Cardiotoxicity Flashcards
Which drugs affect cardiac function directly?
Doxorubicin, cyclophosphamide, trastuzumab
Which drugs affect afterload?
Bevacizumab via hypertension
Which drugs affect preload?
Imatinib through fluid retention
Which drugs affect heart rate?
Ifosfamide via arrhythmias
Which drugs can cause cerebrovascular disease?
Cisplatin, flourouracil
Name some examples of anthracyclines?
Doxorubicin, daunorubicin, epirubicin, idarubicin
Differentiate between the classifications of anthracycline induced cardiotoxicity?
Acute cardiotoxicity - occurs after a single source of chemotherapy, and where clinical manifestations appear soon after the end of the treatment.
Early onset chronic cardiotoxicity - develops within months post-treatment cessation, and usually manifests itself as a dilated and hypokinetic cardiomyopathy leading to HF.
Late-onset chronic cardiotoxicity - develops years or even decades after the end of chemotherapy
Where does Dox accumulate in the cell and why?
In the inner mitochondrial membrane due to its high binding affinity for cardiolipin
Binding of dox and cardiolipin leads to a disruption in which pathway?
Leads to a disruption of the activity of the complexes I, III, IV in the electron transport chain
Do cardiomyocytes express TopIIB or TopIIA?
TopIIB
Anthracyclines form a complex with TopIIA or TopIIB?
TopIIB
Name the two treatment options for treating DIC.
- Drug administration via continuous infusion or liposome encapsulation
- Simultaneous use of a cardio-protective agent, such as dexrazoxane along with Dox treatment
Where does dexrazoxane bind?
Competes for the ATP binding site of topoisomerase IIbeta (interferes with the formation of anthracycline-DNA-topoisomerase IIbeta - complex, preventing DNA double-strand breaks and cardiomyocyte death)
Name some flouropyridines.
5-Flourouracil
Capecitabine
What is the current treatment for FIC?
Stop 5-FU or capecitabine treatment. Start anti-anginal treatment with nitrates or CCBs. Anti-oxidants (Probucol).
