Immunopharmacology Flashcards
How is the immunosuppressive function of steroids utilize for therapy
- prevention of allograft rejection
- treatment of autoimmune diseases
how do corticosteroids interfere with Cell traffic or accumulation
-decreases access of immune cells to target tissue
a. Lymphocytopenia and monocytopenia - redistribution of cells out
of vascular space
b. Prevent neutrophil adherence to endothelium
c. Inhibit action of chemotactic factors
How do corticosteroids interfere with cell function
a. Interferes with macrophage antigen processing
b. Blocks the actions of lymphokines
c. Inhibits binding to Fc receptors
Describe the toxicity that corticosteroid therapy can cause
a. Suppression of adrenal-pituitary axis. Acute adrenal insufficiency on abrupt withdrawal
b. Cushing’s Syndrome
When is corticosteroid use contraindicated
in presence of existing infection
-bc it suppresses the immune system which would further exacerbate the infection
Are corticosteroids usually prescribed alone
no they are usually prescribed in combination with cyclosporin and cytotoxic agents
What is the corticosteroid drug
Prednisolone
Describe the general mechanism of action for Cytotoxic Agents and when they would be best used as therapy
and how is it usually administered
- In response to an antigen, immune cells proliferate in a synchronized manner with a burst of mitotic division. Cytotoxic agent kill these rapidly proliferating cells.
- Best used at the time of initial exposure to antigen. Will kill a high percentage of the precursor cells. Get em’ early!!
- Relevant clone stimulated by antigen will be killed. Other immune cells and clones not stimulated by antigen will be spared. So basically only if it was stimulated by the antigen with the drug have an effect on it
- Usually administered in a low daily dosage to block immunoproliferation continually.
Azathioprine
- class of drug
- Mechanism of action and selectivity if applicable
- method of administration
- therapeutic uses
- side effects
-cytotoxic agent
-A purine anti-metabolite that inhibits purine biosynthesis
and thereby inhibits DNA synthesis. Inhibits De Novo and Salvage pathways.
-Metabolized to 6-mercaptopurine
-Orally active
-Used to inhibit rejection of transplanted organs and in some autoimmune diseases as rheumatoid arthritis.
-Bone marrow depression is major side effect.
Gastrointestinal and hepatic toxicity may occur.
Azathioprine is a drug that inhibits both the De Novo pathway and the Salvage pathway of DNA synthesis. What drug (that is also a cytotoxic agent) only inhibits one of these pathways, and which pathway is it?
Mycophenolate Mofetil
it only inhibits the De Novo pathway of DNA synthesis, so it has no effect on the salvage pathway
this is why is is lymphocyte selective, bc lymphocytes only use the de novo pathway. but all other cells that can also use the salvage pathway are unaffected by this drug
Cyclophosphamide (Cytoxan ®)
- class of drug
- Mechanism of action and selectivity if applicable
- method of administration
- therapeutic uses
- side effects
- cytotoxic agent
1) An alkylating agent that results in cross-linking of DNA to kill replicating and non-replicating cells.
2) Toxic effect more pronounced on B-cells so more effective in suppressing humoral immunity. (Bc although T cells are effected, they regenerate so quickly it doesn’t really cause an impact)
3) Orally active.
4) Used in the treatment of autoimmune diseases in
combination with other drugs. Not effective in preventing graft rejection.
5) Bone marrow depression is major side effect.
Methotrexate
- class of drug
- Mechanism of action and selectivity if applicable
- therapeutic uses
- side effects
-cytotoxic agent
1) Inhibitor of dihydrofolate reductase - inhibits folate
dependent steps in purine synthesis - inhibits DNA synthesis.
2) Used to treat autoimmune diseases.
3) Hepatic toxicity.
Conversion of dihydrofolate to its active form, tetrahydrofolate, is blocked by
methotrexate’s (MTX) inhibition of the enzyme dihydrofolate reductase (DHFR).
Thymidine Synthase (TS).
What is Mycophenolate Mofetil metabolized to
mycophenolic acid.
Describe Mycophenolate Mofetil mechanism of action and selectivity
a. Lymphocyte selective immunosuppressant
1) Inhibits IMP Dehydrogenase
IMP → GMP Necessary for de novo purine synthesis
No effect on salvage pathway
2) Lymphocytes, unlike other cells, cannot make GMP via
salvage pathway – must use de novo pathway. Thus, selectively toxic for lymphocytes.
3) Inhibits lymphocyte proliferation and expression of cell
surface adhesion molecules.
4) More selective than azathioprine or methotrexate but
equally effective.
