improve physical funtion
95
Strong rationale that weight reduction may:
delay progression, reduce symptoms, improve function, lower impact of comorbidities and reduces incidence
96
Who are surgical candidates for knee replacements?
usually those who "fail" other treatments (no relief from other therapies despite trials), pain progressed to unacceptable (at rest or night pain), joint is structurally unstable, not yet developed muscle weakness, deconditioning, can medically withstand stress of surgery
97
What is arthroplasty?
Total joint replacement. Surgical replacement of a damaged/diseased joint or joint components with a prosthetic joint or joint components. LAST RESORT for patients with severe knee OA. Replacement usually lasts ~10 years
98
What is a tibial osteotomy?
Removal of a wedge shaped portion of tibia or add material. Change alignment and redistribute body weight. Transfer stress to a less worn area of the knee, helping to relieve pain. Treat a varus (bowlegged), deformity ar the knee resulting from past trauma or srugery, congenital deformity and/or degenerative disease. Candidates for tibial osteotomies may eventually require a knee repalcement
99
Risk associated with surgery
risk associated with anesthesia, infection developing in the artificial joint (requires removal of the artificial joint and treatment of the infection), development of blood clots, loosening of the joint, can damage meniscus, ligaments, and patellar ligament and nerves
100
After a total hip arthroplasty, what are the movements to be avoided in the first 6-8 weeks?
extreme bending (flexion) of the hip beyond 90 degrees, corssing legs, turning the operated hip inward or outward (internal/external rotation)
101
Most common form of crystal induced arthritis?
Gout (uric acid crystals)
102
Calcium pyrophsophate dihydrate arthritis?
Chondrocalcinosis or pseudogout or pseudo-arthritis or pseudo0rheumatoid arthritis. CPPD crystals present in synovial fluid. Overproduction of extracellular pyrophsophate, treat with NSAIDs or glucocorticoid
103
Why does lead cause gout?
Damages kidneys and you to retain uric acid --> carried by the bloodstream to big toe or foot were the uric acid turns into needle like crystals
104
Gout risk factors
Males, postmenopausal women, overproduction of urate from inherited enzyme defects, obesity, purine rich foods, accelerated ATP degradation, underexcretion of uric acid
105
How is alcohol related to gout?
Ethanol accelerates ATP bbreakdown, increases uric acid (ATP --> ADP + AMP, AMP --> uric acid), guanosine in beer is catabolized to uric acid.
106
What can cause underexcretion of uric acid ?
Thiazide diuretics, exogenous insulin, beta blockers, cyclosporine, hypertension (reduced renal blood flow), metabolic syndrome, obesity, renal failure
107
treatment of gout
NSAIDs of glucocorticoids in acute gout. Urate lowering therapy, cessation of alcohol use, weight loss, replace thiazide diuretics with another anti-hypertensice
108
Progression of gout
asymptomatic hyerurinecmia --> acute intermittent gout --> advanced gout
109
Most common spot of gout?
first metatarsophalangeal joint
110
What is RA?
A chronic, systemic, inflammatory disease. Inflammation of the synovium of joints. Joint damage, pain, loss of function, disability.
111
What is the pathogenesis of RA and what causes its progression?
Pathogenesis is progressive inflammation of the synovium and destruction of joint architecture. Persistence and progression regulated by immune mediators.
112
When is peak incidence of RA?
Between 4th and 6th decades...affects all ages, though
113
Percentage of RA patients that have a monocylic course that ablates within 2 years?
20%, the rest will have polycyclic or progressive course
114
Is there a genetic predisposition for RA?
Yes, multiple genes involved (dizygotic twin 6 times more likey, monozygotic twin 30 times more likely). Genetic basis not sufficient to explain trigger for disease. Many different genes involved, and each make only small contribution to disease susceptibility
115
Risk factors for RA
2.5x higher in women, smoking, age
116
Most common joints affected by RA?
Hand and wrist. MCP, PIP often involved...the DIPs are usually spared
117
Percentage of joints affected by RA in the first year?
90% of joints
118
What triggers an immune response?
Antigen/foreign cell
119
What can an antigen be?
a virus, cells from another person
120
What is an autoimmune disease?
Immune system responds to body's own cells or tissues
121
Body cells have what attached to them?
MHC/HLA complexes (major histocompatability complex or human leuokocyte antigens)
122
What do killer T cells do?
Attack cells that have an antigen on them
123
What do natural killer cells do?
Recognize foreign cells with no self-MHC complex
124
What do helper T cells do?
Help to coordinate the immune response by stimulating antibody production, calling in phagocytes, activate other T cells
125
What is auto-immunity?
An antigen-specific immune response to an auto-antigen that leads to disease. Immune system is launching an attack on its own body --> antibodies are produces and react against a body constituent, failure to recognize constituent as "self"
126
What is a consistent feature of RA?
T-cells infiltrating the synovium.
127
What is the auto-antigen in RA?
Not defined
128
What two types of cells comprise the lining layer in normal synovium?
Macrophage like synoviocytes (MLS)-phagocytic. Fibroblast like synoviocytes (FLS)-systhesize matrix proteins (collagen, hyaluronan)
129
What happens to the synovium in RA?
Increased lining cells (MLS and FLS) cuasing increased dpeth of lining (tissue proliferates), acts as a source of inflammatory cytokines and proteases, proliferating tissue into joint cavity and cartilage = pannus. Sublining --> edema, blood vessel proliferation (because blood supply is needed for proliferating tissue), accumulation of T and B lymphocytes, plasma cells. natural killer cells
130
What is pannus?
Proliferating tissue into joint cavity and cartilage in RA
131
What are the key features of a joint in RA?
Hyperplastic synovial membrane, infiltration of lymphocytes and macrophages, pannus infiltrates the cartilage and surrounding bone
132
What are the 3 stages of RA?
1) Swelling of the synovial lining --> pain, warmth, stiffness, redness and swelling around joint 2) Formation of pannus --> rapid division and growth of cells --> thickening of synovium, covers cartilage, destroys joint capsule and bone. 3) Destruction of bone and cartilage: synovial and immune cells release enzymes, destroying cartilage. Synovial and immune cells release cytokines, RANKL --> bone erosion. Bone and cartilage destruction can cause involved joint to lose its shape and alignment, more pain, and loss of movement
133
Cytokines involved in RA?
MLS, FLS, T cells and synovial cells produce pro-inflammatory cytokines (TNF alpha, GM-CSF, interleukins) and inhibitory cytokines suppress inflammation in part, but theyaare overwhelmed by the pro-inflammatory cells
134
What do cytokines do in RA?
ACtivate chondroblasts to releast proteinases, which destroy the cartilage. Cyokines also stimulate osteoclasts, RANKL production by fibroblasts and T cells
135
What happens to synovial fluid in RA?
Increase synovial fluid volume --> manifests as swelling. Increased neutrophils which release proteinases and cytokines
136
How is cartilage destroyed in RA?
Chondrocytes, synovial cells (MLS, FLS), neutrophils are activated by IL-1, TNF alpha, IL-17 and immune complexes. Chondrocytes release enzymes (MMPs, collageneases, proteinases) that destroy cartilage. Protease inhibitors are present, but overwhelmed by enzymes doing degradation
137
Steps in cartilage destruction in RA
Inflammation of synovium (pannus), leads to increase in synovial fluid volume, neutrophils, and T and B cells to the joint ---> Increased cytokine production by T cells, B cells, synovial cells (MLS, FLS) --> Neutrophils, synovial cells, chondrocytes release destructive enzymes in response to IL 1, TNF-a, IL17, immune cells ---> cartilage destruction
138
Mechanism of bone erosion in RA
RANKL expression by T cells and FLS --> activation of osteoclasts (leads to bone erosion). Cytokine activation by osteoclasts
139
What are the radiological findings in RA that are different than OA?
Bony erosions at joint margins (don't see in OA, osteophytes in OA). Joint space narrowing (also see in OA)
140
Lab tests that can be used to help with diagnosis of RA, although no lab test, histological finding or radiographic feature confirms RA
Rheumatoid Factor, erythrocytes sedmenation rate and CRP
141
2 categories of articular manifestations in RA
1) Reversible signs and symptoms related to inflammatory synovitis 2) Irreversible structural damage caused by synovitis--begins in 1st and 2nd year (caused by every cycle of synovitis)
142
Synovitis symptoms tend to fluctuate, but structural damage progresses linearly as function of prior synovitis
Synovitis = inflammation of synovial membrane
143
Morning stiffness associated with RA?
>2 hours (OA is 5-10 min)
144
Structural damage in RA to the joint
Cartilage loss, erosion of peri-articular bone, irreversible (symptoms that fail to respond to aggressive therapy (e.g. corticosteroid injection won't make symptoms due to joint damage feel any better), radiographs show loss of joint space, bone on bone creptius---high pitches screehe detectable on palpation or auscultation
145
Determinants of disease outcome in RA
RF or other antibodies, low SES or educational status, disability indicators, joint erosions, elevated CRP and ESR, family history of severe RA, female gender, genes
146
Secondary complications of RA
Increased risk of CVD and death, disability, drug side effects, increased risk of fracture (independent of BMD)
147
Two groups of drug therapy for RA
Control symptoms (NSAIDs and Analgesics), and those that limit joint damage (Disease Modifying Anti-Rheumatic Drug)
148
2 types of DMARDs
Traditional DMARDS and biologic agents
149
What do DMARDs do?
Prevent joint erosions and damage. Control active synovitis and other features of disease. No evidence that DMARDs can "heal" disease. Should be used when diagnosis is established. Vary greatly in mechanism of action. Can be used with NSAIDs or corticosteroids.
150
What do traditional DMARDs?
Target cellular components (B and T cells) --> target cellular components of immune/inflammatory response (i.e. B cell and T cell for RNA/DNA production in immune cells),
151
Side effects of traditional DMARDs
Can affect bone marrow and liver, therefore, requires regular WBC checks and liver function tests
152
Most common DMARD
Methotrexate (well established long-term efficacy)
153
What are biological agents for RA?
Derived from or resemble naturally-occurring molecules. Genetically engineered to target cytokines (anti TNF-alpha, antibody agents, IL-1 receptor anatagonists). Blocks message to increase inflammatory cells
154
Side effects of biologic agents
Infection, reports of fatal infections and TB
155
Why are biologic agents such as Inflixmab, Humira, and Enbrel used sparingly?
Very expensive, used when other treatments are not effective and often used in vombo with methotrexate
156
Surgery in RA
Tendon repair and transfer, carpel tunnel release, total joint replacement, arthrodesis (fusion) of ankles, wrists, fingers, and toes. Stabilization of unstable cervical vertebrae
157
When do you refer for surgery in RA
Refer for surgical opinion when, despite non-surgical management the following persist: persisent pain due to joint or soft tissue damage, decreasing joint function, joint in unstable, deformity progresses, persistent synovitis in joint, can withstand surgery, not deconditioned
158
What are your therapeutic goals during an RA flare-up?
Pain reduction, modify activities/use, prevent atrophy
159
What are your therapeutic goals be as an RA flare-up resolves?
Increase ROM, maintain strength, prevent arophy
160
What are your therapeutic when RA is stable?
Maintain/increase CV fitness, maintain/increase muscle strength
