Inflammatory Arthritis Flashcards
What is rheumatoid arthritis?
A chronic inflammatory autoimmune disease characterised by inflammation of the synovial joints.
This results in use-related pain, stiffness and loss of movement in the affected joints.
What is rheumatoid factor?
Is a protein produced by the immune system that can attack healthy tissue in the body.
What increases in the blood when there is inflammation in the body?
CRP = C-reactive protein ESR = Erthyrocyte sedimentation rate (ESR)
What does the ESR indicate?
The inflammatory activity in the body.
What does the CRP measure?
Blood test marker for inflammation in the body,
Explain the synovial joint inflammation process.
increased production of inflammatory proteins leads to enzymes activated that destroys the lining of the joint.
Which exposes the underlying bone resulting in pain.
What is the synovium?
connective tissue that lines inside of the joint capsule.
What are the risk factors of RA?
Genetics - predisposition
Lifestyle - smoking (causes faster loss of bone density), overweight
Gender - Women are more likely to develop RA than men.
Infection - Bacterial and viral DNA has been found in synovial membrane
what % of the population does RA affect?
0.5 - 1% of population, predominately women.
what are the 4 domains (criteria) in determining rheumatoid arthritis?
- Joint involvement
- Duration of synovitis
- Acute phase reactants
- Serology
What are the current tests available for RA?
Rheumatoid factor Anti-CCP antibodies ESR CRP DAS scores Ultrasound/MRI and X-rays to assess synovitis/angiogenesis/erosions
What is a DAS score?
Disease Activity Score is a measure of disease activity in RA.
- Count the number of swollen joints (out of 28)
- Count the number of tender joints (out of 28)
The score ranges between 2.0 - 10.0
What DAS score is considered ‘in remission’
less than < 2.6
What DAS score indicates low disease activity?
less than < 3.2
What does a DAS score greater than 5.1 imply?
active disease
What substances in the blood indicates RA?
Anti-CCP antibodies
Rheumatoid factor
What do NSAID drugs act on?
Inhibit COX-1 and COX-2 inhibitors of the inflammatory pathway.
Also has an impact on the gastro-protective pathways
What pain relief would be the first treatment choice for a patient who is breastfeeding?
Ibuprofen
Diclofenac
List non-selective Cox NSAIDs -
Ibuprofen Naproxen Diclofenac Indomethacin Piroxicam
List Cox-2 selective NSAIDs -
Celecoxib
Meloxicam
Why are patients with a higher risk of cardiac events not recommended Cox-2 selective NSAIDs?
COX-2 has a role in platelet function - inhibition of COX-2 LEADS TO MORE FREQUENT THROMBO-EMBOLIC EVENTS. = more myocardial infarctions
should only be used short term
What is the main cause of GI morbidity with NSAIDs use?
Gastric erosions
Gastric ulcers
Where are the adverse effects of NSAIDs?
Renal
GI tract
Why is non cox-2 selective NSAIDs better?
More efficacious
What other drug is given with Cox-2 inhibitor (cost-effective)
Proton pump inhibitor
What happens when NSAIDs target the cox-2 pathway?
Anti-inflammatory effects without GI side effects.
Leads to more thrombosis-embolic events
What are the adverse effects of NSAIDs in the GI tract?
What is the cause of this?
Dyspepsia (indigestion)
Nausea
Vomiting
Haemorrhage
Inhibition of protective action of PG’s on gastric mucosa
PGE2 and PGI2 inhibit gastric acid secretion
What are the adverse effects of NSAIDs on Renal function, what is its cause?
Renal failure
Nephritis
Nephrotoxicity
Due to the inhibition of PGE2 and PGI2 mediated vasodilation of renal medulla and glomeruli and decreased creatinine clearance
What are the other side effects of NSAIDs and the cause
Bronchospasm
Skin rash
Allergic reactions
Due to hypersensitivity
What is bronchospasm?
Airways (bronchial tubes) go into spasm and contract
Due to irritation, inflammation or an allergic reaction of the airways
Why are corticosteroids used in RA?
Corticosteroids are anti-inflammatory and immunosuppressive, they can provide fast, temporary relief while waiting for DMARDs and biologics to take effect
What is methotrexate?
DMARD (Disease modifying anti-rheumatic drugs)
it inhibits dihydrofolate reductase
What is monotherapy?
The treatment of disease with a single drug.
In the case of RA, treatment with one DMARD
What is combination therapy?
When 2 or more drug therapies are given together to improve the outcome
Give examples of DMARDs:
Methotrexate
Sulphasalazine
Leflunomide
Azathiprine
What are the adverse effects of methotrexate that need close monitoring?
Bone marrow toxicity
Hepatic toxicity
Pulmonary involvement - pneumonitis
Mouth ulcers
What does the tumour necrosis factor (TNF) do?
Drives the inflammatory pathway.
Blocks the co-factors from being produced
What are the 3 anti- TNF (alpha) drugs that are widely used/ available?
Infiximab
Adalimumab
Ethanercept
What is rheumatoid factor?
IgM antibody to IgG
Can be detected in certain assays
Its also found in 5% of healthy controls
It can be found in other conditions such as infections and malignancy
RF is a feature of polyclonal B cell activation
What are some properties of Anti-CCP antibodies? (made of)
detects the citrullination of arginine in proteins.
arginine residue (+ve charged) is changed to citrulline residue (neutral) mediated by Peptidylarginine deiminase (PAD) enzymes
Sensitive test for RA, if detected it could mean a patient has a more erosive and aggressive disease
What is thromboxin A2 involved in? (COX 1 & 2)
Platelet aggregation
What is PGI2 involved in?(COX 1 & 2)
Gastro-protection
What is PGE2 involved in?(COX 1 & 2)
Inflammation and pain
What are the Leukotrienes involved in?
Inflammation and the development of gastric lesions
What are the main effects of NSAIDs in the gut?
Reduce mucus and bicarbonate production
Why are corticosteroids used in RA?
They bind to the corticosteroid receptor
The complex translocates to nucleus
Binds to the glucocorticoid response element
Increases trascription of anti-inflammatory genes.
inhibits pro-inflammatory mediators
What is the target of the biologic Tocilizumab?
Anti-IL-6
What is the target of the biologic Rituximab?
B cell depletion
What is the target of the biologic Anakinra?
Anti-IL-1
What is the total cost of RA in the Uk per year?
£3.8 - £4.75 billion
