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Clinical Pharmacology > 13) Cancer Chemotherapy > Flashcards

13) Cancer Chemotherapy Flashcards

1
Q

What is the log kill ratio?

A

Giving treatments that will kill 10^x cancer cells, reducing tumour size

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2
Q

Why is chemotherapy dose fractionated?

A

To allow normal cells to recover between doses

Tumour cells will recover slower due to damage/mutation to DNA repair genes

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3
Q

Which tumours have high sensitivity to chemotherapy?

A

Lymphoma, neuroblastoma

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4
Q

Which tumours have low sensitivity to chemotherapy?

A

Prostate, brain tumours

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5
Q

What are some classes of cytotoxic agents?

A

Antimetabolites
Alkylating agents
Intercalating agents
Spindle poisons

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6
Q

What is the mechanism of action of alkylating agents?

A

Covalently bond to nucleophilic target sites on DNA, leading to inter and intra-strand adducts and inhibition of DNA synthesis

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7
Q

What are some intercalating agents?

A

Anthracyclin, bleomycin

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8
Q

What is the mechanism of action of anthracyclins?

A

Molecular ring structure that allows them to intercalate between DNA base pairs. Affect topoisomerase II enzyme causing apoptosis

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9
Q

What is the mechanism of action of bleomycin?

A

Binds to DNA and intercalates

Can also chelate with Fe2+ to form free radicals that attack phosphodiester bonds

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10
Q

What is the mechanism of action of 5-fluorouracil?

A

Analogue of uracil and competes for binding site of thymidylate synthase preventing incorporation of pyramidines into DNA

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11
Q

What is the mechanism of action of methotrexate?

A

Inhibits dihydrofolate reductase preventing purine production

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12
Q

What are the constituents of mitotic spindle?

A

Alpha and beta tubulin

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13
Q

What is the mechanism of action of taxoids (spindle poison)?

A

Bind to beta tubulin subunit stabilising microtubules and inhibiting disassembly, can’t pull chromosomes apart

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14
Q

What is the mechanism of action of vinca alkaloids (spindle poison)?

A

Bind to beta tubulin subunit preventing microfilament formation, so no spindle formation

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15
Q

How can cancer become resistant to chemotherapy?

A

Decreased entry or increased efflux of agent
Inactivation of agent in cell
Enhanced repair of DNA lesions produced by alkylation
Drug target expression upregulated

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16
Q

What factors are considered before giving chemotherapy?

A

Performance score - how they are functioning
Clinical stage
Prognostic factors and molecular markers
Side effects

17
Q

What are some common routes of administration for chemotherapy?

A

IV - central catheter, Hickman line
S/c injection
Direct intralesional

18
Q

What are some general side effects of chemotherapy?

A 
Alopecia
Mucositis
N&V
Myelosuppression
Diarrhoea
19
Q

What pharmacological considerations need to be undertaken when starting a patient on chemotherapy?

A

Narrow therapeutic window
Significant side effects
Dose alterations - BMI, liver and renal function
Treatment phasing

20
Q

What can cause abnormalities in absorption of chemotherapy?

A

N&V

Gut problems

21
Q

What can cause abnormalities in distribution of chemotherapy?

A

Weight loss

Ascites

22
Q

What can cause abnormalities in elimination of chemotherapy?

A

Liver and renal dysfunction

Other medications

23
Q

What can cause abnormalities in the protein binding of chemotherapy?

A

Low albumin

Other drugs

24
Q

Give examples of drug interactions involving chemotherapy drugs:

A

Vincristine and itraconazole - more neuropathy

Methotrexate and penicillin/NSAIDs

25
Q

How should chemotherapy be monitored?

A

Response of cancer
Drug levels
Organ damage

26
Q

What is salvage chemo?

A

Chemotherapy for relapsed disease

27
Q

What specific renal side effects can chemotherapy have?

A

Acute renal failure due to hyperuricemia caused by rapid tumour lysis

28
Q

What specific gastrointestinal side effects can chemotherapy have?

A

GI perforation at site of tumour

Mucositis

29
Q

What specific haematological side effects can chemotherapy have?

A

Disseminated intravascular coagulopathy

Haematological toxicity - neutrophils, RBC, platelets

30
Q

What specific hair and skin side effects can chemotherapy have?

A

Alopecia

Skin toxicity - Beau’s lines on nails, bleomycin

31
Q

What specific cardiac side effects can chemotherapy have?

A

Cardiomyopathy

Arrhythmias

32
Q

What specific respiratory side effects can chemotherapy have?

A

Pulmonary fibrosis - bleomycin

Clinical Pharmacology (24 decks)

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