Cancer Chemotherapy Flashcards
What are the four types of traditional agents
- Alkylating agents,
- Antimetabolites,
- Cytotoxic antibiotics,
- Plant derivatives.
Describe the mechanism of alkylating agents?
They form covalent bonds with suitable nucleophilic substances (bond to DNA in two positions) in the cell under physiological conditions. This causes intrastand crosslinking of DNA.
What are the alkylating agents groups and name an example?
1) Nitrogen mustards eg, Cyclophosphamide.
2) Ethylenimines, eg, Thiotepa.
3) Alkylsulphonates, eg, Busulphan.
4) Hydrazines and Triazines, eg, Temozolomide.
5) Nitrosoureas, eg, Lomustine.
6) Platinum base compounds, eg, Cisplatin
Name the main groups of antimetabolites and their mechanism?
Mimic normal cell metabolites
1) Antifolates, eg, methotrexate.
2) Antipyrimidines, eg, 5-flurouricil,
3) Antipurines, eg, mercaptopurine
Name some examples of cytotoxic antibiotics and their mechanism
Antitumour antibiotics which produce their effects mainly by direct action on DNA. eg, Anthracyclins (Doxorubicin), dactinomycin, bleomycin and mitomycin
Describe the mechanism of plant derivates and some examples.
Spindle poisons - Either affect microtubule function and prevent mitotic spindle formation or topoisomerase 1/2 inhibitors.
1) Vinca alkaloids, eg, vincristine. (spindle poison)
2) Taxanes, eg, paclitaxcel. (spindle poison)
3) Camptothecins, eg, Irinotecan. (Topoisomerase 1 inhibitor)
4) Etoposide - DNA binding/ topoisomerase 2 binding.
What are the main drawbacks of chemotherapy for cancer?
- Targets cell proliferation rather than the cancer specific features of invasion and metastasis. Healthy cells which have a high rate of growth and multiplication include cells of bone marrow, GI mucosa, hair and skin.
- Non-specific cell killers.
- Potential development of resistance.
- Can leave some cells remaining.
- Non compliance due to nasty side effects
What is tumour lysis syndrome and their features?
- It is an acute side effect and a metabolic emergency which occurs due to rapid cell lysis and large amounts of cell metabolites entering the blood.
- Characterised by hyperuricaemia, hyperphosphataemia and hypocalcaemia. If untreated can lead to acute renal failure, cardiac arrest and death.
Describe the effects of chemotherapy on the bone marrow
Myelosuppression - Reduced production of actively dividing cells which provide immunity, oxygen transport and clotting common with many chemotherapy agents.
What is used in bone marrow side effects?
Recombinant human granulocyte-colony stimulating factors, (eg, filgrastim) to reduce incidence/duration of myelosupression
What are some of the gastro-intestinal?
1) Nausea and vomiting,
2) loss of appetite,
3) Constipation (give laxatives),
4) Diarrhoea (give anti-diarrhoeal eg, loperamide)
Describe what drugs have varying different emetigenic properties and the treatment
- Highly emetogenic = cisplatin.
- Moderately emetogenic = doxorubicin.
- Mildly emetogenic - etoposide.
Treatment choices’ are between use of benzodiazepine, use of steroids, and anti-emetics.
Describe some of specific side-effect mucositis.
Ulceration, dry mouth, pain and taste alterations.
What are some other side effects?
- Fatigue,
- Body image side-effects dur to hair loss, weight changes.
- Peripheral neuropathy,
- Altered renal function and,
- Delayed effects such as infertility or secondary malignancy.
Describe and name anticancer drugs
Monoclonal antibodies and small molecules such as:
- Rituximab (Targets B cell surface proteins in B cell lymphomas).
- Trastuzumab (herceptin) which targets epidermal growth factor receptor 2 and used in breast cancer.
- Imatinib (Gleevac) inhibits bcr-abl gene signalling pathways and is used in chronic myeloid leukaemia.
