Flashcards in Chemotherapy Drugs Deck (45):
What are the differences between a benign tumour and a malignant tumour?
-Loss of function
-Ability to metastasize
-Lack invasive properties
-Unable to metastasize
What is an oncogene?
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels. Most normal cells will undergo a programmed form of rapid cell death (apoptosis) when critical functions are altered.
In tumours there are mutations in apoptotic genes. ______ is expressed with stabilises ______. There is an overexpression of growth factors. Leading to ________ which is growth of new blood vessels.
How does a primary tumour metastasise?
- primary tumour produces enzymes which breakdown ECM
- Invades nearby tissue
- grows new blood vessels (angiogenesis)
- cells transported via blood or lymphatic vessels
What are the difficulties in treating cancer?
- may be asymptomatic until late stages
- detection methods not 100% reliable
may be hard to find primary tumour
- cancer cells are very similar to normal cells
- difficult to exploit biochemical differences ie. therapy to toxic to normal tissue
in a solid tumour cells occupy 1 of 3 compartments. What are these?
A. dividing cells
B. Resting cells (in G) phase capable of dividing
C. cells no longer dividing but contribute to tumour volume
* only cells in compartment A susceptible to most cytotoxic drugs
Drugs affect all RAPIDLY DIVIDING normal tissues. What are the toxic effects of chemotherapy?
- Bone marrow suppression ?
- impaired wound healing
- loss of hair (hair follicle cells are rapidly dividing cells)
- Damage to GI epithelium (inc. mouth)
- Growth stunted in children
- Reproductive system - sterility
- teratogenicity ?
- bleeding/ bruising (due to lack of platelets/ clotting factors)
- nausea and vomiting
- kidney damage
What are the possible targets for anti-cancer drugs?
- hormonal regulation of tumour growth
- defective cell cycle controls
What are the different classes of anticancer drugs?
- cytotoxic (alkylating, antimetabolities, antibiotics, plant derivatives)
- Hormones and their antagonist
- Monoclonal antibodies
- Protein kinase inhibitors
Cytotoxic drugs such as alkylating, antimetabolities, antibiotics and plant derivative. How do they work?
- Block DNA synthesis/ prevent cell division
How do hormone and their antagonist work?
- suppress opposing hormone secretion or inhibit their actions
How do monoclonal antibodies work?
- target specific cancer cells
How do protein kinase inhibitors work?
- block cell signalling pathways in rapidly diving cells
Alkylating agents work by targeting cells in S phase and form convalent bonds with DNA to prevent uncoiling. this inhibits replication. What are the side effects of alkylating agents with pro-longed use?
- sterility (especially in men)
- increase risk of non-lymphocytic leukaemia (AML)
Classes of alkylating agents are
- nitrogen mustards
- Platinum compounds
What are examples of nitrogen mustards?
- mechlorethamine (1st anti-cancer drug)
- estramustine (prostate cancer)
Examples of nitrogen mustards are melphan, chlorambucil and bendamustine. What types of cancer are these used to treat?
- melphan - multiple myeloma, childhood neuroblastoma, localised soft-tissue sarcoma of the extremities
- chlorambucil/ bendamustine - lymphomas, chronic leukaemias
cyclophosphamide is a prodrug and can be administer orally. its activated in the ...
liver to phosphoramide mustard and acrolein
- acrolein causes haemorrhagic cystitis, this can be prevented by administering large volumes of fluid.
nirosoureas are highly lipid. carmustine is given by IV. Lomustine is given orally. What kind of cancers do they treat?
Carmustine - multiple myeloma, non-hodgkins lymphomas and brain tumours (glioblastomas
Lomustine - hodgkins disease resistant to conventional therapy, malignant melanoma and certain solid tumours
Platinum compounds binds to RNA and binds to purine bases. resistance may develop. An example of these drugs is cisplatin, what does this treat?
head and neck
What is an example of a platinum compound drug used to treat cancer of the testes, lung, cervical, bladder, head/neck and ovarian.
given through slow IV
Cisplatin is a platinum compound, what is its side effects?
V. nephrotoxic – requires hydration/ infusion
Causes severe nausea/ vomiting
Risk of tinnitus, peripheral neuropathy, hyperuricaemia (gout) + anaphylaxis
alkylating agents. Busulfan is selective for bone marrow. what is it used to treat?
What is procarbazine used to treat?
- can cause hypersensitivity rash
Antimetabolities are folate antagonist which is essential for DNA synthesis. An example of this is methotrexate what does this drug inhibit ?
Methotrexate is given by IM, IV or intrathecally. what are the problems with this drug?
- drug mostly excreted in urine
- NSAIDs can reduce excretion - increased toxicity
- tumour may develop resistance
Flurouracil, capecitabine, cytarabine and gemcitabine are examples of pyrimidine analogues. How do these work?
- Compete with C and T bases which make up RNA + DNA → inhibits DNA synthesis
- less well absorbed orally than methotrexate
An example of cytotoxic antibiotics is doxorubicin. How does this work?
- binds to DNA and inhibits DNA/RNA synthesis
- Inhibits topoisomerase II
What can doxorubicin cause?
- cardiac dysrhythmias/ heart failure in high doses
- must be careful to avoid extravasation at injection site = local necrosis
Another cytotoxic antibiotic is Bleomycin. This is active against non-dividing cells unlike most cytotoxic drugs which are active against dividing cells. What are the side effects of Bleomycin?
- mucocutaneous reactions (mouth sores, hair loss, fungal infection)
- hyperpyrexia ( fever/high temperature )
- pulmonary fibrosis
Plant derivatives work by preventing polymerisation of tublin and prevents spindle formation. these effects only happen during mitosis phase. What are examples of these drugs?
taxanes ( paclitaxel, docetaxel)
plant derivatives are relatively non-toxic except vincristine. what are the side effects of vincristine?
- tingling, abdo cramps, jaw pain
Vincristine, vinblastine and vindesine are all plant derivatives that work by preventing spindle formation. What are they used to treat?
some solid tumours (breast and lung cancer)
hormones are used in treatment of cancer in hormone sensitive tissues such as breast, prostate and ovaries. The hormones usually are used as antagonist with opposing actions of the hormones. how do they work?
inhibit hormone action or synthesis to disrupt tumour growth
rarely cures disease but can reduce symptoms
Ethinyloestradiol and diethylstilbestrol can cause nausea, fluid retention, thrombosis, impotence and gynaecomastia( enlargement of males breasts ). How do they work?
- antagonists of androgen dependent prostate cancer (used in palliative patients)
progestogens such as megestrol, medroxyprogesterone and norethiserone are used to treat what?
GnRH analogues such as goserelin, buserelin, leuprorelin and triptorelin are used to treat prostate cancer and advanced breast cancer in premenopausal women. How do they work?
inhibit GnRH released
this decreases LH, FSH and testosterone
cytotoxic drugs are often given in combination why?
- to increase cytotoxicity with increasing general toxicity
- decrease chance of developing resistance to individual drugs
Cytoxic drugs are often given in large doses every 2-3 weeks why??
- allows bone marrow to regenerate
- decrease risk of developing resistance to individual drugs
- more effective than several small doses
What drugs are given to control side effects?
ondansetron/ graniestron - stops cytotoxic drug-induced vomiting
- lorazepam - anti-anxiety drug
- stem cell transplant
- lenograstim - used to boost stem cell production - speed recovery of immune system
Alkylating drugs such as N mustards, nitrosoureas and platinum compounds. what are there mechanisms of action?
cross linking with DNA strands
Antimetabolites such as folate antagonist, purine/pyrimidine analogues have what mechanism of action?
Blocking synthesis of DNA and/or RNA
Cytotoxic antibiotics such as doxorubicin, bleomycin, dactinomycin and mitomycin have what mechanism of action?
inhibit enzyme involved in DNA synthesis or degrade DNA
Plant derivative such as vinca alkaloids, taxanes and etoposide have what mechanism of action?
inhibit spindle formation
hormones, hormone antagonist/ analogues in cancer treatment have what mechanism of action?
inhibit hormone action or synthesis to disrupt tumour growth