Cancer

Question 1

2 groups of anticancer drugs

Answer 1

cytotoxic drugs

endocrine based drugs

Question 2

cytotoxic drugs (7)

Answer 2

• Alkylating agents
• Platinum analogues
• Anti-metabolites
• Microtubule inhibitors
• Topoisomerase 1 inhibitor
• Topoisomerase 2 inhibitor
• Cytotoxic antibiotics
  (PAC MATT)

Question 3

Endocrine based drugs (7)

Answer 3

PAAGGES

1. Selective estrogen receptor modulators (SERM)/ downregulator
2. Aromatase inhibitors
3. Glucocorticoids
4. Anti-androgens
5. Estrogens
6. GnRH analogues/ antagonists
7. Progestins

Question 4

Alkylating Agents Drugs groups (5)

Answer 4

cytotoxic drug

1) Nitrogen Mustards (bifunctional alkylating agents): mechlorethamine, cyclophosphamide, melphalan, chlorambucil
2) Nitrosoureas (-stine): carmustine, lomustine, semustine
3) Alkyl sulfonates: Busulfan
4) Ethylenimines: Thiotepa
5) Triazenes: Dacarbazine, procarbazine

Question 5

Alkylating Agents MOA

Answer 5

form covalent bonds with DNA, crosslinking DNA
Disrupts DNA replication and transcription
Cause breaks in double and single strand DNA
non-specific phase

Question 6

Alkylating Agents ADR

Answer 6

1. Acute: nausea and vomiting, vesicant
2. Delayed:
   - myelosuppression (leukopenia, thrombocytopaenia)
   - alopecia (hair falling off in patches)
   - haemorrhagic cystitis
   - interstitial nephritis
   - pulmonary fibrosis/ILD
   - increased secondary malignancies esp AML (acute myeloid leukemia),
   Subfertility

Question 7

Platinum analogues drugs (3)

Answer 7

(-platin)
cisplatin (1st deg)
carboplatin (2nd deg)
oxaliplatin (3rd deg)

Question 8

Platinum analogues MOA

Answer 8

DNA adduction cause intra-strand crosslinks, and less inter-strand crosslinks
non-specific phase (like alkylating agents)

Question 9

Platinum analogues ADR + contraindication

Answer 9

1. Acute: nausea and vomiting (cisplatin)
2. Delayed:
   - myelosuppression
   - nephrotoxicity
   - peripheral sensory neuropathy (cisplatin and oxaliplatin)
   contraindicated when creatinine clearance <60ml/min, can still be used in mild renal impairment

Question 10

Anti-metabolites drugs

Answer 10

Restrict flow of precursors for DNA replication:
- methotrexate
- 5-fluorouracil
- 6-thioguanine
- 6mercaptopurine
- gemcitabine
- cytosine arabinoside
Incorporate into DNA and produce stress signals
- 5FU
- 6-TG
- 6-MP
- gemcitabine
- ara-C

Question 11

Anti-metabolites MOA

Answer 11

Highly cell cycle-specific

• Interfere with enzymes or reactions necessary for nucleic acid (purine and pyrimidine) synthesis
• restricts flow of precursors required for DNA replication
• or incorporate into DNA and produce stress signals

Question 12

Methotrexate mechanism + used in what cancers

Answer 12

Inhibits dihydrofolate reductase (DHFR), so FH4 cannot be formed = prevent thymidine monophosphate synthesis
used for breast cancer + lymphomas

Question 13

5-Fluorouracil mechanism + used in what cancer

Answer 13

inhibits thymidylate synthase, causing DNA damage

used for colorectal cancer

Question 14

Cytotoxic antibiotics drugs

Answer 14

Anthracyclines: 
- doxorubicin
- daunorubicin
- Idarubicin
epirubicin
Others: 
- Mitomycin C
- Bleomycin

Question 15

Cytotoxic antibiotics MOA

Answer 15

1) Inhibits DNA and RNA synthesis by intercalating between base pairs of the DNA/RNA strand, thus preventing DNA replication
2) Creates iron-mediated free oxygen radicals that damage the DNA and cell membranes.
3) Inhibition of Topoisomerase II
4) Alter membrane fluidity and ion transport

Question 16

Cytotoxic antibiotics ADR

Answer 16

• Cardiac toxicity
• Local toxicity
• Nausea, vomiting, alopecia
• Myelosuppressive (decrease in immunity cells): dose limiting toxicity

Question 17

Microtubule inhibitors MOA

Answer 17

• Inhibit cell division by disrupting microtubule function
• Separation of chromatids during mitosis requires changes in the polymerisation of the protein tubulin
• Microtubules are formed by the self-assembly of tubulin
• Microtubules link the centrioles to the kinetochores. Polymerisation-depolymerisation drives mitosis
• Improper attachment of microtubules to kinetochores activates the mitotic
checkpoint

Question 18

Microtubule inhibitors ADR

Answer 18

• Hypersensitivity
• Myelosuppression
• peripheral neuropathy
• myalgia (muscle ache/pain)
• bradycardia (esp. taxol)

Question 19

vinblastine vs paclitaxel

Answer 19

vinblastine - prevent elongation of the microtubule

paclitaxel - prevent shortening/ depolymerisation