Chemotherapy

Question 1

Methotrexate mechanism?

Answer 1

Inhibit DHFR enzyme -> decrease purine synthesis

Question 2

5-fluoracil (antimetabolite) mechanism?

Answer 2

Uracil analogue -> irreversibly inhibits thymidilate synthesis -> decrease pyrimidine synthesis

Question 3

Alkylating agents mechanism?

Answer 3

Covalently bond to DNA forming inter/intra strand links between nucleophillic groups -> inhibits replication/transcription -> cell death

Question 4

Antimetabolite mechanism?

Answer 4

Decrease production of purines/pyrimidines -> inhibit DNA synthesis (S phase of cycle)

Question 5

Intercalating agents mechanism?

Answer 5

Fit between DNA base pairs (bulky ring structure) -> transcription/replication -> non-ligated, free DNA strands produced -> apoptosis

Question 6

Spindle poisons mechanism?

Answer 6

Prevent disassembly (taxoids) or formation (vinca alkaloids) of spindles -> prevent equal separation of chromosomes during mitosis -> apoptosis of daughter cells!

Question 7

Chemotherapy- distribution PKs

Answer 7

Cancer changes tissue proportions, less fat, more plasma -> calculate BMI and body surface area to calculate dose and check plasma [drug]
Heavily protein bound!!

Question 8

Chemotherapy general ADRs

Answer 8

Alopecia, nausea, mucositis, AKI (tumour lysis!), myelosuppression

Question 9

Which chemotherapy drugs cause peripheral neuropathy?

Answer 9

Alkylation agents, spindle poisons

Question 10

Bleomycin ADR

Answer 10

Pulmonary fibrosis

Question 11

Intercalating agents ADR

Answer 11

Cardiotoxicity

Question 12

DDIs?

Answer 12

Combine drugs with minimal ADR overlap, all agents at HIGHEST dose, for SHORTEST time, and gaps between treatment for immune recovery!

Question 13

Monitoring?

Answer 13

[drug] in plasma

ADRs- ECG, lung function, LFTs, renal function