Cardio Toxicity Flashcards
QTc prolongation criteria
QTc at least 500 ms
or
QTC of at least 60 ms from baseline
Drugs that cause QTc prolongation
AntiArrhythmics
AntiBiotics
AntipsyChotics
AntiDepressants
AntiEmetics
AntiFungals
Antiarrhythmics causing QTc
Amiodarone, sotalol, dofetilide
Antibiotics causing QTc
Fluoroquinolones, macrolide (erythromycin)
Antidepressants causing QTc
Citalopram, TCAs
Antiemetics causing QTc
Ondansetron
Antifungals
-azoles
T/F: QTc prolongation is concentration-independent
FALSE: risk increases with concentration
Non-modifiable risk factors for QTc prolongation
- Age >65
- Female gender
- Genetic predisposition
- Cardiac disease
Modifiable risk factors for QTc prolongation
- Diuretics
- Electrolyte abnormalities
- > 1 QT-prolonging agent
- Organ function
Approach to QTc prolongation
- Avoid QTc prolonging agents when >450 ms pretreatment
- Reduce dose or discontinue if QTc changes >60 ms from pretreatment
- Discontinue prolonging agent if QTc increases to >500 ms
- Maintain K >4 and Mg >2 mEq/L
- Avoid multiple QTc prolonging agents
- Avoid QTc prolonging agents with hx of drug-induced QTc prolongation
Torsade de pointes treatment
- Avoid offending agent
- Magnesium (look at K and Ca too)
- Transcutaneous pacing
- Isoproterenol infusion
Torsades magnesium
No pulse = push
Pulse = infusion
What should you do if the patient is hemodynamically unstable at any point?
Cardio conversion or defibrillation
Isoproterenol
B1 and B2 - increase HR to reset rhythm
Immediate onset
Given continuous infusion
What are some side effects of isoproterenol?
Angina, chest pain
What should you monitor on isoproterenol?
HR, BP, ECG
Mechanisms of drug induced HF
- Na/volume retention
- Direct cardiotoxicity -> cardiomyopathy
- Negative inotropy
Drugs causing Na/fluid retention HF
NSAIDs
Steroids
Thiazolidinediones
Drugs causing cardiomyopathy HF
Chemo drugs*
Biologic agents
Alcohol
Drugs causing negative inotropy HF
Non-DHP CCBs
Beta-blockers
NSAIDs and steroids and HF
Cause HF due to Na/fluid retention
- Avoid if possible, minimize duration/dose if necessary
- NSAIDs also increase vascular resistance
Thiazolidinediones and HF
Cause HF due to Na/fluid retention
BBW: avoid in NYHA III-IV HF
Can progress towards HF
Chemo drugs in HF
Cause HF due to cardiomyopathy
Anthracyclines***
Alkylating agents
Alcohol in HF
Cause HF due to direct toxic effect on myocardium
Main biologic causing HF by cardiomyopathy
Trastuzumab
Anthracycline-induced cardiomyopathy HF
Doxorubicin, daunorubicin
TOP2B inhibition causes DNA breakdown and cell death
- Limit lifetime dose to 550 mg/m^2
Dexrazoxane can be given to prevent toxicity (but hard to be indicated)
Treatment-related anthracycline toxicity risk factors
- Cumulative dose >400 mg/m^2
- Dosing schedules
- Previous anthracycline therapy
- Radiation therapy
- Co-administration of other potential cardiotoxic agents
Patient-related anthracycline toxicity risk factors
- Age
- CV disease or risk factors
- Obesity
- Smoking
- Gender? (not really)
Trastuzumab-induced cardiomyopathy HF
HER2 antagonist for breast cancer
REVERSIBLE cardiomyopathy upon discontinuation
Reduced NO -> RAAS activation -> HF
Trastuzumab considerations
No mf’r contraindications but should avoid in HF hx
- Evaluate LVEF in all patients
BBW: LVEF reduction and HF development
Trastuzumab toxicity treatment
- Dose-adjustment based on LVEF
- Consider dose reduction or discontinuation if HF develops
- Consider HF meds during treatment if EF declines (ACE/ARB/BB)
When to avoid Non-DHP CCBs?
Patients with EF<40%
When to avoid beta-blockers?
Acute HF exacerbation
Myocardial ischemia and acute coronary syndrome mechanisms
- Increased HR and contractility
- Increased coronary resistance (vasospasm)
- Coronary artery thrombosis/vasospasm
- Increased cardiovascular risk
Main agents that cause myo. ischemia and ACS
Cocaine & NSAIDs
Cocaine-induced MI: chest pain
Aspirin (acutely)
IV benzos (gold standard for sympathomimetic crisis)
Cocaine-induced MI: persistent HTN
IV benzos
2nd line: IV nitroglycerin
Cocaine-induced MI: other acute options
Consider beta blockers…?
NSAID-induced cardiotoxicity
COX-2 blockade -> vasoconstriction, platelet aggregation -> MI/stroke
Increased risk of serious CV thrombotic events
Risk factors for acute MI with NSAIDs
Increase risk 20-50%
- Early in therapy (rapid <7d)
- Higher doses (1200mg ibuprofen, 750mg naproxen)
Which factors for NSAIDs do not affect MI risk?
- Selective vs. nonselective
- Duration of therapy
Does NOT matter
