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CPT > L16 - Chemotherapy > Flashcards

L16 - Chemotherapy Flashcards

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1
Q

Imatinib

A

Tyrosine kinase inhibitor
Tumour selective (targeted)
Fewer side effects

  • blocks the catalytic aspect of tyrosine kinase which prevents the formation of abnormal proteins
  • prevents chronic myeloid leukaemia
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2
Q

Purines

A

Adenine and Guanine

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3
Q

Pyridimines

A

Cytosine and thymine (uracil in RNA)

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4
Q

Factors that affect tumour growth

A
  • growth fraction
  • duration of the cell cycle
  • rate of cell loss
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5
Q

Number of cells required for detection of tumour

A

1 x 10^9

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6
Q

Number of cells of tumour not viable for life

A

1 x 10^12

  • short window for detection
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7
Q

When does Chemotherapy work

A

Only works when cells are in the cell cycle

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8
Q

Fractional cell kill hypothesis

A
  1. When chemotherapy drug is administered tumour cells and other rapidly dividing cells decrease e.g. in bone marrow
  2. The bone marrow cells recover more quickly than tumour cells therefore the next cycle of chemotherapy is given when bone marrow cells have recovered
  3. Overall, there is minor reduction in bone marrow cells therefore give supportive treatment
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9
Q

Cancers that have a high sensitivity to chemotherapy

A 
Lymphomas 
Germ cell tumour 
Small cell lung carcinoma 
Neuroblastoma 
Wilm’s tumour
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10
Q

Cancers that have a moderate sensitivity to chemotherapy

A 
Breast 
Bladder 
Ovary 
Cervical 
Colorectal
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11
Q

Cancers that have a low sensitivity to chemotherapy

A

Prostate
Renal cell carcinoma
Endometrial
Brain tumours

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12
Q

Cytotoxic agents

A

Antimetabolites - inhibit DNA synthesis
Alkylating agents - act on DNA to impair replication
Intercalating agents - prevent DNA transcription and duplication
Spindle poisons - prevent mitosis

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13
Q

Alkylating agents mechanism of action

A
  • Forms a ligands bond between 2 DNA strands therefore the DNA cannot uncoil for the replication fork when dividing
  • Single strand break occurs - cell dies by apoptosis or necrosis
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14
Q

Platinum compounds

A

Formation of platinated inter and intrastrand adducts (ligand bonds) causing inhibition of DNA synthesis

Intrastrand adducts:
G-G 55%
G-A 31%

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15
Q

Antimetabolite example and mechanism

A

Methotrexate:
- inhibits dihydrofolate reductase therefore inhibits purine synthesis

5 - fluorouracil

  • thymidylate synthase inhibitor
  • inhibits purine synthesis
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16
Q

Spindle poisons mechanism of action

A

Microtubule binding agents

  • inhibits polymerisation
  • stimulate polymerisation and inhibit depolymerisation

No spindle fibre formation therefore sister chromatids are not separated to opposite poles in anaphase preventing cell replication

17
Q

Spindle poisoning agent examples

A

Taxoids:

  • promote assembly of tubulin (polymerisation)
  • prevents disassembly (depolymerisation)
  • cell becomes rigid therefore cannot divide

Vinca alkaloids
- prevent spindle formation

18
Q

Resistance to alkylating agents

A
  1. Tumour cells recognise the alkylating agent and pumps it back out of the cell using a channel
    - Decreases the entry or increases the exit of the alkylating agent
  2. Inactivates the alkylating agent as glutathione mops up the active moiety of the agent and neutralises it
  3. Enhanced repair of DNA lesions produced by alkylation
19
Q

Chemotherapy use

A

Used in cancer depending on:

  • performance score
  • clinical stage of tumour
  • prognostic factors
  • cytogenetic markers
  • side effects vs anticipated best outcome
20
Q

Chemotherapy routes of administration

A 
IV - common 
Oral 
SC - convenient in the community 
Body cavity - bladder or pleural effusion
Intralesional - directly into cancerous area 
Intrathecal - in CSF 
Topical 
IM
21
Q

IV pump

A

PICC

  • peripherally inserted central catheter
  • common but can damage veins in repeated used

Hickman line

  • central line to SVC
  • prevents infection as increased macrophages near skin
22
Q

Side effects of chemotherapy

A
  • Nausea and vomiting - directly acts on chemoreceptor trigger zone
  • diarrhoea
  • bladder cystitis
  • sterility
  • myalgia
  • neuropathy
  • alopecia
  • pulmonary fibrosis - bleomycin (worse with oxygen) - carry card
  • cardiotoxicity - cardiomyopathy and arrhythmia with cyclophosphamide
  • renal failure
  • myelosuppression
  • phlebitis
  • mucositis - mouth sores and GI bleeds
23
Q

ADRs of chemotherapy - due to treatment

A

Acute renal failure
- hyperuricaemia due to rapid tumour lysis leads to precipitation of urate crystals in renal tubules

GI perforation at site of tumour particularly lymphoma

  • peritonitis
  • artificial feed to limit damage and better control

DIC
- onset within hours of treatment for acute myeloid leukaemia

24
Q

Vomiting

A

Acute phase - 4-12 hours

Delayed phase - 2-5 days

Chronic phase - up to 14 days

25
Q

Alopecia

A

Hair thins at 2-3 weeks
Markedly with cyclophosphamide, vinca alkaloids and doxorubicin
Minimal with platinums

26
Q

Skin toxicity

A

Local

  • irritation and thrombophlebitis of veins
  • extravasation (chemotherapy out of vein)

General -bleomycin

  • hyperkeratosis
  • hyperpigmentation
  • ulcerated pressure sores
27
Q

Hyperpigmentation chemotherapies

A

Busulphan
Doxorubicin
Cyclophosphamide
Actinomycin D

28
Q

Chemotherapy dose factors

A
  • BMI
  • drug handling i.e. liver or renal function
  • comorbidities
29
Q

Variability of chemotherapy response

A

Abnormal absorption
- N+ V and gut problems

Abnormal distribution

  • weight loss
  • ascites

Abnormal excretion
- liver and renal dysfunction

Abnormal protein binding

  • low albumin
  • drug interactions
30
Q

Drug interactions

A

Increase plasma levels of chemotherapy

  • vincristine and itraconazole - antifungals that increase neuropathy
  • capecitabine (oral 5FU) with warfarin, St John’s Wart and grapefruit juice
  • ## methotrexate with penicillin and NSAIDs
31
Q

Monitoring chemotherapy

A
  • radiological imaging
  • tumour marker blood test
  • bone marrow/ cytogenetics
  • drug assays - for drug level
  • check organ damage - eGFR, U+Es, LFTs, echocardiogram

CPT (23 decks)

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