Systemic Anti-Cancer Treatment

Question 1

What is the difference between purine and pyridamine bases?

Answer 1

Purines have a double ring structure and pyridamines only have one ring.

Question 2

Describe base pairings?

Answer 2

Guanine and cytosine pair together and adenine and thymine pair together.

Question 3

Which enzyme causes hydrogen bonds between bases to break and seperate the two polynucleotide strands?

Answer 3

DNA helicase

Question 4

Name 3 examples of microtubule inhibitors

Answer 4

Docetaxel, paclitaxel and eribulin (plus ‘emtansine’ portion of TDM1

Question 5

What is the mechanism of microtubule inhibitors?

Answer 5

Bind to beta tubulin subunits within the microtubule (stabilises them) and as a result the spindle apparatus cannot properly segregate the chromosome during mitosis. The spindle assembly checkpoint detects abnormalities and results in cell cycle arrest in G2 phase.

Question 6

Name 2 examples of topoisomerase I inhibitors

Answer 6

Irinotecan and Topotecan

Question 7

Name 3 examples of Topoismoerase 2 inhibitors

Answer 7

Etoposide, doxorubicin, epirubicin

Question 8

How do topoisomerase inhibitors work?

Answer 8

Topoisomerase is an enzyme which relaxes supercoils within the DNA. Inhibition prevents DNA repair.

Question 9

Name an mTOR inhibitor

Answer 9

Evorolimus

Question 10

What is the mechanism of an mTOR inhibitor?

Answer 10

Leads to blockage in progression from G1 to S phase, also expresses hypoxia inducible factor which decreases expression of VEGF.

Question 11

Name 3 examples of alkylating agents

Answer 11

Platinums, nitrogen mustards (ifosfamide), non nitrogen mustard methylating agents (temozolamide)

Question 12

What is the mechanism of alkylating agents?

Answer 12

Forms cross links between purine bases

Question 13

Name 2 examples of pyridamine analogues

Answer 13

Gemcitabine and capecitabine/5FU

Question 14

What is the mechanism of pyridamine analogues?

Answer 14

Become phosphorylated within the cell and its metabolites because incorporated into DNA as ‘false base pairs’

Question 15

Name 2 examples of antibiotic chemotherapies?

Answer 15

Bleomycin and Mitomycin

Question 16

How do antibiotic chemotherapies work?

Answer 16

Bind to iron creating free radicals and causing single and double stranded DNA breaks.

Question 17

Name 2 examples of VEGFi

Answer 17

Tizotinib and Bevacizumab

Question 18

Name 4 examples of multi targeted TKI

Answer 18

Sunitinib, pazopanib, caboxantanib, sorafenib, lenvatinib and axitinib

Question 19

Name two examples of anti-folate drugs?

Answer 19

Methotrexate and pemetrexed

Question 20

What is the mechanism of antifolate drugs?

Answer 20

Reduced folate synthesis which is essential in the synthesis of DNA

Question 21

Name an example of CYP17A1 inhibitor?

Answer 21

Abiaterone

Question 22

How do CDK46i work?

Answer 22

Stop CDK46 forming a complex within cyclin D1 therefore inhibiting phophorylation of tumour suppressor gener Rb. Halting cell cycle progression from G1 to S phase.

Question 23

Name example of non steroidal competitive androgen receptor inhibitors?

Answer 23

Enzalumatamide and darolutamide

Question 24

What is the difference between TPS and CPS in PDL1 expression?

Answer 24

TPS- expression of receptor in tumour cells vs total number of cells
CPS- expression of receptor on tumour and stromal cells (lymphocytes and macrophages) vs total number of cells.

Question 25

Common chemotherapy causes of PPE

Answer 25

5FU/capecitabine, doxorubicin and docetaxel

Question 26

Does vinorelbine fatigue respond to dose reduction

Answer 26

Often not

Question 27

What is the mechanism by with anthracyclines cause cardiomyopathy?

Answer 27

Dose dependent as a result of oxidative stress and apoptotic loss of cardiomyocites.

Question 28

When should bevacizumab be held in the prescence of proteinuria?

Answer 28

If >2g protein/24hrs or 4+ protein on dipstick

Question 29

Which prostate cancer drugs can interfere with anti-epileptics?

Answer 29

Enzalutamide is a potent induce and can affect concentration of antiepileptics such as carbamazepine, clonazepam, phenytoin and valproate.

Question 30

Which prostate cancer drug should be avoided with high fat meals?

Answer 30

Abiaterone, increases exposure

Question 31

Do C450 inducers increase or reduce exposure to other drugs?

Answer 31

Reduce

Question 32

Do CP450 inhibitors increase or reduce exposure to other drugs?

Answer 32

Increase

Question 33

Name 3 common CP450 inducers

Answer 33

Rifampicin, phenytoin and carbamazepine

Question 34

Name 3 common CP450 inhibitors?

Answer 34

Clarithyromycin, ciprofloxacin, grapefruit juice, amiodarone

Question 35

Name three chemotherapy drugs to avoid if eGFR <30ml/min

Answer 35

Capecitabine, pemetrexed and cisplatin

Question 36

In liver dysfunction which two drugs should always have a dose reduction?

Answer 36

Taxane and epirubicin

Question 37

Define Cmax in pharmacokinetics

Answer 37

Max concentration achieved following administration of drug, depends on route

Question 38

Define Tmax in context of pharmacokinetics

Answer 38

Time at which the maximum concentration of a drug is reach

Question 39

Define clearance in the context of pharmacokinetics

Answer 39

Measure of the elimination of a drug expressed by volume/time.

Question 40

Which drug can cause bluish discolouration of sclera, fingernails and urine?

Answer 40

Mitoxantrone (leukaemia, lymphoma, breast and prostate) appaz…