Antineoplastic Pharmacology Flashcards
Methotrexate
Antineoplastic - Cytotoxic Antimetabolite - Folic Acid Analog
MOA: Inhibits DHFR ∴ Can’t convert DHF to THF ∴ Inhibits purine synthesis ∴ DNA/RNA synthesis inhibited
Resistance d/t impaired transport into cell, altered DHFR, increased DHFR expression
Toxicity: INTERSTITIAL PNEUMONITIS and NEPHROTOXICITY
Leucovorin used to reverse toxicity
5-Fluorourail
Antineoplastic - Cytotoxic Antimetabolite - Pyrimidine Analog
MOA: 5FU converted into FdUMP in cell which inhibits Thymidylate Synthetase ∴ can’t convert dUMP to dTMP ∴DNA damage and cell death
Resistance d/t amplification of Thymidylate Synthetase
Capecitabine is a 5FU produrg w/ increased oral bioavailability
Capecitabine
Antineoplastic - Cytotoxic Antimetabolite - Pyrimidine Analog - 5FU produrg w/ increased oral bioavailability
MOA: 5FU converted into FdUMP in cell which inhibits Thymidylate Synthetase ∴ can’t convert dUMP to dTMP ∴DNA damage and cell death
Resistance d/t amplification of Thymidylate Synthetase
Cytarabine
Antineoplastic - Cytotoxic Antimetabolite - Pyrimidine Analog. MOA: converted to AraCMP in cell by Deoxycytidine Kinase. AraCMP to AraCTP then intercalated into DNA. Only kills cells in S-Phase of Cell cycle. Toxicity: CEREBELLAR SYNDROME = dysarthria, nystagmus, ataxia. Resistance d/t loss of Deoxycytidine Kinase, decreased transport across membrane, increased cytidine deaminase (which increases destruction of cytarabine)
Gemcitabine
Antineoplastic - Cytotoxic Antimetabolite - Pyrimidine Analog. MOA: incorporated into DNA, decreases synthesis, inhibits ribonucleotide reductase (RNR) ∴ decrease dNTPs ∴ decreases DNA synthesis
Resistance: decreased activity of deoxycytidine kinase (required for intercalation into DNA), tumors that increase deoxycytidine will also increase resistance
6-Thioguanine
Antineoplastic - Cytotoxic Antimetabolite - Purine Analog
HGPRT converts 6TG to Thio-GMP (active form) which is then incorporated into DNA, Thio-GMP also blocks purine synthesis.
Resistance: Decreased HGPRT
Shared MOA w/ 6-Mercaptopurine
6-Mercaptopurine
Antineoplastic - Cytotoxic Antimetabolite - Purine Analog HGPRT converts 6MP to Thio-IMP, then Thio-GMP (active form) then incorporated into DNA, and also blocks purine synthesis. TMPT inhibits action of 6MP. Pts w/ polymorphisms in TPMT can have toxicity of 6MP action d/t loss of function of TPMT.
Shared MOA w/ 6-Thioquanine
Fludarabine
Antineoplastic - Cytotoxic Antimetabolite - Purine Analog
Prodrug. MOA: deoxycytidine kinase activates it in cell to tri-phosphate form, incorporated into DNA/RNA, inhibits DNA pol and RNR ∴ reduces RNA function (translation into protein) Resistance: decreased deoxycytidine kinase and drug efflux from cell
Cladribine
Antineoplastic - Cytotoxic Antimetabolite - Purine Analog MOA: deoxycytidine kinase activates it in cell to tri-phosphate form then incorporated into DNA ∴ strand breaks, also inhibits RNA
Resistance: decreased deoxycytidine kinase, drug efflux, increased RNR expression
Cyclophosphamide
Antineoplastic - Cytotoxic Alkylating Agent - Nitrogen Mustard. MOA: rxn b/t alkyl group and 7nitrogen spot on guanine (in DNA) ∴ causes intrastrand linking and crosslinking ∴ strand breakage. Cell cycle non-specific cytotoxicity.
Used to tx solid tumors and hematological malignancies. Adverse effects: myelosuppression, nausea, vomiting, HEMORRHAGIC CYSTITIS caused by acrolein. Co-administration w/ mensa inactivates acrolein.
Mechlorethamine
Antineoplastic - Cytotoxic Alkylating Agent - Nitrogen Mustard.
MOA: rxn b/t alkyl group and 7nitrogen spot on guanine (in DNA) ∴ causes intrastrand linking and crosslinking ∴ strand breakage. Cell cycle non-specific cytotoxicity.
Carmustine (BCNU)
Antineoplastic - Cytotoxic Alkylating Agent - Nitrosourea.
MOA: rxn b/t alkyl group and 7nitrogen spot on guanine (in DNA) ∴ causes intrastrand linking and crosslinking ∴ strand breakage. Cell cycle non-specific cytotoxicity.
Used to tx brain tumors (wafer insertion post-surg)
Very lipophilic ∴ crosses BBB. Causes profound myelosuppression.
Cisplatin
Antineoplastic - Cytotoxic Non-Classical Alkylating Agent
MOA: DNA cross-linkages w/o classical alkyl group
Adverse Effects: Peripheral motor and sensory neuropathy, nephrotoxicity (kidney damage is reduces w/ increased hydration - so give this drug w/ IV saline)
Carboplatin
Antineoplastic - Cytotoxic Non-Classical Alkylating Agent
MOA: DNA cross-linkages w/o classical alkyl group
Less nausea, myelosuppression is dose-limiting factor
Oxaliplatin
Antineoplastic - Cytotoxic Non-Classical Alkylating Agent
MOA: DNA cross-linkages w/o classical alkyl group
Vinblastine
Antineoplastic - Cytotoxic Plant Derivative - Vinca Alkaloid - MOA: prevent microtubule formation. Kills in mitosis: dissolution of mitotic spindle and chromosomes can’t separate. No neuro problems as seen in Vincristine (but increased risk of myelosuppression)
Vincristine
Antineoplastic - Cytotoxic Plant Derivative - Vinca Alkaloid - MOA: prevent microtubule formation. Kills in mitosis: dissolution of mitotic spindle and chromosomes can’t separate. Adverse Effect: NEURO ISSUES
Paclitaxel
Antineoplastic - Cytotoxic Plant Derivative - Taxane - MOA: antimicrotubule agent, prevents destruction of microtubules, mitotic spindle can’t be destroyed in mitosis, bone marrow toxicity is the dose-limiting factor. Adverse Effect: hypersensitivity, PERIPHERAL NEUROPATHY
Often used w/ filgrastim (GSF) to decrease myelosuppression
Irinotecan
Antineoplastic - Cytotixic Plant Derivative - Campthothecin Analog - MOA: topoisomerase I inhibitor
Topotecan
Antineoplastic - Cytotixic Plant Derivative - Campthothecin Analog - MOA: topoisomerase I inhibitor
Etoposide
Antineoplastic - Cytotixic Plant Derivative
MOA: topoisomerase II inhibitor
Doxorubicin
Antineoplastic - Cytotoxic Antibiotic
MOA: intercalates w/ DNA, inhibiting DNA polymerase, topoisomerase II ∴ DNA double strand breaks
Adverse SFx: IRREVERSIBLE CARDIOMYOPATHY - this risk is reduced if co-administered w/ Dexrazoxane (iron chelator)
Bleomycin
Antineoplastic - Cytotoxic Antibiotic
MOA: small peptide, binds DNA and causes single and double strand breaks. Arrests cell in G2 phase. Minimal myelosuppression and immunosuppression. Pulmonary toxicity is dose-limiting factor
Prednisone
Antineoplastic - Glucocorticoid
MOA: inhibits lymphocyte proliferation (treatment for leukemias and lymphomas), reduces ICP assoc w/ brain tumors, decreases nausea and vomiting caused by chemo
Dexamethasone
Antineoplastic - Glucocorticoid
MOA: inhibits lymphocyte proliferation (treatment for leukemias and lymphomas), reduces ICP assoc w/ brain tumors, decreases nausea and vomiting caused by chemo
Tamoxifen
Antineoplastic - estrogen receptor antagonist
Decreases growth rate for estrogen dependent breast cancers
Anastrozole
Antineoplastic - aromatase inhibitor
Prevents testosterone conversion to estrogen. Used to tx breast cancer in post-menopausal women
Flutamide
Antineoplastic - androgen receptor antagonist
Used to tx prostate acncer. MOA: prevents dihydrotestosterone from binding to androgen receptors
Leuprolide
Antineoplastic - GnRH receptor antagonist
Leads to desensitization of GnRH receptors on pituitary, anterior pituitary secretes LH and FSH in response to GnRH from hypothalamus ∴ testosterone formation ∴ feeds prostate cancer growth. Leuprolide interrupts this cycle
Goserelin
Antineoplastic - GnRH receptor antagonist
Leads to desensitization of GnRH receptors on pituitary, anterior pituitary secretes LH and FSH in response to GnRH from hypothalamus ∴ testosterone formation ∴ feeds prostate cancer growth. Leuprolide interrupts this cycle
Degarelix
Antineoplastic - GnRH receptor antagonist
Leads to desensitization of GnRH receptors on pituitary, anterior pituitary secretes LH and FSH in response to GnRH from hypothalamus ∴ testosterone formation ∴ feeds prostate cancer growth. Leuprolide interrupts this cycle
