Block 2_8 - Immunopharmacology Flashcards
1
Q
Immunosuppressant Drugs (in general)
- Mechanism
- Use
- Side Effects
A
- Block proliferation or interaction of immune cells or block actions or release of cytokines
- treat autoimmune diseases; prevent allograft rejection
- rapidly proliferating cells - bone marrow, liver, or GI tract
- increased incidence of infection
2
Q
Prednisolone
- role in cell traffic or accumulation
- cell function
- use
- toxicity
- contraindication
A
Adrenocortical Steroid
- Cell traffic or accumulation - reduce access of cells to target tissue
- Lymphocytopenia and monocytopenia - redistribution of cells out of vascular space
- prevent neutrophil adherence to endothelium
- inhibit action of chemotactic factors
- Cell Function
- Interferes with macrophage antigen processing
- blocks the actions of lymphokines
- inhibits binding to Fc Receptors
- autoimmune diseases and to prevent graft rejection
- Toxicity
- suppression of APA (adrenal-pituitary axis). Acute adrenal insufficiency on abrupt withdrawal
- Cushing’s Syndrome
- existing infection
3
Q
Cytotoxic Agents
A
Azathioprine
Cyclophosphamide
Methotrexate
Mycophenolate Mofetil
4
Q
Cyclosporine-like Drugs
A
Cyclosporine
Tacrolimus
Sirolimus
5
Q
Azathioprine
- metabolized to
- route of admin
- mechanism
- Use
- Toxicity
A
- metabolized to 6-mercaptopurine
- orally active
- purine anti-metabolite that inhibits purine biosynthesis and thereby inhibits DNA synthesis. Inhibits the De Novo and Salvage pathways
- used along with glucocorticoid to inhibit rejection of transplanted organs; some autoimmune diseases as rheumatoid arthritis
- Bone marrow suppression; GI and hepatic toxicity may occur
6
Q
Cyclophosphamide
- mechanism
- more effective in doing what
- route of administration
- Use
- side effects
A
- an alkylating agent that results in cross-linking of DNA to kill replicating and non-replicating cells
- toxic effects are more pronounced on B-cells so more effective in suppressing humoral immunity
- orally active
- used in the treatment of autoimmune diseases in combination with other drugs. Not effective in preventing graft rejection
- Bone marrow depression is a major side effect
7
Q
Methotrexate
- mechanism of action
- Use
- side effects
A
- inhibitor of dihydrofolate reductase - inhibits folate dependent steps in purine synthesis (blocks conversion of dihydrofolate to its active form tetrahydroflate) - therefore inhibits DNA synthesis
- used to treat autoimmune diseases - not used in allograft rejection
- hepatic toxicity
8
Q
Mycophenolate Mofetil
- General Info
- Mechanism of Action (3 things)
- Route of Admin
- Use (combo use with other drugs?)
- Use #2
- Side Effects
- Contraindications
A
1. General Info
Metabolized to the active mycophenolic acid (active ingredient is not absorbed as well - the ester form is absorbed better)
2. Mechanism of Action
Lymphocyte selective immunosuppressant
- a. inhibits IMP Dehydrogenase (IMP -> GMP)
- Necessary for de novo purine synthesis
- no effect on salvage pathway
- b. Selectivity for lymphocytes - unlike other cells, they cannot make GMP via the salvage pathway - must use the de novo pathway.
- c. inhibits lymphocyte proliferation and expression of cell surface adhesion molecules
- Route of Admin: Orally Active
- Use: Used with cyclosporine and corticosteroids to prevent renal allograft rejection. Allows lower dose of cyclosporine to be used so less toxicity
5. Use #2: used to treat autoimmune diseases - rheumatoid arthritis and refractory psoriasis
- side effects - infection, leukopenia, anemia
- Contraindications: pregnancy, active GI disease, reduced renal function and infections
9
Q
Cyclosporine
- general info
- mechanism of action
- Route of administration
- Use
- Toxicity
A
- a lipophilic peptide antibiotic - Immunosuppression - Calcineurin Inhibitor
- binds to a cellular receptor (cyclophilin) and inhibits calcium dependent phosphatase (Calcineurin). Blocks activation of transcription factor (NFAT) necessary for IL-2 production (phosphorylated = inactive)
- inhibits mRNA synthesis that codes for lymphokines as IL-2
- by blocking IL-2 synthesis, it blocks T cell helper function so inhibits T cell proliferation and cytotoxicity
- since it is not lymphotoxic, it is more selective in its action
- orally active
- prevent rejection of transplanted organs. More effective than other agents used with fewer side effects. Used in some autoimmune diseases.
- Nephrotoxicity is a major side effect. Hepatotoxicity may occur
10
Q
Tacrolimus (comparable to what drug?)
- mechanism of action
- spectrum of action
- toxicity
A
- Cyclosporine
- Immunosuppression - Calcineurin Inhibitor
- it binds FK binding protein (FK BP-12). Same mechanism of action as cyclosporine –> binds to calcineurin and inhibit its activity so NFAT is not dephosphorylated - Spectrum of action is the same as cyclosporine but 50-100x more potent
- less nephro- and hepatotoxicity
11
Q
Sirolimus
- Overall action
- mechanism of action
- Use
A
- inhibits T-Cell activation and proliferation downstream of IL-2
- Binds FKBP-12. It binds and inhibits mTOR, a kinase involved in cell cycle progression. Blocks G1-> S transition (mTOR normally phosphoyrlates and regulates the signaling pathway)
- same use as cyclosporine (prevent rejection of transplanted organs. Some autoimmune diseases)
- also used in coating of cardiac stents to prevent cells from coating stent and reoccluding artery
