Drug-Induced Cardiac Disease

Question 1

Torsades de Pointes

Answer 1

life-threatening polymorphic ventricular tachycardia
risk increases with QTc prolongation

Question 2

Normal QTc

Answer 2

< 470 ms men
< 480 ms women

Question 3

Drug-Induced QTc Prolongation

Answer 3

QTc 500 ms or greater
OR
QTc increase of 60 ms or more from baseline

Question 4

QTc Prolongation - Drugs

Answer 4

antiarrhythmics
antibiotics
antipsychotics
antidepressants
antiemetics
antifungals

Question 5

Antiarrhythmics - Agents

Answer 5

amiodarone
sotalol
dofetilide

Question 6

Antibiotics - Agents

Answer 6

fluoroquinolones
macrolides

Question 7

Antipsychotics - Agents

Answer 7

typical (haloperidol, chlorpromazine)

Question 8

Antidepressants - Agents

Answer 8

citalopram
TCAs

Question 9

Antiemetics - Agents

Answer 9

ondansetron

Question 10

Antifungals - Agents

Answer 10

-azole antifungals

Question 11

TdP - Risk Factors (non-modifiable)

Answer 11

age > 65
female gender
genetic predisposition
cardiac disease

Question 12

TdP - Risk Factors (modifiable)

Answer 12

diuretic treatment
electrolyte abnormalities
more than 1 QT-prolonging agents
organ function

Question 13

Approach to DI QT Prolongation

Answer 13

avoid in patients with pre-treatment intervals > 450 ms
decrease dose or d/c if QTc increases more than 60 from baseline
d/c if increases to > 500
maintain K > 4 and Mg > 2
avoid more than 1 QT-prolonging drug concurrently
avoid in patients with history of drug-induced TdP

Question 14

DI TdP - Treatment

Answer 14

stop offending drug(s)
if pulse present - Mg infusion
if no pulse - Mg push
transcutaneous pacing
isoproterenol / epinephrine / atropine infusion

Question 15

Drug-Induced Heart Failure - Causes

Answer 15

sodium & volume retention
direct cardiotoxicity -> cardiomyopathy
negative inotropy

Question 16

HF due to Sodium & Volume Retention - Drugs

Answer 16

NSAIDs
steroids
thiazolidinediones

Question 17

HF due to Cardiomyopathy - Drugs

Answer 17

chemotherapeutic agents
biologic agents (trastuzumab)
alcohol

Question 18

HF due to Negative Inotropy - Drugs

Answer 18

non-DHP calcium channel blockers
beta-blockers

Question 19

Chemotherapeutic Agents

Answer 19

anthracyclines (doxorubicin, daunorubicin)
alkylating agents

Question 20

Anthracycline-Induced Cardiotoxicity - Risk Factors

Answer 20

cumulative dose > 400 mg/m2
dosing schedules
previous anthracycline therapy
radiation therapy
concurrent cardiotoxic agents

Question 21

Trastuzumab-Induced Cardiomyopathy - Risk Factors

Answer 21

advanced age
presence of CV comorbidities
previous anthracycline therapy

Question 22

Trastuzumab-Induced Cardiomyopathy - Mechanism

Answer 22

inhibition of HER2 receptors –>
- increased ROS
- reduced NOS expression
- reduced NO bioavailability
- increased angiotensin II

Question 23

Trastuzumab - BBW

Answer 23

left ventricular cardiac dysfunction, disabling cardiac failure, cardiomyopathy, cardiac death

avoid with history of HF

Question 24

Trastuzumab-Induced Cardiomyopathy - Treatment

Answer 24

dose adjustment based on LVEF
consider d/c if HF develops
ACE inhibitors / ARBs
beta-blockers

Question 25

Drug-Induced Myocardial Ischemia & ACS - Mechanisms

Answer 25

increased HR & contractility (increased oxygen demand)
vasospasm (decreased oxygen supply)
coronary artery thrombosis
increased CV risk

Question 26

Cocaine-Induced MI - Pathophysiology

Answer 26

cocaine inhibits reuptake of norepi -> increased norepi concentrations -> enhanced alpha-1-mediated vasoconstriction of coronary arteries

Question 27

Cocaine-Induced MI - Treatment

Answer 27

chest pain -> aspirin & benzos
persistent HTN -> benzos & IV nitroglycerin

Question 28

NSAID-Induced Cardiotoxicity - Mechanism

Answer 28

COX-2, blocked by NSAIDs, prevents PGI-2 & TXA-2 from fulfilling the functions of:
- vascular vasodilation
- decreased platelet aggregation

… leading to MI or stroke

Question 29

NSAIDs - BBW

Answer 29

may cause an increased risk of serious CV thrombotic events, MI, and stroke, which can be fatal

Question 30

NSAID-Induced Acute MI - Risk

Answer 30

early in therapy (within 7 days)
> 1200 mg / day of ibuprofen
> 750 mg / day of naproxen
risk increased by 20-50 %