Chemotherapy and immunosuppressive drugs Flashcards
What is chemotherapy?
Administration of chemical reagents which have a specific and toxic effect on neoplastic cells
Why are neoplastic cells most susceptible to chemotherapy?
Because they are rapidly cycling cells. There are consequences though because even though it does target neoplastic cells, chemotherapeutics also target GI mucosa and bone marrow.
Cells in which stage of the cell cycle are least susceptible to chemotherapeutic drugs?
Cells in G0 (plateau growth phase)
The therapeutic index for chemotherapeutic drugs is __________
Narrow
Chemotherapy is most effective for which three tumors?
- Leukemia
- Lymphoma
- TVT (transmissible venereal tumor)
Chemotherapy is an effective adjuvant for which highly metastatic tumors?
- Canine osteosarcoma
- Feline mammary carcinoma
What is chemotherapy not good at treating (three)?
- Bulky local disease
- The shrinkage of large masses prior to surgery
- Palliation of very large or painful tumors
What is the most efficient method of selecting chemotherapeutic drugs?
Choose multiple drugs that each target different parts of the cell cycle
Local therapy should be used for ________ disease
Local
Systemic therapy should be used for __________ disease
Systemic
What are the six main classes of chemotherapeutic drugs? Name an example of each
- Antimetabolites (ex. methotrexate, cytosine arabinoside, azathioprin)
- Alkylating agents (ex. cyclophosphamide, chlorambucil, melphalan)
- Mitotic inhibitors (ex. vincristine, vinblastine, taxol)
- Anti-tumor antibiotics (ex. doxorubicin (Adriamycin) and mitoxantrone)
- Miscellaneous
- Targeted therapy (ex. Palladia)
Name two drugs in the miscellaneous chemotherapeutic category and describe their mechanisms
- L-asparaginase (deprives cells of the amino acid asparagine, which is essential for growth and survival)
- Platinum analogues (covalently bind to DNA, preventing replication)
What is the mechanism behind the antimetabolite chemotherapeutic class?
Antimetabolites work by acting as analogs (mimics) of naturally occurring substances within cells, which disrupts essential cellular functions such as DNA synthesis and leads to cell death
What is the mechanism behind the alkylating agent chemotherapeutic class?
Alkylating agents work by adding alkyl groups to DNA, RNA, and proteins, which damages the DNA and prevents further cell division
What is the mechanism behind the mitotic inhibitor chemotherapeutic class?
Mitotic inhibitors work by inhibiting components of the mitotic machinery, which is essential for segregating chromosomes during cell division (leads to cell cycle arrest)
What is the mechanism behind the anti-tumor antibiotic class?
Anti-tumor antibiotics work by forming complexes with DNA causing free radical formation
What is the mechanism behind the drug ‘Palladia’?
It is a tyrosine kinase inhibitor (mast cell tumors express high levels of this receptor)
What are four factors to consider regarding chemotherapy safety?
- Dedicate a safe storage area (labelled fridge)
- Use proper equipment (PPE, respirators, closed system drug transfer device)
- Designate a drug administration area (quiet, appropriate restraint)
- Appropriate patient care (use gloves, dispose of bedding properly)
What type of drug class is most commonly used to treat immune mediated diseases in cats and dogs?
Glucocorticoids
Name six examples of conditions that are commonly treated with immunotherapeutics
- Immune mediated disease
- IBD
- Skin disease
- Glomerulonephritis
- Neurological conditions (ex. myasthenia gravis)
- Cancer
What are four main side effects of glucocorticoids?
- Iatrogenic hyperadrenocorticism
- Increased risk of diabetes mellitus
- Calcinosis cutis
- Hypertension and destabilization of cardiac disease
Side effects are generally worse in dogs versus cats.
Name five immunotherapeutics that can be used in place of glucocorticoids
- Cyclosporine (Atopica)
- Azathioprine
- Chlorambucil
- Mycophenolate mofeti
- Leflunomide
What is the mechanism behind cyclosporine?
It inhibits T-lymphocyte function
Which immunotherapeutics listed do not suppress both the humoral and cell-mediated immune system?
- Azathioprine (suppresses cell-mediated immunity and macrophage function)
- Cyclosporine (suppresses only cell-mediated immunity)
