Pharmacology Anti-Cancer Drugs

Which cell-cycle specific agents (CCS) act on the S phase?

Hydroxyurea, Antimetabolites

Which cell-cycle specific agents (CCS) act on the G1S phase?

Topoisomerase II inhibitors

Which cell-cycle specific agents (CCS) act on the G1M phase?

Topoisomerase I inhibitors

Which cell-cycle specific agents (CCS) act on the M phase?

Taxanes, vinca alkaloids

What is an example of a vascular endothelial growth factor (VEGF) inhibitor?

Bevacizumab

What is an example of a HER2 neu inhibitor?

Trastuzumab (herceptin)

What is an example of a ribonucleotide reductase inhibitor?

Hydroxyurea

What is an example of an Anti-CD20?

Rituximab

What are the BCR-ABL TK inhibitors?

Bosutinib, Imatinib, Nilotinib, Dasatinib, Ponatinib

What is the name of the epidermal growth factor TK inhibitor?

Erlotinib

What are the "natural" anticancer drug classes?

Anthracyclines, vinca alkaloids, topoisomerase inhibitors, taxanes, & antitumor antibiotics

What are adverse effects associated with anticancer drugs?

Bone marrow suppression, alopecia, hepatotoxicity, renal toxicity, infertility, hypersensitivity, teratogenesis, GIT toxicity, neurotoxicity, hemorrhagic cystitis, cardiotoxicity, pulmonary toxicity, tumor lysis syndrome

When is the onset of bone marrow suppression after initiation of anticancer drugs?

7-10 days

When is recovery from bone marrow suppression after discontinuing use of an anticancer drug?

2-3 weeks

Which blood cells are affected first by bone marrow suppression associated with anticancer drugs?

WBCs

What is the result of WBC destruction during anticancer drug use?

Predisposition to infections

What is the result of platelet destruction during anticancer drug use?

Bleeding

What is the result of RBC destruction during anticancer drug use?

Anemia, fatigue

Which anticancer drugs precipitate infertility?

Most alkylating agents

Why are anticancer drugs highly emetogenic?

Stimulation of vomiting center/CTZ

Which drugs can prevent vomiting associated with anticancer drug use?

Ondansetron, antihistamines

What drug decreases incidence of stomatitis associated with anticancer drug use?

Amifostine

Which anticancer drug causes peripheral neuropathy?

Vincristine

Which anticancer drugs can cause hemorrhagic cystitis?

Cyclophosphamide, Ifosfamide

What is the toxic metabolite that causes hemorrhagic cystitis with use of certain anti-cancer drugs?

Acrolein

Which drugs are used to prevent hemorrhagic cystitis with use of certain anti-cancer drugs?

Mesna, NAC

Which anticancer drugs precipitate heart failure?

Daunorubicin, Doxorubicin,

Trastuzumab

Which drug is cardioprotective, decreasing incidence of cardiotoxicity with use of certain anticancer drugs?

Dexrazoxane

Which anticancer drugs cause pulmonary toxicity?

Bleomycin, Melphalan, Busulfan, Mitomycin

What is tumor lysis syndrome?

Spontaneous lysis of cell during treatment with anticancer drugs leading to release of intracellular contents

In what cancers is TLS common?

Lyphoma/leukemia

What strategies are used to prevent tumor lysis syndrome (TLS)?

Adequate hydration, urinary alkalization, rasburicase, and allopurinol

What are the alkylating agents?

Ifosfamide, Cyclophosphamide, Busulfan, Carmustine, Lomustine, Thiotepa, Mechlorethamine, Melphalan, Dacarbazine, Procarbazine, Chlorambucil

What is the mechanism of action of alkylating agents?

Directly damage cellular DNA by producing highly reactive imonium ion that binds N7 on guanine, leading to cross-link formation and DNA strand breakage

What adverse effect is specific to the alkylating agents?

All are carcinogenic

Which alkylating agents causes CNS toxicity?

Dacarbazine

What are the uses of cyclophosphamide?

Broad-spectrum anticancer agent + SLE/MS/AHA

What is the clinical use of melphalan?

Multiple myeloma

What are examples of platins?

Cisplatin, carboplatin, oxaliplatin

What is the mechanism of action of platins?

Similar to alkylating agents

What are the adverse effects of platins?

Nephrotoxicity, ototoxicity

Bleomycin acts specifically on which phase of the cell cycle?

G2M

What is the mechanism of action of anti-tumor antibiotics?

Bind to DNA via intercalation between specific bases and block the synthesis of DNA, RNA, or both

Which anti-tumor antibiotic is a peptide containing a DNA-binding domain on one end and an iron-binding domain on the other?

Bleomycin

Which anti-tumor antibiotic causes serious, dose-limiting pulmonary fibrosis?

Bleomycin

Which anti-tumor antibiotic causes negligible myelosupression and can be combined with other myelosuppressive drugs for that reason?

Bleomycin

What are the Anthracyclines?

Doxorubicin, daunorubicin

Which anti-cancer antibiotics have four major mechanisms of action?

Doxorubicin, daunorubicin

Which anti-cancer antibiotic(s) can cause acute cardiotoxicity characterized by arrhythmias, condition defects, & carditis?

Doxorubicin, daunorubicin

Which anti-cancer antibiotic(s) can cause chronic cardiotoxicity characterized by DCM, HF due to free radical generation?

Doxorubicin, daunorubicin

What is the mechanism of action of hydroxyurea?

Ribonucleotide reductase (RR) inhibitor, S phase specific

What agent promotes HbF formation in sickle cell anemia?

Hydroxyurea

What are the clinical uses of hydroxyurea?

Sickle cell anemia, polycythemia vera

What are the antifolates?

Methotrexate, Pemetrexed

Which antimetabolite is a folic acid analog and high affinity inhibitor of DHFRase that halts the synthesis of DNA, RNA, & proteins?

Methotrexate

Which drug acts by Leucovorin rescue?

Methotrexate

What are the immunosuppressant uses of anti-folates?

RA, IBD

What are examples of purine analogs?

Azathioprine, 6-MP, 6-TG, fludarabine, cladribine

What are the clinical uses of purine analogs?

RA, IBD

What are the adverse effects of purine analogs?

Tumor lysis syndrome leading to hyperuricemia

What are the pyrimidine analogs?

Capecitabine, 5 fluorouracil, gemcitabine, cytarabine

Which pyrimidine analog forms a ternary complex with thymidylate synthase and

reduced folate, a reaction critical for thymidinemonophosphate (dTMP) synthesis?

5-FU

Which pyrimidine analog inhibits DNA synthesis via "thymine less death?"

5-FU

Which pyrimidine analog causes Hand-foot syndrome?

5-FU

What is Hand-foot syndrome?

Painful erythema, swelling associated with 5-FU

How is Hand-foot syndrome treated?

Dexamethasone

What are the vinca alkaloids?

Vincristine, vinblastine, vinorelbine

Which cell specific agent inhibits tubulin polymerization, thus inhibiting mitosis?

Vinca alkaloids

What are the adverse effects of vinblastine?

Myelosuppression, SIADH

What are the adverse effects of vincristine?

Neurotoxicity, myelosuppression, SIADH

What are the adverse effects of vinorelbine?

Myelosuppression, SIADH

What are the taxanes?

Paclitaxel, docetaxel

What is the mechanism of action of the taxanes?

Mitosis inhibitor

What are the topoisomerase II inhibtors?

Posides

What is the mechanism of action of topoisomerase II inhibitors?

Inhibits topoisomerase II, thus inhibiting DNA synthesis and function

What is the mechanism of action of topoisomerase I inhibitors?

Inhibits topoisomerase I resulting in DNA damage

Which topoisomerase inhibitor is used in combination with 5-FU and leucovorin in advanced CRC?

Irinotecan

Which drug is a differentiating agent for APL?

Arsenic trioxide

What is the clinical use of L-asparaginase?

ALL

What is the mechanism of action of Erlotinib?

EGFR/EFGR kinase inhibitors

What is the mechanism of action of temsirolimus and everolimus?

mTOR inhibitor

What is the mechanism of action of Bosutinib, Imatinib, Nilotinib, Dasatinib, and Ponatinib?

BCR-ABL Kinase

Inhibitors

What is the mechanism of action of Trastuzumab?

HER2 inhibitor

What is the clinical use of Trastuzumab?

HER-2 positive breast cancer

What is the A/E of Trastuzumab?

Cardiotoxicity