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CPT > Lecture 26 - Chemotherapy > Flashcards

Lecture 26 - Chemotherapy Flashcards

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1
Q

What type of drugs do we use to treat cancer?

A

CDK4/6 inhibitors
Tyrosine Kinase Inhibitors
Monoclonal antibodies
PARP inhibitors
Cytotoxic chemotherapy

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2
Q

What is the structure of DNA?

A

Double helix of nucleotides that are anti-parallel

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3
Q

What are nucleotides?

A

Sugar-phosphate-base

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4
Q

What are the purines?

A

Adenine
Guanine

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5
Q

What are the pyridimines?

A

Cytosine
Thymine (Uracil in RNA)

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6
Q

What is transcription?

A

DNA conversion to RNA

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7
Q

What is translation?

A

RNA conversion to amino acids which code for protiens

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8
Q

What are the stages in the cell cycle?

A

G1
S
G2
M

G0 not in the cell cycle

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9
Q

What is G0?

A

Stage not in the cell cycle where the cell is not growing to replicate

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10
Q

What is G1?

A

When the cell is carrying out its normal functions and producing protiens to prepare for DNA synthesis

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11
Q

What is S phase in the cell cycle?

A

DNA replicates

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12
Q

What is G2?

A

DNA moves to opposite poles of the cell and the cell prepares to divide

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13
Q

What is M?

A

Mitosis (cell division)

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14
Q

What type of cells do chemotherapy agents target?

A

Cells that are rapidly growing/dividing

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15
Q

What is the definition of growth fraction?

A

The proportion of cells dividing at any given time

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16
Q

What is growth fraction used to measure?

A

Tumour sensitivity to chemotherapeutic agents

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17
Q

What does a large growth fraction indicate in terms of sensitivity to chemotherapeutic agents?

A

Tumours with large growth factors = more responsive to chemo

So higher sensitivities

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18
Q

Why do multiple cycles of chemotherapy agents normally have to be used?

A

Tumours are Heterogeneous
So some cells are proliferating (killed by chemo), others dying or lying dormant (not killed) so multiple cycles are required to eradicate remaining and re-growing cells

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19
Q

What is the fraction cell kill hypothesis?

A

Where a given dose of chemotherapy is given which kills a constant PROPORTION of a tumour cell population rather than a constant number of cells

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20
Q

What is a neoadjuvant?

A

When chemotherapy is given before surgery or radiotherapy for the primary cancer

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21
Q

What is an adjuvant?

A

When a chemotherapy agent is given AFTER surgery to excise the primary ailing to reduce relapse risk (e.g breast cancer)

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22
Q

What is the palliative use of chemotherapy?

A

Treat current or anticipated symptoms without curative intent

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23
Q

What is the primary use of chemotherapy?

A

1st line treatment of cancer
Often in haematological cancers aims for curative intent and remission

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24
Q

What is the salvage use of chemotherapy?

A

For released disease

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25
Q

How does Growth fraction usually relate to the size of a tumour?

A

When tumour volume low, Growth fraction = High (so adjuvant chemotherapy given)

Tumour volume high = Low Growth Fraction (less actively dividing)

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26
Q

What are some highly sensitive tumours to chemotherapy?

A

Lymphomas
Germ cell tumours
Small cell lung cancer
Neuroblastoma
Wilms tumour

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27
Q

What are some cancers with low chemo sensitivity?

A

Prostate
Renal cell
Brain tumours
Endometrial

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28
Q

What is the very basic basis for how chemotherapy drugs work?

A

They interfere with the processes in cell growth and repair helping reduce cancer cells ability to grow and proliferate

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29
Q

What happens once the cancer cells get damaged by a chemotherapeutic agent?

A

Cant repair damage so apoptosis occurs

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30
Q

What is the general function if anitmetabolites?

A

Affect DNA synthesis

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31
Q

What is the general function if alkylating agents?

A

Affect/modify DNA

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32
Q

What point of the cell cycle do spindle poisons work at?

A

Mitosis (division)

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33
Q

What is an example of an alkylating agent?

A

Carmustine

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34
Q

What is the mechanism of action of Alkylating agents like carmustine?

A

Add alkyl groups leading to the DNA cross linking leading to defects in DNA replication

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35
Q

What are some examples of platinum compounds as chemotherapy agents?

A

Cisplatin
Oxaliplatin

36
Q

What is the mechanism of action of platinum compounds like cisplatin and oxaliplatin as chemotherapy agents?

A

Forms palatinates inter and Intra strand adducts leading to inhibiton of DNA synthesis

37
Q

What are 2 examples of Antimetabolites as chemotherapy agents?

A

5-fluorouracil
Methotrexate

38
Q

What is the mechanism of action of 5-flurouracil as an antimetaboblite/chemotherapy agent?

A

Inhibits enzyme Thymidylate synthase
So less Thymidine is made
This leads to less dTMP (Thymidine base)
So inhibits/impairs DNA synthesis

39
Q

What is the mechanism of action of Methotrexate as an anti metabolite/chemotherapy agent?

A

Inhibits Dihydrofolate REDUCTASE stopping dihydrofolate being converted to Tetrahydrofolate

So disrupts folate cycle impairing DNA synthesis leading to apoptosis

40
Q

What are 2 types of spindle poisons?

A

Taxoids

Vinca alkaloids.

41
Q

What stage of the cell cycle do spindle poisons work in?

A

Mitosis (premetaphase)

42
Q

What is an example of a taxoid (spindle poison)?

A

Paclitaxel

43
Q

What is the mechanism of action of taxoids like paclitaxel as a spindle poison?

A

Promotes assembly and prevents disassembly of spindle fibres

44
Q

What is an example of a vinca alkaloid?

A

Vincrisitine

45
Q

What is the mechanism of action of vinca alkaloids like Vincristine as spindle poisons?

A

Prevent spindle formation

46
Q

What are the side effects of chemotherapy?

A

Affects rapidly dividing cells

Alopecia
Nausea + Vomiting
Myelosuppression
Renal failure
Cardio toxicity
Pulmonary fibrosis
Mucositis
Many side effects

47
Q

What causes vomiting in chemotherapy?

A

Direct action of chemotherapy drugs on central Chemoreceptors trigger zone (CTZ)

48
Q

What are the chemotherapy agents which cause the worst Alopecia?

A

Doxorubicin
Vinca alkaloids (vincristine)
Cyclophosphamide

49
Q

What technique can be used to help reduce Alopecia with chemotherapy?

A

Scalp cooling caps

50
Q

How do scalp cooling caps work to reduce Alopecia?

A

Reduce blood flow to the scalp
Less chemo agents reach the hair

51
Q

What are some local skin toxicity problems seen with some chemotherapy agents?

A

Irritation
Thrombophlebitis of veins
Extravasation

52
Q

What is extravasation?

A

When the chemo agent leaks out of the blood vessels leading to burns in the subcutaneous tissues

53
Q

What are some toxic effects to the skin with bleomycin?

A

Hyperkeratosis
Hyperpigmentation
Ulcerated pressure sores

54
Q

What are some chemotherapeutic drugs that can cause hyperpigmentation?

So what should patients avoid?

A

Bisulphan
Doxorubicin
Cyclophosphamide
Actinomycin D

Sunlight

55
Q

What is damaged in mucositis and why is it often a side effect of chemotherapy?

How does it present:

A

GI tract epithelia damaged since they are rapidly proliferating

Worst in oropharynx

Sore mouth/throat
Diarrhoea
GI bleed

56
Q

What are some chemo drugs that cause cardio-myopathy?

A

Doxorubicin
High dose cyclophosphamide

57
Q

What should be done before giving a patient doxorubicin?

A

Echocardiogram

To see if heart function is good enough

58
Q

What are some chemo drugs that can cause arrythmias (syncope, palpitations, dizziness)?

A

Cyclophosphamide
Etoposide

59
Q

What are some chemotherapy drugs that can cause pulmonary fibrosis?

A

Bleomycin
Cyclophosphamide
Melphalan
Chlorambucil
Mitomycin C

60
Q

What it’s the most common cause of death from chemotherapy toxicity?

A

Myelosuppression

61
Q

What cells are commonly affected as a result of Myelosuppression by chemo agents?

A

Neutrophils
Platelets
Erythrocytes

62
Q

What are some haematological risks of chemotherapy toxicity?

A

Neutropenic sepsis
Anaemia
Thrombocytopenia (Bleeding and bruising)

63
Q

What are the chemotherapy agents causing ototoxicty and nephrotoxicity?

A

Cisplatin
Carboplatin

64
Q

What are the chemotherapy agents causing peripheral neuropathy?

A

Vincristine

65
Q

What are the main chemotherapy causing pulmonary fibrosis?

A

Bleomycin
Busulfan

66
Q

What is the main side effect of methotrexate, 5-Flurouracil and other anti-metabolites azathioprine?

A

Myelosuppression

67
Q

What chemotherapy drug is causes Haemorrhagic cystitis as a major side effect?

A

Cyclophosphamide

68
Q

What are the 2 main drugs causing cardio toxicity?

A

Doxorubicin
Trastuzumab

69
Q

What is the aim of combination therapy?

A

Balancing activity of the drug with its safety to Maximise treatment

70
Q

What are some routes of adminstration of chemo drugs?

A

IV most common
PO (most convenient but depends on oral bioavailability)
SC
Intrathecal (into the CSF by lumbar puncture for a haematological malignancy)

71
Q

What are some IV pumps for chemo drugs?

A

PICC line
Hickman line

72
Q

What causes variability in pharmacokinetics in chemotherapy?

A

Abnormalities in absorption
Abnormalities in distribution
Abnormalities in elimination
Abnormalities in protein binding

73
Q

What can cause abnormalities in chemotherapy drug absorption?

A

Nausea and vomiting
Compliance
Gut problems

74
Q

What can cause abnormalities in chemotherapy drug distribution?

A

Weight loss
Reduced body fat
Ascites

75
Q

What can cause abnormalities in chemotherapy drug elimination?

A

Liver and renal dysfunction
Other medications

76
Q

What can cause abnormalities in chemotherapy drug protein binding?

A

Low albumin (malnourished patients)
Other drugs

77
Q

What side effect does the interaction of vincristine and itraconazole have?

A

Neuropathy

78
Q

If both capecitabine (oral 5-FU) and warfarin are being taken, what should warfarin be changed to?

A

DOAC like apixaban

79
Q

What do you have to be careful prescribing with methotrexate?

A

Penicillin
NSAIDs

80
Q

What should you be careful taking with capecitabine (oral 5-FU)?

A

St John’s Wort
Grapefruit juice

81
Q

How can acute renal failure be caused by chemotherapy?

A

Rapid breakdown of tumour causes Hyperuricaemia
Urate crystals form in renal tubules causing AKI

82
Q

What side effect can chemohave on the GI system in lymphoma?

A

GI perforation at site of tumour

83
Q

Treatment of what cancer can lead to DIC?

A

Acute myeloid leukaemia

84
Q

How can you monitor response of cancer in chemo?

A

Radiological imaging
Tumour markers in blood tests
Bone marrow/cytogenetics

85
Q

How can you check chemo drug levels in blood and check for organ damage?

A

Drug assays

Organ damage:
-creatinine clearance
-echocardiogram

86
Q

What determines the dose of chemotherapy drugs for a patient?

A

Surface area
BMI
How their organs can handle it
General well-being (comorbities)

CPT (30 decks)

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