Cancer Flashcards
How do antimetabolites work?
-Inhibition of DNA synthesis
What are the examples of antimetabolites?
- Methotrexate
- 5-fluorouracil
- Capecitabine
- 6-Mercaptopurine
What are the types of chemotherapy drugs?
- Antimetabolites
- Alkylating agents
- Spindle poisons
- Intercalating agents
How do alkylating agents work?
- Formation of bonds in DNA strand or between 2 strands. Replication is impaired
- Lack of replication results in a break and apoptosis of the cell
What are examples of spindle poisons?
- Taxoids
- Vinca alkaloids (Vincristine)
How do spindle poisons work?
Inhibition of Mitosis.Microtubule-binding agents affect microtubule dynamics in 2 ways
-Inhibit polymerization and -Stimulate polymerization and prevent depolymerisation
What are examples of alkylating agents?
- Platinum compounds (cisplatin)
- Bulsulphan
- Cyclophosphamide
How do intercalating agents work?
- Prevention of transcription
- Interclating between base pairs of DNA/RNA strand
What are examples of intercalating agents?
- Doxorubicin
- Actinomycin D
How does methotrexate work?
-Inhibition of dihydrofolate reductase so less purine to make amino acids
How does 5-Fluorouracil work?
-Inhibition of 5-FdUMP. So pyrimidines can’t be incorporated into DNA so cell dies
How do platinum compounds work?
- Formation of platinated inter- and intrastrand adducts leading to inhibition of DNA synthesis
- DACH platinum adducts are bulky and thought to be more effective in inhibiting DNA synthesis than platinum adducts
How do taxoids work?
-Promote assembly and prevent microtubule falling apart
How do vinca alkaloids work?
-Prevents spindle formation
What are some examples of intercalating agents?
- Doxorubicin
- Actinomycin D
What are some mechanisms of resistance demonstrated by chemotherapy drugs?
- Decreased entry or increased exit of agent
- Inactivation of agent in cell though action of protein such as gluthathione
- Enhanced repair of DNA lesions produced by alkylation
What are some side effects of Chemotherapy?
- Acute renal failure
- GI perforation at the site
- DIC
- Vomiting
- Alopecia
- Skin Toxicity
- Mucositis
- Cardiotoxicity
- Lung toxicity
- Haematological toxicity
What are some important drug interactions demonstrated by chemotherapy drugs?
- Vincristine and itraconazole (a commonly used antifungal) leads to more neuropathy
- Capecitabine (oral 5FU) and warfarin
- Methotrexate - caution with prescribing penicillin, NSAIDs
- Capecitabine and St Johns Wort, grapefruit juice
What causes variability is treatment methods of chemotherapy?
- Abnormalities in absorption (N+V, compliance, gut problems)
- Abnormalities in distribution (Weight loss, reduced body fat, ascites etc)
- Abnormalities in elimination (Liver and renal dysfunction, other meds)
- Abnormalities in protein binding (Low alb, other drugs)
What are some examples of vinca alkaloid?
- Vincristine
- Vinblastine
Microtubule inhibitors
What are some examples of taxoids?
-Paclitaxel
What are specific ADRs of Alkylating Agents?
- Peripheral, sensory and motor neuropathy
- High frequency ototoxicity
What are specific ADRs for Mitotic Spindle Inhibitors?
Neurotoxicity: glove and stocking peripheral neuropathy
What are specific ADRs of Anthracycline Antibiotics such as Doxorubicin?
-Cardiotoxic
What is tamoxifen’s mechanism of action?
- Tamoxifen is a SERM (selective oestrogen receptor modulator) and acts as antagonist of the oestrogen receptor in breast tissue
- Prodrug metabolised by liver to its active form which can competitively bind to oestrogen receptors
- Causes cells to remain in the G0 and G1 phase of the cell cycle
- To be eligible for therapy those with breast cancer must be ER positive
What are side effects of Tamoxifen?
- Hot flushes/sweat
- Increased DVT/PE risk
- Weight gain
- Increased risk of endometrial cancer.
