ANTICANCER DRUGS Flashcards
Name at least 2 alkylating agents
- chorambucil
- cyclophosphamide
- carmustine (-mustines)
- dacarbazine (-carbazines)
MOA of alkylating agents
alkyl group forms covalent bond with DNA -> cross linkage/ strand breakage -> inhibit DNA replication -> apoptosis
majory site of alkylation is N7 position of guanine
Adverse effects of alkylating agents
- nausea, vomiting
- myelosuppresion
- alopecia
- pulmonary fibrosis
- increased 2ndary malignancies
Possible resistance mechanisms for alkylating agents
- decreased drug transportation into cell
- increased capacity to repair DNA lesions
- increased expression of glutathione associated proteins (help with DNA repair)
What are cell cycle non-specific drugs?
drugs that kill throughout cell cycle
1. alkylating agents
2. platinum analogues
3. cytotoxic antibiotics
4. topoisomerase inhibitors
What are cell cycle specific drugs?
drugs that kill specific parts of cell cycle during replication
1. anti-metabolites (S phase)
2. microtubules inhibitors
Name 3 platinum analogues?
- cisplatin
- carboplatin
- oxaliplatin
MOA of platinum analogues
act like alkylating agents, increase cross-linking of DNA preventing DNA replication= apoptosis
Adverse effects of platinum analogues
- myelosuppression
- nephrotoxicity
- peripheral sensory neuropathy
How are platinum analogues cleared?
R.E unchanged
When is cisplatin contradicted?
creatine clearance < 60ml/min
Can carboplatin be used in mild renal impairment?
yes, use with dose adjusment
Anti cancer drugs that are antimetabolites?
- methotrexate
- 5-fluorouracil
HIGHLY CELL SPECIFIC: S PHASE
MOA for methotrexate
inhibit dihydrofolate reductase needed for recyling of folate, i inhibit synthesis of thymidine monophosphate
methotrexate clinical indication?
tumours eg breast cancer and lymphoma
MOA of 5-fluorouracil
inhibit thymidylate synthase, misincoporation into RNA and DNA => damage
inactivtaed by being converted to dihydrofluoracil by dihydropyrimidine dehydrogenase