Controlled Beta‐Receptor Blockade with Esmolol and Flestolol

Abstract

Beta-receptor-blocking agents are commonly used in the management of various cardiovascular diseases. Recently, esmolol, a pharmacokinetically novel cardioselective beta-receptor-blocking agent, has been introduced for use in the treatment of critically ill patients. It is devoid of intrinsic sympathomimetic activity and in doses used clinically, it has no direct depressant effect on the heart. Esmolol is an ester and is metabolized by choline-esterase to ASL 8123, an inactive molecule. Esmolol has an elimination half-life of nine minutes which accounts for its ultrashort duration of action. This unique pharmacokinetic property provides two advantages over other longer-acting beta-receptor-blocking agents. First, the magnitude of beta-receptor blockade can be titrated to a desired level. Second, if adverse effects are experienced, reducing the dosage or terminating the infusion results in rapid reversal of its pharmacological effects. Another ultrashort-acting, non-cardioselective beta-receptor blocking agent, flestolol is undergoing clinical evaluation. Esmolol has been approved for the management of supraventricular tachycardia. The clinical safety of these novel drugs will expand the use of beta-receptor-blocking agents in the management of cardiovascular diseases in critically ill patients.

Evaluating a Possible Pharmacokinetic Interaction between Remifentanil and Esmolol in the Rat

“…8,16,17 After iv administration, esmolol is rapidly metabolized into an inactive acid metabolite and methanol ( Figure 2). 23,24,27 Following a 2-h infusion, esmolol had an apparent volume of central compartment of 867 mL/kg and a total body clearance of 285 mL/min/kg in healthy volunteers. 28 Clearance in dogs was 360 mL/min/kg after 60-min infusions of 25, 50, and 100 µg/kg/min.…”

A Historical Perspective on the Development of β‐Adrenergic Blockers

“…Since intravenous propranolol was introduced for arrhythmias, intravenous forms of atenolol and metoprolol have become available for use in the hyperacute phase of myocardial infarction (MI), 27 and intravenous labetalol has been approved for use in hypertensive emergencies. Esmolol, an ultra‐short‐acting β 1 ‐selective agent with a unique metabolic pathway related to hepatic and blood esterases, is also available for the treatment of arrhythmias 28,29 . Recently, it has been observed that there are genetic polymorphisms that can influence the hepatic metabolism of various β‐blocking drugs including propranolol, metoprolol, timolol, and carvedilol 20,23,30,31 …”

“…Esmolol, an ultrashort-acting β 1 -selective agent with a unique metabolic pathway related to hepatic and blood esterases, is also available for the treatment of arrhythmias. 28,29 Recently, it has been observed that there are genetic polymorphisms that can influence the hepatic metabolism of various β-blocking drugs including propranolol, metoprolol, timolol, and carvedilol. 20,23,30,31…”

“…1 Subsequently, oral acebutolol, a drug with both β 1 -selectivity and ISA, was approved as a treatment for patients with ventricular arrhythmias, 1 and intravenous esmolol, a β 1 -adrenergic blocker, was approved for intravenous use to treat supraventricular arrhythmias. 28,38 Finally, oral sotalol, a nonselective β-blocker with unique type III antiarrhythmic effects, was approved as a treatment for both supraventricular and ventricular arrhythmias. 1,39,40 As antiarrhythmic drugs, no other group of agents have shown the long-term safety profile exhibited by β-blocking agents.…”

The negative inotropic effect of esmolol on isolated cardiac muscle

“…Esmolol is a short-acting beta adrenergic receptor blocking agent for intravenous use with great clinical value (1). Its haemodynamic and electrophysiological effects are similar to those of other beta blockers (2).…”