Anti Cancer Drugs Flashcards
Non modifiable risk factors of cancer
Genetics
Age: eg prostate Ca
Sex related.
Race.
Modifiable risk factors or cancer
Environmental Exposure
Chemical carcinogen
Infections
Principle of Cancer Chemotherapy
-Ca chemo cause petal cytotoxic events
- attack is directed at metab sites essential for replication
-lack of specificity of current anti-cancer drugs
- proliferating cells are more susceptible to chemo than non proliferating
-Recommended in disseminated cases or minor metastases following surgery/radiation
-destruction of cells follow first order kinetics: given dose destroys constant fraction of cells
-in most cases combination therapy is more effective
Advantages of combination therapy of anti cancer drugs
Maximal effect within range of tolerable toxicity
Improve effectiveness against broader spectrum
Delay/reduce development of resistance
The mutagenic ability of cancer is worse when what particular anti cancer agent is used
Alkylating agents
Anti cancer drugs are classified into
Cell cycle specific agents
Cell cycle non specific agents
Cell cycle specific agents are divided into
Antimetabolites: S-phase eg methotrexate
Topoisomerase II inhibitors : G1 to S
Taxanes: M phase
Vinca alkaloids: M phase
Anti microtubule inhibitors: M phase
Anti Tumor antibiotics: G2 to Mphase eg bleomycin
Cell cycle non specific agents
Alkylating agents; bulsafan, camestine, cyclophosphamide
Anti tumor antibiotics
Topoisomerase I inhibitors
Platinum analogues
Antracyclins
AntiMetabolites are further classified into
Antifolates: Methrotrexate
Fluoropyrimidines: 5-fluorouracil, capacitabine
Deoxycytidine analogues: Cytarabine
Purine antagonists: Mecaptopurine, 6-thioguanine
What is the MOA of Methotrexate
Binds at the active site of dihydrofolate reductase thereby inhibiting synthesis of tetrahydrofolate and consequently thymidilate
Methotrexate is converted to ………… upon which it’s cytotoxic effects rests
Polyglutamate metabolite
A common side effects of anti folate’s
Myelosupression
What is used to reverse severe adverse effects in patients with methotrexate overdose
Leucovorin
What anti folate is used to treat mesothelioma and non-small cell lung cancer
Pemetrexate
Examples of antifolates used as anti cancer drugs
Methotrexate
Pemetraxate
Pralatrexate
When 5-fluorouracil is activated it gives three metabolites namely;
FdUMP: 5 -fluoro- 2’-deoxyuridine- 5’ monophosphate
FUTP
FdUTP
Function/MOA of FdUMP
Formation of complex with thymidilate synthase reduces production of folate
Function/MOA of FUTP
Incorporated into RNA, interferes with RNA processing
Function/MOA of FdUTP
Incorporated into cellular DNA, inhibits of DNA synthesis
Fluoropyrimidines used in anti cancer therapy
5-fluorouracil, capecitabine
Capecitabine is converted to 5-fluorouracil by……….. which is found in abundance in solid tumors
Thymidine phosphorylase
Citrabine is a prodrug, it is converted to its main cytotoxic metabolite by the enzyme
Deoxycitidine kinase
The main cytotoxic metabolite of citarabine
Citrabine triphosphate
MOA of citarabine
Inhibit DNA polymerase alpha and beta…blocking DNA synthesis
Citarabine is used in the treatment of
Hematologic malignancy(AML)
Purine antagonists are classified into
6-thiopurines
Fludarabine
Cladribine
6-mecaptopurine is inactive and is metabolized into two forms namely:
Monophosphate form
Triphosphate form
The monophosphate form of mecaptopurine functions to
Inhibit several enzymes of denovo synthesis of purine nucleotide
The triphosphate form of mecaptopurine functions to
It’s incorporated into RNA and DNA producing defective RNA and DNA
Mecaptopurine is metabolized to inactive forms by
Xanthine oxidase
A common xanthine oxidase inhibitor prescribed with 6-mercaptopurine
Allopurinol
The MOA of fludarabine and cladribine
Triphosphate metabolite inhibits DNA polymerase alpha and beta thereby interfering DNA synthesis
Alkylating agents exert their cytotoxicity by
Transfer of their alkyl groups to cellular constituents
The major site of alkylation within DNA is
N7 portion of the guanine
Alkylation of guanine results in
Misreading
Depurination
In the MOA of alkylating agents, Intramolecular cyclisation of alkylating agents form
Ethylene imonium ion
When are replicating cells most susceptible to alkylating agents
Late G1 and S phase of cell cycle
Resistance to alkylating agents can be acquired from
Increased capability to repair DNA lesions
Decreased transport of alkylating agents into the cell
Increased expression/activity of glutathione and glutathione associated proteins
Increased glutathione 5 transferase activity
The most widely used alkylating agent
Cyclophosphamide
Alkylating agents that cross blood brain barrier used in treatment of tumors are called
Nitrosurea
Nitrosourea includes
Carmustine
Lomustine
Streptozocine
Semustine
The nitrosurea used in the treatment of brain tumors
Carmustine and lomustine
Carmustine and lomustine is used majorly to treat
Brain tumors
Streptozocine a type of Nitrosourea is specifically used to treat
Insulinoma
