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Y2 - CPT > Lecture 26 - Chemotherapy > Flashcards

Lecture 26 - Chemotherapy Flashcards

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
How does Growth fraction usually relate to the size of a tumour?
When tumour volume low, Growth fraction = High (so adjuvant chemotherapy given) Tumour volume high = Low Growth Fraction (less actively dividing)
26
What are some highly sensitive tumours to chemotherapy?
Lymphomas Germ cell tumours Small cell lung cancer Neuroblastoma Wilms tumour
27
What are some cancers with low chemo sensitivity?
Prostate Renal cell Brain tumours Endometrial
28
What is the very basic basis for how chemotherapy drugs work?
They interfere with the processes in cell growth and repair helping reduce cancer cells ability to grow and proliferate
29
What happens once the cancer cells get damaged by a chemotherapeutic agent?
Cant repair damage so apoptosis occurs
30
What is the general function if anitmetabolites?
Affect DNA synthesis
31
What is the general function if alkylating agents?
Affect/modify DNA
32
What point of the cell cycle do spindle poisons work at?
Mitosis (division)
33
What is an example of an alkylating agent?
Carmustine
34
What is the mechanism of action of Alkylating agents like carmustine?
Add alkyl groups leading to the DNA cross linking leading to defects in DNA replication
35
What are some examples of platinum compounds as chemotherapy agents?
Cisplatin Oxaliplatin
36
What is the mechanism of action of platinum compounds like cisplatin and oxaliplatin as chemotherapy agents?
Forms palatinates inter and Intra strand adducts leading to inhibiton of DNA synthesis
37
What are 2 examples of Antimetabolites as chemotherapy agents?
5-fluorouracil Methotrexate
38
What is the mechanism of action of 5-flurouracil as an antimetaboblite/chemotherapy agent?
Inhibits enzyme Thymidylate synthase So less Thymidine is made This leads to less dTMP (Thymidine base) So inhibits/impairs DNA synthesis
39
What is the mechanism of action of Methotrexate as an anti metabolite/chemotherapy agent?
Inhibits Dihydrofolate REDUCTASE stopping dihydrofolate being converted to Tetrahydrofolate So disrupts folate cycle impairing DNA synthesis leading to apoptosis
40
What are 2 types of spindle poisons?
Taxoids Vinca alkaloids.
41
What stage of the cell cycle do spindle poisons work in?
Mitosis (premetaphase)
42
What is an example of a taxoid (spindle poison)?
Paclitaxel
43
What is the mechanism of action of taxoids like paclitaxel as a spindle poison?
Promotes assembly and prevents disassembly of spindle fibres
44
What is an example of a vinca alkaloid?
Vincrisitine
45
What is the mechanism of action of vinca alkaloids like Vincristine as spindle poisons?
Prevent spindle formation
46
What are the side effects of chemotherapy?
Affects rapidly dividing cells Alopecia Nausea + Vomiting Myelosuppression Renal failure Cardio toxicity Pulmonary fibrosis Mucositis Many side effects
47
What causes vomiting in chemotherapy?
Direct action of chemotherapy drugs on central Chemoreceptors trigger zone (CTZ)
48
What are the chemotherapy agents which cause the worst Alopecia?
Doxorubicin Vinca alkaloids (vincristine) Cyclophosphamide
49
What technique can be used to help reduce Alopecia with chemotherapy?
Scalp cooling caps
50
How do scalp cooling caps work to reduce Alopecia?
Reduce blood flow to the scalp Less chemo agents reach the hair
51
What are some local skin toxicity problems seen with some chemotherapy agents?
Irritation Thrombophlebitis of veins Extravasation
52
What is extravasation?
When the chemo agent leaks out of the blood vessels leading to burns in the subcutaneous tissues
53
What are some toxic effects to the skin with bleomycin?
Hyperkeratosis Hyperpigmentation Ulcerated pressure sores
54
What are some chemotherapeutic drugs that can cause hyperpigmentation? So what should patients avoid?
Bisulphan Doxorubicin Cyclophosphamide Actinomycin D Sunlight
55
What is damaged in mucositis and why is it often a side effect of chemotherapy? How does it present:
GI tract epithelia damaged since they are rapidly proliferating Worst in oropharynx Sore mouth/throat Diarrhoea GI bleed
56
What are some chemo drugs that cause cardio-myopathy?
Doxorubicin High dose cyclophosphamide
57
What should be done before giving a patient doxorubicin?
Echocardiogram To see if heart function is good enough
58
What are some chemo drugs that can cause arrythmias (syncope, palpitations, dizziness)?
Cyclophosphamide Etoposide
59
What are some chemotherapy drugs that can cause pulmonary fibrosis?
Bleomycin Cyclophosphamide Melphalan Chlorambucil Mitomycin C
60
What it’s the most common cause of death from chemotherapy toxicity?
Myelosuppression
61
What cells are commonly affected as a result of Myelosuppression by chemo agents?
Neutrophils Platelets Erythrocytes
62
What are some haematological risks of chemotherapy toxicity?
Neutropenic sepsis Anaemia Thrombocytopenia (Bleeding and bruising)
63
What are the chemotherapy agents causing ototoxicty and nephrotoxicity?
Cisplatin Carboplatin
64
What are the chemotherapy agents causing peripheral neuropathy?
Vincristine
65
What are the main chemotherapy causing pulmonary fibrosis?
Bleomycin Busulfan
66
What is the main side effect of methotrexate, 5-Flurouracil and other anti-metabolites azathioprine?
Myelosuppression
67
What chemotherapy drug is causes Haemorrhagic cystitis as a major side effect?
Cyclophosphamide
68
What are the 2 main drugs causing cardio toxicity?
Doxorubicin Trastuzumab
69
What is the aim of combination therapy?
Balancing activity of the drug with its safety to Maximise treatment
70
What are some routes of adminstration of chemo drugs?
IV most common PO (most convenient but depends on oral bioavailability) SC Intrathecal (into the CSF by lumbar puncture for a haematological malignancy)
71
What are some IV pumps for chemo drugs?
PICC line Hickman line
72
What causes variability in pharmacokinetics in chemotherapy?
Abnormalities in absorption Abnormalities in distribution Abnormalities in elimination Abnormalities in protein binding
73
What can cause abnormalities in chemotherapy drug absorption?
Nausea and vomiting Compliance Gut problems
74
What can cause abnormalities in chemotherapy drug distribution?
Weight loss Reduced body fat Ascites
75
What can cause abnormalities in chemotherapy drug elimination?
Liver and renal dysfunction Other medications
76
What can cause abnormalities in chemotherapy drug protein binding?
Low albumin (malnourished patients) Other drugs
77
What side effect does the interaction of vincristine and itraconazole have?
Neuropathy
78
If both capecitabine (oral 5-FU) and warfarin are being taken, what should warfarin be changed to?
DOAC like apixaban
79
What do you have to be careful prescribing with methotrexate?
Penicillin NSAIDs
80
What should you be careful taking with capecitabine (oral 5-FU)?
St John’s Wort Grapefruit juice
81
How can acute renal failure be caused by chemotherapy?
Rapid breakdown of tumour causes Hyperuricaemia Urate crystals form in renal tubules causing AKI
82
What side effect can chemohave on the GI system in lymphoma?
GI perforation at site of tumour
83
Treatment of what cancer can lead to DIC?
Acute myeloid leukaemia
84
How can you monitor response of cancer in chemo?
Radiological imaging Tumour markers in blood tests Bone marrow/cytogenetics
85
How can you check chemo drug levels in blood and check for organ damage?
Drug assays Organ damage: -creatinine clearance -echocardiogram
86
What determines the dose of chemotherapy drugs for a patient?
Surface area BMI How their organs can handle it General well-being (comorbities)

Y2 - CPT (30 decks)

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