Immune System and Malignant Disease Flashcards
Give two examples of antimetabolites used in chemotherapy.
- 5-fluorouracil
* Methotrexate
What is the mechanism of action of 5-fluorouracil?
Inhibits thymidylate synthase (can’t produce thymine for DNA synthesis)
What is the mechanism of action of methotrexate?
Dihydrofolate reductase inhibitor (can’t produce thymine for DNA synthesis)
What is an example of a vinca alkaloid?
Vincristine
What is the mechanism of action of vincristine?
Inhibits microtubule assembly, prevent cell replication
What is an example of a taxane?
Paclitaxel
What is the mechanism of action of paclitaxel?
Inhibits microtubule depolymerisation - so attach to chromatids but can’t pull then pull them to opposite poles
What is an example of a platinum compound?
Cisplatin
What is the mechanism of action of cisplatin?
Inhibits DNA replication by forming covalent bonds between intra- and inter-strands of DNA (adducts)
What are some of the ADRs of chemotherapy?
- Lungs - Pulmonary fibrosis
- Heart - Cardiotoxicity, phlebitis
- GI - nausea, vomiting, diarrhoea and mucositis
- Urinary - cystitis, renal failure
- Muscles - Myalgia
- Bones - Myelosuppression
- Nerves - Neuropathy
- Skin/hair - local reaction, alopecia
What are the specific chemotoxicities of cisplatin?
Ototoxicity and nephrotoxicity
What are the specific chemotoxicities of vincristine?
Peripheral neuropathy
What are the specific chemotoxicities of methotrexate and 5-fluorouracil?
Myelosuppression
What are the specific chemotoxicities of cyclophosphamide?
Heamorrhagic cystitis
What are 3 examples of anti-proliferative immunosuppressants?
- Azathioprine
- Cyclophosphamide
- Mycophenolate mofetil
What are 2 examples of calcineurin inhibitors?
- Ciclosporin
* Tacrolimus
What are calcineurin inhibitors used for?
- Transplantation
- Atopic dermatitis
- Psoriasis
What is the mechanism of action of calcineurin inhibitors?
Active against T helper cells - prevent production of IL-2 via calcineurin inhibition
When is mycophenolate mofetil used?
- Transplantation
* Induction and maintenance for lupus nephritis/vasculitis maintenance
What is the mechanism of action of mycophenolate mofetil?
Prodrug
Inhibits IMD, needed for guanosine synthesis - impairs B and T cell proliferation but spares other rapidly dividing cells (due to guanosine salvage pathways in other cells)
What are the ADRs of mycophenolate mofetil?
- Nausea and vomiting
- Diarrhoea
- Myelosuppression
What is the mechanism of action of cyclophosphamide?
An alkylating agent - crosslinks DNA so it can’t replicate
When is cyclophosphamide used?
- Lymphoma, leukaemia and solid cancers
* Lupus nephritis
How is cyclophosphamide excreted?
Kidneys
What are the toxicities associated with cyclophosphamide?
- Increased risk of bladder cancer, lymphoma and leukaemia
* Infertility (related to accumulative dose and age)
