cytokine and cytokine receptor inhibitors

Question 1

TNFa inhibitors - 2 mechanisms
all drugs are administered via iv , possible side effects include infection at injection site and can treat rheumatoid arthritis, IBS and psoriasis.

Answer 1

The soluble receptor blocks the TNF-a ligand from binding to TNF-a receptor

The TNF-a mab is bound to the TNF-a receptor preventing TNF-a from bounding to the receptor

(there are TNF-a receptors on macrophages, chondrocytes, osteoclasts and synovial fibroblasts )

Question 2

Abatacept: ( CTLA-4)

Answer 2

• -anti CD80/86 OR ANTI-B7
  -abatacept binds to CD80/86 and prevents co-stimulation and t-cell activation which leads to t cell anergy ( apoptosis) (when t cells aren’t activated they die)

Question 3

rituximab

Answer 3

CD20 monoclonal antibody, rituximab binds to CD20 which initiates complement dependent cytotoxicity. leads 90% reduction in pheripheral b cells. which lasts for months.

Question 4

Tocilizumab (anti-IL-6 ) mab

Answer 4

IL-6 involved in activating chondrocytes, osteoclasts resulting in destruction of cartilage. also involved in differentiation of t-helper to th1 cells and differentiation to b-cells.

Question 5

JAK-STAT pathway

Answer 5

A transcription pathway where the JAK proteins transfer a phosphate group to the STAT molecule. The p-stat dimer then translocates into nucleus and acts as a transcription factor.

Question 6

JAK-stat inhibitor Tofacitinib

Answer 6

INhibitor of JAK 1,2,3, cytokines this effects include il-6 and interferon -y . Adverse effects: infections(herpes), liver and lipid abnormalities and lower rbc count.