Drug-Induced Cardiac Disease- Drug-Induced HF Flashcards
3 causes of drug-induced HF
Sodium and volume retention
Direct cardiotoxicity
Negative inotropy
Drugs that can cause sodium and volume retention
NSAIDs, steroids, TZDs
Mechanism of drug-induced HF for NSAIDs and steroids
Both of them are global anti-inflammatory agents
Decreases prostaglandins in the kidney → allows for vasodilation of the afferent and efferent arterioles and Na and H2O excretion –> increase the rate of sodium and water retention –> symptoms of fluid overload and HF exacerbation
In drug-induced HF, NSAIDs also do what?
Increase systemic vascular resistance by increasing the pressure the LV has to push against
In HF patients, what should you do with NSAIDs and steroids?
Avoid use if possible, but if necessary, use at minimum doses and duration
Drugs that can cause direct cardiotoxicity
chemo agents, biologics, alcohol
Chemo agents that can cause direct cardiotoxicity
doxorubicin, daunorubicin (anthracyclines)
Anthracycline mechanism of damage
Inhibition of TOP2B causes DNA breakdown and cell death. When the cells die…
Increased free radicals of O2
Defective mitochondrial biogenesis
Causing cell death of cardiac myocytes and we’re releasing free radicals → damages the adjacent cardiac myocytes
Medication to prevent cardiotoxicity
Dexarozane, binds to TOP2B to prevent anthracycline binding
Anthracycline cardiotoxicity treatment-related risk factors
Cumulative dose of anthracyclines (>400mg/m2)
Dosing schedules
Previous anthracycline therapy
Radiation therapy
Coadministration of potentially cardiotoxic agents
Anthracycline cardiotoxicity patient-related risk factors
Older age
Preexisting CVD or risk factors
Obesity
Smoking
Gender (but there’s not a lot of clear cut evidence on this)
Lifetime cumulative dose max of anthracyclines
550mg/m2
Biologic that can cause drug-induced HF
Trastuzumab
Is cardiotoxicity caused by anthracyclines reversible?
No
Is cardiotoxicity caused by trastuzumab reversible?
Yes, just very slowly once it’s D/C’ed