Page 239 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 13 Drugs Used in Heart Failure 225

Pharmacokinetics,
Subclass, Drug Mechanism of Action Effects Clinical Applications Toxicities, Interactions
BETA BLOCKERS
• Carvedilol Competitively blocks β 1 Slows heart rate • reduces Chronic heart failure: To slow Oral • duration 10–12 h • Toxicity:
receptors (see Chapter 10) blood pressure • poorly progression • reduce mortality Bronchospasm, bradycardia,
understood other effects in moderate and severe heart atrioventricular block, acute
failure • many other cardiac decompensation • see
indications in Chapter 10 Chapter 10 for other toxicities
and interactions
• Metoprolol, bisoprolol, nebivolol: Select group of b blockers that have been shown to reduce heart failure mortality
CARDIAC GLYCOSIDE
+
+
• Digoxin (other Na /K -ATPase inhibition results Increases cardiac contractility Chronic symptomatic heart Oral, parenteral • duration
2+
glycosides are used in reduced Ca expulsion and • cardiac parasympathomimetic failure • rapid ventricular rate 36–40 h • Toxicity: Nausea,
2+
outside the USA) increased Ca stored in effect (slowed sinus heart rate, in atrial fibrillation • has not vomiting, diarrhea • cardiac
sarcoplasmic reticulum slowed atrioventricular been shown to reduce arrhythmias
conduction) mortality but does reduce
rehospitalization
VASODILATORS
Venodilators: Releases nitric oxide (NO) Venodilation • reduces Acute and chronic heart Oral • duration 4–6 h • Toxicity:
• Isosorbide dinitrate • activates guanylyl cyclase preload and ventricular failure • angina Postural hypotension,
(see Chapter 12) stretch tachycardia, headache •
Interactions: Additive with other
vasodilators and synergistic
with phosphodiesterase type 5
inhibitors
Arteriolar dilators: Probably increases NO Reduces blood pressure Hydralazine plus nitrates may Oral • duration 8–12 h • Toxicity:
• Hydralazine synthesis in endothelium and afterload • results in reduce mortality in African- Tachycardia, fluid retention,
(see Chapter 11) increased cardiac output Americans lupus-like syndrome
Combined arteriolar Releases NO spontaneously Marked vasodilation Acute cardiac IV only • duration 1–2 min
and venodilator: • activates guanylyl cyclase • reduces preload and decompensation • Toxicity: Excessive hypotension,
• Nitroprusside afterload • hypertensive emergencies thiocyanate and cyanide
(malignant hypertension) toxicity • Interactions: Additive
with other vasodilators
BETA-ADRENOCEPTOR AGONISTS
• Dobutamine Beta 1 -selective agonist Increases cardiac Acute decompensated IV only • duration a few
• increases cAMP synthesis contractility, output heart failure minutes • Toxicity: Arrhythmias
• Interactions: Additive with
other sympathomimetics

• Dopamine Dopamine receptor agonist Increases renal blood flow Acute decompensated heart IV only • duration a few
• higher doses activate β and • higher doses increase failure • shock minutes • Toxicity: Arrhythmias
α adrenoceptors cardiac force and blood • Interactions: Additive with
pressure sympathomimetics
BIPYRIDINES
• Milrinone Phosphodiesterase type 3 Vasodilator; lower peripheral Acute decompensated heart IV only • duration 3–6 h
inhibitor • decreases cAMP vascular resistance • also failure • increases mortality in • Toxicity: Arrhythmias
breakdown increases cardiac chronic failure • Interactions: Additive with
contractility other arrhythmogenic agents

NATRIURETIC PEPTIDE
• Nesiritide Activates BNP receptors, Vasodilation • diuresis Acute decompensated failure IV only • duration 18 min
increases cGMP • has not been shown to • Toxicity: Renal damage,
reduce mortality hypotension, may increase
mortality
NEPRILYSIN INHIBITOR
• Sacubitril (used only Inhibits neprilysin, thus Vasodilator Chronic failure • combination Oral • duration 12 h • used only
in combination with reducing breakdown of ANP reduces mortality and in combination with ARB
valsartan [ARNI]) and BNP; valsartan inhibits rehospitalizations • Toxicity: Hypotension,
action of angiotensin on its angioedema
receptors