Cancer Therapy & Immunomodulators Flashcards
Heterogenous group of drugs
Induces cellular damage thru GENERATION OF INTRA-STRAND CROSSLINKS IN DNA
Covalent binding to nucleic acids is facilitated by the generation of ____________ –> affects DNA/RNA synthesis
Is cell cycle non-specific?
Alkylating Agents
Covalent binding to nucleic acids is facilitated by the generation of CARBONIUM ION GROUPS –> affects DNA/RNA synthesis
Cell cycle non-specific (exert maximum cytotoxicity at late G1 and S phase)
PD of nitrogen mustards
Cyclophosphamide
PD of nitrosoureas
Lomustine
PD of platinum agents
Cisplatin
PD of platinum agents
Cisplatin
Toxic effect of nitrogen mustards due to ACROLEIN
Other toxic effects:
Nausea/vomiting
Bone marrow depression
Hemorrhagic cystitis
Can be precvented by (1) hydration and (2) use of sulfhydryl donors (eg MESNA and NAC - N-acetylcysteine)
PD of nitrosoureas: Lomustine
Lipid soluble — CONSEQUENCE?
Used in CNS tumors
PO given
Used to treat hodgkin’s lymphoma
Lipid solubility of lomustine enables cumulative delayed myelosuppression, lowers bioavailabiloty of the drug
PD of platinum agent: Cisplatin
Water-soluble complex build around a central Pt atom (reacts with water to release Cl- –> Pt complex binds w/ DNA)
Given IV
What are the multiple indications of administering Cisplatin?
Head and neck tumors
Thoracic, germ cell/testicular cancers
Genitourinary cancers
PD of platinum agent: Cisplatin
Water-soluble complex build around a central Pt atom (reacts with water to release Cl- –> Pt complex binds w/ DNA)
Given IV
What are the toxic effects of Cisplatin?
Nausea - use 5HT3 receptor antagonists
Renal - hydration and diuresis needed
Neurologic (paresthesia of feet and hands)
Ototoxicity (high freq hearing loss and tinnitus)
Low myelotoxicity
Give other alkylating agents apart from
N mustards - cyclophosphamide
Nitrosoureas - lomustine
Pt agent - cisplatin
Dacarbazine
Temozolomide
Procarbazine
Analogs of natural compounds that inhibit purine synthesis
Antimetabolites
How do antimetabolites interfere with nucleic acid synthesis? Give 2 hehe
Competition of binding sites of enzymes
Incorporation into nucleic acids –> inhibits normal function –> apoptosis
Stage of cell cycle in which antimetabolites has high specificity?
Are alkylating agents non-specific?
S phase
Alkylating agents are cell cycle non-specific (exert maximum cytotoxicity at G1 and S)
Stage of cell cycle in which antimetabolites has high specificity?
Are alkylating agents non-specific?
S phase
Alkylating agents are cell cycle non-specific (exert maximum cytotoxicity at G1 and S)
PD of antifolate angents
Methotrexate
PD of pyrimidine analogues
Fluorouracil
PD of purine analogue
Fludarabine
What is the PD of antifolate?
What is its main function?
Methotrexate
Main function: interfere with THYMIDYLATE SYNTHESIS
Competitive antagonist of DHFR - dihydrofolate reductase
Does methotrexate have high lipid solubility?
Methotrexate, PD of antifolate agents, has poor lipid solubility, can’t cross BBB, no high dose regimen to treat primart CNS lymphoma is needed
But high dose regimens may cause nephrotoxicity, need for folinic acid rescue
Give 2 antimetabolites that inhibit thymidylate synthase
Methotrexate and Fluorouracil
Indication for fluorouracil use?
To be used with oxiplatin and irinotecan
Colorectal cancer
Give two prodrugs of fluorouracil
Are these administered PO?
Capecitabine and Tegafur (coffee and toga)
Administered PO (fluorouracil is administered Iv or topically)
Toxic effects of pyrimidine analogues
Cytopenias - anemia, thrombocytopenia
GI disturbances - diarrhea, abdominal pain, nausea
Stomatitis - oral ulcers, usu treated with ice chips
What enzyme is inhibited by fludarabine, purine analogue PD?
What enzyme is inhibited by methotrexate and fluorouracil?
Ribonucleotide reductase - inhibited by fludarabine
Thymidylate synthase - inhibitrd by methotrexate and fluorouracil
