Pharmacology - Antineoplastic Flashcards
Therapeutic goal of antineoplastics
Eliminate all cancer cells
All evidence of cancer is eliminated
Reduce/control pain
Improve well-being
Correct physiologic abnormalities
Therapeutic targets of antineoplastics
Rapidly diving cells
Cancer cell-specific antigens
Tyrosine kinase
(Multiple targets make treatment difficult)
Main toxicity of antineoplastic drugs
Myelosuppression
- neutrophils (mostly) WBC below 750* adjust
- platelets (sometimes)
- anemia (unlikely)
Common irritations of antineoplastic drugs
Mucosal cells of GI (slog off)
Diarrhea
Vomiting
Ulceration
What toxicity is uncommon in animals? What is the exception?
Hair loss
Dogs don’t have continuously growing hair (except poodles)
Agent specific effects (6)
Nausea
Phlebitis
Cellulitis / necrosis (extravastion)
Nephrotoxicity (esp in ‘platins)
Peripheral neuritis
Acute tumor lysis syndrome
Targets of antineoplastic drug resistance
Genetically altered
Reduced cellular uptake (MDR1, p-glyco)
Drug in activation
Decreased activation of prodrugs
Decreased rate of cell division
Increase in DNA repair system
Common protocols for cancer treatment
Treat multiple targets
Alternate week therapy
Function of cyclophosphamide
Form covalent bond w DNA
DNA is now useless for translation/scription
Cyclophosphamide activation
Prodrug activated in liver
Adverse effects of cyclophosphamide
Myelosuppression (neutropenia & thrombocytopenia)
Nausea & vomiting (high doses in cats)
Alopecia (when applicable)
Extreme adverse effects in cats taking high doses of cyclophosphamide
Reversible neurotoxicity in cats (CNS)
**sterile necrotizing hemorrhagic cystitis -metabolites in urine= acrolein
Sterile necrotizing hemorrhagic cystitis
-common side effect in what drug? What species?
- treatment
Cyclophosphamide = cats
Dose in morning, ample time for excretion
Increase water consumption, urination
Mesna - binds to metabolites
Vincristine function
Microtubule binding agents
Arrests mitosis, cell cycle, apoptosis or necrosis
Adverse effects of vincristine
Dose dependent leukopenia (mild)
Thrombocytopenia, anemia is rare
Peripheral neuropathy (CNS)
How should vincristine be administered?
IV only
Is extremely irritating, can cause blisters
Doxorubicin features
Common antibiotic, similar function as floroquinalones
Inhibit topoisomerase I & II - nick DNA strands
Acute toxicity of doxorubicin
EKG changes, brief cardiac arrest
Weight loss, anorexia, diarrhea, vomiting
Myelotoxic - neutropenia (up to 3w)
Lymphoid atrophy
Chronic toxicity in doxorubicin
Hair loss
Testicular atrophy
Dose dependent cardiac toxicity (arrhythmias, cardio myopathy) liposomal dose forms are safer
L-asparaginase features
Enzyme, destroy exogenous supplies
Notable adverse effects of L-asparaginase
Anaphylaxis
Pancreatitis
Decrease clotting factors, esp fibrinogen
NOT myelosuppressive
Prednisone/prednisolone
Direct cytotoxicity
Dosing of antineoplastic drugs
Distributed by weight (mg/kg) or surface area (mg/M^2)
Antineoplastic drugs with little reaction potential
L-asparaginase
Cyclophosphamide
Monoclonal antibodies
Antineoplastic drugs with inflammatory reactions
5-FU
Methotrexate
Antineoplastic drugs with irritant reactions
Carboplatin
Bleomycin
Antineoplastic drugs with exfoliant reactions
Liposomal doxorubicin
Cisplatin
Taxanes
Antineoplastic drugs with vesicant reactions
Tissue necrosis/blisters
Doxorubicin
Vincristine
What drugs should not be administered with a needle/butterfly cannula?
Irritants, exfoliants, vesicants
