Flashcards in 2: Immunosuppressants Deck (54)
what does immunopharmacology involve?
-production of vaccines and immunization
-treatment of inflammation
-fungal, viral, and bacterial infections
-infections due to parasites
what induces autoimmune diseases?
hyperactive T cell immune response
what causes immune suppression and incompetence?
hypoactive response of T cell immunity
role of each:
-helper T cells
-cytotoxic T cells
-suppressor T cells
helper: coordination of immune response
cytotoxic: remove virus-infected cells from the body
suppressor: temper immune response when it's overactive
purpose of immunosuppressants
inhibit normal immune response following organ transplantation or overactive immune response associated with autoimmune disorders
what part of the immune response do immunosuppressants work best for?
primary immune response
-efficacy depends on the type of immune response
-best results when treatment begun before exposure to Ag
define acute rejection
-occurs 24h to weeks post transplant
-mediated by T cells and cytokine release
how is immunosuppression achieved?
different classes of immunosuppressants that:
-decrease amount of lymphocytes
-divert lymphocyte traffic
-block pathways involved in lymphocytic response
classes of immunosuppressants
1. regulators of gene expression
2. alkylating agents
3. inhibitors of de novo purine synthesis
4. inhibitors of de novo pyrimidine synthesis
5. kinase and phosphatase inhibitors
6. protein immunosuppressants
what drugs are regulators of gene expression?
adrenocortical steroids - prednisone, prednisolone
what parts of immunosuppression are adrenocortical steroids used for?
induction and maintenance therapy
function of adrenocortical steroids
-reduce circulating lymphocyte levels
-block lymphocyte activation required for Ag presentation
-block T cell proliferation
(inhibit IL-2 gene expression, which is required for clonal expansion of B and T cells)
what drugs are alkylating agents?
what drugs are inhibitors of de novo purine synthesis?
azathioprine, 6-mercaptopurine (first gen)
mizoribine, mycophenolate mofetil (MMF) (second gen)
what parts of immunosuppression are alkylating agents and purine synthesis inhibitors used for?
induction and maintenance
function of alkylating agents and purine synthesis inhibitors
-block or interfere with DNA/RNA synthesis and function
-prevent clonal expansion of B and T cells
chemically describe MMF
-ester prodrug -> active form: mycophenolic acid
function of MMF
inhibits inosinse 5'-monophosphate DH
side effects of MMF
GI shit and events related to bone marrow suppression (leukopenia, anemia, thrombocytopenia)
does NOT have CV risk or chronic nephrotoxic secondary effects
what drugs are inhibitors of de novo pyrimidine synthesis?
MOA of de novo pyrimidine synthesis
inhibit dihydroorotate DH
usefulness of the leflunomide derivative, FK778?
no benefit for using FK778 over MMF - also seems more difficult for patients to tolerate
what drugs are kinase and phosphatase inhibitors?
what parts of immunosuppression are kinase and phosphatase inhibitors used for?
induction and maintenance therapy (block signaling pathways that stimulate IL-2 production)
where does cyclosporine come from?
the fungus Tolypocladium inflatum Gams
how is cyclosporine administered? dosing?
IV or p.o.
given 4-24h before transplant, continued after with lower doses at weekly intervals
where does cyclosporine concentrate?
in the red and white blood cells
PK of cyclosporine
metabolized by liver
mainly excreted in feces
toxicity of cyclosporine
renal (proximal tubule) - limiting factor
may induce systemic HTN