Lecture 8 - immunosuppressant drugs Flashcards
what is rheumatoid arthritis?
- chronic inflammatory condition of joints where there is inflammation of synovium and erosion of cartilage and bone.
- increases risk of cardiovascular disease
- genetic component
symptoms of rheumatoid arthritis
- joint swelling of parallel joints
- joint stiffness in morning
- loss of weight
treatments for rheumatoid arthritis
- treated with disease-modifying anti-rheumatic drugs (DMARDs) and NSAIDs
- DMARDs may halt or reverse disease where NSAIDs treat symptoms
what does T cell activation lead to?
activation of immune cells called macrophages
what mediators does macrophages release?
cytokines (IL-1) and TNF-alpha which are involved in driving the inflammatory response
what drug is an antagonist for folic acid?
Methotrexate - used to treat rheumatoid arthritis but has immunosuppressant activity
DMARDs used to control inflammatory response
Penicillamine and Sulfasalazine
immunosuppressant used to treat transplant rejection
Cyclosporin
role of calcineurin
- is a phosphate enzyme that is regulated by calcium
- target is NFKB (transcription factor) that increases production of IL-1 and TNF-alpha.
action of cyclosporin
- limits activity of NFKB by binding to calcineurin so IL-1 and TNF-alpha cannot be produced
action of glucocorticoids
- acts as a represser (prednisolone) by binding to glucocorticoid receptor to inhibit transcription of inflammatory cytokines
monoclonal antibody that recognises TNF-alpha
Adalimumab - has to be injected
Inflammatory respiratory diseases
COPD and Asthma
Anti-asthmatic drugs
- salbutamol (B2 adrenoreceptor agonist)
- anti-inflammatory agents like prednisolone (steroid drug) and omalizumab (monoclonal antibody)
Allergic rhinitis (Hayfever)
- activation of mast cells in nasal mucosa and conjunctivae
- symptoms; nasal congestion, sneezing, allergic conjunctivitis
- effects upper airways
Symptoms of allergic asthma
- attacks of wheezing, shortness of breath and cough.
- bronchial hyper-sensitivity resulting in bronchoconstriction.
Early phase asthma
characterised by mast cells secreting histamine in bronchi and is reversible
late phase asthma
due to cytokines (leukocytes) and eosinophils forcing an inappropriate inflammatory response in lungs resulting in tissue damage and airway and remodelling.
what does activation of histamine receptors lead to?
activation of prostaglandins to drive bronchoconstriction and leads to increase vascular permeability where fluid enters the lungs and other immune cells.
drug to treat late phase asthma
steroid drugs like prednisolone or biological drugs
unwanted side effects of chronic steroid use
- develop into Cushing’s syndrome
symptoms are hypertension, abdominal air. poor wound healing, cataracts and muscle wastage
New therapies for treating asthma
- using humanised monoclonal antibodies and soluble receptors to recognise IgE
- small molecules that are prostaglandin D2 receptor antagonists
