Chemotherapy Flashcards
How can chemotherapeutic drug be classified?
Classification I:
Cell cycle specific vs Cell cycle non-specific
Classification II:
- Directly acting cytotoxic drugs:
- alkylating agents
- antimetabolites
- natural products
- miscellaneous - Indirectly acting drugs:
- corticosteroids
- oestrogen + ERMs
- 5-alpha reductase inhibitors
- GNRH agonists
- Progestins
Give examples of cell cycle NON specific chemo drugs.
Cyclophosphamide Chlorambucil Cisplatin Actinomycin-D L-asparaginase
How does Cyclophosphamide work?
Main effects due to its metabolic phosphoramide mustard
forms irreversible DNA cross-links
leads to cell apoptosis
How does Chlorambucil work?
Alkylating agent/nitrogen mustard
Produces its anti-cancer effects by interfering with DNA replication and damaging the DNA within cells (cross-linking, adding alkyl groups to bases, mutations)
Damage to DNA induces cell cycle arrest and cellular apoptosis
(accumulation of p53 and activation of BCL2)
How does Cisplatin work?
Cross-links DNA (especially purine bases) and interferes with mitosis
causes cellular apoptosis
How does Actinomycin-D work?
Inhibits transcription by binding DNA at the transcription initiation complex and preventing elongation of RNA chain by RNA polymerase
How does L-asparaginase work?
converts l-asparagine to aspartic acid and ammonia
deprives cancerous cells of circulating l-asparagine leading to cell death (as cancer cells cannot synthesis asparagine on their own)
Give examples of chemo drug(s) that block G1 phase in the cell cycle.
Vinblastine
Give examples of chemo drug(s) that block S phase in the cell cycle.
MTX
6-Mercaptopurine
5-Fluorouracil
Give examples of chemo drug(s) that block G2 phase in the cell cycle.
Bleomycin
Etoposide
Topotecan
Daunorubicin
Give examples of chemo drug(s) that block M phase in the cell cycle.
Vincristine
Vinblastine
Paclitaxel
Docetaxel
How do alkylating agents work as chemotherapeutic drugs?
Crosslink guanine nucleobases in DNA double helix strands
strands are unable to coil and separate
this is necessary in DNA replication, therefore the cells can no longer divide
Give examples of alkylating agents.
- Nitrogen mustards: meclorethamine, melphalan, chlorambucil, cyclophosphamide, ifosfamide
- Ethyleneimine: thiotepa
- Alkyl sulfonate: Busulfan
- Nitrosureas: carmustine, lomustine, streptozocin
- Triazine: dacarbazine, temozolamide
How do antimetabolites works as chemotherapeutic drugs?
Interfere with DNA production and therefore cell division and tumour growth
Either (1) become a part of the DNA and block S phase in the cell cycle OR (2) interfere with RNA synthesis
Also inhibits thymidine synthesis via thymidylate synthase and therefore selectively inhibits DNA synthesis
Give examples of antimetabolite drugs.
- Folate antagonists: MTX
- Purine antagonists: 6-Mercaptopurine, 6-hioguanine, Azathioprine
- Pyrimidine antagonists: 5-Fluorouracil, Cytarabine, gemcitabine
Give examples of natural products used in chemotherapy.
- antibiotics
- vinca alkaloids
- taxanes
- enzymes (l-asparaginase)
- epipodophyllotoxins
- camptothecin analogs
- biological response modifiers
List antibiotics used as chemotherapy.
actinomycin D doxorubicin bleomycin daunorubicin mitomycin C
How do vinca alkaloids work? List examples of vinca alkaloids.
Anti-mitotic and anti-microtubule agents
act upon tubulin and prevent it from forming into microtubules –> prevent microtubule polymerisation
this is necessary for cell division, therefore it stops cells growth
prevent mitotic spindle formation
Examples:
- vincristine
- vinblastine
- vinorelbine
How do taxanes work as chemotherapy? list examples of taxanes.
Disrupt microtubule function
Stabilise the GDP-bound tubulin
Inhibit cell division as Depolymerisation is prevented
Examples:
- paclitaxel
- docetaxel
What are epipodophyllotoxins? Give examples.
They inhibit topoisomerase II
Examples:
1. Etoposide: prevents re-ligation of DNA strands and therefore causes DNA to break –> error in DNA synthesis = apoptosis
- Teniposide: inhibition of topoisomerase II (prevent DNA from unwinding)
What is Topotecan? What is its MOA?
A camptothecin analog
prevents topoisomerase I from re-ligating DNA
the trapped topoisomerase-I complexes accumulation to stimulate apoptosis
disruption also prevents DNA replication and causes cell death
What is Irinotecan? What is its MOA?
A camptothecin analog
Inhibits topoisomerase I via active metabolite (SN-38) and therefore prevents DNA replication and transcription
Give examples of biological response modifiers.
Interferons and interleukins
Give an example of a corticosteroid that can be used as a chemotherapeutic drug.
Prednisolone
can bind to glucocorticoids response elements and therefore can enhance or inhibit gene expression
