Anti Cancer Drugs

Question 1

Non modifiable risk factors of cancer

Answer 1

Genetics
Age: eg prostate Ca
Sex related.
Race.

Question 2

Modifiable risk factors or cancer

Answer 2

Environmental Exposure
Chemical carcinogen
Infections

Question 3

Principle of Cancer Chemotherapy

Answer 3

-Ca chemo cause petal cytotoxic events
- attack is directed at metab sites essential for replication
-lack of specificity of current anti-cancer drugs
- proliferating cells are more susceptible to chemo than non proliferating

-Recommended in disseminated cases or minor metastases following surgery/radiation

-destruction of cells follow first order kinetics: given dose destroys constant fraction of cells

-in most cases combination therapy is more effective

Question 4

Advantages of combination therapy of anti cancer drugs

Answer 4

Maximal effect within range of tolerable toxicity

Improve effectiveness against broader spectrum

Delay/reduce development of resistance

Question 5

The mutagenic ability of cancer is worse when what particular anti cancer agent is used

Answer 5

Alkylating agents

Question 6

Anti cancer drugs are classified into

Answer 6

Cell cycle specific agents
Cell cycle non specific agents

Question 7

Cell cycle specific agents are divided into

Answer 7

Antimetabolites: S-phase eg methotrexate

Topoisomerase II inhibitors : G1 to S

Taxanes: M phase

Vinca alkaloids: M phase

Anti microtubule inhibitors: M phase

Anti Tumor antibiotics: G2 to Mphase eg bleomycin

Question 8

Cell cycle non specific agents

Answer 8

Alkylating agents; bulsafan, camestine, cyclophosphamide
Anti tumor antibiotics
Topoisomerase I inhibitors
Platinum analogues
Antracyclins

Question 9

AntiMetabolites are further classified into

Answer 9

Antifolates: Methrotrexate
Fluoropyrimidines: 5-fluorouracil, capacitabine
Deoxycytidine analogues: Cytarabine
Purine antagonists: Mecaptopurine, 6-thioguanine

Question 10

What is the MOA of Methotrexate

Answer 10

Binds at the active site of dihydrofolate reductase thereby inhibiting synthesis of tetrahydrofolate and consequently thymidilate

Question 11

Methotrexate is converted to ………… upon which it’s cytotoxic effects rests

Answer 11

Polyglutamate metabolite

Question 12

A common side effects of anti folate’s

Answer 12

Myelosupression

Question 13

What is used to reverse severe adverse effects in patients with methotrexate overdose

Answer 13

Leucovorin

Question 14

What anti folate is used to treat mesothelioma and non-small cell lung cancer

Answer 14

Pemetrexate

Question 15

Examples of antifolates used as anti cancer drugs

Answer 15

Methotrexate
Pemetraxate
Pralatrexate

Question 16

When 5-fluorouracil is activated it gives three metabolites namely;

Answer 16

FdUMP: 5 -fluoro- 2’-deoxyuridine- 5’ monophosphate

FUTP

FdUTP

Question 17

Function/MOA of FdUMP

Answer 17

Formation of complex with thymidilate synthase reduces production of folate

Question 18

Function/MOA of FUTP

Answer 18

Incorporated into RNA, interferes with RNA processing

Question 19

Function/MOA of FdUTP

Answer 19

Incorporated into cellular DNA, inhibits of DNA synthesis

Question 20

Fluoropyrimidines used in anti cancer therapy

Answer 20

5-fluorouracil, capecitabine

Question 21

Capecitabine is converted to 5-fluorouracil by……….. which is found in abundance in solid tumors

Answer 21

Thymidine phosphorylase

Question 22

Citrabine is a prodrug, it is converted to its main cytotoxic metabolite by the enzyme

Answer 22

Deoxycitidine kinase

Question 23

The main cytotoxic metabolite of citarabine

Answer 23

Citrabine triphosphate

Question 24

MOA of citarabine

Answer 24

Inhibit DNA polymerase alpha and beta…blocking DNA synthesis

Question 25

Citarabine is used in the treatment of

Answer 25

Hematologic malignancy(AML)

Question 26

Purine antagonists are classified into

Answer 26

6-thiopurines Fludarabine Cladribine

Question 27

6-mecaptopurine is inactive and is metabolized into two forms namely:

Answer 27

Monophosphate form Triphosphate form

Question 28

The monophosphate form of mecaptopurine functions to

Answer 28

Inhibit several enzymes of denovo synthesis of purine nucleotide

Question 29

The triphosphate form of mecaptopurine functions to

Answer 29

It’s incorporated into RNA and DNA producing defective RNA and DNA

Question 30

Mecaptopurine is metabolized to inactive forms by

Answer 30

Xanthine oxidase

Question 31

A common xanthine oxidase inhibitor prescribed with 6-mercaptopurine

Answer 31

Allopurinol

Question 32

The MOA of fludarabine and cladribine

Answer 32

Triphosphate metabolite inhibits DNA polymerase alpha and beta thereby interfering DNA synthesis

Question 33

Alkylating agents exert their cytotoxicity by

Answer 33

Transfer of their alkyl groups to cellular constituents

Question 34

The major site of alkylation within DNA is

Answer 34

N7 portion of the guanine

Question 35

Alkylation of guanine results in

Answer 35

Misreading Depurination

Question 36

In the MOA of alkylating agents, Intramolecular cyclisation of alkylating agents form

Answer 36

Ethylene imonium ion

Question 37

When are replicating cells most susceptible to alkylating agents

Answer 37

Late G1 and S phase of cell cycle

Question 38

Resistance to alkylating agents can be acquired from

Answer 38

Increased capability to repair DNA lesions Decreased transport of alkylating agents into the cell Increased expression/activity of glutathione and glutathione associated proteins Increased glutathione 5 transferase activity

Question 39

The most widely used alkylating agent

Answer 39

Cyclophosphamide

Question 40

Alkylating agents that cross blood brain barrier used in treatment of tumors are called

Answer 40

Nitrosurea

Question 41

Nitrosourea includes

Answer 41

Carmustine Lomustine Streptozocine Semustine

Question 42

The nitrosurea used in the treatment of brain tumors

Answer 42

Carmustine and lomustine

Question 43

Carmustine and lomustine is used majorly to treat

Answer 43

Brain tumors

Question 44

Streptozocine a type of Nitrosourea is specifically used to treat

Answer 44

Insulinoma