Drug-Induced Cardiac Disease Flashcards
Torsades de Pointes
life-threatening polymorphic ventricular tachycardia
risk increases with QTc prolongation
Normal QTc
< 470 ms men
< 480 ms women
Drug-Induced QTc Prolongation
QTc 500 ms or greater
OR
QTc increase of 60 ms or more from baseline
QTc Prolongation - Drugs
antiarrhythmics
antibiotics
antipsychotics
antidepressants
antiemetics
antifungals
Antiarrhythmics - Agents
amiodarone
sotalol
dofetilide
Antibiotics - Agents
fluoroquinolones
macrolides
Antipsychotics - Agents
typical (haloperidol, chlorpromazine)
Antidepressants - Agents
citalopram
TCAs
Antiemetics - Agents
ondansetron
Antifungals - Agents
-azole antifungals
TdP - Risk Factors (non-modifiable)
age > 65
female gender
genetic predisposition
cardiac disease
TdP - Risk Factors (modifiable)
diuretic treatment
electrolyte abnormalities
more than 1 QT-prolonging agents
organ function
Approach to DI QT Prolongation
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
DI TdP - Treatment
stop offending drug(s)
if pulse present - Mg infusion
if no pulse - Mg push
transcutaneous pacing
isoproterenol / epinephrine / atropine infusion
Drug-Induced Heart Failure - Causes
sodium & volume retention
direct cardiotoxicity -> cardiomyopathy
negative inotropy
HF due to Sodium & Volume Retention - Drugs
NSAIDs
steroids
thiazolidinediones
HF due to Cardiomyopathy - Drugs
chemotherapeutic agents
biologic agents (trastuzumab)
alcohol
HF due to Negative Inotropy - Drugs
non-DHP calcium channel blockers
beta-blockers
Chemotherapeutic Agents
anthracyclines (doxorubicin, daunorubicin)
alkylating agents
Anthracycline-Induced Cardiotoxicity - Risk Factors
cumulative dose > 400 mg/m2
dosing schedules
previous anthracycline therapy
radiation therapy
concurrent cardiotoxic agents
Trastuzumab-Induced Cardiomyopathy - Risk Factors
advanced age
presence of CV comorbidities
previous anthracycline therapy
Trastuzumab-Induced Cardiomyopathy - Mechanism
inhibition of HER2 receptors –>
- increased ROS
- reduced NOS expression
- reduced NO bioavailability
- increased angiotensin II
Trastuzumab - BBW
left ventricular cardiac dysfunction, disabling cardiac failure, cardiomyopathy, cardiac death
avoid with history of HF
Trastuzumab-Induced Cardiomyopathy - Treatment
dose adjustment based on LVEF
consider d/c if HF develops
ACE inhibitors / ARBs
beta-blockers
Drug-Induced Myocardial Ischemia & ACS - Mechanisms
increased HR & contractility (increased oxygen demand)
vasospasm (decreased oxygen supply)
coronary artery thrombosis
increased CV risk
Cocaine-Induced MI - Pathophysiology
cocaine inhibits reuptake of norepi -> increased norepi concentrations -> enhanced alpha-1-mediated vasoconstriction of coronary arteries
Cocaine-Induced MI - Treatment
chest pain -> aspirin & benzos
persistent HTN -> benzos & IV nitroglycerin
NSAID-Induced Cardiotoxicity - Mechanism
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
NSAIDs - BBW
may cause an increased risk of serious CV thrombotic events, MI, and stroke, which can be fatal
NSAID-Induced Acute MI - Risk
early in therapy (within 7 days)
> 1200 mg / day of ibuprofen
> 750 mg / day of naproxen
risk increased by 20-50 %
