Chemotherapy Mechanisms and Drug Effects

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Questions and Answers

What is the primary mechanism of action for CCNS drugs?

Inhibit dihydrofolate reductase

Activate purine synthesis

Alkylate nucleophilic groups on DNA bases (correct)

Cross-link RNA bases

Which of the following is a common adverse effect of CCNS drugs?

Cardiac arrhythmias

Increased hair growth

Increased appetite

Bone marrow suppression (correct)

Which of the following is a characteristic of methotrexate?

Antagonist of folic acid (correct)

Alkylating agent

Inhibitor of thymidylate synthase

Works in the G2 phase

What is one of the main uses of leucovorin in relation to methotrexate?

Reduce toxicity on normal cells Signup and view all the answers

What is the end result of fluorouracil's action on cells?

Thymineless death of cells Signup and view all the answers

Which of the following adverse effects is specifically associated with methotrexate long-term use?

Hepatotoxicity Signup and view all the answers

Cytarabine is specifically designed to act in which phase of the cell cycle?

S phase Signup and view all the answers

Which mechanism contributes to the resistance against fluorouracil?

Increased thymidylate synthase activity Signup and view all the answers

What is the primary role of anticancer drugs that are classified as cell cycle-specific (CCS)?

They target tumor cells only during a specific phase of the cell cycle. Signup and view all the answers

Which of the following is NOT considered a common cause of cancer?

Overconsumption of vitamins Signup and view all the answers

What type of drug resistance is primarily associated with increased DNA repair mechanisms in tumor cells?

Resistance to alkylating agents and cisplatin Signup and view all the answers

Which anticancer drug is associated with the resistance mechanism of thiol trapping agents?

Cisplatin Signup and view all the answers

What is the primary factor that enhances the effectiveness of both CCS and CCNS drugs?

When a large proportion of the tumor cells are proliferating. Signup and view all the answers

Which enzyme's alteration contributes to methotrexate resistance in tumor cells?

Dihydrofolate reductase Signup and view all the answers

What characteristic is accurate for cell cycle-nonspecific (CCNS) drugs?

They can kill both cycling and resting tumor cells. Signup and view all the answers

Which of the following factors is primarily responsible for an increased resistance to anticancer drugs?

Increased synthesis of the enzyme affected by the drug Signup and view all the answers

How can tumor cells develop resistance to purine and pyrimidine antimetabolites?

By decreasing the activity of enzymes converting prodrugs. Signup and view all the answers

What is the purpose of neoadjuvant chemotherapy?

To improve the efficacy of subsequent local therapies. Signup and view all the answers

Which of the following describes primary induction chemotherapy?

Used as the initial treatment where no other option exists. Signup and view all the answers

What role does P-glycoprotein play in cancer drug resistance?

It aids in the efflux of anticancer drugs from resistant cells. Signup and view all the answers

In what way does adjuvant chemotherapy support cancer treatment?

It reduces the risk of recurrence after local treatments. Signup and view all the answers

Which group of drugs includes procarbazine, known for its alkylating properties?

Other drugs acting as alkylating agents. Signup and view all the answers

What is a common feature of increased enzyme activity in tumor cells regarding anticancer drugs?

It contributes to the inactivation of these drugs. Signup and view all the answers

Which of the following is NOT a type of alkylating agent?

Fluorouracil. Signup and view all the answers

What is the primary mechanism of action for anthracyclines?

They intercalate between DNA base pairs and inhibit topoisomerase II. Signup and view all the answers

Which drug is classified as a CCNS drug and acts by cross-linking DNA?

Mitomycin Signup and view all the answers

What is the main side effect associated with the use of Imatinib?

Diarrhea and fluid retention Signup and view all the answers

What type of therapy does Trastuzumab represent?

Growth Factor Receptor Inhibitor Signup and view all the answers

Which of the following best describes the mechanism of action of Bleomycin?

It generates free radicals that bind to DNA and cause strand breaks. Signup and view all the answers

Which drug is known for inducing apoptosis by blocking proliferative signals from the bcr-abl oncogene?

Imatinib Signup and view all the answers

What is the primary action of Cetuximab in cancer treatment?

It recognizes and binds to the EGFR. Signup and view all the answers

What distinguishes nilotinib from other tyrosine kinase inhibitors?

It exhibits activity against mutant forms of bcr-abl. Signup and view all the answers

What is the primary mechanism of action of gemcitabine triphosphate?

It causes chain termination in DNA. Signup and view all the answers

What characterizes the mechanism of action of vinca alkaloids?

They block the formation of the mitotic spindle. Signup and view all the answers

Which of the following is a characteristic of etoposide's mechanism of action?

It induces DNA breakage through topoisomerase II inhibition. Signup and view all the answers

What is the role of taxanes in cancer treatment?

They interfere with microtubule disassembly. Signup and view all the answers

What type of cancer cells are most affected by camptothecins like topotecan?

Cells in the late S and G2 phases. Signup and view all the answers

Which of the following substances is classified as an anthracycline?

Doxorubicin Signup and view all the answers

What is the consequence of increased efflux of vinca alkaloids from tumor cells?

Development of drug resistance. Signup and view all the answers

What is the primary action of antibiotics in cancer treatment?

They disrupt the DNA structure. Signup and view all the answers

What is the primary mechanism of action for gefitinib and erlotinib?

They inhibit EGFR’s tyrosine kinase domain. Signup and view all the answers

What is one of the side effects associated with the use of tamoxifen?

Endometrial hyperplasia and neoplasia. Signup and view all the answers

Which drug binds to a surface protein in non-Hodgkin’s lymphoma cells?

Rituximab Signup and view all the answers

What is the role of bevacizumab in cancer treatment?

Prevents VEGF from interacting with its receptors. Signup and view all the answers

Which of the following is an androgen receptor antagonist used in prostatic carcinoma?

Flutamide Signup and view all the answers

What is the mechanism of action for Leuprolide analogs?

Inhibit release of gonadotropins from the pituitary. Signup and view all the answers

What side effect is commonly associated with Leuprolide treatment?

Gynecomastia Signup and view all the answers

Which chemotherapy agent is commonly associated with cardiotoxicity?

Epirubicin Signup and view all the answers

Study Notes

Cancer Chemotherapy

Cancer is the second leading cause of death in the United States, accounting for 1 in 4 deaths.
Cancer is characterized by defects in the normal control mechanisms of cell survival, proliferation, and differentiation.
Invasive and metastatic processes, along with metabolic abnormalities, lead to tumor-related symptoms and death if the neoplasm isn't treated.

How Cancer Starts

Normal cells transform into abnormal cells.
Abnormal cells multiply, leading to malignant cancer.
Cancer cells grow their own blood vessels (angiogenesis).
Cancer cells invade surrounding tissue.

Causes of Cancer

Environmental Exposure: Exposure to ionizing radiation, chemical carcinogens (e.g., tobacco smoke, azo dyes, aflatoxins, asbestos, benzene).
Viruses: Hepatitis B (HBV), Hepatitis C (HCV), Epstein-Barr virus (EBV), Human herpesvirus 4 (HHV-4), HIV (associated with Hodgkin's and non-Hodgkin's lymphomas).
Gene Mutations: Mutations or deletions in oncogenes or tumor suppressor genes.

The Stages of the Cell Cycle

G1 (Gap/Growth 1) Phase: The cell grows.
S (Synthesis) Phase: DNA is synthesized or duplicated.
G2 (Gap 2) Phase: DNA is checked for errors; the cell grows more.
M (Mitosis) Phase: Mitosis occurs.

Anti-Cancer Drugs

Anticancer Drugs: Alkylating agents, Antimetabolites, Natural products, Antitumor antibiotics, Miscellaneous, Hormonal.
- Specific examples include: Cyclophosphamide, cisplatin, 5-Fluorouracil, methotrexate, etoposide, bleomycin.

Cell Cycle-Specific (CCS) Drugs

Drugs targeting specific phases of the cell cycle.
Active during specific phases of the cell cycle.

Cell Cycle-Nonspecific (CCNS) Drugs

These drugs do not target specific phases of the cell cycle.
Active in both cycling and resting cells.

Resistance to Anti-Cancer Drugs

Increased DNA Repair: A faster repair rate can lead to drug resistance.
Thiol Trapping Agents: Some tumor cells produce substances that interact with anticancer drugs.
Changes in Target Enzymes: Mutations in enzymes targeted by drugs can cause resistance.
Decreased Activation of Prodrugs: Reduced enzyme activity can prevent activation of drugs.
Inactivation of Anticancer Drugs: Increased activity of enzymes can inactivate drugs.
Decreased Drug Accumulation: Reduced uptake prevents high drug concentrations.

Cancer Treatment Modalities

Primary Induction Chemotherapy: Drug therapy for hematologic cancers and advanced solid tumors.
- Goals: curative (in some cases), palliative (in most cases)
Adjuvant Chemotherapy: Chemotherapy given after primary treatment (e.g., surgery or radiation). Goal: reduce the risk of recurrence and improve survival.
Neoadjuvant Chemotherapy: Chemotherapy given before primary treatment (e.g., surgery or radiation). Goal: make the primary treatment more effective.

Cancer Chemotherapeutic Drugs

Alkylating Agents:
- Nitrogen mustards (chlorambucil, cyclophosphamide, mechlorethamine)
- Nitrosoureas (carmustine, lomustine)
- Alkyl sulfonates (busulfan)
- Others (cisplatin, dacarbazine, procarbazine)
- Mechanism of Action: Form reactive molecules that alkylate DNA.
Adverse Effects: Generally dose-related; occur primarily in rapidly growing tissues (bone marrow, digestive tract, reproductive system). Common issues: nausea and vomiting.

2. Antimetabolites

Folic acid antagonists
Purines
Pyrimidines
- Specific examples include methotrexate, mercaptopurine, thioguanine, fluorouracil, cytarabine, gemcitabine.
Mechanism of Action: These drugs are similar to essential molecules but interfere with DNA and RNA synthesis. They are mostly cell-cycle specific, acting during the S phase.

3. Natural Product Antitumor Drugs

Vinca alkaloids
Podophyllotoxins
Camptothecins
Taxanes
- Specific examples include: Vincristine, Etoposide, Topotecan, Paclitaxel.
Mechanism of Action: Diverse mechanisms affecting mitosis and cell division.

4. Antibiotics

Anthracyclines (Doxorubicin, Daunorubicin)
Bleomycin
Mitomycin
Mechanism of Action: Some act by intercalating into DNA, others cause free radical damage and inhibit DNA synthesis.

5. Targeted Therapy

Tyrosine Kinase Inhibitors: Imatinib, Dasatinib, Nilotinib, Bosutinib,
Growth Factor Receptor Inhibitors: Trastuzumab, Cetuximab, Panitumumab, Bevacizumab
Mechanism of Action: Imatinib inhibits the tyrosine kinase activity of the bcr-abl protein, leading to the death of cml cancer cells.

6. Hormonal Chemotherapy

Gonadal Hormone Antagonists: Tamoxifen, Toremifene, Flutamide, Leuprolide.
Mechanism of Action: Tamoxifen interferes with estrogen receptors. Leuporlide interferes with the hormones that encourage cell growth.

Chemotherapy Antidotes

5H3 Antagonists: Ondansetron, Metoclopramide
Folinic Acid: For methotrexate toxicity.
Dexrazoxane: Used to minimize certain anthracycline associated toxicity.
Mesna: Used to prevent certain types of chemotherapy-induced side effects, like bladder inflammation.
Opioids: Loperamide, diphenoxylate/atropine to treat diarrhea.

Drug Summary Table

Includes sub-classes, mechanism of action, clinical applications, acute toxicities, and chronic toxicities for various chemotherapy drugs.

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Description

Test your knowledge on the mechanisms of action and adverse effects associated with cell cycle non-specific (CCNS) and cell cycle-specific (CCS) anticancer drugs. This quiz covers drugs like methotrexate, fluorouracil, and cytarabine, along with their roles and resistance mechanisms. Perfect for students of pharmacology and oncology.