Cytotoxic chemotherapy (ignore) Flashcards
Describe the cell cycle
The stages of the cell cycle are divided into two major phases: interphase and the mitotic (M) phase.
During interphase, the cell grows and makes a copy of its DNA.
During the mitotic (M) phase, the cell separates its DNA into two sets and divides its cytoplasm, forming two new cells.
Interphase:
- G1 - cell grows physically larger, copies organelles, and makes the molecular building blocks it will need in later steps
- S - cell synthesizes a complete copy of the DNA in its nucleus. It also duplicates a microtubule-organizing structure called the centrosome
- G2 - cell grows more, makes proteins and organelles, and begins to reorganize its contents in preparation for mitosis
M phase:
- Mitosis - the nuclear DNA of the cell condenses into visible chromosomes and is pulled apart by the mitotic spindle, a specialized structure made out of microtubules. Mitosis takes place in four stages: prophase, metaphase, anaphase and telophase
- In cytokinesis, the cytoplasm of the cell is split in two, making two new cells.
G0 - cells may exit the G1 phase and enter resting state called the G0 phase
Define what is meant by remission
A decrease in or disappearance of signs and symptoms of cancer. In partialremission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, althoughcancer still may be in the body.
What are the 2 main classifications of cytotoxic drugs and explain what is meant by them ?
- Cell cycle specific -Tumour specific (relatively) – they may be more specific to rapidly didiving tumors. Duration of exposure more important than dose
- Non-cell cycle specific - Non-tumour specific; damage normal stem cells. Cumulative dose more important than duration
What are the 2 main types of cell cycle specific cytotoxic chemotherapy agents ?
Antimetabolites - Antimetabolites are types of chemotherapy treatments that are very similar to normal substances within the cell. When the cells incorporate these substances into the cellular metabolism, they are unable to divide.
Mitotic spindle inhibitors - chemo treatments derived from plants
What are the 2 main types of mitotic spindle inhibitors ?
- Vinca alkaloids: Vincristine, Vinblastine
- Taxanes: Paclitaxel and Docetaxel.
These 2 types of agents are known as antimicrotubule agents
What are the main types of antimetabolite chemotherapy agents and what is there actions?
- Methotrexate - Folic acid antagonist (inhibits dihydrofolate reductase)
- Hydroxyurea - impaired deoxynucleotide synthesis (ribonucleotide reductase)
- Cytarabine (Cytosine arabinoside) - Pyrimidine antagonist
- Fludarabine - Adenosine deaminase inhibitor
- 6-Mercaptopurine - Purine antagonist
What are the main 2 classes on non-cell specific chemotherapy ?
- Ankylating agents - Alkylating agents are most active in the resting phase of the cell.
- Cytotoxic antibiotics - act during multiple phases of the cell cycle
Give examples of ankylating agents and how they work
Chlorambucil / melphalan:
- Bind covalently to bases of DNA (adducts)
- Produces DNA strand breaks (mutation) by free radical production
Platinum derivatives - Cis-platinum / carboplatin – used more in solid tumour and oncology practice
Give examples of cytotoxic chemo and how they work
Anthracyclines: daunorubicin / doxorubicin / idarubicin:
- DNA intercalation: reversible
- Impairs RNA transcription
- Strand breaks in DNA (free radicals)
What are the immediate general side effects of cytotoxic chemo ?
- Nausea and vomiting
- Hair loss (alopecia)
- Liver and renal dysfunction
- Bone marrow suppression - infection, anaemia, bleeding
What is the specific side effect to be wary of, for someone on a vinca alkaloid ?
Neuropathy - particularly peripheral, if continued on these drugs it can become irreversible
What is the specific side effect to be wary of in Anthracyclines
Cardiomyopathy
What are some of the signs and symptoms of cardiomyopathy ?
- Shortness of breath or trouble breathing, especially with physical exertion
- Fatigue
- Swelling in the ankles, feet, legs, abdomen and veins in the neck
What are some of the long-term side effects associated with Alkylating agents ?
- Infertility
- Secondary malignancy
What is the idea of combination chemo ?
- Use non-cross resistant drug combinations
- Use non-overlapping toxicity spectra
- To have an additive / synergistic mechanisms of action – i.e. attack tumour in more than one way may improve changes of success
How can stem cells be obtained from a patient and what are the different ways in which stem cells can be transplanted to a patient ?
Can be obtained from the bone or the blood (using drug to pull it out of the blood)
Stem cells can be autologous or allgenic in origin i.e. from themselves or from a donor either a sibling or someone unrelated
For autologous transplantation patients often have there stem cells resuced and stored prior to intense chemo so that once bone marrow has been wiped out and hopefully the cancer then they can have their own health stem cells transplanted back into them
