Anti-cancer Drugs

Question 1

Name the 4 main classes of anti-cancer drugs used in chemotherapy

Answer 1

Alkylating agents
Platinums
Antimetabolites
Spindle poisons

Question 2

List the following for: Alkylating agents

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects
• Warnings / contraindications

Answer 2

Anti-cancer

Carmustine
Cyclophosphamide

Alkylating agents

• Causes cross linking of DNA by binding covalently to alkyl groups and DNA
• DNA is unable to complete normal replication – goes into cell arrest
• Cell is either repaired or undergoes apoptosis

- Haemorrhagic cystitis (Cyclophosphamide)
Other:
- Nausea / vomiting
- Alopecia
- Skin toxicity
- Mucositis
- Cardio toxicity
- Lung toxicity
- Neutropenic sepsis / anaemia / bleeding and bruising
- Acute renal failure
- GI perforation in lymphoma
- DIC in acute myeloid leukaemia

• Narrow therapeutic index
• Significant side effect profile

Question 3

List the following for: Platinums

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects
• Warnings / contraindications

Answer 3

Anti-cancer

Cisplatin
Oxaliplatin

Platinums

Action is closely related to alkylating agent action
Forms covalent bonds which are formed in inter-strands and intra-strands
Cisplatin - smaller so easier to ligate out
Oxaliplatin - bulky so harder to ligate out, useful in tumours where Cisplatin is ineffective

• Ototoxicity
• Nephrotoxicity
• Less hair loss than others
  Other:
• Nausea / vomiting
• Alopecia
• Skin toxicity
• Mucositis
• Cardio toxicity
• Lung toxicity
• Neutropenic sepsis / anaemia / bleeding and bruising
• Acute renal failure
• GI perforation in lymphoma
• DIC in acute myeloid leukaemia
• Narrow therapeutic index
• Significant side effect profile

Question 4

List the following for: Antimetabolites

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects
• Warnings / contraindications
• Important drug reactions

Answer 4

Anti-cancer

5-Fluorouracil
Methotrexate

Antimetabolites

• Interfere with normal cell metabolism of nucleic acids
  5-Fluorouracil
• Inhibits thymidylate synthase (converts dUMP to dTMP)
• Less dTMP which is needed for the synthesis of thymine - DNA pyrimidine
  Methotrexate
• Inhibits dihydrofolate reductase enzyme (converts dihydrofolate into tetrahydrofolate)
• Inhibits folate cycle which is needed for the synthesis of DNA purines

- Myelosuppression (Methotrexate)
Other:
	Nausea / vomiting
	Alopecia
	Skin toxicity
	Mucositis
	Cardio toxicity
	Lung toxicity
	Neutropenic sepsis / anaemia / bleeding and bruising
	Acute renal failure
	GI perforation in lymphoma
	DIC in acute myeloid leukaemia
	Narrow therapeutic index
	Significant side effect profile
	Capecitabine (5-Fluorouracil) and Warfarin
	Capecitabine (5-Fluorouracil) and St Johns Wort and grapefruit juice
	Methotrexate – caution with penicillin and NSAIDs

Other:

• Nausea / vomiting
• Alopecia
• Skin toxicity
• Mucositis
• Cardio toxicity
• Lung toxicity
• Neutropenic sepsis / anaemia / bleeding and bruising
• Acute renal failure
• GI perforation in lymphoma
• DIC in acute myeloid leukaemia
• Narrow therapeutic index
• Significant side effect profile
• Capecitabine (5-Fluorouracil) and Warfarin
• Capecitabine (5-Fluorouracil) and St Johns Wort and grapefruit juice
• Methotrexate – caution with penicillin and NSAIDs

Question 5

List the following for: Spindle poisons

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects
• Warnings / contraindications
• Important drug reactions

Answer 5

Anti-cancer

Taxoids
Vinca alkaloids - Vincristine

Spindle poisons

- Affects microtubules in the M phase of the cell cycle
Taxoids
- Prevent disassembly of microtubules
- Stabilises microtubules
- M phase can’t finish
Vinca alkaloids
- Prevent assembly of microtubules
- No M phase

• Peripheral neuropathy (Vincristine)
• More hair loss for vinca alkaloids
  Other:
• Nausea / vomiting
• Alopecia
• Skin toxicity
• Mucositis
• Cardio toxicity
• Lung toxicity
• Neutropenic sepsis / anaemia / bleeding and bruising
• Acute renal failure
• GI perforation in lymphoma
• DIC in acute myeloid leukaemia
• Narrow therapeutic index
• Significant side effect profile
• Vincristine and Itraconazole – increased peripheral neuropathy