Flashcards in Anti-inflammatories II Deck (64)
What is rheumatoid arthritis?
Inflammation of the synovium of the joints
With autoimmune components
What are the risk factors of rheumatoid arthritis?
What are the symptoms of rheumatoid arthritis?
- Swelling of the joints and pain
- Poor sleep is associated
- Can by symmetrical or not
- Can spread to other parts of the body
What is the inflammatory reaction underlying rheumatoid arthritis?
1) Activation of TH1 (T-cells)
2) Leads to activation of MACROPHAGES, which infiltrate the area and secrete CYTOKINES
3) Leads to the recruitment activation of other cells at the area of inflammation
4) All the cells together cause erosion of the cartilage and bone - causing joint damage
What are the cytokines released by macrophages in the lead up to rheumatoid arthritis?
What are the cells recruited by cytokines in the lead up to rheumatoid arthritis?
What do fibroblasts do?
Try to resolve tissue damage BUT by doing so can cause damage - by lots of deposition of extracellular matrix proteins
What drugs can decrease the level of damage in rheumatoid arthritis?
- Large structure
- Folic acid antagonist
- Cytotoxic and immunosuppressant activity
- Has a sulphate group
3) Drugs with metal ions
- Free radical scavengers to reduce tissue damage
What are immunosuppresants?
Drugs which lower the bodys ability to reject transplanted tissues
What do imminosupressants do?
Inhibit the induction phase of an inflammatory response:
- Work directly at the level of the immune cells to suppress their activity and inhibit the transcription of proinflammatory cytokines
What is ciclosporin and what does it do?
An immunosupressant drug with helps to supress transplant rejection
What is the normal action in the cell, regarding cyclophilin and nf kappa b?
1) Cyclophillin usually binds to calcineurin
2) Calcineurin binds to Ca released in immune reactions - activating the calcineuin
3) Calcineurin (a phosphatase) removes phosphatase from nf kappa b (a transcription factor found in many cells)
4) Dephosphorylated nf kappa b can move into the nucleus and control the transcription proinflammatory cytokines
How does ciclosphorin work?
1) Binds to cyclophilin
2) Blocks the activation of calcineurin
3) Nf kappa b remains in the cytosol
4) Pro-inflammatory response is reduced and some cytokine production is inhibited
Which drugs repress transcription of pro-inflammatory mediators in immune cells?
How do glucocorticoids work?
Enter cells and translocate into the NUCLEUS - regulate at the level of transcription of pro-inflammatory mediators
What is a 'cytokine' and what can they do?
What are examples of cytokines?
ANY protein or polypeptide MEDIATORS which are synthesised or released by cells of the immune system during INFLAMMATION
They can act DIRECTLY on cells or AMPLIFY inflammation by inducing the formation of OTHER inflammatory mediators
How can new drugs be developed that are more effective than glucocoticoids or ciclosphorin?
What are these new drugs called?
Can be developed to target SPECIFIC cytokines
How do biopharmaceuticals delivered?
They are INJECTED
What molecules are biopharmaceuticals?
How do biopharmaceuticals work?
They are SPECIFICALLY directed to pro-inflammatory cytokines with high affinity
What is a type of biopharmaceutical and how does it work?
Humanised monoclonal antibodies:
- Bind to TNF alpha released from macrophages
- Preventing it from activating other cell types which cause tissue damage
Why is is important that the Fc region of a humanised monoclonal antibody is the equivalent to that of a human antibody?
To prevent rejection
So that they are treated like normal antibodies
Why mimic the soluble receptors made for cytokines by the body?
To bind up cytokines and prevent them from binding to their receptors
What causes asthma?
Chronic inflammation of the airways
Why do the symptoms of asthma become greater overime?
- Airways become sensitised
- Smooth muscle controlling the airways expand and become more sensitive to triggers
(Bronchial hyper-activity becomes greater overtime)
What are the treatments of asthma?
1) Salbutamol (bronchodilator)
2) Glucocorticoids (anti-inflammatory agent)
What causes a resistance to salbutamol?
1) Overuse of inhalers causing de-sensitisation of the receptors
2) Polymorphisms in the Beta-2 adrenoreceptors causing a reduction in efficacy of salbutamol
What is the pathology of asthma?
1) Atopic trigger (allergen)
2) Airways constricted upon exposure, due to immune cells accumulating in the airways
3) Stronger response several hours later - inflammatory response
- Cytokines released
What can the 2nd stage of asthma lead to?
Irreversible damage to the airways