Immunopharmacology Flashcards
What are the purposes of immunosuppressive drugs?
(1) Prevention of organ transplant rejection
(2) Treatment of autoimmune diseases (e.g. Multiple Sclerosis, Lupus, Rheumatoid Arthritis, Chron’s disease, Type I Diabetes)
What is the cellular basis for rejection? (4)
(1) Antigen presenting cell (e.g. dendritic cell) from the donor organ activates T cells (CD4 + T cells)
(2) T cells produce Interleukin 2 (IL-2; a cytokine)
(3) IL-2 stimulates the proliferation of T cells and the production of additional cytokines that stimulate the proliferation of multiple types of immune cells: T cells, B cells, macrophages, etc
(4) Activated immune cells then attack the transplanted organ (allograft)
What drugs are the signaling inhibitors? What are their adverse effects?
(1) Cyclosporine
(2) Tacrolimus
- Adverse effects: nephrotoxicity, hepatotoxicity, neurotoxicity
(3) Sirolimus
- Adverse effects: hyperlipidemia
Cyclosporine: Mechanism of action
- Cyclosporine binds to Cyclophilin in T cell
- The complex between Cyclosporine and Cyclophilin inhibits Calcineurin activity which prevents the activation of the transcription factor which prevents IL-2 function
Tacrolimus: Mechanism of action
- Tacrolimus binds to FK506
- The complex between Tacrolimus and FK506 inhibits Calcineurin activity which prevents the activation of the transcription factor which prevents IL-2 function
Which corticosteroid is used as an immunosuppressant drug in transplant rejection? What is the mechanism of action?
- Prednisone
- Inhibits cytokine production
Prednisone: Adverse effects
- Insomnia, hypomania, ulcers
What drugs are the proliferation inhibitors? What are their adverse effects?
(1) Cyclophosphamide
(2) Methotrexate
(3) Mycophenolate Mofetil
- proliferation- associated toxicities (e.g. myelosuppression)
Cyclophosphamide: Mechanism of action
- Selectively kills rapidly proliferating immune cells (e.g. T cells, B cells)
Methotrexate and Mycophenolate: Mechanism of Action
- There are antimetabolites
- Methotrexate: Folate antagonist
- Mycophenolate Mofetil: Inhibits nucleic acid synthesis
Sirolimus- Mechanism of action
- Sirolimus binds to FK506
- The complex between these two things inhibits mTOR protein kinase
Rh (D) immune globulin: Background
- Rh (D) negative mother will generate antibodies to Rh (D) antigen on the erythrocytes of Rh (D) positive newborn
- The mother will be exposed to the newborn erythrocytes shortly after giving birth
What happens if an Rh (D) negative mother is pregnant with a second child who is Rh (D) positive and did not receive the immune globulin?
- The antibodies that developed in the mother will cross the placenta and cause child to have hemolytic anemia and ultimately kill the child
What does the Rh (D) immune globulin do? When do you need to administer this?
- Rh (D) immune globulin kills the erythrocytes that are developing the antigen so that you can have another child that is Rh (D) positive later in life
- Have to administer this within 72 hours or the mother will have already developed the Rh (D) antibodies and the immune globulin will NOT work
What are the clinically useful monoclonal antibodies? (2) What are they used to treat?
(1) Muromonab- CD3 (OKT-3)
(2) Anti-IL-2 receptor antibodies (Daclizumab)
- acute transplant rejection
