drug induced cardio disorders

main drug induced cardio disorders

htn, arrhythmias, acute coronary syndrome, left ventricular systolic dysfunction + heart failure

mechanism of drug induced htn

drug works on multiple things: SNS activation, RAAS activation, Na retention, increased cardiac output, increased peripheral vascular resistance

risk factors for drug induced htn

hx of htn, decreased egfr (esp <60), metabolic syndrome, older age

which drug classes can cause drug induced htn

VEGF + tyrosine kinase inhibitors, calcineurin inhibitors, NSAIDs, corticosteroids, erythropoiesis-stimulating agents, OCPs, serotonin norepi receptor antagonists, stimulants, drugs of abuse

examples of VEGF + tyrosine kinase inhibtors

bevacizumab, sunitinib, sorafenib, ponatinib

what are VEGF + tyrosine kinase inhibitors used for

chemotherapy for renal, cell, thyroid, and other advanced solid tumors

tx for VEGF + tryrosine kinase inhibitor induced htn

ccbs, acei, k-sparing diuretics

calcineurin inhibitors

potent immunosuppressive drugs used to prevent post transplant rejection

adr is htn!

calcineurin inhibitor examples

cyclosporine, tacrolimus

tx for calcineurin inhibitor induced htn

thiazies (HCTZ)! → selectively block sodium chloride cotransporter (NCC) which may reduce htn

how to NSAIDs induce htn

prostaglandins regulate vascular tone → COX-2 inhibition decreases prostaglandin production → increases na+ + h2o retention → increased BP!

constricts the afferent arteriole → potential kidney damage!

black box warning of NSAIDs

increased risk of serious cardio thrombotic events, MIs, stroke

cox-2 inhibitors have lower gi risk but higher cardio risk!

how to corticosteroids cause htn

increases bp from na+ and h2o retention through mineralocorticoid receptor activity

in which pts is steroid induced htn common

cushing’s syndrome! and other pts taking for other reasons

corticosteroid with no mineralocorticoid

dexamethasone

what are erythropoiesis-stimulating agents used to treat

anemia, CKD, and pts receiving chemo

tx for erythropoiesis-stimulating agent induced htn

dose reduction or changing route from IV to IM

what is responsible for oral contraceptive induced htn

exogenous estrogen and progesterone!

OCP black box warning

endometrial cancer, breast cancer, may increase risk of blood clots, strokes, and heart attacks

what are serotonin norepi receptor antagonists used for

used for tx of GAD, MDD, OCD, PTSD, migraines, panic disorders

examples of serotonin norepi receptor antagonists

desvenlafaxine, venlafaxine, duloxetine

venlafaxine → increase bp by 9% w/ doses >300mg/d (monitor closely)

drugs of abuse that can cause htn

MDMA, PCP, methamphetamines, cocaine → all cause cns sympathetic excess/activation

chronic use → arterial stiffness + athersclerosis → htn

types of arrhythmias caused by drugs

bradyarrhythmia, supraventricular arrhythmia (afib, atrial flutter), qt prolongation, torsade de pointe

mechanisms of arrhythmias

structural abnormalities or electrical changes → affect action potential → cardiac arrhythmias

drug induced bradyarrhythmia

hr <60 bpm, caused by a depressant effect on sinus node automaticity

noncardiac drugs: phenytoin, TCAs, lithium, digoxin, acetylcholine inhibitors

cardiac drugs, bb, ccbs, proarrhythmic drugs

how do acetylcholinesterase inhibitors cause bradyarrhythmia

high ach levels increase parasympathetic tone in SA node → bradyarrhythmia

what are acetylcholinesterase inhibitors used to treat

mild to moderate alzheimer’s

examples of acetylcholinesterase inhibitors

donepezil, neostigmine, physostingmine, pyridostigmine

examples of antiarrhythmics

amiodarone, flecainide, ivabradine, propafenone

→ adverse effects correlates to total amiodarone exposure

which pt population is at higher risk of bradyarrhythmias d/t anti arrhythmics

elderly and those w/ hx of afib or mi

drug induced afib

most common type of arrhythmias but can have serious consequences (eg. stroke)

basically when atria beats irregularly

noncardiac drugs: antidepressants, antipsychotics, anesthetics

cardiac drugs: sympathetic activating agents, antiarrhythmics, diuretics

common afib risk factors

hf, htn, chd, cancer

how do sympathetic activating agents cause afib

sympathomimetic agents activate adrenergic receptors directly by increases norepi and epinephrine (catecholamines)

SNS activation can increase ca2+ dependent cardiac activity → trigger arrhythmias

examples of sympathetic activating agents

dopamine, dobutamine

how do loop and thiazide diuretics caused arrhythmias

cause hypokalemia!! → associated w increased risk of arrhythmias

examples of loop diuretics that cause arrhythmias

furosemide, bumetanide, torsemide, ethacrynic acid

examples of thiazide diuretics that cause arrhythmias

HCTZ, chlorthalidone, indapamide

how do positive inotropes cause arrhythmias

they strengthen contractions of the heart → arrhythmias!

examples of positive inotropes that cause arrhythmias

milrinone, dobutamine, dopamine

torsades de pointe

life threatening arrhythmia!, esp when QTc >500 ms

risk factors for torsades de pointe

qt interval (QTc) >500 ms

female, age >65, bradycardia, acute mi, electrolyte abnormalities, HFrEF, concomitant admin of ≥ 2 QT prolonging drugs

drugs that cause TdP

antiarrhythmics: disopyramide, procainamide, quinidine, sotalol

macrolides: azithromycin, clarithromycin, erythromycin

fluoroquinolones: ciprofloxacin, levofloxacin, moxifloxacin

antifungals: fluconazole, ketoconazole, pentamidine, voriconazole

antipsychotics: haloperidol, ziprasidone

antidepressants: citalopram, escitalopram

antiemetics: droperidol, granisetron, ondansetron

opioids: methadone

others: cocaine, cilostazol, donepezil

clinical presentation of acute coronary syndrome

chest pain, dyspnea, sudden/heavy sweating, racing heartbeat, lightheadedness/dizziness, fainting, unusual fatigue

types of acs

non st elevation: unstable angina, NSTEMI

st elevation: STEMI

drugs associated w/ CV risk factors

corticosteroids: htn, dyslipidemia, dm

cyclosporine, tacrolimus: htn, dyslipidemia

NSAIDs/cox2 inhibitors: htn (minimal)

erythropoietin: htn

HAART: dyslipidemia

all can cause MACE (major adverse cardio events, eg. mi, fatal cad, stroke, death)

main drugs associated w/ MACE

NSAIDs, combined ocps, highly ctive antiretroviral therapy (HAART), erythropoietin

what is HAART used for

management + tx of HIV

how do erythropoiesis-stimulating agents cause acs

increase blood viscosity + platelet activation

Hb increase of >1g/dl over 2 wks may increase risk

make sure to use lowest dose possible for essential therapy

left ventricular systolic dysfxn (LVSD)

left ventricular complication that can lead to hf

heart failure

chronic condition when heart cannot pump adequate blood to organs

clinical presentation of LVSD and HF

sob, swelling of feet + legs, fatigue, difficulty sleeping at night

drug induced LVSD

cytotoxic agents (anthracyclines, trastuzumab)

antipsychotics (clozapine)

TCAs

anthracycline examples

daunorubicin, doxorubicin, idarubicin

how does anthracyclines cause LVSD

irreversible cardiotoxicity (decreased systolic fxn and global longitudinal strain, increased diastolic dysfxn) → cytoplasmic vacuolization, cardiac fibrosis, myofibril loss

what is the lifetime dose and what should you consider in anthracycline induced LVSD

450-500 mg/m²

consider cardioprotection w/ dexrazoxane

how does trastuzumab cause LVSD

humanized mab that targets HER-2 receptor for BCA → reversible cardiotoxicity

what is the lifetime dose and what should you consider in trastuzumab induced LVSD

no lifetime dose

drug cessation

clozapine induced LVSD

associated w/ cardiomyopathy + myocarditis

more common during rapid drug titration!

drugs that exacerbate HF

NSAIDs, cox-2 inhibitors, corticosteroids, thiazolidinediones, negative inotropes

thiazolidinedione induced HF

used for dm tx! (pioglitazone, rosiglitazone)

increases fluid reabsorption in the distal nephron and vascular permeability in adipose tissue

black box warning for thiazolidinediones

cause/exacerbate congestive HF

negative inotrope induced HF

weakens contractions + slows hr

bb: slow hr + should not be initiated during acute hf exacerbation

non dhp ccbs: more negative inotrope effects than dhp ccbs

generally avoid in pt w/ systolic hf even if it is for tx of angina/htn