Heart Failure Flashcards
Drugs used for systolic heart failure?
- Diuretics
- Spironolactone
- Inhibitors of angiotensin (ACE-inhibitors / ARBs)
- Direct vasodilators
- b-adrenoceptor antagonists (b-blockers)
- Inotropic agents
Drugs used for diastolic heart failure?
- Diuretics
- ACEI /ARBs
- b-adrenoceptor antagonists (b-blockers)
- Calcium-channel antagonists
Diuretic MOA in HF?
• Relieve pulmonary congestion & peripheral edema
• Reduce symptoms of volume overload (eg,
orthopnea)
• plasma volume à venous return to the heart
(preload)
à cardiac workload & O2 demand
• Also afterload (reducing plasma volume à BP)
Diuretic clinical applications in heart failure?
• Integral component of treatment for congestive symptoms
and/or intravascular volume overload
• No evidence of a mortality benefit with thiazide or
loop diuretics alone
Thiazide diuretics : patients with hypertensive heart
disease (with congestive symptoms). Often ineffective as
monotherapy due to weak diuretic effect
Loop diuretics : more effective diuretics than thiazides
(useful if edema present)
ACE inhibitor role in heart failure?
• Agents of choice in HF
decrease vascular resistance & BP à cardiac output (afterload)
decrease salt & H20 retention ( preload)
decrease long-term remodeling of the heart
ACE inhibitors improve symptoms in patients with HF,
decrease incidence of hospitalization & MI, and
prolong survival
ACE inhibitors recommended and suggested for who in regards to HF?
Captopril / Enalapril / Lisinopril
Recommended for all patients with:
• symptomatic heart failure
• asymptomatic patients with decreased LVEF or
history of MI
Suggested for patients:
• at high risk of developing heart failure due to
atherosclerotic disease, obesity, diabetes
mellitus or hypertension
ACE inhibitor AE?
• Hypotension, • Persistent dry cough • Hyperkalemia • Angioedema • Acute renal failure (patients with bilateral renal artery stenosis) • Teratogenic
ARB moa, use, and AE in heart failure?
Candesartan / Valsartan Potent competitive antagonists of angiotensin type I receptor DO NOT affect bradykinin levels Clinical Application In HF Substitute for patients who can’t tolerate ACE inhibitors (severe cough or angioedema) Adverse Effects Similar to ACE inhibitors (no cough) Teratogenic
Direct vasodilators MOA in HF?
Hydralazine + isosorbide dinitrate
increase vasodilation -> decrease cardiac preload
increase arterial dilation -> systemic arteriolar resistance & decrease afterload
• Concurrent use of two oral vasodilators: hydralazine
& isosorbide dinitrate can produce sustained
improvement in LVEF
Vasodilator Site of Dilating Action
Hydralazine- Arterioles
Nitrates- Veins and Venules
ACE inhibitors- Arterioles and Veins
Direct vasodilators clinical applications?
• Concurrent use of hydralazine & isosorbide dinitrate
recommended for use in patients:
• who cannot tolerate ACEI or ARB
or,
• in African American patients with advanced
heart failure as an adjunct to standard therapy
Direct vasodilators AE?
Hydralazine & isosorbide dinitrate
Headache, dizziness
Hydralazine
Tachycardia, peripheral neuritis, lupus-like syndrome
Contraindications
Sildenafil
Beta blocker use in HF?
Studies demonstrate reverse cardiac remodeling &
reduction in mortality & hospitalization (30-40% in
patients with NYHA II-IV HF)
• decrease HR and decrease contractility & inhibition of renin release (b1 receptors)
• Prevent deleterious effects of norepinephrine on cardiac
muscle fibers -> decrease remodeling, hypertrophy etc
• Can get initial exacerbation of symptoms (start at low
dose & gradually increase over several weeks)
Clinical applications of beta blockers in HF?
Recommended in addition to an ACEI for patients with:
- symptomatic heart failure
- asymptomatic patients with a decreased LVEF
or history of MI
NB. USE CAUTIOUSLY in decompensated HF and are
contraindicated in cardiogenic shock
Beta blocker AE?
• Same as all b-blockers
• Use cautiously in asthmatics and patients with severe
bradycardia
• Fluid retention (upon initial treatment) – an increasing
dose of concurrent diuretic may help
Spironolactone role and moa in heart failure?
Patients with advanced heart disease have elevated
aldosterone levels due to:
• angiotensin stimulation
• reduced hepatic clearance
MOA
Aldosterone antagonist à prevents Na+ retention,
myocardial hypertrophy & hypokalemia
Spironolactone clinical applications and AE in HF?
Clinical Application in HF
+ ACE inhibitors are shown to decrease
morbidity & mortality in patients with severe
heart failure
Adverse Effects
Hyperkalemia (esp. in patients taking ACEIs/ARBs,
K+ supplements or who have renal failure)
GI disturbances (gastritis, peptic ulcer)
CNS effects (lethargy, confusion)
Endocrine abnormalities (gynecomastia, decreased
libido, menstrual irregularities)
What is digoxin?
Ionotropic agent
• Cardiac glycoside
• Derived from digitalis (foxglove) plant
• Widely used in treatment of HF
• Digoxin can decrease the symptoms of heart failure,
increase exercise tolerance and decrease rate of
hospitalization, but DOES NOT increase survival
Disadvantages of Digoxin?
Disadvantages
• Narrow therapeutic margin
• Unfavourable, complicated pharmacokinetics
• Drug sensitivity varies between patients
• Drug sensitivity may change during therapy
• Severe, potentially lethal adverse effects
Digoxin MOA?
Positively inotropic
• Increases force of heart contraction
Negatively chronotropic
• Decreases heart rate
• Inotropic action : increase cytoplasmic Ca2+ concentration that enhances contractility of cardiac muscle and -> increases cardiac output • also • enhances vagal tone -> decrease HR • reduces sympathetic activity • reduces peripheral resistance -> decrease myocardial O2 demand
Digoxin MOA on membrane and flux calcium?
• [Ca2+]i must be lowered for cardiac muscle to relax
• Na+/Ca2+ exchanger extrudes Ca2+ from myocyte
• Concentration gradient determines net ion movement
• Inhibiting active transport of Na+ decreases Na+
concentration gradient & ability for Ca2+ to leave cell
• Increased cellular Na+ is exchanged for Ca2+
• Ca2+ is retained intracellularly -> increased [Ca2+]i
• If Na+/K+ ATPase is extensively inhibited ->
dysrhythmias
Summary of Digoxin effects?
• Effects of digoxin result from direct action on cardiac
muscle as well as indirect actions (autonomic
effects):
• increase force and velocity of myocardial systolic
contraction (+ve inotropic action)
• decrease in the degree of activation of SNS & renin angiotensin system (-ve chronotropic action)
• Slowing of the HR & decrease conduction velocity through AV node (-ve chronotropic and –ve dromotropic
action)
Digoxin clinical applications?
• HF with atrial fibrillation (main application)
• Can be used (in addition to ACEI & b-blocker) to
decrease symptoms, increase exercise tolerance &
decrease rate of hospitalization
Digoxin PK?
• Very potent (narrow safety margin) • Widely distributed (including CSF) • t ½ = ~36-40 h • Accumulates in muscle à large Vd (loading dose required)
Digoxin AE?
Digoxin toxicity = one of most common ADRs
• Cardiac effects: arrhythmias, characterized by slowing of
AV conduction (atrial arrhythmias)
• GI effects: anorexia, nausea & vomiting
• CNS effects: headache, fatigue, confusion, blurred vision,
alteration of color perception, halos on dark objects