Chemo IV Antimetabolites Flashcards
Methotrexate- Mech of Action
POLYGLUTINATED AND RETAINED WITHIN CANCER CELLS
INHIBIT DIHYDROFOLATE REDUCTASE= PREVENT PURINE SYNTHESIS
target= dihydrofolate reducase
Methotrexate- Cell Cycle Specificity
S PHASE
Methotrexate- Kinetics
PROTEIN BOUND- ADMINISTRATION WITH OTHER DRUGS MAY POTENTIATE TOXICITY
DISTRIBUTES THROUGH TOTAL BODY WATER- CONTRAINDICATED IN ASCITES AND PLEURAL EFFUSION
EXCRETED BY KIDNEY- CAUTION IN KIDNEY DISEASE
EXCRETED AS A SALT OF A WEAK ACID- OTHER DRUGS ALSO EXCRETED THIS WAY MAY PREENT EXCRETION- ASPIRIN, PENICILLINS
HIGH DOSES CROSS BBB
MORE SOLUBLE IN ALKALINE, THUS ALKALINIZE URINE TO PROMOTE EXCRETION–>ADD SODIUM BICARB
Methotrexate- Clinical Use
INTRATHECAL ADMINISTRATION FOR CARCINOMATOUS OR LLYMPHOMATOUS MENINGITIS
breast cancer leukemia lymphoma rheumatoid arthritis psoriasis
Methotrexate- Toxicities
MYELOSUPPRESSION- LIMITING
mild nausea and vomiting, stomatitis
can rescue bone marrow and intestinal epithelial cells from drug effects via administration of Leucovorin (tetrahydrofolate)- these cells have less polyglutinated drug than the cancer cells
Premetrexed- Mech of Action
Anti-folate- inhibits thymidine syntahse
Premetrexed- Cell Cycle Specificity
S PHASE
Premetrexed- Clinical Use
lung cancer
mesothelioma
Premetrexed- Toxicities
Myelosuppresion- limiting
rash
stomatitis
diarrhea
hand-foot syndrome
pretreatment w/ B-12 and oral folic acid decreases the amount of myelosuppression
Cytarabine (cytosine arabinoside), Gemcitabine- Mech of Action
active form is triphosphate form activated by kinases
INHIBITS DNA POLYMERASE BY INCORPORATING INTO DNA AND INHIBITING TEMPLATE FUNCTION AND CHAIN ELONGATION
target= DNA
Cytarabine (cytosine arabinoside), Gemcitabine- Cell Cycle Specificity
S PHASE
Cytarabine (cytosine arabinoside)- Kinetics
Short half life- coupled with cell cycle specificity means the drug has SCHEDULE DEPENDENT CYTOTOXICITY
Cytarabine (cytosine arabinoside)- Clinical Use
ACUTE LEUKEMIA
intrathecal administration for carcinomatous or lymphomatous meningitis
Gemcitabine- Kinetics
not schedule dependence
Gemcitabine- Clinical Use
PALLIATIVE TREATMENT OF PANCREAS AND LUNG CANCER
Cytarabine (cytosine arabinoside), Gemcitabine- Toxicities
MYELOSUPPRESSION- LIMITING
HIGH DOSE CAN CAUSE CEREBELLAR TOXICITY AND CONJUNCTIVITIS
hepatic toxicity nausea vomiting hair loss stomatitis
5-Fluorouracil- Mech of Action
phosphorylated to triphosphate form and converted to fdUMP
FDUMP INHIBITS THYMIDYLATE SYNTHETASE AND DECREASES PRODUCTION OF THYMINE, ALSO INCORPORATES INTO DNA AND RNA
target= thymidylate synthetase, DNA, RNA
5-Fluorouracil- Cell Cycle Specificity
S PHASE
5-Fluorouracil- Kinetics
OFTEN GIVEN WITH RADIATION AS A RADIATION SENSITIZER
LEUCOVORIN POTENTIATES EFFECTS OF 5-FU, MORE EFFECTIVE BUT ALSO MORE SIDE EFFECTS
5-Fluorouracil- Clinical Use
Breast cancer
head and neck cancer
GI cancers
5-Fluorouracil- Toxcities
RASH STOMATITIS DIARRHEA MILD MYELOSUPPRESSION HYPERPIGMENTION (SUN SENSITIVITY) chest pain (coronary artery vasospasm) cerebellar ataxia excess alcrimation hand-foot syndrome
Capecitabine- Mech of Action
produrg of 5-FU
cleaved to active form by enzyme mostly expressed in cancer cells
Capecitabine- Cell Cycle Specificity
S PHASE
Capecitabine- Kinetics
oral replacement for 5-FU
