Immunosuppressants and Anti-cancer drugs

Question 1

difference between anti-inflammatory drugs (corticosteroids) and immunosuppressants

Answer 1

the difference lies in which cells they target: anti-inflammatory drugs target any inflammatory cell whereas immunosuppressants target mainly the T cells

Question 2

clinical uses for immunosuppressants

Answer 2

used mainly for transplant rejection and autoimmune diseases

Question 3

types of immunosuppressants (3 types)

Answer 3

1. calcineurin inhibitors
   - cyclosporine A and tacrolimus
2. mTOR inhibitors
   - sirolimus
3. cytotoxic immunosuppressants
   - azathioprine

Question 4

mechanism of action of calcineurin inhibitors

Answer 4

[cyclosporin A and tacrolimus]

• inhibits cytokine gene transcription and synthesis
• inhibits T cell proliferation

Question 5

mechanism of action of mTOR inhibitors

Answer 5

[sirolimus]

• inhibits cytokine-mediated T and B cell proliferation by stimulating cell cycle arrest

Question 6

side effects of immunosuppressants (general 3H’s + calcineurin specific + mTOR specific + cytotoxic immunosuppressants)

Answer 6

generally:

• hyperglycemia
• hyperlipidemia
• hypertension

calcineurin-specific:

• nephrotoxicity
• neurotoxicity

mTOR-specific:
- thrombocytopenia

cytotoxic immunosuppressant-specific:
- leukopenia, anemia, thrombocytopenia

Question 7

mechanism of action for cytotoxic immunosuppressants

Answer 7

used as an anti-cancer drug

- functions as a structor analog that impedes DNA synthesis

Question 8

side effect of chemotherapy drugs in terms of secondary malignancy

Answer 8

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)

Question 9

general side effect of anti-cancer drugs

Answer 9

acute side effects:

• nausea/vomiting
• weight loss
• myelosuppression
• alopecia

late organ toxicity:
- neurotoxicity/hepatotoxicity/nephrotoxicity

Question 10

what are the 2 general groups of anti-cancer drugs

Answer 10

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

Question 11

example of cytotoxic antibodies

Answer 11

anything-rubicin

Question 12

example of alkylating agent

Answer 12

chlorambucil

Question 13

example of platinum-based drug

Answer 13

cisplatin

Question 14

example of microtubule inhibiting drug

Answer 14

vinblastine

Question 15

example of antimetabolite

Answer 15

methotrexate (also used in RA)

Question 16

MOA of rubicins (cytotoxic antibodies)

Answer 16

directly target cancer cells

Question 17

MOA of chlorambucil (alkylating)

Answer 17

disrupts DNA replication and transcription

Question 18

MOA of cisplatin (platinum-based)

Answer 18

forms DNA adducts

Question 19

MOA of vinblastin (microtubule inhibitor)

Answer 19

prevents microtubule formation

Question 20

MOA of methotrexate (antimetabolite)

Answer 20

restricts flow of precursor molecules for DNA replication and transcription

Question 21

MOA of topoisomerase inhibitor

Answer 21

inhibits topoisomerase from forming cuts in the DNA = disrupts supercoiling