Page 238 - Basic _ Clinical Pharmacology ( PDFDrive )

224 SECTION III Cardiovascular-Renal Drugs

pulmonary capillary wedge pressure are particularly useful in patients Vasodilators in use in patients with acute decompensation include
with acute myocardial infarction and acute heart failure. Patients nitroprusside, nitroglycerine, and nesiritide. Reduction in after-
with acute myocardial infarction are often treated with emergency load often improves ejection fraction, but improved survival has
revascularization using either coronary angioplasty and a stent, or a not been documented. A small subset of patients in acute heart
thrombolytic agent. Even with revascularization, acute failure may failure will have dilutional hyponatremia, presumably due to
develop in such patients. increased vasopressin activity. A V and V receptor antagonist,
1a
2
Intravenous treatment is the rule in drug therapy of acute conivaptan, is approved for parenteral treatment of euvolemic
heart failure. Among diuretics, furosemide is the most commonly hyponatremia. Some clinical trials have indicated that this drug
used. Dopamine or dobutamine are positive inotropic drugs with and related V antagonists (tolvaptan) may have a beneficial
2
prompt onset and short durations of action; they are most useful effect in some patients with acute heart failure and hyponatremia.
in patients with failure complicated by severe hypotension. Levo- However, vasopressin antagonists do not seem to reduce mortality.
simendan has been approved for use in acute failure in Europe, Clinical trials are under way with the myosin activator, omecamtiv
and noninferiority has been demonstrated against dobutamine. mecarbil.

SUMMARY Drugs Used in Heart Failure

Pharmacokinetics,
Subclass, Drug Mechanism of Action Effects Clinical Applications Toxicities, Interactions
DIURETICS
• Furosemide Loop diuretic: Decreases NaCl Increased excretion of salt Acute and chronic heart Oral and IV • duration 2–4 h
and KCl reabsorption in thick and water • reduces cardiac failure • severe hypertension • Toxicity: Hypovolemia,
ascending limb of the loop of preload and afterload • edematous conditions hypokalemia, orthostatic
Henle in the nephron (see • reduces pulmonary and hypotension, ototoxicity,
Chapter 15) peripheral edema sulfonamide allergy
• Hydrochlorothiazide Decreases NaCl reabsorption in Same as furosemide, but Mild chronic failure • mild- Oral only • duration 10–12 h
the distal convoluted tubule much less efficacious moderate hypertension • • Toxicity: Hyponatremia,
hypercalciuria • has not been hypokalemia, hyperglycemia,
shown to reduce mortality hyperuricemia, hyperlipidemia,
sulfonamide allergy
• Three other loop diuretics: Bumetanide and torsemide similar to furosemide; ethacrynic acid not a sulfonamide
• Many other thiazides: All basically similar to hydrochlorothiazide, differing only in pharmacokinetics
ALDOSTERONE ANTAGONISTS
• Spironolactone Blocks cytoplasmic aldosterone Increased salt and water Chronic heart failure Oral • duration 24–72 h (slow
receptors in collecting tubules excretion • reduces • aldosteronism (cirrhosis, onset and offset) • Toxicity:
of nephron • possible remodeling adrenal tumor) Hyperkalemia, antiandrogen
membrane effect • hypertension • has been actions
shown to reduce mortality
• Eplerenone: Similar to spironolactone; more selective antimineralocorticoid effect; no significant antiandrogen action; has been shown to reduce mortality
ANGIOTENSIN ANTAGONISTS
Angiotensin-converting Inhibits ACE • reduces AII Arteriolar and venous Chronic heart failure Oral • half-life 2–4 h but given
enzyme (ACE) inhibitors: formation by inhibiting dilation • reduces • hypertension • diabetic in large doses so duration
• Captopril conversion of AI to AII aldosterone secretion renal disease • has been 12–24 h • Toxicity: Cough,
• reduces cardiac remodeling shown to reduce mortality hyperkalemia, angioneurotic
edema • Interactions: Additive
with other angiotensin
antagonists
Angiotensin receptor Antagonize AII effects at AT 1 Like ACE inhibitors Like ACE inhibitors • used in Oral • duration 6–8 h • Toxicity:
blockers (ARBs): receptors patients intolerant to ACE Hyperkalemia; angioneurotic
• Losartan inhibitors • has been shown edema • Interactions: Additive
to reduce mortality with other angiotensin
antagonists
• Enalapril, many other ACE inhibitors: Like captopril
• Candesartan, valsartan, many other ARBs: Like losartan

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