Introduction to Chemotherapeutics Flashcards
What is a chemotherapeutic agent?
A drug used to treat cancers by causing cell death or stopping cells from dividing
What routes of administration of chemotherapeutic agents can be used?
Oral
Injection
IV infusion - often given slowly and can be irritant if leakage
Topical - less common in veterinary to prevent ingestion
How are chemotherapeutic drugs used?
Used alone e.g., lymphoma
Used in conjunction with radiotherapy and/or surgery e.g., mast cell tumours
What are cytotoxic drugs?
‘indiscriminate’
inhibit mitosis and/or damage DNA
kill rapidly dividing cells
What cells do cytotoxic drugs target?
Rapidly dividing cells
e.g., neoplastic cells
Also GI tract epithelium and bone marrow cells (body has to compensate, leads to adverse effects)
What are some examples of commonly used cytotoxic agents for lymphoma?
vincristine, doxorubicin, chlorambucil, cyclophosphamide
What are the newer chemotherapeutic agents used?
Targeted therapy against specific receptors, signalling pathways and antigens
Give examples of targeted chemotherapeutic therapies
Tyrosine kinase inhibitors for mast cell tumours in dogs -masitinib, toceranib
Monoclonal antibodies vs specific tumour antigens
What are the limitations of cytotoxic drugs?
Palliative not curative
Toxicity limits dosage and dosage frequency
What is the maximum tolerated dose?
highest dose with ‘acceptable’ side effects
What is the aim of metronomic chemotherapy?
Aims: delay or slow disease progression not kill cancer cells
Inhibits angiogenesis (development of new blood vessels - inhibits blood supply to cancer cells)
Modulates immune response to cancer cells
Which cytotoxic drugs are cell cycle non-specific?
doxorubicin
cyclophosphamide
lomustine
chlorambucil
Which cytotoxic drugs are cell cycle specific?
vincristine
vinblastine
cytarabine
What are the classes of chemotherapeutic drugs?
alkylating agents
plant alkaloids
anti-metabolites
anti-tumour antibiotics
platinum analogs
Tyrosine kinase inhibitors
What is the mode of action of alkylating agents?
Alkyl group binds to and cross links DNA
Give examples of alkylating agents
chlorambucil
cyclophosphamide
lomustine
melphalan
What is the clinical use of alkylating agent - chlorambucil
low grade lymphoma (cats)
immune mediated diseases
What is the clinical use of alkylating agent - cyclophosphamide?
lymphoma
haemangiosarcoma
metronomic chemotherapy
What is the clinical use of alkylating agent - lomustine?
lymphoma
mast cell tumour
What is the clinical use of alkylating agent - melphalan?
myeloma
What are the adverse effects of alkylating agents?
Myelosuppression
GI signs
Sterile haemorrhagic cystitis (cyclophosphamide)
Hepatotoxicity (lomustine)
What is the mode of action of plant alkaloids?
bind to tubulin cells and disrupt mitotic spindle
Give examples of plant alkaloids
Vincristine
Vinblastine
What is the clinical use of plant alkaloid - vincristine?
Lymphoma, leukaemia
What is the clinical use of plant alkaloid - vinblastine?
mast cell tumour
What are the adverse effects of plant alkaloids?
GI signs
Myelosuppression
Irritant if leaks from vein
Peripheral neuropathy
What is the mode of action of anti metabolites?
Inhibit use of cell metabolites used in growth and cell division
Give an example of an anti metabolite
Cytarabine
What is the clinical use of the anti metabolite cytrabine?
Lymphoma with CNS involvement
What are the adverse effects of anti metabolites?
Myelosuppression
GI signs
Alopecia
Hepatotoxicity
What is the mode of action of anti-tumour antibiotics?
Inhibit topoisomerase-II causing breakage of DNA and cell death; forms free radicals
What are examples of anti-tumour antibiotics?
Doxorubicin
Mitoxantrone
What is the clinical use of anti-tumour antibiotic - doxorubicin?
lymphoma
haemangiosarcoma
What is the clinical use of anti-tumour antibiotic - mitoxantrone?
lymphoma
haemangiosarcoma
What are the adverse effects of anti-tumour antibiotics?
Myelosuppression
GI signs
Extreme irritation if leaks from vein
Alopecia
Cumulative cardiotoxicity (dogs)
Nephrotoxic (cats)<
What is the mode of action of platinum analogs?
Bind platinum to DNA causing cross linkage and cell death
What is an example of a platinum analog?
carboplatin
What is the clinical use of the platinum analog carboplatin?
osteosarcoma
carcinomas
What are the adverse effects of platinum analogs?
Myelosuppression
GI signs
What is the mode of action of tyrosine kinase inhibitors?
Inhibit various TK receptors
What are examples of tyrosine kinase inhibitors?
Toceranib
Masitinib
What is the clinical use of the TK inhibitor - toceranib?
mast cell tumour
What is the clinical use of the TK inhibitor - masitinib?
mast cell tumour
immune mediated diseases
What are the adverse effects of TK inhibitors?
Weight loss
GI signs
Alopecia
Nephrotoxicity
How can the benefit of chemotherapeutic drugs be maximised?
treat small tumours with a high growth fraction - plenty of rapidly dividing cells to target
Cell cycle specific drugs kill a limited number of cell each dose - repeat doses as often as possible and use combinations of drugs to target different phases in different ways
How can the harm of chemotherapeutic drugs be minimised?
Be aware of adverse effects - symptomatic treatments, monitor patient, communicate with owner
Ensure quality of life is maintained
How can chemotherapeutic drugs cause harm to humans?
direct exposure
metabolites excreted by pets
