Chemotherapy Agents Flashcards
antineoplastic drugs produce a proportional kill cell, what does this mean?
It means that a proportion, e.g. 95%, of the cells present may be eliminated during a single course of treatment. this is why multiple treatmetns are often needed to eradicate the cancer
many cytotoxic drugs have a therapeutic index of 1, what does this mean in terms of toxicity?
it means that the therapeutic dose is essentially the same as the toxic dose.
What GI side effects are common from antineoplastic drugs?
anorexia mucosal ulceration, diarrhoea, oral mucositis, N&V
which chemo drugs is oral mucositis (sore mouth) most common with?
fluorouracil, methotrexate and the anthracyclines
what unwanted effects from chemotherapy agents are there on the bone marrow?
myelosuppression leading to neutropenia, thrombocytopenia and anaemia.
how many days after a cycle of chemo does myelosuppression tend to occur?
7-10days after
there is a high risk of what 2 things occuring with bone marrow suppression from chemo agents?
infection (neutropenic sepsis)
and
haemorrhage (thrombocytopenia)
what two chemotherapy agents pare particularly known for causing sterility? which two chemo agents can cause permanent male infertility?
cyclophosphamide or cytarabine.
alkylating agents or procarbazine can cause permanent male infertility.
what does extravasation of IV chemo drugs cause?
if anticancer drugs leak from a vein into the surrounding tissues, they can cause local tissue necrosis.
what is tumour lysis syndrome caused by?
rapid breakdown of malignant cells during chemo causing them to release their intracellular contents.
What abnormalities would you see in tumour lysis syndrome?
Hyperuricaemia, hyperkalaemia, hyperphosphataemia, hypocalcaemia
What are the consequences of tumour lysis syndrome?
arrhythmias
or
renal damage
breakdown of what causes hyperuricaemia in tumour lysis syndrome?
nucleic acids
why do you get hypocalcaemia in tumour lysis sydrome?
because you get precipitation of calcium phosphate.
tumour lysis syndrome is most common with treatmetn of which haematological cancers?
non-Hodgkin’s lymphoma, Burkitt’s lymphoma and acute leukaemias
how do you manage tumour lysis syndrome?
ensure good hydration (>2.5L/day) and give allopurinol (a xanthine oxidase inhibitor) to reduce production of uric acid. or those at high risk can be given rasburicase (recombinant urate oxidase) to enhance uric acid breakdown
what can be given to pts at high risk of tumour lysis syndrome? what is its mechanism of action?
rasburicase - recombinant urate oxidase whcih enhances uric acid breakdown.
What are some of the symptoms of chemotherapy-induced peripheral neuropathy?
pain, tingling, numbness, cold sensations in hands and feet.
due to damage to sensory nerves
Name 2 alkylating agents
chlorabmucil
cyclophosphamide
what is the mechanism of action of alkylating drugs
covalently bind to DNA preventing DNA replication and mRNA transcription
name 2 cytotoxic antibiotics
doxorubicin, bleomycin
what is the mechanism of action of cytotoxic abx?
several possible MOAs:
- intercalation - blocking reading of DNA template during replication and translation
- Histone eviction – displace histone proteins from the chromatin structure, disrupting the processes that detect and repair damaged DNA.
- Free radical attack – metabolism of the drug releases radicals which cause DNA damage
- Membrane effects – interference with membrane function
Name 3 platinum compounds
carboplatin
cisplatin
oxaliplatin
what is the MOA of platinum compounds?
they generate a reactive complex that creates cross-links between guanine nucleotides within DNA strands. They thus block replication and transcription.
what class of antineoplastic drug is methotrexate?
antimetabolite - folic acid antagonist
what is the MOA of methotrexate?
blocks purine and thymidylate synthesis and inhibits synthesis of DNA, RNA and protein.
is methotrexate safe to use if the pt has significant renal impairment?
No
what type of antineoplastic drug is mercaptopurine?
purine antagonist
what type of antineoplastic drug is capecitabine?
a pyrimidine antagonist
what is the MOA of base analogue antimetabolites?
interfere with DNA synthesis
name a common vinca alkaloid
vincristine
what is the MOA of vincristine?
bind to tubulin, inhibiting polymerisation and assembly of microtubules, thus producing M-phase arrest of mitosis. Because microtubules are essential for numerous other cellular functions – including maintaining cell shape, motility and transport between organelles – the vinca alkaloids also affect the nonmitotic cell cycle.
what is the MOA of topotecan?
inhibit topoisomerase I, which is important in DNA transcription and translation. Used for lung, cervical or ovarian cancer.
What is the MOA of etoposide?
Active during the G2 phase and binds to the complex of DNA and topoisomerase II, an enzyme that regulates DNA supercoiling by introsucing double-strand breaks. The etoposide-bound complex inhibits DNA replication by preventing relegation of the DNA and leads to cell apoptosis.
what cancers is etoposide used to treat?
small-cell lung cancer, lymphomas and testicular cancer.
what is the MOA of docetaxel and paclitaxel?
promote the assembly of microtubules, but inhibit their depolymerisation leading to the formation of stable and nonfunctional microtubular bundles in the cell. The cell is inhibited during G2 and M phases of the cell cycle
What is the role of tyrosine kinases in cancer cells?
involved in the signalling pathways that control cell division, gene transcirption, motility and apoptosis.
What is the MOA of bevacizumab?
inhibits VEGF receptor (a tyrosine kinase receptor) and reduces tumour angiogenesis
bevacizmab is used as part of the first-line treatment of what cancers?
metastatic CRC, lung cancer and renal cell carcinoma
what are the unwanted effects of bevacizumab?
mucocutaneous bleeding, GI perforation, impaired wound healing
what is the MOA of imatinib?
inhibits signals from the PDGF receptor family and Bcr-Abl. it is used to treat CML, ALL and a variety of rare tumours.
what is the MOA of bortezomib?
it is a proteasome inhibitor. proteasomes degrade proteins. Bortezomib is a boron-containing peptide that inhibits the catalytic site of the 26S proteasome. This probably reduces the degradation of pro-apoptotic proteins such as p53, leading to programmed cell death.
what cancer is particularly sensitive to proteasome inhibitors such as bortezomib?
multiple myeloma
what is tthe MOA of tamoxifen?
binds to oestrogen receptors and shows both oestrogenic effects on bone and antioestrogenic effects on breast tissue. Tamoxifen inhibits oestrogen-regulated genes and reduces the secretion of growth factors by tumour cells. Tumour cells are mainly affected in the G2 pahse of the cell cycle
what are unwanted effects of tamoxifen?
hot flushes, amenorrhea (in pre-menopausal women), vaginal bleeding (in post-menopausal women). It is a CYP3A4 inhibitor so reduces metabolism of warfarin.
what class of drugs does anastrazole belong to?
aromatase inhibitor
what is the MOA of aromatase inhibitor anastrazole
aromatase is an enzyme that converts androgens to oestrogens. Anastrazole reduces oestrogen production in postmenopausal women, who produce oestrogen mainly from androstenedione and testosterone in many tissues. Aromatase is also present in cells of 2/3rd of breast cancers. Aromatase inhibitors are used in post-menopausal women to treat breast cancers that are oestrogen-dependent.
what cancer are aromatase inhibitors used to treat?
breast cancer - Aromatase inhibitors are used in post-menopausal women to treat breast cancers that are oestrogen-dependent.
name an androen receptor antagonist used to suppress prostate ca cells
flutamide
what class of drug is buserelin?
gonadorelin analogue
what is buserelin used to treat?
prostate ca
