Mechlorethamine: - Class - Mechanism - Cell Cycle Profile - Therapeutic Uses Special details (about it's metabolism and administration)

- Alkylating Agent - Cross links DNA to block replication and txn - CCNS - Hodgkin's Lymphoma (MOPP) This drug is not excreted, and must be given IV

Cyclophosphamide: - Class - Mechanism what is the exact binding site? - Cell Cycle Profile - How does this drug become activated? - Toxicity What drug is administered to manage toxicity??? How does this drug work? - Uses

- Alkylating Agent - Cross links DNA to block replication and txn, binds Guanine N-7 - CCNS - The liver activates Cyclophosphamide and iphosphamide using a cytochrome P450; this oxidative activation cleaves off Acrolein, opening the molecule for DNA binding. - Hemorrhagic cystitis, SIADH MESNA, it binds to Acrolein - Burkitt's lymphoma, acute lymphocytic leukemia, autoimmune diseases

Chlorambucil: - Class - Mechanism - Cell Cycle Profile - Toxicity - Uses

- Alkylating Agent - Cross links DNA to block replication and txn, binds Guanine N-7 - CCNS - Hepatotoxicity - chronic lymphocytic leukemia

Estramustine Phosphate: - This drug is a mustard + ___ (look at the name). - Mechanism what about the mechanism sets this drug apart from others in its class? - Cell Cycle Profile Route of administration and activation - when is this drug used?

- estradiol - binds to beta tubulin works as an anti mitotic rather than alkylating agent - CCNS: M given orally, phosphate cleaved during absorption - used as palliative treatment in metastatic or progressive prostate cancer

Busulfan: - Class (not a nitrogen mustard) - Cell Cycle Profile - Toxicity - Use, what's the drawback?

- bis-methyl sulfonate - CCNS - pulmonary fibrosis and hyper pigmentation of the skin - CML, only extends life by ~9 months

Carmustine (BCNU), Lomustine (CCNU), Semustine (methyl-CCNU) - Class - Cell Cycle Profile - Toxicity What's so special about these drugs that makes them first line treatment for brain tumors??? - what's released when these drugs are broken down?

- Nitrosoureas - CCNS - pulmonary fibrosis and nephrotoxicity they're highly lipophilic - breakdown in vivo liberates alkylating and carbamylating species

Procarbazine (Mulatane, MOPP): - Class - Cell Cycle Profile - mechanism Special Details (hint: this is an MAO inhibitor)

- Nitrosourea - CCNS - react covalently with nucleic acids, decreasing DNA, RNA, protein synthesis, and inhibiting G1 to S transition avoid use with MAOIs and alcohol

Dacarbazine (DTIC), Temozolomide (T): - Class - Mechanism - Cell Cycle Profile

- Nitrosourea - methylates DNA and RNA - CCNS

Cisplatin: - Class - Mechanism - Cell Cycle Profile Toxicity What drug can you give to control this toxicity? - Which drugs should you never prescribe with a platin? - name two drugs of the same class that are less toxic

- Platinum-containing drug - Binds to guanine, forming intrastrand crosslinks - CCNS nephrotoxicity and ototoxicity, peripheral neuropathy furosemide, causes forced diuresis and improves renal clearance, also prevent with amifostine and chloride diuresis - Aminoglycosides - Oxaliplatin, Carboplatin

Doxorubicin: - class - which enzyme - mechanism - cell cycle profile toxicity which drug controls this toxicity - uses - name one other drug with a similar mechanism, but is less cardiotoxic

- anthracycline - topoisomerase ii - intercalates DNA, causes single and double stranded breaks, inhibits repair, histone eviction - CCNS cardiotoxicity controlled with dexrazoxane - breast cancer, sarcoma, MOPP-resistant Hodgkin's (Anthracyline-BVD) - Epirubicin

Daunorubicin: - class - which enzyme - mechanism - cell cycle profile - toxicity name one other drug with a similar mechanism, but is less cardiotoxic

- anthracycline - topoisomerase ii - intercalates DNA, causes single and double stranded breaks, inhibits repair, histone eviction - CCNS - cardiotoxicity Idarubicin

Mitoxantrone: - which enzyme - mechanism how is this drug's mechanism different from Doxorubicin - cell cycle profile - toxicity

- topoisomerase ii - intercalates DNA, causes single and double stranded breaks, inhibits repair, histone eviction does NOT form free radicals - CCNS - cardiotoxicity, lower than doxo or daunorubicin

Epipodophyllotoxins (Etoposide + Tenopside): - which enzyme - mechanism - cell cycle profile - therapeutic uses

- topoisomerase ii - forms ternary complex, prevents re-ligation of DNA strands - CCS: S and G2 - testicular, small cell lung cancer

Camptothecin, Topotecan, Irinotecan: - class - which enzyme - mechanism - cell cycle profile - toxicity

- camptothecin analogs - topoisomerase i - forms ternary complex - CCS: S - severe diarrhea

Bleomycins: - drug class - mechanism - cell cycle profile toxicity - therapeutic uses

- antibiotic - bind reduced iron in cells and cause free radical production - CCS: G2 pulmonary fibrosis, minor myelosuppression, cutaneous reactions, low grade fever - advanced testicular carcinoma

Dactinomycin: - drug class - mechanism - cell cycle profile - toxicity - therapeutic uses

- antibiotic - intercalate DNA, prevent transcription, single strand DNA breaks - CCNS - oral and GI ulceration, stomatitis - methotrexate resistant choriocarcinoma, Wilm's tumor, Rhabdomyosarcoma, Ewing's sarcoma, gestational trophoblastic malignancy

Streptozocin - class - primary use - toxicity

- nitrosoureas, this one was listed with carmustine and lomustine for some reason - pancreatic cancer - pulmonary fibrosis and nephrotoxicity

Methotrexate - Class - Mechanism - Cell cycle profile - Toxicity what drug is administered with MTX and why?

- folic acid analog - inhibits dihydrofolate reductase, blocks synthesis of thymidylate and purines - CCS: S - mucositis: oral and GI ulceration, hepatotoxicity, pulmonary toxicity Leucovorin, doesn't need DHF reductase to become active THF, saves the body from myelosuppression

5-Fluorouracil - Class - Mechanism - Cell cycle profile - Toxicity

- pyrimidine analog - inhibits thymidylate synthase, incorporates into DNA and RNA - CCNS; G1, S - oral and GI ulceration

Chemotherapy Drugs Flashcards by Joseph Edward

Mechlorethamine:

Class
Mechanism
Cell Cycle Profile
Therapeutic Uses
Special details (about it’s metabolism and administration)

Alkylating Agent
Cross links DNA to block replication and txn
CCNS
Hodgkin’s Lymphoma (MOPP)
This drug is not excreted, and must be given IV

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Cyclophosphamide:

Class
Mechanism
what is the exact binding site?
Cell Cycle Profile
How does this drug become activated?
Toxicity
What drug is administered to manage toxicity??? How does this drug work?
Uses

Alkylating Agent
Cross links DNA to block replication and txn, *binds Guanine N-7
CCNS
The liver activates Cyclophosphamide and iphosphamide using a cytochrome P450; this oxidative activation cleaves off Acrolein, opening the molecule for DNA binding.
Hemorrhagic cystitis, SIADH
MESNA, it binds to Acrolein
Burkitt’s lymphoma, acute lymphocytic leukemia, autoimmune diseases

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Chlorambucil:

Class
Mechanism
Cell Cycle Profile
Toxicity
Uses

Alkylating Agent
Cross links DNA to block replication and txn, *binds Guanine N-7
CCNS
Hepatotoxicity
chronic lymphocytic leukemia

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Estramustine Phosphate:

This drug is a mustard + ___ (look at the name).
Mechanism
what about the mechanism sets this drug apart from others in its class?
Cell Cycle Profile
Route of administration and activation
when is this drug used?

estradiol
binds to beta tubulin
works as an anti mitotic rather than alkylating agent
CCNS: M
given orally, phosphate cleaved during absorption
used as palliative treatment in metastatic or progressive prostate cancer

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Busulfan:

Class (not a nitrogen mustard)
Cell Cycle Profile
Toxicity
Use, what’s the drawback?

bis-methyl sulfonate
CCNS
pulmonary fibrosis and hyper pigmentation of the skin
CML, only extends life by ~9 months

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Carmustine (BCNU), Lomustine (CCNU), Semustine (methyl-CCNU)

Class
Cell Cycle Profile
Toxicity
What’s so special about these drugs that makes them first line treatment for brain tumors???
what’s released when these drugs are broken down?

Nitrosoureas
CCNS
pulmonary fibrosis and nephrotoxicity
they’re highly lipophilic
breakdown in vivo liberates alkylating and carbamylating species

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Procarbazine (Mulatane, MOPP):

Class
Cell Cycle Profile
mechanism
Special Details (hint: this is an MAO inhibitor)

Nitrosourea
CCNS
react covalently with nucleic acids, decreasing DNA, RNA, protein synthesis, and inhibiting G1 to S transition
avoid use with MAOIs and alcohol

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Dacarbazine (DTIC), Temozolomide (T):

Class
Mechanism
Cell Cycle Profile

Nitrosourea
methylates DNA and RNA
CCNS

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Cisplatin:

Class
Mechanism
Cell Cycle Profile
Toxicity
*What drug can you give to control this toxicity?
Which drugs should you never prescribe with a platin?
name two drugs of the same class that are less toxic

Platinum-containing drug
Binds to guanine, forming intrastrand crosslinks
CCNS
nephrotoxicity and ototoxicity, peripheral neuropathy
*furosemide, causes forced diuresis and improves renal clearance, also prevent with amifostine and chloride diuresis
Aminoglycosides
Oxaliplatin, Carboplatin

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Doxorubicin:

class
which enzyme
mechanism
cell cycle profile
toxicity
*which drug controls this toxicity
uses
name one other drug with a similar mechanism, but is less cardiotoxic

anthracycline
topoisomerase ii
intercalates DNA, causes single and double stranded breaks, inhibits repair, *histone eviction
CCNS
cardiotoxicity
*controlled with dexrazoxane
breast cancer, sarcoma, MOPP-resistant Hodgkin’s (Anthracyline-BVD)
Epirubicin

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Daunorubicin:

class
which enzyme
mechanism
cell cycle profile
toxicity
name one other drug with a similar mechanism, but is less cardiotoxic

anthracycline
topoisomerase ii
intercalates DNA, causes single and double stranded breaks, inhibits repair, *histone eviction
CCNS
cardiotoxicity
Idarubicin

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Mitoxantrone:

which enzyme
mechanism
how is this drug’s mechanism different from Doxorubicin
cell cycle profile
toxicity

topoisomerase ii
intercalates DNA, causes single and double stranded breaks, inhibits repair, histone eviction
does NOT form free radicals
CCNS
cardiotoxicity, lower than doxo or daunorubicin

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Epipodophyllotoxins (Etoposide + Tenopside):

which enzyme
mechanism
cell cycle profile
therapeutic uses

topoisomerase ii
forms ternary complex, prevents re-ligation of DNA strands
CCS: S and G2
testicular, small cell lung cancer

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Camptothecin, Topotecan, Irinotecan:

class
which enzyme
mechanism
cell cycle profile
toxicity

camptothecin analogs
topoisomerase i
forms ternary complex
CCS: S
severe diarrhea

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Bleomycins:

drug class
mechanism
cell cycle profile
toxicity
therapeutic uses

antibiotic
bind reduced iron in cells and cause free radical production
CCS: G2
pulmonary fibrosis, minor myelosuppression, cutaneous reactions, low grade fever
advanced testicular carcinoma

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Dactinomycin:

drug class
mechanism
cell cycle profile
toxicity
therapeutic uses

antibiotic
intercalate DNA, prevent transcription, single strand DNA breaks
CCNS
oral and GI ulceration, stomatitis
methotrexate resistant choriocarcinoma, Wilm’s tumor, Rhabdomyosarcoma, Ewing’s sarcoma, gestational trophoblastic malignancy

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Streptozocin

class
primary use
toxicity

nitrosoureas, this one was listed with carmustine and lomustine for some reason
pancreatic cancer
pulmonary fibrosis and nephrotoxicity

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Methotrexate

Class
Mechanism
Cell cycle profile
Toxicity
what drug is administered with MTX and why?

folic acid analog
inhibits dihydrofolate reductase, blocks synthesis of thymidylate and purines
CCS: S
mucositis: oral and GI ulceration, hepatotoxicity, pulmonary toxicity
Leucovorin, doesn’t need DHF reductase to become active THF, saves the body from myelosuppression

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5-Fluorouracil

Class
Mechanism
Cell cycle profile
Toxicity

pyrimidine analog
inhibits thymidylate synthase, incorporates into DNA and RNA
CCNS; G1, S
oral and GI ulceration

Cytarabine, Cytosar

Class
Mechanism
Cell cycle profile
Toxicity

pyrimidine analog
inhibit DNA pol alpha, incorporate into DNA
CCS: S
oral ulceration

Gemcitabine

Class
Mechanism
Cell cycle profile

pyrimidine analog
inhibits DNA synthesis with many mechanisms
CCNS

Mercaptopurine

Class
Mechanism
Cell cycle profile
Toxicity
Which drug inhibits the activity of mercaptopurine?

purine analog
inhibits synthesis of adenine and guanine by blocking conversion of insinuate to purine precursors
CCS: S
cholestasis, oral and intestinal ulcers
allopurinol

Cladribine, Fludarabine

Class
Mechanism
Use

ADA inhibitor
blocks conversion of adenosine to inosine, buildup of dATP leads to cellular toxicity, no DNA synthesis
hairy cell leukemia

Vincristine, Vinblastine, vinorelbine

Class
Mechanism
Cell cycle profile
Toxicity

Vinca Alkaloid
binds to soluble tubulin, inhibits assembly of mitotic spindle during metaphase of mitosis
CCS: M
peripheral neuropathy, alopecia, nephrogenic SIADH secretion, myelosuppression

Paclitaxel (taxol), Docetaxel - Class - Mechanism - Cell cycle profile - Toxicity

- Yew alkaloid - binds to polymerized microtubule and prevents depolymerization - CCS: M - peripheral neuropathy (dose limiting)

IFN-alpha - Class (really obvious) - Mechanism - Cell cycle profile

- cytokine (duh.) - inhibits tumor growth via host immune system, has some direct activity - CCNS, slows the progression through the cell cycle

Prednisone: - Class - Mechanism - Therapeutic uses

- hormone - anti-inflammatory, causes apoptosis in leukemic cells - Hodgkin's lymphoma (MOPP), acute leukemias, relapsed hairy cell lymphoma

synthetic progesterone and it's derivatives - Class - Mechanism - uses

- progestin - used in hormone responsive cancers expressing progesterone receptor, blocks progesterone from binding and ceases growth - post surgical endometrial carcinoma and metastatic renal cancer

Tamoxifen, toremifine - Class - Therapuetic use (hint: they're hormonal) * which is not a steroid?

- anti-estrogens - used in estrogen receptor positive breast and lung cancer * tamoxifen is not a steroid

Casodex, eulixin, nilandron - Class - Mechanism - what do you combine them with for total ablation?

- anti-androgens - prevent tes and dihydrotes from binding to the cancer cell - leuprolide, which is an LHRH agonist and keeps LH from being released, thereby decrease tes production

Bevuczimab (avastin) - Class - Mechanism

- antibody | - blocks VEGF-R and prevents angiogenesis

Denusomab - Class - Mechanism

- antibody | - blocks RANK/RANKL in bone (think dense-usomab)

Trastuzumab - Class - Mechanism

- antibody | - blocks HER-2 positive breast and gastric cancers

Imatinib (Gleevac) - Class - Mechanism - Therapeutic uses

- targeted inhibitor - blocks the BCR-ABL kinase protein resulting from the Philadelphia chromosome - CML

Erlotinib, Gefitinib - Class - Mechanism

- targeted inhibitor | - blocks EGFR signaling

Crizotinib - Class - Mechanism - Therapeutic uses

- targeted inhibitor - blocks ALK-1 kinase - non small cell lung cancer (10% of pts are positive for ALK-1)

Venetoclax - Class - Mechanism - Therapeutic uses

- anti-apoptotic inhibitor - binds Bcl-2 and - refractory chronic lymphocytic leukemia

Vorinostat, Romidepsin - Class - Mechanism

- epigenetic signaling | - histone deacetylase (HDAC) inhibition (keeps the chromatin in tight conformation)

OLAPARIB - Class (which process within the cell does it target?) - Mechanism

- target DNA repair | - PARP-1 inhibitor

Amirubicin - Class - Advantage

- anthracylin (like doxorubicin) | - reduced cardiotoxicity

Fulvestrant - Class - Advantage

- estrogen receptor blocker | - lacks partial receptor activity, useful for estrogen responsive cancers

Abraxane - Class - Advantage

- IV nanoparticle, paclitaxel bounds to albumin | - cremophor-free (cremephor is a previously used vehicle known to cause anaphylaxis)

Picoplatin - Class - Advantage

- platinum containing | - doesn't cause platinum resistance

- Why do cancer cells (and cells in general) take up Melphalan? (what is it about this drug's structure? - Also, how does Melphalan cause cell death?

- Melphalan has a phenylalanine side chain | - Attached to the side chain is a nitrogen mustard, which cross-links (alkylates) guanines at the N-7 position.

which drug should be avoided with EtOH?

Procarbazine (don't drink and drive the Pro-car)

which drug inhibits ribonucleotide reductase?

hydroxyurea