Immunosuppressants and Anti-cancer drugs Flashcards
difference between anti-inflammatory drugs (corticosteroids) and immunosuppressants
the difference lies in which cells they target: anti-inflammatory drugs target any inflammatory cell whereas immunosuppressants target mainly the T cells
clinical uses for immunosuppressants
used mainly for transplant rejection and autoimmune diseases
types of immunosuppressants (3 types)
- calcineurin inhibitors
- cyclosporine A and tacrolimus - mTOR inhibitors
- sirolimus - cytotoxic immunosuppressants
- azathioprine
mechanism of action of calcineurin inhibitors
[cyclosporin A and tacrolimus]
- inhibits cytokine gene transcription and synthesis
- inhibits T cell proliferation
mechanism of action of mTOR inhibitors
[sirolimus]
- inhibits cytokine-mediated T and B cell proliferation by stimulating cell cycle arrest
side effects of immunosuppressants (general 3H’s + calcineurin specific + mTOR specific + cytotoxic immunosuppressants)
generally:
- hyperglycemia
- hyperlipidemia
- hypertension
calcineurin-specific:
- nephrotoxicity
- neurotoxicity
mTOR-specific:
- thrombocytopenia
cytotoxic immunosuppressant-specific:
- leukopenia, anemia, thrombocytopenia
mechanism of action for cytotoxic immunosuppressants
used as an anti-cancer drug
- functions as a structor analog that impedes DNA synthesis
side effect of chemotherapy drugs in terms of secondary malignancy
many of these drugs are DNA damaging to the normal cells - leads to more genomic instability that may increase risk for secondary malignancy (especially those that cause DNA breaks)
general side effect of anti-cancer drugs
acute side effects:
- nausea/vomiting
- weight loss
- myelosuppression
- alopecia
late organ toxicity:
- neurotoxicity/hepatotoxicity/nephrotoxicity
what are the 2 general groups of anti-cancer drugs
those that are not cell-cycle specific:
- C: cytotoxic antibodies
- A: alkylating agents
- P: platinum-based drugs
those that are cell-cycle specific:
- M: microtubule inhibiting drugs
- A: antimetabolites
- T: topoisomerase inhibitors
example of cytotoxic antibodies
anything-rubicin
example of alkylating agent
chlorambucil
example of platinum-based drug
cisplatin
example of microtubule inhibiting drug
vinblastine
example of antimetabolite
methotrexate (also used in RA)
MOA of rubicins (cytotoxic antibodies)
directly target cancer cells
MOA of chlorambucil (alkylating)
disrupts DNA replication and transcription
MOA of cisplatin (platinum-based)
forms DNA adducts
MOA of vinblastin (microtubule inhibitor)
prevents microtubule formation
MOA of methotrexate (antimetabolite)
restricts flow of precursor molecules for DNA replication and transcription
MOA of topoisomerase inhibitor
inhibits topoisomerase from forming cuts in the DNA = disrupts supercoiling
