Chemotherapy Study Notes

Overview of Chemotherapy

• Introduction to specific anti-cancer drugs and drug classes

  • Focus on cell cycle nonspecific vs. cell cycle specific agents

  • Importance of patient condition when administering these medications

Cell Cycle Nonspecific Drugs

Alkylating Agents

• Mechanism of Action

  • Add an alkyl group to DNA

  • Creates strong cross links that cannot be broken

  • Prevents DNA from untwisting, inhibiting DNA function and replication

  • Result: Impairs protein synthesis, disallows mRNA formation

  • Leads to apoptosis or cell death after exiting the G0 resting phase

• Most Common Agent

  • Cyclophosphamide

  • Administration

    • Given IV or orally

    • Important to reflect on pharmacokinetics of each route

  • Adverse Effects

    • Specific side effects related to faster replicating tissues

    • Systemic effects: cardiotoxicity, pulmonary toxicity

Anti-Cancer Antibiotics

• Classification

  • Chemically classified as antibiotics

  • High toxicity: reserved primarily for neoplastic diseases

• Mechanism of Action

  • Directly act on DNA

  • Insert themselves between base pairs, preventing DNA replication and RNA synthesis

• Common Anti-Cancer Antibiotics

  • Anthracyclines:

  • Examples: Doxorubicin, Daunorubicin

  • Trade Names and Usage

    • Indicated for various types of cancer treatment

• Adverse Effects

  • Systemic effects such as cardiovascular problems, GI distress, allergic reactions

  • Peripheral neuropathies, muscle pain, joint pain

Anti-Cancer Hormones

• Nature and Use

  • Cell cycle nonspecific

  • Often used as adjuvant therapy with surgery, radiation, or other drugs

• Mechanisms of Action

  • Inhibit cancer cells directly

  • Create negative feedback mechanisms to decrease endogenous hormonal stimulation

  • Block effects of naturally occurring hormones

• Specific Examples for Estrogen-Reactive Cancers

  • Tamoxifen: Estrogen receptor blocker

  • Used for breast and uterine cancers stimulated by estrogen

  • Mechanism: Antagonist that binds and prevents receptor activation

  • Side Effects: Nausea, vomiting, hot flashes

  • Selective Estrogen Receptor Modulators

  • Block receptors in cancerous tissues (breast, uterus) while stimulating them in bones, skin, cardiovascular tissue to minimize adverse effects

  • Aromatase Inhibitors

  • Functions by inhibiting the enzyme responsible for estrogen biosynthesis

  • Result: Decrease intracellular estrogen production

Platinum Coordination Complexes

• Nature and Mechanism

  • Heavy metal compounds, act as alkylating agents

  • Form strong cross links between DNA strands, preventing DNA translation and replication

• Common Agent

  • Carboplatin, used in the treatment of ovarian cancer

  • Common Side Effects: General systemic effects like peripheral neuropathies

Cell Cycle Specific Drugs

Anti-Metabolites

• Target Specific Phase

  • Specifically inhibit the S phase (synthesis phase) of the cell cycle

• Mechanism of Action

  • Incorporate into genetic material, impairing replication

  • Occupy enzymes responsible for synthesis of genetic material components

• Common Anti-Metabolites

  • Fluorouracil and Methotrexate:

  • Side Effects: More pronounced in rapidly replicating tissues (GI tract, bone marrow, skin, hair)

Anti-Cancer Antibiotics (Cell Cycle Specific)

• Mechanism of Action

  • Direct inhibition of DNA-related enzymes, disrupts DNA synthesis

  • Affects the S phase of the cell cycle

• Common Agent

  • Bleomycin: Indications for various treatments and common adverse effects

Antimicrotubule Class

• Role in Cell Division

  • Microtubules guide mitotic apparatus, essential for cell division

• Drug Classes

  • Vinca Alkaloids: Prevent formation of microtubules

  • Example: Vincristine

  • Taxanes: Prevent breakdown of microtubules

  • Example: Paclitaxel – important for case studies

Topoisomerase Inhibitors

• Mechanism of Action

  • Inhibit topoisomerase enzymes essential for DNA replication

  • Can create breaks in both strands of the DNA double helix leading to DNA destruction and cell death

• Types of Topoisomerase

  • Two main enzymes with drugs associated with each

  • Importance of reviewing generic names and common adverse effects associated with these medications.