Chemotherapy Flashcards
What are the principles behind fractional cell kill hypothesis for chemotherapy?
Chemo given as a bolus
Kills all cells - tumour and bone marrow
Bone marrow cells recover more quickly
Next bolus is given when bone marrow cells have recovered, but tumour cells haven’t
What are the different sites of action for chemotherapy agents?
DNA synthesis - antimetabolites
DNA - alkylating agents
DNA transcription and duplication - intercalating agents
Mitosis - spindle poisons
What is the method of action of alkylating agents?
Formation of covalent bonds with DNA nucleosides => disruption of DNA structure => prevents replication
Difficult to repair DNA due to platinum agent
How do tumour cells become resistant to alkylating agents?
Decreased entry or increased exit of chemo agent - pumps on cell surface recognising agent then expelling it
Inactivation of agent in cell
Enhanced repair of DNA lesions
What are some examples of anti-metabolite chemo agents?
5-flurouracil
Methotrexate
How does 5-flurouracil act as a chemo agent?
Inhibits thymidylate synthase
Inhibits DNA synthesis
How does methotrexate act as a chemotherapy agent?
Inhibits dihydrofolate reductase
Inhibits folate synthesis => inhibits purine synthesis
Therefore inhibits DNA synthesis
How do spindle poisons act as chemotherapy agents?
Target microtubules in mitosis
Chromosomes can’t align and separate properly
Inhibit polymerisation
Stimulate polymerisation and inhibit depolymerisation
How can a pts response to chemotherapy be predicted?
Performance score
Clinical stage of tumour
Prognostic factors - involving biological factors
Molecular/cryogenic markers
What are some route of administration for chemo?
IV - most common PO - depends on bioavailability SC - convenient in community Into body cavity - bladder Intralesional - directly into cancerous area Intrathecal - lumbar puncture or omayya reservoir Topical IM
What is a PICC line?
IV into the arm
Connected to a pump
Can be done as an outpatient
What is a Hickman line?
IV into SVC
Tunnelling through the skin prevents from infection
Connected to chemo pump
What are some side effects of chemotherapy?
Mucositis Alopecia Pulmonary fibrosis Nausea and vomiting Diarrhoea Cardiotoxicity Local reaction Renal failure
What is a cause of acute renal failure from chemotherapy?
Rapid tumour lysis => hyperuricaemia => precipitation of urate crystals in renal tubules
What is a cause of vomiting from chemotherapy?
Direct action on CTZ
Also multifactorial
Unusual to not to be able to control the vomiting
What causes local skin reactions from chemo?
If chemo doesn’t go into the vein properly
Causes irritation and thrombophlebitis
How does mucositis present as a side effect from chemo?
Sore mouth/throat
Diarrhoea
GI bleeds
Secondary infection eg thrush
What causes abnormalities in absorption of chemo agents?
Nausea and vomiting
Compliance
Gut problems
What cause abnormalities in distribution of chemo agents?
Weight loss
Reduced body fat
Ascites
What causes abnormalities in elimination of chemo agents?
Liver and renal dysfunction
Taking other meds
What causes abnormalities in protein binding of chemo agents?
Low albumin
Taking other drugs
Describe the effects of haematological toxicity from chemo
Most frequent cause of death from toxicity
Neutropenia => increased risk of sepsis
Also affects platelet levels
What are some important drug interactions of chemotherapy?
Vincristine and itraconazole (anti-fungal) => neuropathy
Methotrexate and penicillin/NSAIDs
Capecitabine and warfarin, St John’s Wort or grapefruit juice
How is chemotherapy treatment monitored?
Response of cancer:
Radiology
Tumour markers
Bone marrow
Monitoring of drug levels
Checks for organ damage:
Creatinine clearance
Echocardiogram
What is neoadjuvant treatment?
Chemo given before surgery/radiotherapy
What is adjuvant treatment?
Chemo given after surgery to remove the primary cancer
Aims to reduce relapse
What is palliative care?
Treats current or anticipated symptoms without intention to cure
What is primary treatment of cancer?
1st line treatment
In many haematological cancers this is with a curative intent
Initially aiming for remission
