Immunopharmacology Flashcards
define immunopharmacology
Immunopharmacology is a vast and complex area of pharmacology that focuses on
primary and secondary disorders of the immune system and the production of modulators of the immune system. It involves the production of vaccines and immunization, the treatment of inflammation, autoimmune diseases, allergies, fungal,viral and bacterial infections, infections due to parasites, and cancer
what do immunosuppressants inhibit?
inhibit normal immune response following organ transplantation or over reactive immune response associated with autoimmune disorders
-work best for primary immune response
immunosuppression following organ transplants
- Acute rejection is defined as rejection that occurs 24 hours to several weeks following organ transplantation; it is mediated mainly by T cels and cytokine
- decrease the amount of lymphocytes, divert lymphocyte traffic, or block pathways involved in lymphocytic response.
types of immunosuppressants
- ) steroids
- ) alkylating agents
- ) inhibitors of de novo purine synthesis
- ) inhibitors of de novo pyrimidine synthesis
- ) kinases and phosphatases inhibitors
- ) protein immunosuppressive drugs
corticosteroids
- used for induction and maintenance of immunosuppression
- reduce levels of circulating lymphocytes
- block lymphocytes activation
- block T cell lymphocyte proliferation-> inhibit IL-2 transcription
what never combine with steroids?
NSAIDs
what drugs to use for organ transplanation
steroids
cytotoxic drugs
why be cautious with steroids?
serious problem with long term utilization
-increases risk of infection, ulcers, hypoglycemia
cytotoxic drugs
azathioprine, cyclophosphamide, methotrexate
- purine antimetabolite-> interferes with DNA synthesis
- prevents clonal expansion of B and T cells
- induction of maintenance of immunosuppression
cytotoxicity of cytotoxic drugs
leukopenia, thrombocytopenia, GI and liver dysfunction
alkylating agent
cyclophosphamide
-interferes with DNA synthesis
inhibitors of de novo synthesis
-inhibit inosine 5’-monophosphate dehydrongenase inhibitor
azathioprine, 6-mercaptopurine
2nd: mizoribine and mycophenolate mofetil (MMF)
methotrexate, polygentamate derivatives
MMF works by
- inosine 5’-monophosphate dehydrogenase inhibitor
- ester prodrug that is hydrolyzed to active drug
- lacks cardiovascular side effects and chronic nephrotoxic syndrome
- side effects: GI disorders, (N&V, diarrhea, ulcers, esophagitis) and bone marrow suppression
induction of maintenance immunosuppression drugs
alkylating agents steroids inhibitors of de novo purine synthesis cyclosporine tacrolimus kinases and phosphatases
inhibitors of de novo pyrimidine synthesis
- inhibit dihydroorotate dehydrongenase
- organ transplant medicine, usually in combination with steroids and tracrolimus
- brequinar, leflunomide, malononitrilamides
kinase and phosphatase inhibitors
cyclosporine and tacrolimus
-organ transplants
cyclosporine
give IV or Per os
- concentrates in red/white blood cells
- metabolized by liver
- excreted in feces
- give 4-24 hours prior to organ transplant and continued for weeks
toxicity of cyclosporine
renal, gingival, neuronal, hepatic, systemic hypertension