PHARMACOLOGY: Cancer Chemotherapy

Question 1

What are the 2 types of chemotherapy drug?

Answer 1

Cell cycle specific
-Targets ONLY actively dividing cells

Cell cycle non-specific
-Target actively dividing cells PLUS quiescent (G0) phase cells, i.e. non-dividing ones

Question 2

What are the 4 classes of chemotherapy drugs?

Answer 2

Alkylating agents
Antimetabolites
Cytotoxic antibiotics
Steroid hormones and antagonists

Question 3

What are the 5 examples of alkylating agents?

Answer 3

Nitrogen mustards
Cisplatin
Temozolomide
Lomustine
Busulphan

Question 4

List 5 examples of nitrogen mustards.

Which class of chemotherapy drugs do these drugs belong to?

Answer 4

Mechlorethamine
Melphalan
Cyclophosphamide
Chlorambuclin
Ifosfamide

(Alkylating agents)

Question 5

What are the 2 types of antimetabolite drugs?

Answer 5

Antifolates (i.e. nucleotide synthesis inhibitors)

Nucleotide analogues

Question 6

Give 3 examples of antifolate drugs.

Which class of chemotherapy drugs do these drugs belong to?

Answer 6

Methotrexate
Ralitrexed
Pemetrexed

(Antimetabolites)

Question 7

Give 6 examples of nucleotide analogues.

Which class of chemotherapy drugs do these drugs belong to?

Answer 7

5-Fluorouracil
Cytarabine
Gumcitabine
Fludarabine
Capecitabine
Mecaptopurines

(Antimetabolites)

Question 8

What are the 2 types of cytotoxic antibiotics?

Answer 8

DNA intercalators

Microtubule inhibitors

Question 9

Give 2 examples of DNA intercalators, and what they act on.

Which class of chemotherapy drugs do these drugs belong to?

Answer 9

Dactinomycin - minor groove of DNA double helix
Doxorubicin - DNA bases

(Cytotoxic antibiotics)

Question 10

Give 1 example of a microtubule inhibitor.

Which class of chemotherapy drugs does this drug belong to?

Answer 10

Vincristine

Cytotoxic antibiotics

Question 11

What are the 2 types of steroid hormone drugs?

Answer 11

Steroid hormones

Hormone antagonists

Question 12

Give 2 examples of steroid hormones given in chemotherapy.

Answer 12

Prednisone

Prednisolone

Question 13

Give 3 examples of hormone antagonists used in chemotherapy, and say what they do.

Answer 13

Tamoxifen - oestrogen receptor agonist/antagonist
Bicalutamide - testosterone receptor antagonist
Prostap - LHRH agonist (therefore inhibits tesosterone production)

Question 14

Outline the mechanism of action of alkylating agents. (3)

Answer 14

1. Form covalent bonds with DNA
   a. Therefore interfere with both transcription and replication
2. Contain 2 reactive groups, meaning they can bond to two different bases:
   a. On the same DNA strand:
   - Prevent DNA transcription

b. On different DNA strands:
- Cross-link the DNA strands together
- Prevent DNA strand separation
- Therefore prevent transcription/replication

Question 15

What is mechlorethamine used for? (2)

How is it administered?

What type of drug is it?

Answer 15

Hodgkin’s lymphoma
Non-Hodgkin’s lymphoma

IV

Nitrogen mustard (alkylating agent)

Question 16

What is melphalan used for? (3)

How is it administered?

What type of drug is it?

Answer 16

Multiple myeloma
Ovarian cancer
Breast cancer

Oral

Nitrogen mustard (alkylating agent)

Question 17

What are the advantages of cyclophosphamide? (2)

What type of drug is it?

Answer 17

1. Prodrug
2. ALDH protects against drug toxicity

Nitrogen mustard (alkylating agent)

Question 18

What type of drug is methotrexate? Outline its mechanism of action. (2)

Answer 18

Antifolate drug (antimetabolite)

MECHANISM OF ACTION:
1. Higher affinity for dihydrofolate reductase than folic acid (i.e. preferential use)

2. Therefore inhibits production of dihydrofolate
   a. This inhibits purine/pyrimidine nucleotide synthesis
   b. This inhibits DNA and RNA synthesis

Question 19

What type of drug is 5-fluorouracil? Outline its mechanism of action. (3)

Answer 19

Nucleotide analogue (antimetabolite)

MECHANISM OF ACTION:

1. Takes the place of normal pyrimidine in DNA bases
2. This inhibits thymidine formation
3. Inhibits DNA synthesis

Question 20

What type of drug is cytarabine? Outline its mechanism of action. (3)

Answer 20

Nucleotide analogue (antimetabolite)

MECHANISM OF ACTION:

1. Activated to form ara-CTP
2. This inhibits DNA polymerase (and therefore DNA replication)
3. Ara-CTP is incorporated into DNA changes (causes DNA chain termination)

Question 21

What type of drug is dactinomycin? Outline its mechanism of action. (2)

Answer 21

DNA intercalator (cytotoxic antibiotic)

MECHANISM OF ACTION:

1. Inserts itself into the minor groove on the outside of the DNA helix
2. This disrupts RNA polymerase function

Question 22

What type of drug is doxorubicin? Outline its mechanism of action. (3)

Answer 22

DNA intercalator (cytotoxic antibiotic)

MECHANISM OF ACTION:

1. Inserts itself between base pairs, binding to the sugar-phosphate DNA backbone
2. This causes local uncoiling
3. This causes impaired DNA and RNA synthesis

Question 23

What type of drug is vincristine? Outline its mechanism of action. (2)

Answer 23

Microtubule inhibitor (cytotoxic antibiotic)

MECHANISM OF ACTION:

1. Vincristine binds to microtubular proteins during mitosis
2. This inhibits tubulin polymerisation
   a. Inhibits normal spindle formation
   b. Disrupts cell division

Question 24

What type of drugs are mercaptopurines? Outline their mechanism of action.

Answer 24

Nucleotide analogue (antimetabolites)

MECHANISM OF ACTION:

1. Purine analogue which is converted into false nucleotides
2. These are incorporated into DNA, and disrupt the DNA helix

Question 25

Out of prednisone and prednisolone, which one is the ACTIVE form?

Answer 25

Prednisolone