Chemo

Question 1

Why do chemo drugs only work on actively dividing cells

Answer 1

They don’t work in the G0 phase, only S phase

Question 2

Describe fractional kill hypothesis

Answer 2

Chemo drugs need to be given in stages to prevent excessive loss of bone marrow cells whilst allowing tumour cell levels to fall to necessary levels

Question 3

Classes of chemo drugs and their site of action

Answer 3

Alkylating agents (DNA synthesis) 
Antimetabolites (DNA synthesis)
Spindle poisons (mitosis)
Intercalating agents (DNA transcription)

Question 4

How do alkylating agents work using an example

Answer 4

Cisplatin allows covalent bonds to form between DNA strands which creates platinated inter and intra strand adducts
This inhibits DNA synthesis

Question 5

Give examples of antimetabolites

Answer 5

Methotrexate

5-fluorouracil

Question 6

MoA of methotrexate

Answer 6

Inhibits DHFR to inhibit folate synthesis so the cell can’t produce purines for DNA

Question 7

MoA of 5-FU

Answer 7

5-FU is activated to 5-FdUMP which inhibits thymidylate synthase so pyramidines can’t be incorporated into DNA

Question 8

Examples of spindle poisons and their MoA

Answer 8

Vinca alkaloids - inhibit polymerisation of microtubules to inhibit mitosis

Taxoids - cause excessive polymerisation of microtubules which inhibits their depolymerisation so sister chromatids can’t move apart during mitosis

Question 9

Mechanisms of chemo resistance

Answer 9

Decreased drug entry
Increased drug exit
Inactivation of drug within cell e.g glutathione
Enhanced DNA repair

Question 10

What factors affect whether someone is suitable for chemo

Answer 10

Type of malignancy 
Performance score
Stage
Tumour markers
Prognostic score

Question 11

Routes of chemo administration

Answer 11

IV - Hickman line into subclavian vein 
PO
SC
Into cavity
Intralesional 
Intrathecal (into CSF) 
Topical

Question 12

Factors requiring dose alteration

Answer 12

Liver and renal function
Body surface area
General health (will outcome outweigh side effects?)

Question 13

When is a cancer clinically detectable

Answer 13

When it contains x10^9 cells

Question 14

When does a cancer cause host death

Answer 14

When it contains x10^12 cells

Question 15

Describe the log kill ratio and it’s relevance to early intervention for cancer

Answer 15

Log kill ratio is the x10^n tumour cells killed
Need to ensure chemo doesn’t allow the tumour to grow but also doesn’t kill too many healthy cells that would cause host death
Therefore outcome improved in early intervention, before clinically detectable

Question 16

List 14 side effects of chemo and which one is most often the dose limiting effect

Answer 16

Vomiting
Alopecia
Skin toxicity
Mucositis
Cardiotoxicity 
Lung toxicity
Haematological toxicity - DOSE LIMITING 
AKI
GI perforation at tumour site
Myelosuppression
Phlebitis
Myalgia
Infertility
Neuropathy

Question 17

Why does chemo cause vomiting and how can it be prevented

Answer 17

Acts on central chemoreceptor trigger zone

Give serotonin or dopamine antagonists

Question 18

Which chemo drugs cause the highest incidence of alopecia

Answer 18

Doxorubicin
Vinca alkaloids
Cyclophosphamide

Question 19

Examples of chemo drugs that commonly cause skin toxicity

Answer 19

Bleomycin - hyperkeratosis, hyperpigmentation, ulcerated pressure sores
Doxorubicin/cyclophosphamide - hyperpigmentation

Question 20

What are Beau’s lines

Answer 20

Horizontal lines in fingernails due to some chemo drugs

Question 21

Examples of chemo drugs that commonly cause cardiotoxicity

Answer 21

Doxorubicin - cardiomyopathy

Cyclophosphamide - arrhythmia

Question 22

Example of chemo drug that commonly causes lung toxicity

Answer 22

Bleomycin - lung fibrosis

Question 23

How might chemo cause AKI

Answer 23

Hyperkalaemia and hyperuricaemia following tumour lysis

Question 24

How are cancers monitored during chemo

Answer 24

Cancer response - markers, imaging
Drug level and side effects
Organ damage - creatinine clearance, ECG

Question 25

What factors in chemo can have an impact on pharmokinetics

Answer 25

Absorption - N&V, gut pathology, compliance
Distribution - weight loss, ascites
Elimination - renal and liver function
Protein binding - low albumin, polypharmacy