Basic Pharmacology of Cancer Chemotherapies Flashcards
Are alkylating agents cell cycle dependent? How do they work?
NO- they are NOT CELL CYCLE DEPENDENT
they form electrophilic bonds in Guanine of DNA which HALTS CELL REPRODUCTION
What are the Nitrogen Mustards? What drugs are included in this category?
Nitrogen Mustards are ALKYLATING AGENTS
CYCLOPHOSPHAMIDE
Melphalan
Chlorambucil
Hemorrhagic cystitis is a toxicity associated with Cyclophosphamide. What causes the bladder toxicity, and how can it be prevented?
Acrolein is a toxic metabolite of cyclophosphomide that causes hemorrhagic cystitis.
Hemorrhagic cystitis can be partially prevented by the use of MESNA- the thiol group of mesna binds the toxic metabolite
What are the Nitrosureas? What category of anti-cancer drugs do they belong to?
“-MUSTINE” + STREPTOZOCIN
CarMUSTINE
LoMUSTINE
SeMUSTINE
Nitrosureas= ALKYLATING AGENTS
What category of drugs can cross the BBB and are therefore useful for the treatment of brain tumors?
NITROSOUREAS (“-mustine +Streptozocin)
What drug destroys pancreatic beta cells & is used to treat insulinomas?
Streptozocin (Nitrosurea Alkylating Agent)
What category of anti-cancer drugs is Busulfan?
Alkylating Agent (Alkyl Sulfonate)
What is Busulfan primarily used to treat?
CML
Ablation of pt’s bone marrow before BM transplantation
What phase of the cell cycle do Antimetabolites target?
S-PHASE
Highly toxic to rapidly proliferating cells (including normal tissue- hair & GI tract)
What drugs are in the antimetabolite category?
Methotrexate (MTX)
5-Fluorouracil (5-FU)
Cytarabine (ara-C)
Azathioprine
6-Mercaptopurine (6-MP)
6-Thioguanine (6-TG)
What is the mechanism of MTX? Can myelosuppression be reversed?
Folic Acid analog inhibits DHFR–>Decreases THF available for conversion of dUMP–>dTMP–>
Decreased dTMP, DNA & protein synthesis
Myelosuppression IS reversible with LEUCOVORIN (folinic acid rescue)
What is the mechanism of 5-FU? Can myelosuppression be reversed?
PYRIMIDINE analog bioactivated to 5F-dUMP–> covalently complexes to folic acid–>
INHIBITS THYMIDYLATE SYNTHASE–> decrease in dTMP
Myelosuppression is NOT REVERIBLE w Leucovorin
What is the mechanism of Cytarabine (Ara-C)?
Pyrimidine Analog (Cytidine) INHIBITS DNA POLYMERASE
What are the toxicities associated w Ara-C?
Leukopenia
Thrombocytopenia
Megaloblastic Anemia
Azathioprine, 6-MP, & 6-TG all share the SAME mechanism of action. What is the mechanism?
What enzyme are these drugs metabolized by? (What drug increases their toxicity?)
PURINE ANALOGS activated by HGPRT & decrease De Novo Purine Synthesis
Metabolized by XANTHINE OXIDASE (Allopurinol increases their toxicity EXCEPT for 6-Thioguanine- 6-TG)
Use 6-TG in pts taking Allopurinol
What is the mechanism of Antitumor Antibiotics? Give examples of antitumor antibiotics
Intercalate DNA strands–> free radical formation
Dactinomycin
Anthracyclines (Doxorubicin, Daunorubicin & Idarubicin)
Bleomycin
What phase of the cell cycle does Bleomycin affect? Mechanism?
G2 & M phase
Complexes with iron & reacts with oxygen–>Induces free radical formation which causes BREAKS in DNA strands
What drugs are Microtubule Inhibitors aka ANTIMITOTICS?
Vinca Alkaloids (Vincristine & Vinblastine)
Paclitaxel & Taxols
What phase of the cell cycle do Vinca Alkaloids (Vincristine & Vinblastine) affect? Mechanism?
M-phase
Bind to TUBULIN & block polymerization of microtubules so that mitotic spindle cannot form.
(Think of Microtubles= M-phase as the VINes of your cells)
What are the toxicities associated with Vincristine & Vinblastine?
Vincristine= NEUROTOXIC (areflexia, peripheral neuritis, paralytic ileus)
VinBLASTine BLASTS Bone marrow (suppression)
What phase of the cell cycle do the Taxenes (Paclitaxel & Docetaxel) act on? Mechanism?
G2 & M-Phase
Bind TUBULIN–> hyperstabilizes polymerized microtubules so the mitotic spindle cannot break down & anaphase can not procede
Does the action of anticancer drugs follow first-order or second- order kinetics?
First Order- rate of elimination is directly proportional to the drug concentration (constant FRACTION of drug is eliminated per unit time)
What is responsible for multidrug resistance of chemotherapeutic agents (ie pumping drugs out of cells)?
P-glycoprotein is an ATP-dependent membrane efflux transporter responsible for pumping drugs out of cells