rheumatoid arthritis Flashcards
rheumatoid arthritis
autoimmune disease
- appears 3rd or 4th decades
- older than 60
- mean and women equal
- progressive disease causing joint deformities and limitation
progression of RA
A) Healthy joint
B) Inflammation of synovial membrane
= membrane thickens
C) Synovial membrane begins to erode articular cartilage (overgrowth referred to as “pannus”)
D) Pannus enzymes destroy articular cartilage
= initiation of synovial space inflammation
E) Complete destruction of joint cavity and fusion of articulating bones
what is joint destruction caused by
autoimmune process
- immune cells cytokines and cytotoxins attack synovial tissue
- TNF: tumor necrosis factor
-IL-1: interleukin-1 - IL-6: interleukin- 6
antiarthritic drugs: 3 groups
1) NSAIDS
2) Glucocorticoids
3) Disease-modifying antirheumatic drugs (DMARDs)
NSAIDs for RA
rapid relief of symptoms
dont prevent joint damage
don’t slow disease
Glucocorticoids for RA
Rapid relief
- via inhibition of prostaglandins
Slow disease progression
Serious TOXICITY with longterm use
DMARs for RA
Reduce joint destruction
Slow disease progression
- interferes with immune and anti-inflammatory responses
3 categories for DMARDs
1) Conventional
- synthesized molecule
- extensive effect on immune system
2) Biologic:
- large molecules produced through recombinant DNA technology
- work on cytokines
3: Targeted:
- latest drug
- synthetic molecules that block specific pathways inside cells of immune system
Recombinant DNA technology
altering genetic materials outside of organism to enhance characteristics
Synthetic peptides
made by chemical peptide synthesis
drug selection for RA
Starting DMARD within 3 months may prevent serious joint injury
NSAIDs given while DMARDs develop (takes months)
Glucocoticoid- used for short-term management of flare-ups
If injury continues another DMARD can be added
Glucocoricoid drug name
Prednisone
Prednisone
powerful anti-inflammatory drugs
POif RA systemic
- can be toxic long-term
One or two joints affected
- interarticular injections are employed
Conventional DMARDs drug name
Methotrexate (M)
Methotrexate
- immunosuppression
First choice DMARD with RA
Works faster than other DMARDs
- 3-6 weeks
Methotrexate Mechanism of action
unclear
Is a folate antagnoist
- folate necessary for DNA synthesis and cellular replication
Process used to reduce B and T lymphocyte activity
Conventional DMARs adverse effects
How to help some side effects
Contraindications
Various toxicities
- hepatic fibrosis
- GI ulceration
- bone marrow suppression
Reduce GI and hepatic effects use supplementation of folic acid
Contraindicated for patients with blood dyscrasias
Methotrexate Interactions
any drug that causes any of adverse effects should not be used with M
Biological DMARs drug
Tumor Necrosis Factor Antagonists (TNF-a)
Prototype: Etanercept
Mechanism of Entanercept
Antagonizing actions of TNF-a during RA
- TNF-a is a main mediator of joint inflammation
- (1) increases osteoclast function
- (2) blocks osteoblast action
= bone mass loss
Entanercept function
Designed etanercept receptors are identical to TFN-a’s
becomes a competitive inhibitor of TFN-a
Adverse Reaction Etanercept (5)
Should not be given to pt with active infection
Black box Warning
Neutropenia: decreased
Skin Reactions: associated with Sub Q injection
Risk of Heart Failure
Targeted DMARDs
Janus Kinase Inhibitors (JAKs)
prototype: Tofacitinib
Tofacitinib
newest drug for RA
JAKs: Intracellular enzymes initiate cytokine signalling as part of a transcription pathway
Inhibiting JAK: inhabitation of immune and inflammatory response
Mechanism of Tofacitnib
competitively bind to JAK binding site
- suppression of cytokine signalling and transcription
Adverse reaction of Tofacitinib
increased risk of infection
