Cancer Chemotherapy Flashcards
What are the four types of traditional chemotherapy agents?
Alkylating agents, antimetabolites, cytotoxic antibiotics, plant derivatives.
Describe the mechanism of alkylating agents
It usually hits guanine residuces, alkylation the 7th nitrogen. This makes it more acidic. The modified guanine can mispair with thymine residues creating a mutation. This DNA damage triggers cell death via apoptosis.
Name the major groups of alkylating agents (NEAHNP)
Nitrogen mustards, Ethylenimines, Alkylsulphonates, Hydrazines and triazines, Nitrosoureas, Platinum based compounds.
Name an examples of a Nitrogen Mustard and it’s mechanism
Eg = Cyclophosphamide.
It is activated by P450 enzymes in the liver where is it converted into aldophosphamide and it is then transported to other tissues where it forms phosphoramide (cytotoxic)
Name an example of alkylsuphonates and its mechanism
Eg = Busulphan.
Has direct effect on the bone marrow depressing the formation of granulocytes and platelets (and red blood cells in high doeses) used in chronic granulocytic leukaemia
Name an example of a nitrosoureas and its mechanism
Eg = lomustine.
Lipid soluble so can cross the BBB and be used against tumours of the brain and meninges
Name an example of a platinum based compound and its mechanism
Eg = cisplatin.
Calcium from the cisplatin dissociates leaving the compound reactive. It causes intrastrand cross-linking which results in local denaturing of the DNA chain.
What are the three major groups withing the antimetabolite class
Antifolate (methotrexate). Antipyrimidines (5-FU) and antipurines (thioguanine)
Name an example of an antifolate and its mechanism
Eg = methotrexate.
Folate analogue so replaces folate in the body therefore interfering with thymidylate synthesis. It is lipid soluble so can pass the BBB.
Name an example of an antipyrimidine and its mechanism
Eg = fluorouracil (5-FU).
It interferes with thymidylate synthesis and therefore inhibits DNA polymerase.
Name an example of an antipurine and its mechanism
Eg, Fludarabine.
Fludarabine in its triphosphate form inhibits DNA polymerase
Name some cytotoxic antibiotics
Anthracyclines, dactinomycin, bleomycin and mitomycin
What is the mechanism of anthracyclines?
Binds to DNA and inhibits DNA and RNA synthesis. Also cytotoxic action mediated through effect on topoisomerase II.
What is the mechanism of Dactinomycin?
Interferes with RNA polymerase and this prevents transcription. Also has an effect on topoisomerase II.
What is the mechanism of bleomycin?
Degrade preformed DNA, causing chain fragmentation and release of free bases.
What is the mechanism of mitomycin?
It cross-links DNA and may also degrade DNA through the generation of free radicles
Name the plant derivatives sub groups
Vinca alkaloids, Taxanes, camptothecins and etoposide
Name an example of vinca alkaloids and its mechanism
Vincristine. It binds to tubulin and prevents polymerisation into microtubules.
Name an example of Taxanes and its mechanism
Paclitaxel and it freezes microtubules
What is the mechanism of camptothecins
Binds to and inhibits topoisomerase 1
Describe the mechanism of etoposide
Inhibits mitochondrial function, nucleoside transport and topoisomerase II
Name other types of anticancer drugs
Hormone inhibitors, monoclonal antibodies, protein kinase inhibitors and miscellaneous agents.
What are some of the major drawbacks of chemotherapy
Targets cell proliferation and not the more lethal properties of invasion and metastasis. Non specific, potential development of resistance, leaves some remaining cells and patient may not comply due to side effects.
What is tumour lysis syndrome?
An acute side effect and metabolic emergancy. Occurs due to rapid cell lysis and large amount of metabolites in the blood. Results in hyperuricaemia (urine acid in blood), hyperphosphataemia, hyperkalaemia and hypocalcaemia. Can lead to acute renal failure, cardiac arrest and death.
What are some of the bone marrow side effects?
Myelosupression (reduced production of cells). Only dividing cells affected. Can use human granulocyte-colony stimulating factors
What are the gastro-intestinal side effects?
Nausea and vomiting (different agents vary on their emetogenic potential), loss of appetite, constipation due to reduced gastic motility (laxitives) an diarrhoea which may need IV fluid support.
What are some mucositis side effects?
Ulceration, dry mouth, pain, taste alterations.
What are some other general side effects of chemotherapy
Fatigue, body image side effects, peripheral neuropathy, altered renal function and delayed effects (infertility or secondary malignancy)
