Drugs for Heart Failure Flashcards
Positively Inotropic Drugs
Digoxin
Dobutamine
Milrinone
Levosimendan
Positively Inotropic Drugs - MoA
Increase cardiac contractility by increasing Ca levels in cardiac myocytes.
Digoxin - MoA
Positive inotropic effect (increase in the force of contraction): increasing intracellular calcium as a result of inhibiting the sodium pump in the plasma membrane. When the sodium pump is inhibited, the concentration of intracellular sodium is increase, thereby increasing the activity of the sodium-calcium exchanger, causing more calcium to enter the cardiac myocyte. The increase in cytoplasmic calcium, stimulates the release of additional calcium from the sarcoplasmic reticulum and increases the rate of myofibril shortening (muscle contraction). These actions increase stroke volume and cardiac output.
Positive Bathmotropic effect
Negative chronotropic effect (a decrease in heart rate):
Increased PNS activity while decreased SNS activity –> decreased HR and AV node conduction velocity, while increased AV node refractory period.
Negative dromotropic effect (decrease in conduction velocity)
Digoxin - Clincal use
Heart failure (esp systolic heart failure, not used to treat diastolic).
It does not treat heart failure, or prolong survival, it reduces symptoms and the need for hospitalization.
Slow ventricular rate in pt with atrial fibrillation (by slowing AV node conduction velocity and increasing AV node refractory period –> increased nr of ectopic impulses transmitted to the ventricles.
Digoxin - Adverse effects
Increased abnormal impulse formation by evoking spontaneous afterdepolarizations (occur during or after cardiac repolarization –> extrasystoles –> tachycardia)
Decreased QT-interval: shortens ventricular action potential duration by accelerating repolarization
Decreased AV node conduction velocity –> increased PR interval –> ST depression –> “hockey stick configuration” on the ST segment
Most common: GI, cardiac and neurologic reactions
Earlies signs of toxicity:
Anorexia
Nausea
Vomiting
Cardiac arrhythmias (AV block, tachyarrhythmias)
Most common digitalis induces arrhythmia: Atrial tachycardia with AV block
Ventricular arrhythmias
Neurologic effects of Digoxin toxicity: blurred vision, yellow-green or blue chromatopsia, seizures.
Hypokalemia can precipitate arrhythmias in patients receiving digoxin.
Gynecomastia: because of some estrogenic activity
Digoxin - Interactions
Antacids and cholestyramine can reduce the absorption of digoxin (should be separated by 2h)
Diltiazem, quinidine, verapamil increase levels –> toxicity
Loop acting thiazide drugs cause hypokalemia –> precipitate digitalis toxicity because reduced K+ concentrations increases digitalis binding to the Na pump.
Digoxin immune fab: antidote. Given iv
Dobutamine - MoA
Selectively stimulates cardiac contractility, and causes less tachycardia then the other b-adrenoceptor agonists.
Activates b2-adrenoceptors in vascular smooth muscle, decreases vascular resistance, CO –> augmenting CO.
Increases ca influx by increasing cAMP levels by way of adenylyl cyclase
Dobutamine - Clinical use
Acute heart failure
Cardiogenic shock
Heart failure
Dobutamine - Adverse effects
Excessive vasoconstriction and tachyarrhythmias
Dobutamine - Interactions
Adrenoceptor agonists and antagonists
Milrinone - MoA
Inhibits type 3 phosphodiesterase, an enzyme that converts cAMP to inactive 5´-AMP. By increasing the concentration of cAMP in myocyte –> stimulates cardiac contractility. It also increases cAMP in vascular smooth muscle and produces vasodilation.
Increases ca influx by increasing cAMP levels by w inhibiting cAMP breakdown by phosphodiesterase.
Milrinone - Clinical use
Short term management of heart failure in patients not responsive to other drugs.
Inotropic support for children awaiting cardiac transplantation.
Other conditions that require myocardial stimulation.
Milrinone - Adverse effects
Long term use: thrombocytopenia, ventricular arrhythmias,
Ass with increased mortality in patients with severe heart failure.
Hypotension
Calcium sensitizer drug
Levosimendan
Levosimendan - MoA
it increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Levosimendan exerts its positive inotropic effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner. It also has a vasodilatory effect, by opening adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle to cause smooth muscle relaxation.
Levosimendan - Clinical use
Acute heart failure
Levosimendan - Adverse effects
Headache
Hypotension
Atrial Fibrillation
Vasodilators
Angiotensin-Converting Enzyme inhibitors (ACE inhibitors) Angiotensin receptor blockers (ARBs) Natriuretic peptide Neprilysin Inhibitor Hydralazine and Nitrates
ACE inhibitors
Ramipril
Enalapril
Lisinopril
ACE inhibitors - MoA
Reduce formation of angiotensin II. Angiotensin II has several actions that contribute to the pathogenesis of heart failure, including vasocontraction and increased secretion of aldosterone and antidiuretic hormone.
Effect:
Decrease plasma V, venous pressure, edema, increase CO by reducing arterial resistance and cardiac afterload.
Counteract adverse effect of angiotensin that contribute to cardiac remodeling in pt with heart failure.
ACE inhibitors - Clinical use
Diabetic nephropathy
Hypertension
Heart failure
Acute myocardial infarction: improve survival when adm within 24h of onset of symptoms.
ARBs
Valsartan
Candesartan
ARBs - MoA
Prevent binding of angiotensin II to AT1 receptor
ARBs - Clinical use
Reduce mortality and hospitalization in persons with heart failure. ARB are indicated for persons who cannot tolerate ACE inhibitors.
Hydralazine and Nitrates - MoA
H-Relaxes arterial smooth muscle
N-Relaxes venous smooth muscle
The combination of these two drugs reduces cardiac preload and afterload, –> reduced venous pressure and edema and increase cardiac output, respectively.
Hydralazine and Nitrates - Clinical use
Used to treat heart failure in pat who cannot tolerate angiotensin inhibitors.
Black patients with heart failure(less effect of ACE inh)
Human B-type natriuretic peptide
Nesiritide
Nesiritide - MoA
Binds to guanylate cyclase receptors in vascular smooth muscle and endothelial cells, leading to increased intracellular concentration of cyclic guanosine monophosphate cGMP. cGMP acts as a second messenger to dilate venous and arterial smooth muscle, thereby leading to reduction in venous and arterial pressure in patients with heart failure.
Leads to reduced pulmonary capillary wedge pressure –> decrease vascular congestion and dyspnea in decompensated pt w heart failure
Nesiritide - Clinical use
Acute decompensated heart failure with dyspnea at rest or with minimal activity.
Nesiritide - Adverse effects
Hypotension
Neprilysin inhibitor
Sacubitril
Sacubitril - MoA
Raises levels of vasoactive peptides (bradykinin, natriuretic peptides) –> decrease cardiac remodeling, vasoconstriction and sodium retention.
Sacubitril - Clinical use
Decrease death rates in pt with systolic heart failure
Decrease hospitialization due to heart failure
Hypertension when comb with ACE inh
B-adrenoreceptor antagonists
Carvediol (a + b)
Metoprolol
Bisoprolol
B-adrenoreceptor antagonists - MoA
The benefits of b-blockers are caused by the ability of these drugs to reduce excessive sympathetic stimulation of the heart and circulation in patients with heart failure.
Carvedilol: increase left ventricular ejection fraction, improve symptoms and slow disease progression
B-adrenoreceptor antagonists - Clinical use
Mild to severe heart failure caused by left ventricular systolic dysfunction.
Carvedilol: all pat with symptomatic heart failure who do not have significant hypotension, pulmonary congestion or AV block.
Carvedilol reduces hospitalization and mortality in persons with heart failure when it is added to a standard treatment regimen
Aldosterone antagonists
Spironolactone
Eplerenone
Aldosterone antagonists - MoA
Compete with aldosterone for the mineralocorticoid receptor in the renal tubules and other tissues. These drugs act on kidneys to increase sodium excretion and decrease potassium excretion.
Aldosterone antagonists - Clinical use
Spironolactone: reduce mortality in severe heart failure
Mild to moderate heart failure
Aldosterone antagonists - Adverse effects
Hyperkalemia
Gynecomastia
Impotence in some male pat.
Diuretics - MoA
Are used to reduce plasma volume and edema, thereby relieve symptoms of volume overload such as dyspnea.
Diuretics - Clinical use
Loop diuretics (bumetanide, furosemide, toresemide) have greater natriuretic act then other and are preferred for reducing plasma volume, must be used carefully to avoid, dehydration, hyponatremia and hypokalemia.
