Arthritis Flashcards
Which kind of arthritis is more relevant in AAI
Rheumatoid arthritis
What causes arthritis?
Antibodies against “self”
Leads to tissue damage
Genetic factors
Can be potentially precipitated by pregnancy, infection, diet, environment
How does an autoimmune disease develop?
Auto antigens are present in everyone but not everyone develops auto antibodies to these (and of those that do, not everyone that has auto antibodies develops auto immune disease)
Self tolerance normally prevents auto antigens activating the immune system but in auto immune disease tolerance is lost and leads to self attack of the immune system
What is osteoarthritis?
Primarily a non inflammatory disorder (synovial joints)
Characterised by cartilage loss
Most commonly affects knees, hips and small hand joints
Link to overweight patients and obesity
What can we expect on diagram of a joint with osteoarthritis?
Bone spur (osteophyte)
Thinned cartilage
Cartilage fragments
Describe the pain in OA and which joints in commonly affects
Worsened by movement Eased by rest Worse at the end of the day Commonly affects; hands knees spine hips Usually unilateral (multiple joints)
Pain management in OA
Steroid injections
NSAID / cox 2 inhibitors
Surgery
When are corticosteroid injections used to treat OA
What drugs can be used
What can these injections cause
Intra-articulated (into the joint)
Moderate to severe pain
Drugs used - triamcinolone, methylprednisolone
Can cause cartilage injury and loss
What is rheumatoid arthritis? Symptoms? Lab test results?
Chronic inflammatory disorder
Signs = joint damage, muscle wastage, deformity
Symptoms are pain stiffness joint swelling joint deformity
Lab tests are increased Wbc and erythrocyte (RBC - stick together and become heavier due to inflammatory response) sedimentation rate
Anaemia, rheumatoid factor (antibodies to IgG in some people)
Epidemiology risk factors in RA
Age Gender Post partum Stress Genetic Smoking
Pain in RA
Improves movement
Worse on waking
Affects small joints
Affects bilateral joints ( systemic inflammation therefore if affects one hand it is likely to develop in the other )
How is rheumatoid arthritis a systemic disease?
Emphasis on joints
Skin eyes vasculitis lungs salivary glands (reduced) pericarditis (inflammation of pericardium)
Aims of treatment of RA
Treatment options
Relieve pain
Modify disease process and prevent joint destruction
Preserve / improve functional ability
Symptomatic relief e.g pain (NSAIDs and PPI) Slow progression of the disease -DMARD -steroids -biologicals
Monitor effectiveness
What is DMARD?
Disease Modifying Anti Rheumatic Drugs
Why must DMARDs be monitored closely?
How are they used in order to avoid adverse effect or poor efficacy?
Can be cytotoxic so must be monitored and counselled closely, reduce cautiously when symptoms are controls and if flare return to previous established dose
What is the main role of DMARDs ?
Directly inhibit cell proliferation
Inhibition of wide variety of cytokines including interleukins, interferons and TNF alpha
What are the draw backs of DMARDs?
No analgesic activity
May take months for benefits to become apparent because turnover of cells
When is DMARDs useful?
When cox inhibitors have not caused response in inflammation
To slow progression of disease
What is the first line treatment of RA
DMARDs place in therapy - Methotrexate
Combination therapy of MTX and one other
Slow onset of action
Used with glucocorticoids until effective
What are he general counselling points for first line treatment of RA (methotrexate and one other DMARD)?
Dose increased gradually Improvement may take some months Monitoring is necessary Nausea Report signs of blood dyscrasias, liver or lung toxicity
List DMARDs
Methotrexate 1st line Sulfasalazine Leflunomide IM gold Less evidence for others
How does methotrexate work?
Inhibits dihydrofolate reductase inhibitor (prevents pyrimidine synthesis)
Immunosuppressant
Weekly dosing
Once a week every week on the same day
How does methotrexate inhibit DHF reductase?
Competes with DHF for enzyme that converts DHF to tetrahydrofolate ( DHF vital for pyrimidine synthesis)
How does methotrexate reducing DHF reductase / tetrahydrofolate / methylene THF, treat RA?
Less DNA synthesis, reduces the proliferation of immune response cells in RA
Describe possible methotrexate toxicity
Nausea Post dose flu Bone marrow Hepatoxicity Lung GIT effects Renal toxicity Blood disorders FOLIC ACID REDUCES SIDE EFFECTS
How can the side effects of methotrexate treatment of RA be minimised?
Folic acid (not taken on the same day as methotrexate)
What are the ADME considerations with methotrexate?
Absorption a unaffected with age
Deceased metabolism and clearance with age so just be clearly monitored as more risk of toxic effects
Interactions with NSAIDs so should avoid OTC Medicines
- renal toxicity
- reduced excretion of MTX
What is the mode of actions of Sulphasalazine? Which arthritis does it treat?
Rheumatoid
Immune suppressant
Metabolised to 5 ASA which inhibits leukotriene and prostanoid synthesis, scavenge free radicals and decrease neutrophil chemotaxis
How can we monitor and look out for ADRs to Sulfasalazine?
GI intolerance - nausea
Blood disorders - bruising, unexplained bleeding
Discolouration of urine and contact lenses
What is Leflunomide’s mode of action and which arthritis does it treat?
Rheumatoid
Immunosuppressant
Metabolised to teriflunomide
Ultimately the same effect on cell proliferation as methotrexate
How does Azathioprine differ from methotrexate
Inhibits purine synthesis and therefore cell proliferation (not pyrimidine)
How and why are steroids used in treatment of rheumatoid arthritis?
Bridge therapy between starting or switching DMARDs
Rapid symptom control
Prednisolone - the risks of the oral steroid
Side effects - PPI must be taken alongside
Bone protection needed as increases risk of osteoporosis
Examples of biologicals ( TNF Alpha blocking) monoclonal antibodies
- the antibodies bind to TNF alpha
Adalimumab
Infliximab
Certilzumab
Golimumab
What is Rituximab?
Monoclonal antibody that removes B cells
Used for treatment of RA
Licensed for use with MTX where treatment of combo DMARDs is not adequate
What is Abatacept?
Biological agent - treatment of RA
B7 protein and CD28 protein must bind at the same time for the antigen presenting cell to communicate with the T cell
Abatacept blocks e B7 binding to CD28
Drugs in development for RA
TNF alpha converting enzyme (TACE INHIBITORS)
Inhibitors of releasing TNF alpha
How organ specific is rheumatoid arthritis?
- not very
