Drugs used in the treatment of heart failure Flashcards
Heart failure (HF
Clinical syndrome associated with symptoms due to abnormalities in
cardiac structure and/or function substantiated by the presence of
increased natriuretic peptide plasma concentrations or objective
evidence of pulmonary or systemic congestion of cardiogenic origin
HF with reduced EF (HFrEF)
HF with LVEF ≤40% (0.4)
HF with mildly reduced EF (HFmrEF)
HF with LVEF 41%49% (0.41-0.49)
HF with preserved EF (HFpEF)
HF with LVEF ≥50% (0.5)
HF with improved EF (HFimpEF
HF with baseline LVEF ≤40% (0.4), a ≥10
point increase from baseline LVEF, and a
second measurement of LVEF >40% (0.4)
Heart failure (HFrEF)
Systolic dysfunction results in a decline in cardiac output leading to the activation of a number of neurohormonal compensatory responses that
attempt to maintain adequate cardiac output, including activation of:
* Sympathetic nervous system (SNS)
* Renin-angiotensin-aldosterone system (RAAS)
* other systems
Primary manifestations of both HFrEF and HFpEF:
- Dyspnea and fatigue, which lead to exercise intolerance
- fluid overload which can result in peripheral oedema and pulmonary congestion.
Class I
Patients with cardiac disease but without limitations of physical activity.
Ordinary physical activity does not cause undue fatigue, dyspnea, or
palpitation.
Class II
Patients with cardiac disease that results in slight limitations of physical
activity. Ordinary physical activity results in fatigue, palpitation, dyspnea, or
angina.
Class III
Patients with cardiac disease that results in marked limitation of physical
activity. Although patients are comfortable at rest, less than ordinary activity
will lead to symptoms.
Class IV
Patients with cardiac disease that results in an inability to carry on physical
activity without discomfort. Symptoms of congestive HF are present even at
rest. With any physical activity, increased discomfort is experienced.
CCF: goals of therapy
- Improve the patient’s quality of life,
- Relieve or reduce symptoms,
- Prevent or minimize hospitalizations,
- Slow progression of the disease, and
- Prolong survival.
First step in the management of chronic HF is to determine
- Classification of HF based upon LVEF and
- Symptomsoms based upon NYHA functional class and/or any precipitating
Stepwise treatment of CCF: STGs and EML
Diuretic
PLUS
ACEI
Add 3rd agent:
carvedilol
OR
Spironolactone
Add 4th agent:
Carvedilol
OR
Spironolactone
Add 5th agent:
Digoxin
Low-ceiling diuretics Thiazides
Hydrochlorothiazide*
High-ceiling diuretics Loop
Furosemide*
Bumetanide
Torasemide
Potassium-sparing Aldosterone antagonists
diuretics
Spironolactone*
Eplerenone
potassium-sparing
Amiloride
Angiotensin-converting
enzyme (ACE) inhibitors
(ACEI
Class I: captopril-like:Captopril
Class II: prodrugs
Enalapril*
Perindopril
Quinapril
Ramipril
Trandolapril
Class III: water soluble Lisinopri
Angiotensin II receptor
blockers (ARBs)
Candesartan
Irbesartan
Losartan*
Telmisartan
Valsartan
Carvedilol: pharmacokinetics
is a non-selective B receptor blocker with additional Alpha 1 blocking.
* Preferred in CCF (dose responsive reduction in mortality)
* Introduce cautiously…start at low dose (3.125mg bd): worsening of CF or
fluid retention may occur during up titration of carvedilol – increase diuretics,
do not increase carvedilol dose until clinically stable
* Dosing for CCF (max doses: 25mg bd – if weight is >85kg 50mg bd)
* Extensive metabolism in the liver with large first-pass effect
(lipophilic)
* Excreted mainly in the bile
- Adverse effects
postural hypotension,
dizziness, oedema of the legs
B-blockers in HF
- Carvedilol, metoprolol and bisoprolol
Spironolactone
Potassium spiring: aldosterone antagonist.
Prolong survival and decrease hospitalizations in patients with HFrEF.
* Considered to reduce the risk of hospitalization in patients with
HFpEF
Digoxin
Digitalis glycoside
positive inotropic effect
(an increase in the force
of contraction), a
negative chronotropic
effect (a decrease in the
heart rate), and a
negative dromotropic
effect (a decrease in
conduction velocity).
Digoxin is unique in its
ability to strengthen
cardiac contraction while
decreasing heart rate.
Digoxin: mechanism of action
Mechanisms by which digoxin exerts its positive inotropic effect on the heart. Digoxin inhibits the sodium pump (ATPase) in the sarcolemma and increases the concentration of intracellular sodium. The high sodium concentration increases the activity of the sodium-calcium exchanger (Ex), thereby causing more calcium to enter or remain inside the cardiac myocyte. Calcium
activates muscle fiber shortening and increases cardiac contractility, which in turn increases stroke volume at any given fiber length
Digoxin: Electrophysiologic and electrocardiographic effects
Figure 12.4 Digoxin causes an increase in parasympathetic (vagal) tone and a decrease in
sympathetic tone. These actions slow the heart rate by decreasing sinoatrial (SA) node automaticity. The increased vagal tone and decreased sympathetic tone also slows the
atrioventricular (AV) node conduction velocity while increasing the AV node refractory period. The
reduced AV conduction velocity increases the PR interval on the electrocardiogram.
Digoxin: pharmacokinetics
- Rate (but not extent) of absorption decreased by food
- Bioavailability varies between preparations (no generic substitution)
- Onset of action 0.5-2 hours (effects last for 6 days)
- Half-life prolonged in renal failure; elimination is renal (50-70%
unchanged) - Narrow therapeutic index: Therapeutic serum concentrations 0.65-
1.1nmol/L - Individualised dosing
Digoxin: adverse effects
Most common adverse effects of digoxin are gastrointestinal, cardiac,
and neurologic reactions.
* Earliest signs of toxicity are anorexia, nausea, and vomiting.
* Arrhythmias, most serious manifestation of digoxin toxicity, atrial
tachycardia with AV block is one of the most common types of
digitalis-induced arrhythmia, but digoxin can also cause ventricular
arrhythmias. Hypokalaemia can precipitate arrhythmias. * Neurologic effects: blurred vision and yellow, green, or blue
chromatopsia (a condition in which objects appear unnaturally
colored). Severe digoxin toxicity can precipitate seizures.
Digoxin: toxicity
Hypokalaemia, hypomagnesaemia, and hypercalcaemia predispose to
toxicity
* Monitoring samples of steady-state serum concentration should be
taken 6-8 hours after last dose
* Patients should be aware of and report signs of toxicity: anorexia,
nauseas and vomiting. CNS signs, headache, drowsiness, facial pain,
depression, mental confusion, disturbed vision
Digoxin: contraindications
- Ventricular arrythmias without HF, Wolf-Parkinson-White syndrome,
hypertrophic obstructive cardiomyopathy, incomplete AV nodal bloc
