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Pharmacology > Chemotherapy > Flashcards

Chemotherapy Flashcards

1
Q

How long does the cell cycle last?

A

Varies from 9 to 43 hours

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2
Q

Why are non-growing micro-metastases often a problem in chemotherapy?

A

It cannot target cells in G0

However can get drugs which push them out of G0

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3
Q

Name some tumours that are highly sensitive to chemotherapy

A

Lymphoma
Germ cell tumours
Neuroblastoma
Wilm’s tumour

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4
Q

Name some cancers which have low sensitivity to chemotherapy

A

Prostate
Renal cell
Brain tumours
Endometrial cancer

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5
Q

What are the different ways tumours can spread?

A

Local
Lymphatic
Blood
Implantation

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6
Q

What are the different options for using chemotherapy?

A

Primary treatment - radical, first line treatment

Adjuvant - post-operative, when at high risk of metastases after removal of the primary tumour

Neoadjuvant - primary treatment in a localised tumour, assess biological responsiveness and before surgery to reduce tumour size

Palliative - in advanced disease

Salvage - in relapsed disease

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7
Q

What is the Philadelphia chromosome?

A

An oncogene where there has been a translocation of 9 to 22

Seen in chronic myeloid leukaemia

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8
Q

Which chemotherapy targets the Philadelphia chromosome?

A

Imatinib

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9
Q

What is the mechanism of action of imatinib?

A

Bcr-Abl tyrosine kinase inhibitor

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10
Q

What is tyrosine kinase?

A

An enzyme that can phosphorylate proteins from ATP

When switched on permanently, can cause unregulated cell growth

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11
Q

What is the mechanism of action of chemo drugs ending in ‘nib’?

A

Inhibit tyrosine kinase

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12
Q

Why is chemo normally administered in pulses?

A

Depletes bone marrow as well as tumour cell population

Allows bone marrow cells to recover and they recover to higher level than cancer cells can in that time

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13
Q

When would chemotherapy be given continuously?

A

When they need a bone marrow transplant

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14
Q

Mechanism of action of antimetabolites?

A

Stop DNA synthesis

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15
Q

Mechanism of action of alkylating agents?

A

Bind to DNA and fix it so that it cannot be unwound and replicated

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16
Q

Mechanism of action of intercalating agents?

A

Affect DNA transcription and duplication

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17
Q

Mechanism of action of spindle poisons?

A

Stop mitosis by preventing polymerisation and depolymerisation of spindle fibres in anaphase

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18
Q

Mechanism of action of platinum?

A

Forms platinated inter- and intra-strand adducts

Each adduct has a large side-group, stopping replication and inhibiting DNA synthesis and apoptosis

19
Q

Mechanism of action of topoisomerase-1 inhibitors?

A

Inhibit re-ligation of a DNA strand when it has been cleaved due to supercoiling
Therefore have single and double stranded breaks, causing apoptosis

20
Q

Mechanism of action of methotrexate as a chemo drug?

A

Inhibits dihydrofolate reductase, stopping production of purines

21
Q

Mechanism of action of 5-fluorouracil?

A

Stops the folate cycle, inhibiting production of pyrimidine bases

22
Q

Mechanism of action of vinca alkaloids and taxoids?

A

Vinca alkaloids - inhibit polymerisation of spindle fibres

Taxoids - inhibit depolymerisation of spindle fibres

23
Q

What is response to chemotherapy based on?

A

Performance score of an individual patient

Clinical stage

Prognostic factors/score

Side effects vs anticipated/best outcome

24
Q

How is the performance score calculated?

A 
0 = full health
1 = jaded - can do activities but struggle at work
2 = cannot work, spends 50% of day resting
4 = bed-bound
5 = dead
25
Q

Routes of administration of chemotherapy drugs?

A

IV

  • bolus
  • infusional bag
  • continuous pump infusion
PO
SC
Into a body cavity
Intralesional 
Intrathecally
Topically
IM
26
Q

Types of IV pumps for chemo?

A

PICC line - a peripherally inserted catheter. Patient can go home with it. Well tolerated.

Hickman line

27
Q

What are the mechanisms of resistance to alkylating agents?

A

P-glycoproteins allow the drug to enter the cell, but can be modified to pump it straight back out again before causing damage

Drug inactivated/neutralised by proteins in the cytoplasm eg glutathione. Bind to it and drug is no longer harmful so cannot get to genetic material in nucleus

Enhanced repair mechanisms of DNA once damage has been done

28
Q

How can renal failure occur with chemo?

A

Often multi-factorial

Hyperuricaemia caused by rapid tumour lysis leads to precipitation of urate crystals in renal tubules

29
Q

What are the different patterns of emesis with chemo?

A

Acute phase: 4-12 hours

Delayed onset: 2-5 days

Chronic phase: persist for up to 14 days

30
Q

Which chemo causes minimal alopecia?

A

Platinum

31
Q

What skin toxicity is there in chemo?

A

Locally

  • irritation and thrombophlebitis of veins
  • local extravasation, goes into surrounding tissue instead of vein, leading to necrosis. Higher risk with poorer veins

General

  • bleomycin can cause hyperkeratosis, hyper-pigmentation, ulcerated pressure sores
  • Beau’s lines on nails
32
Q

How does mucositis present with chemo?

A

(GI epithelial damage)
Sore mouth and throat with many ulcers - commonly worse in oropharynx
Diarrhoea
GI bleed

33
Q

What problems with the heart can chemo cause?

A

Cardiac myopathy (doxorubicin and cyclophosphamide)

Arrhythmias (cyclophosphamide and etoposide)

34
Q

What lung toxicity can chemo cause?

A

Pulmonary fibrosis

-do not give oxygen, makes it worse

35
Q

Give a summary of ADRs of chemo

A 
Acute renal failure
GI perforation at site of tumour
Disseminated intravascular coagulopathy
Vomiting
Alopecia
Skin toxicity - thrombophlebitis, extravasation, hyper pigmentation
Mucositis
Cardio-toxicity - cardiac myopathy and arrhythmias
Haematological - neutrophils and platelets 
Cystitis
Myalgia
Neuropathy 
Sterility
36
Q

How can absorption of chemo be affected?

A

Nausea and vomiting

Compliance

37
Q

How can abnormalities in distribution of chemo occur?

A

Can sit in ascitites
Weight loss
Reduced body fat

38
Q

How can abnormalities in elimination of chemo occur?

A

Liver and renal dysfunction

Other medications

39
Q

How can abnormalities in protein binding occur in chemo?

A

Low albumin

Other drugs

40
Q

Important DDIs of chemo?

A

Vincristine and itraconazole (anti fungal) - increased neuropathy

Capecirabine (oral 5-FU) and warfarin

Methotrexate and penicillin or NSAIDs

Cepcitabine and St. John’s Wort or grapefruit juice

41
Q

What factors affect the dose of chemo given?

A

The patient’s BMI and/or surface area

Drug handling ability of the patient eg liver function, renal function

General well-being - performance status and co-morbidities

42
Q

How is the response of cancer to chemo monitored?

A

Radiological imaging

Tumour marker blood tests

Bone marrow cytogenics

43
Q

What other monitoring is done with chemo?

A

Drug levels eg methotrexate drug assays to ensure clearance from the blood

Organ damage eg creatinine clearance of echocardiogram

44
Q

What is the ultimate measure of trial outcomes?

A

Overall survival

Pharmacology (23 decks)

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