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
Risk factors for trastuzumab-induced cardiotoxicity
Advanced age, presence of CV comorbidities, previous treatment with anthracyclines
Trastuzumab mechanism
Inhibition of HER2 proteins and human ERBB2 (?) signaling in cardiac myocytes, both necessary for growth and repair of cardiac muscles. When they can’t grow and repair → increases breakdown and cell death
Trastuzumab’s effects on ROS, NOS, NO, and angiotensin II
Increased ROS
Reduced NOS expression
Reduced NO bioavailability
Increased angiotensin II
Trastuzumab CIs
There are no CIs based on the manufacturer, but it’s best to be avoided in patients with HF history
Trastuzumab monitoring
Evaluate LVEF in all patients prior to and during treatment
Trastuzumab treatment
dose adjust based on LVEF
Consider dose reduction or D/C if HF develops
Consider using HF medications during treatment if EF declines
Alcohol mechanism to cause cardiotoxicity
direct toxic effect on the myocardium
Drugs that can cause negative inotropy
Non-DHP CCBs (diltiazem, verapamil), beta-blockers
How do non-DHP CCBs cause negative inotropy?
Decrease amount of squeeze the heart has to do; makes the muscle more tired so it can’t work as effectively
Avoid non-DHP CCBs in patients with what EF?
<40% (HFrEF)
Beta-blockers and HF
In stable HF, they can decrease long-term cardiomyopathy; over time, they can increase or maintain heart function
Avoid beta-blockers in what patients?
Patients with acute HF exacerbations
