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WEEK 23:
Chemotherapy
| Question | Answer |
|---|---|
| cancer treatment includes | surgery, radiation therapy (radiotherapy), chemotherapy, and palliative care |
| types of chemotherapy | neo-adjuvant and adjuvant |
| neo-adjuvant chemotherapy | chemotherapy given before surgery or radiation therapy |
| adjuvant chemotherapy | chemotherapy given after surgery or radiation therapy |
| chemotherapy meaning | use of cytotoxic drugs to manage malignancies which target DNA synthesis and mitosis |
| cytotoxic drugs | kill rapidly dividing cells carried out in cycles with induction and maintenance phases and are dosed based on body surface area (BSA) |
| how are cytotoxic drugs dosed | based on body surface area (BSA) |
| cell cycle phases includes (4) | G1, S, G2, and M |
| G1 phase | growth preparation for DNA synthesis |
| S phase | DNA synthesis |
| G2 phase | growth preparation for mitosis |
| M phase | mitosis |
| why are multiple drug regimens given | because different classes work in different way and attack different sites of cell division and reduces toxicity |
| why are cycles of chemotherapy given | to achieve total cell kill, to limit toxicity, and typically given as 3 week cycles |
| cell cycle specific agents (CCS) include | antimetabolites and plant alkaloids |
| cell cycle non specific agents (CCNS) include | alkylating agents and antibiotics |
| specific examples of CCS agents | vinca alkaloids, taxanes, and podophyllin alkaloids |
| examples of CCNS agents | anthracyclines |
| CSS agents and link to cell cycle | CSS are phase dependent (only kill cells passing through certain stages) and target dividing cells |
| CCNS agents and link to cell cycle | CCNS work at any phase and damage DNA directly |
| CCS agents (5) | 5-fluorouracil, methotrexate, vincristine, paclitaxel, and etoposide |
| CCNS agents examples (3) | cisplatin (platinum compound), cyclophasphamide, and doxorubicin (anthracycline) |
| 5-fluorouracil works on what part of the cell cycle | S |
| methotrexate works on what part of the cell cycle | S |
| vincristine works on what part of the cell cycle | S and M |
| paclitaxel works on what part of the cell cycle | G2 and M |
| etoposide works on what part of the cell cycle | S and G2 |
| examples of antimetabolites (2) | methotrexate and 5-fluorouracil |
| methotrexate | folate antagonist |
| 5-fluorouracil | pyrimidine antagonist or false substrates |
| examples of plant alkaloids (3) | vinca alkaloids (vinblastine and vincristine), taxanes (paclitaxel), and podophyllin alkaloids (etoposide) |
| example of vinca alkaloids | vinblastine and vincristine |
| example of taxanes | paclitaxel |
| example of podophyllin alkaloids | etoposide |
| examples of alkylating agents (2) | cyclophosphamide and platinum compounds |
| example of platinum compound | cisplatin |
| examples of antibiotics (2) | anthracyclines (doxorubicin, idarubicin, and daunorubicin) and dactinomycin and bleomycins |
| examples of anthracyclines (3) | doxorubicin, idarubicin, and daunorubicin |
| hormonal agents examples (2) | oestrogen and androgen inhibitors eg tamoxifen |
| examples of biologics (2) | aromatase inhibitors (anastrozole) and tyrosine kinase inhibitors (imatinib) |
| function of antimetabolites | type of CCS agents which interfere with metabolic pathways in DNA synthesis in S phase eg methotrexate and 5-fluoruracil |
| mechanism of methotrexate | folate antagonist which inhibits purine synthesis so cant make DNA. Normally folate -> tetrahydrofolate (active form) via DHF reductase which uses thymidylate synthetase to convert DUMP to DTMP (U to T) for DNA synthesis |
| mechanism of 5-fluorouracil | false substrate/ pyrimidine analogue incorporated into DNA as false metabolites and lead to damage to DNA. Normally folate -> tetrahydrofolate using DHF reductase but thymidylate synthetase cannot convert DUMP to DTMP so no DNA synthesis |
| mechanism of action of vincristine | is a vinca alkaloid which acts on S and M phase and act as microtubule inhibitors which inhibit formation of mitotic spindle |
| mechanism of action of paclitaxel | is a taxane which acts on G2 and M phase and act as a microtubule stabiliser (stabilises spindle fibres producing similar effects to vina alkaloids) |
| mechanism of action of etoposide | is a podophyllin alkaloid which acts on S and G2, functioning as a topoisomerase II inhibitor (prevents ligation of DNA leading to breaks in DNA strand and eventually cell death) |
| most commonly used alkylating agent | cyclophosphamide |
| mechanism of action of cyclophosphamide | CCNS agent and alkylating agent causing cross linking of DNA leading to defectivr DNA replication |
| mechanism of action of platinum compounds eg cisplatin | CCNS agent and alkylating agent which causes inhibition of DNA synthesis by cross linking guanine residues |
| features of cisplatin | highly emetogenic (cause vommiting) agent and is nephrotoxic |
| what combination of drugs is used successfully for treating testicular cancer | vinblastine and bleomycin |
| idarubicin feature | causes cardiac toxicity |
| mechanism of action of idarubicin eg antibiotic doxorubicin | CCNS agent and alkylating agent that has cytotoxic actions (interfere nucleotide synthesis by intercalating DNA strands, inhibit topoisomerase II, and generate free radicals toxic to the heart) |
| side effects of anticancer drugs | inhibit ALL fast growing cells eg hair, myelosuppression (except vincristine and bleomycin), chemotherapy induced nausea and vomiting (CINV) especially with platinum compounds, cardiotoxicity (anthracycline antibiotics), hair loss, and infertility |
| how to overcome reduced WBC | use granulocyte CSF (G-CSF) which act as bone marrow growth factors |
| how can pain relief be achieved | use strong opioids eg morphine and diamorphine |
| side effects of opioids | constipation and nausea |
| palliative care options (reliving symptoms - 3) | pain relief, syringe drivers (continuous flow of drugs device given under skin) , and hospice care |
Created by:
kablooey
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