[04.07] Anti-Neoplastic Drugs V2.3.pdf

Similar mechanism of action

What do drugs under a specific chemotherapy group generally share?

Side effects

What topic related to anticancer agents is emphasized as common board exam questions?

NCCN Guidelines

What guidelines do specialists in Internal Medicine (IM) or Oncology primarily follow for treatment algorithms?

DNA

What is the primary target molecule for most anti-cancer drugs?

DNA inhibitors

What type of drug is used to stop the rapid replication of cancer cells?

Alkylating Agents

Which drug group sticks to DNA, stops DNA synthesis, and destroys the actual DNA?

They bind to DNA bases but do not look like DNA (purines/pyrimidines)

What is the chemical difference between alkylating agents and antimetabolites?

Antimetabolites

Which drug group affects DNA synthesis and the cell cycle by mimicking purines and pyrimidines?

Folic acid synthesis

Antimetabolites are reagents related to what specific biological synthesis process?

Plants

Where do Natural Products anticancer drugs originate?

Mitosis cycle or M Phase (cellular replication)

What phase of the cell cycle do the majority of Natural Products act on?

Hormone dependent

For what condition are Hormonal Anticancer Agents used (e.g., breast and prostate cancers)?

Fixed proportion

According to the Log-Kill Hypothesis, anti-cancer drugs kill what quantity of a tumor cell population?

Acts like a ‘half life’

What concept is the Log-Kill Hypothesis compared to?

Non specific for cancer cells (also target normal cells)

Why does chemotherapy generally cause weakness, vomiting, and hair loss?

Increase the proportion of cancer or tumor cells being killed

What is the rationale for using drug combinations in chemotherapy?

G0 Phase (Quiescent phase)

What phase of the cell cycle involves no cell division and no cellular components being made?

They do not have a G0 Phase (always continue cell division)

How are tumor or cancer cells characterized in relation to the G0 phase?

S Phase (DNA Synthesis)

What phase involves the replication of the DNA Genome and where purines and pyrimidines increase in number?

Cell Cycle Nonspecific Drugs (CCNS)

What anti-cancer agents act on tumor stem cells when traversing the cell cycle and when in the resting (G0) phase?

Cell Cycle Specific Drugs (CCS)

What anti-cancer agents act selectively on tumor stem cells when they are traversing the cell cycle, and not when they are in G0 phase?

M Phase

What cell cycle phase do Vinblastine, Vincristine, and Paclitaxel act on?

Alkylating Agents, Antitumor Antibiotics (Doxorubicin), Nitrosoureas, Cisplatin

What four drug types/agents are classified as Cell Cycle Nonspecific (CCNS) drugs acting in G0?

Antimetabolites

What class of drugs acts primarily on the S Phase?

Bleomycin

Which drug is listed as being very specific to the G2 Phase?

Blood cancers (e.g. lymphomas or leukemias)

In what type of cancer is Primary Induction Chemotherapy usually seen?

Neoadjuvant Therapy

What treatment is used before local therapy (surgery) for tumor debulking and to lessen blood vessel supply?

Adjuvant Chemotherapy

What treatment is done after local treatment to reduce the risk of local and systemic recurrence?

Rescue Therapy

What treatment modality involves the alleviation of toxic effects by giving specific drugs?

Methotrexate

Which anti-cancer agent's toxic effect is reduced folic acid levels leading to hepatotoxicity?

Leucovorin/Folinic Acid

What is the rescue drug for Methotrexate toxicity?

Cyclophosphamide

Which anti-cancer agent causes Hemorrhagic cystitis?

Mesna

What is the rescue drug for Cyclophosphamide-induced hemorrhagic cystitis?

Doxorubicin

Which anti-cancer agent causes Dilated cardiomyopathy and heart failure?

Dexrazoxane

What is the rescue drug for Doxorubicin-induced cardiotoxicity?

Cisplatin

Which anti-cancer agent causes Nephrotoxicity, acoustic toxicity, and peripheral neuropathy?

Amifostine

What is the rescue drug for Cisplatin?

Bind to DNA bases to halt DNA replication

What is the General MOA of Alkylating Agents?

Form DNA cross-links that disrupt DNA base pairing

What is the primary effect of Alkylating Agents?

Alkylating agent

What drug class does Cyclophosphamide belong to?

Acrolein

What metabolite causes hemorrhagic cystitis associated with Cyclophosphamide?

Platinum-based Alkylating Agent

What is the drug class designation for Cisplatin?

Testicular cancer, ovarian cancer, bladder cancer, lung cancer

What are four clinical uses of Cisplatin?

Mannitol with forced hydration

What can be administered to decrease Cisplatin-induced nephrotoxicity?

Osmotic diuretic

What is the drug class/function of Mannitol?

Procarbazine

Which alkylating agent causes a Disulfiram-like reaction?

Forms hydrogen peroxide (oxygen-free radical) which generates free radicals that cause DNA strand scission

What is a unique MOA feature shared by Procarbazine and Dacarbazine?

Hodgkin’s lymphoma, Non-Hodgkin’s lymphoma, Brain tumors

What are three clinical uses of Procarbazine?

Leukemogenic

What key toxicity distinguishes Procarbazine from Dacarbazine?

Phototoxicity

What is a notable side effect of Dacarbazine?

Chronic myelogenous leukemia

What is the clinical use of Busulfan?

Pulmonary fibrosis

What is a key toxicity of both Busulfan and Bleomycin?

Spares the bone marrow

What is a noted characteristic of Busulfan?

B for Baga

What is the mnemonic used to remember Busulfan and Bleomycin causing Pulmonary Fibrosis?

Nitrosourea Alkylating Agent

What is the drug class designation for Carmustine?

Highly lipophilic

What characteristic of Carmustine allows ease of passage through the blood-brain barrier?

Brain tumors

What cancer is Carmustine clinically used for due to its ability to cross the BBB?

Inhibits dihydrofolate reductase

What is the MOA of Methotrexate?

Thymidylate, Amino acids, Purine nucleotides

Methotrexate decreases the synthesis of what three crucial substances?

Choriocarcinoma, Acute leukemias, Breast cancer

What are three cancer uses of Methotrexate?

Dihydrofolate reductase

What enzyme does Trimethoprim inhibit (similar to Methotrexate)?

Purine

What type of antimetabolite is 6-Mercaptopurine (6-MP)?

Inhibits de novo purine nucleotide synthesis

What is the MOA of 6-Mercaptopurine?

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

What enzyme activates 6-Mercaptopurine?

Allopurinol and febuxostat

What two drugs inhibit 6-MP metabolism by inhibiting xanthine oxidase?

Significantly increases bone marrow suppression

What is the consequence of giving purine derivatives with anti-uric acid agents?

Irreversible inhibitor

How is Allopurinol classified in its action on xanthine oxidase?

Pyrimidine

What type of antimetabolite is 5-Fluorouracil (5-FU)?

Inhibits thymidylate synthase

What is the MOA of 5-Fluorouracil?

Thymineless death of cells

What is the outcome of 5-FU inhibiting thymidylate synthase?

Gastrointestinal irritation, Bone marrow suppression, Alopecia

What are three key toxicities of 5-Fluorouracil?

Cytarabine

Which S-phase specific antimetabolite causes neurotoxicity, including cerebellar dysfunction and peripheral neuritis?

Inhibits ribonucleotide reductase

What is a specific MOA feature of Cytarabine (and Gemcitabine)?

Pancreatic cancer

What is a primary clinical use of Gemcitabine?

Vinca alkaloid

What drug class does Vincristine belong to?

Prevents microtubule assembly, causing cell arrest at metaphase

What is the MOA of Vincristine?

Peripheral neuritis

What is a key toxicity of Vincristine?

Vinblastine

Which vinca alkaloid causes more bone marrow suppression than Vincristine?

Kaposi’s sarcoma

What cancer, caused by HHV8, is treated with Vinblastine?

Mayapple plants

From what plant do Podophyllotoxins (like Etoposide) come?

Inhibits DNA topoisomerase II (DNA gyrase)

What is the MOA of Etoposide?

E - "two" - poside

What is the mnemonic for Etoposide's MOA?

Camptothecin

What drug class does Topotecan belong to?

Inhibits DNA topoisomerase I

What is the MOA of Topotecan?

Topotec - "one"

What is the mnemonic for Topotecan's MOA?

Advanced breast and ovarian cancers

What are two clinical uses of Paclitaxel?

Prevents microtubule disassembly into tubulin monomers

What is the MOA of Taxanes (e.g., Paclitaxel)?

Vinca alkaloids

Which natural product class inhibits microtubule assembly?

Taxanes

Which natural product class inhibits microtubule disassembly?

Anthracycline

What drug class does Doxorubicin belong to?

Intercalates between base pairs

What is one MOA feature of Doxorubicin (and Bleomycin)?

Ejection fraction lowers on 2D echo

What clinical finding signals that Doxorubicin administration should be stopped?

Busulfan

Which alkylating agent causes pulmonary fibrosis (B for Baga)?

Inhibits DNA-dependent RNA synthesis

What is a unique MOA feature of Actinomycin D (Dactinomycin)?

Wilms’ tumor

What is a key clinical use of Actinomycin D?

Tyrosine Kinase Inhibitors

What drug class does Imatinib belong to?

Inhibits tyrosine kinase activity of the protein product of bcr-abl oncogene

What is the MOA of Imatinib (in CML)?

Chronic myelogenous leukemia (CML) and Gastrointestinal stromal tumor (GIST)

What are the two primary clinical uses of Imatinib?

Inhibits c-kit tyrosine kinase

What is the MOA of Imatinib (in GIST)?

Cytochrome P450 system

Imatinib interacts with drugs that depend on what enzyme system?