Cardio Toxicity

Question 1

QTc prolongation criteria

Answer 1

QTc at least 500 ms
or
QTC of at least 60 ms from baseline

Question 2

Drugs that cause QTc prolongation

Answer 2

AntiArrhythmics
AntiBiotics
AntipsyChotics
AntiDepressants
AntiEmetics
AntiFungals

Question 3

Antiarrhythmics causing QTc

Answer 3

Amiodarone, sotalol, dofetilide

Question 4

Antibiotics causing QTc

Answer 4

Fluoroquinolones, macrolide (erythromycin)

Question 5

Antidepressants causing QTc

Answer 5

Citalopram, TCAs

Question 6

Antiemetics causing QTc

Answer 6

Ondansetron

Question 7

Antifungals

Answer 7

-azoles

Question 8

T/F: QTc prolongation is concentration-independent

Answer 8

FALSE: risk increases with concentration

Question 9

Non-modifiable risk factors for QTc prolongation

Answer 9

• Age >65
• Female gender
• Genetic predisposition
• Cardiac disease

Question 10

Modifiable risk factors for QTc prolongation

Answer 10

• Diuretics
• Electrolyte abnormalities
• > 1 QT-prolonging agent
• Organ function

Question 11

Approach to QTc prolongation

Answer 11

• 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

Question 12

Torsade de pointes treatment

Answer 12

1. Avoid offending agent
2. Magnesium (look at K and Ca too)
3. Transcutaneous pacing
4. Isoproterenol infusion

Question 13

Torsades magnesium

Answer 13

No pulse = push

Pulse = infusion

Question 14

What should you do if the patient is hemodynamically unstable at any point?

Answer 14

Cardio conversion or defibrillation

Question 15

Isoproterenol

Answer 15

B1 and B2 - increase HR to reset rhythm
Immediate onset
Given continuous infusion

Question 16

What are some side effects of isoproterenol?

Answer 16

Angina, chest pain

Question 17

What should you monitor on isoproterenol?

Answer 17

HR, BP, ECG

Question 18

Mechanisms of drug induced HF

Answer 18

1. Na/volume retention
2. Direct cardiotoxicity -> cardiomyopathy
3. Negative inotropy

Question 19

Drugs causing Na/fluid retention HF

Answer 19

NSAIDs
Steroids
Thiazolidinediones

Question 20

Drugs causing cardiomyopathy HF

Answer 20

Chemo drugs*
Biologic agents
Alcohol

Question 21

Drugs causing negative inotropy HF

Answer 21

Non-DHP CCBs
Beta-blockers

Question 22

NSAIDs and steroids and HF

Answer 22

Cause HF due to Na/fluid retention
- Avoid if possible, minimize duration/dose if necessary
- NSAIDs also increase vascular resistance

Question 23

Thiazolidinediones and HF

Answer 23

Cause HF due to Na/fluid retention
BBW: avoid in NYHA III-IV HF
Can progress towards HF

Question 24

Chemo drugs in HF

Answer 24

Cause HF due to cardiomyopathy
Anthracyclines***
Alkylating agents

Question 25

Alcohol in HF

Answer 25

Cause HF due to direct toxic effect on myocardium

Question 26

Main biologic causing HF by cardiomyopathy

Answer 26

Trastuzumab

Question 27

Anthracycline-induced cardiomyopathy HF

Answer 27

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)

Question 28

Treatment-related anthracycline toxicity risk factors

Answer 28

- Cumulative dose >400 mg/m^2 - Dosing schedules - Previous anthracycline therapy - Radiation therapy - Co-administration of other potential cardiotoxic agents

Question 29

Patient-related anthracycline toxicity risk factors

Answer 29

- Age - CV disease or risk factors - Obesity - Smoking - Gender? (not really)

Question 30

Trastuzumab-induced cardiomyopathy HF

Answer 30

HER2 antagonist for breast cancer REVERSIBLE cardiomyopathy upon discontinuation Reduced NO -> RAAS activation -> HF

Question 31

Trastuzumab considerations

Answer 31

No mf'r contraindications but should avoid in HF hx - Evaluate LVEF in all patients BBW: LVEF reduction and HF development

Question 32

Trastuzumab toxicity treatment

Answer 32

- Dose-adjustment based on LVEF - Consider dose reduction or discontinuation if HF develops - Consider HF meds during treatment if EF declines (ACE/ARB/BB)

Question 33

When to avoid Non-DHP CCBs?

Answer 33

Patients with EF<40%

Question 34

When to avoid beta-blockers?

Answer 34

Acute HF exacerbation

Question 35

Myocardial ischemia and acute coronary syndrome mechanisms

Answer 35

- Increased HR and contractility - Increased coronary resistance (vasospasm) - Coronary artery thrombosis/vasospasm - Increased cardiovascular risk

Question 36

Main agents that cause myo. ischemia and ACS

Answer 36

Cocaine & NSAIDs

Question 37

Cocaine-induced MI: chest pain

Answer 37

Aspirin (acutely) IV benzos (gold standard for sympathomimetic crisis)

Question 38

Cocaine-induced MI: persistent HTN

Answer 38

IV benzos 2nd line: IV nitroglycerin

Question 39

Cocaine-induced MI: other acute options

Answer 39

Consider beta blockers...?

Question 40

NSAID-induced cardiotoxicity

Answer 40

COX-2 blockade -> vasoconstriction, platelet aggregation -> MI/stroke Increased risk of serious CV thrombotic events

Question 41

Risk factors for acute MI with NSAIDs

Answer 41

Increase risk 20-50% - Early in therapy (rapid <7d) - Higher doses (1200mg ibuprofen, 750mg naproxen)

Question 42

Which factors for NSAIDs do not affect MI risk?

Answer 42

- Selective vs. nonselective - Duration of therapy Does NOT matter