Lecture 8 - immunosuppressant drugs

Question 1

what is rheumatoid arthritis?

Answer 1

• chronic inflammatory condition of joints where there is inflammation of synovium and erosion of cartilage and bone.
• increases risk of cardiovascular disease
• genetic component

Question 2

symptoms of rheumatoid arthritis

Answer 2

• joint swelling of parallel joints
• joint stiffness in morning
• loss of weight

Question 3

treatments for rheumatoid arthritis

Answer 3

• treated with disease-modifying anti-rheumatic drugs (DMARDs) and NSAIDs
• DMARDs may halt or reverse disease where NSAIDs treat symptoms

Question 4

what does T cell activation lead to?

Answer 4

activation of immune cells called macrophages

Question 5

what mediators does macrophages release?

Answer 5

cytokines (IL-1) and TNF-alpha which are involved in driving the inflammatory response

Question 6

what drug is an antagonist for folic acid?

Answer 6

Methotrexate - used to treat rheumatoid arthritis but has immunosuppressant activity

Question 7

DMARDs used to control inflammatory response

Answer 7

Penicillamine and Sulfasalazine

Question 8

immunosuppressant used to treat transplant rejection

Answer 8

Cyclosporin

Question 9

role of calcineurin

Answer 9

• is a phosphate enzyme that is regulated by calcium
• target is NFKB (transcription factor) that increases production of IL-1 and TNF-alpha.

Question 10

action of cyclosporin

Answer 10

• limits activity of NFKB by binding to calcineurin so IL-1 and TNF-alpha cannot be produced

Question 11

action of glucocorticoids

Answer 11

• acts as a represser (prednisolone) by binding to glucocorticoid receptor to inhibit transcription of inflammatory cytokines

Question 12

monoclonal antibody that recognises TNF-alpha

Answer 12

Adalimumab - has to be injected

Question 13

Inflammatory respiratory diseases

Answer 13

COPD and Asthma

Question 14

Anti-asthmatic drugs

Answer 14

• salbutamol (B2 adrenoreceptor agonist)
• anti-inflammatory agents like prednisolone (steroid drug) and omalizumab (monoclonal antibody)

Question 15

Allergic rhinitis (Hayfever)

Answer 15

• activation of mast cells in nasal mucosa and conjunctivae
• symptoms; nasal congestion, sneezing, allergic conjunctivitis
• effects upper airways

Question 16

Symptoms of allergic asthma

Answer 16

• attacks of wheezing, shortness of breath and cough.
• bronchial hyper-sensitivity resulting in bronchoconstriction.

Question 17

Early phase asthma

Answer 17

characterised by mast cells secreting histamine in bronchi and is reversible

Question 18

late phase asthma

Answer 18

due to cytokines (leukocytes) and eosinophils forcing an inappropriate inflammatory response in lungs resulting in tissue damage and airway and remodelling.

Question 19

what does activation of histamine receptors lead to?

Answer 19

activation of prostaglandins to drive bronchoconstriction and leads to increase vascular permeability where fluid enters the lungs and other immune cells.

Question 20

drug to treat late phase asthma

Answer 20

steroid drugs like prednisolone or biological drugs

Question 21

unwanted side effects of chronic steroid use

Answer 21

• develop into Cushing’s syndrome
  symptoms are hypertension, abdominal air. poor wound healing, cataracts and muscle wastage

Question 22

New therapies for treating asthma

Answer 22

1. using humanised monoclonal antibodies and soluble receptors to recognise IgE
2. small molecules that are prostaglandin D2 receptor antagonists