Chemotherapeutics and Immune System Drugs Notes

Chemotherapeutics and Immune System Drugs Notes

Definitions

  • Neoplasia: Abnormal cell growth leading to more division or failure to die through apoptosis.
    • Can be benign (non-cancerous) or malignant (cancerous).
  • Apoptosis: Programmed cell death essential for removing old or damaged cells.

Cancer Characteristics

  • Self-sufficiency in growth signals: Cancer cells generate their own signals for growth.
  • Insensitivity to antigrowth signals: Cancer cells ignore signals that would normally stop growth.
  • Evade apoptosis: Cancer cells can avoid programmed cell death.
  • Unlimited replication potential: Cancer cells can replicate indefinitely.
  • Promote angiogenesis: Cancer cells can grow new blood vessels.
  • Tissue invasion and metastasis: Cancer cells can invade surrounding tissues and spread to other parts of the body.

Principles of Chemotherapy

  • Most effective against rapidly growing tumors because these cells are more sensitive to DNA damage.
  • Common side effects include damage to:
    • Bone marrow (most common side effect).
    • Gastrointestinal tract.
    • Reproductive organs.
    • Hair follicles (less pronounced in pets).
  • Drug dosing typically based on surface area (mg/m²) rather than body weight, though smaller animals may require body weight dosing.

Chemotherapy Drugs

  • Used in combinations for enhanced effectiveness:
    • Toxicity and side effects may include:
    • Anorexia, nausea, vomiting, diarrhea (due to CRTZ or damage).
    • Bone marrow depression (myelosuppression).
    • Possible hair loss in certain breeds (e.g., poodles, terriers).
    • Cystitis, cardiomyopathy, anaphylaxis due to specific drugs.
    • Many are vesicants, risking severe tissue necrosis upon leakage outside of veins.

Antineoplastic Drugs Categories

  • Alkylating agents: Cell cycle-nonspecific; cross-link DNA strands to prevent replication (e.g., Cyclophosphamide).
  • Anthracyclines: Derived from Streptomyces; interfere with RNA/protein synthesis (e.g., Doxorubicin - strong vesicant and can cause cardiac toxicity).
  • Antimetabolites: Affect S phase of cell cycle; analogs of DNA building blocks inhibiting protein synthesis (e.g., Methotrexate - contraindicated in cats).
  • Antitubulin agents (Vinca alkaloids): Affect M phase; inhibit mitosis (e.g., Vincristine, Vinblastine).
  • Glucocorticoids: High doses can have lympholytic action for treating lymphoma (e.g., Prednisone).
  • Miscellaneous: Includes platinum drugs (e.g., Carboplatin, Cisplatin - contraindicated in cats) and asparaginase.

Biologic Response Modifiers

  • Help alter the relationship between tumors and patients; improve the anti-tumor response. Most used as adjuncts:
    • Agents include: Interferons, Thymosins, Cytokines, monoclonal antibodies.

Monoclonal Antibodies

  • Identical immunoglobulin molecules, assisting in targeting specific conditions.
    • Examples:
    • Solensia (for arthritic cats, monthly injection).
    • Librela (for arthritic dogs, monthly injection).
    • Cytopoint: Neutralizes IL-31, reducing itch signals (canine).
    • Canine Parvoviral Monoclonal Antibody: Selectively binds parvovirus, conditionally licensed by USDA.

Immunosuppressive Drugs

  • Used for various immune-mediated disorders (e.g., lupus, hemolytic anemia).
  • Mechanisms often involve interference with cell cycle stages or cellular messengers:
    • Examples:
    • Azathioprine: Antimetabolite, affects S phase; inhibits T and B lymphocytes.
    • Cyclosporine: Inhibits T lymphocyte proliferation and cytokines.
    • Metronidazole: Antibacterial and immunosuppressive.
    • Corticosteroids: Immunosuppressant at high doses.

Additional Immunosuppressants

  • Tacrolimus: Topical for various dermal conditions.
  • Pimecrolimus: Topical, similar to tacrolimus.
  • Apoquel: Janus kinase inhibitor for pruritis control in dogs.
  • Mycophenolate mofetil: Treats conditions like hemolytic anemia and IBD.