Pharmacology and Pharmacokinetics of Esmolol

Abstract

Esmolol is an ultra-short-acting beta-adrenergic blocking agent that possesses minimal partial agonist activity or direct membrane depressant activity. The short duration of action of esmolol is attributable to rapid enzymatic hydrolysis by red blood cell esterases, forming ASL-8123 and methanol. Experiments in the constant-flow-perfused isolated canine hindlimb indicate that therapeutic (beta blocking) doses of esmolol lack direct vascular effects and alpha-adrenergic blocking activity and that therapeutic doses do not interfere with vascoconstrictor effects of peripheral sympathetic nerve stimulation. Esmolol produces cardiac electrophysiologic and hemodynamic effects consistent with those of beta blockade. Specifically, esmolol decreases heart rate, depresses atrioventricular nodal conduction, and decreases determinants of myocardial oxygen demand. The beneficial antiarrhythmic and infarct-size limiting effects of esmolol have been demonstrated in several experimental models. Whereas beta blockers in general are effective in settings of supraventricular arrhythmias, sinus tachycardia, and myocardial ischemia, esmolol provides the added dimension of "titratability." Thus, the short duration of action of esmolol allows for very rapid titration to a preferred steady-state level of beta blockade; rapid adjustment to different steady-state levels of beta blockade, as may be required by changing status of the patient, and rapid disappearance of beta blockade following discontinuation of esmolol infusion, should this be necessary in the event of deleterious cardiac hemodynamic effects. Thus, esmolol is ideally suited for use in the treatment of patients in whom beta blockade is desirable, but in whom level of beta blockade must be very carefully modulated.

Quantitative Structure – Pharmacokinetic Relationships for Plasma Clearance of Basic Drugs with Consideration of the Major Elimination Pathway

“…Esmolol has extremely high CL of 290 ml/min/kg and it was highly under-predicted by the model. This may be due to its unique metabolism through rapid hydrolysis by red blood cell esterases (36). Oxycodone seems to be over-predicted by the model (CL 6.1 ml/min/kg, CL pred 19.77 ml/min/kg).…”

Feasibility of Intravenous Administration of Landiolol Hydrochloride for Multislice Computed Tomography Coronary Angiography Initial Experience

“…Landiolol hydrochloride, a new 1-selective agent that has a pharmacological resemblance to esmolol, 19,20 was used in this study for reducing HR. It has previously been demonstrated that landiolol hydrochloride has greater 1-selectivity and a shorter elimination half-life (t1/2) than esmolol.…”

Effect of Esmolol on the Ventricular Fibrillation Threshold

“…Following an intravenous bolus and initiation of a constant infusion, there is a 2.5-min distribution time followed by steady-state blood levels as well as a steadystate beta-adrenergic blockade. Upon dis continuation of infusion, the effects of betaadrenergic blockade are no longer evident after 10-20 min [5], In vitro studies have demonstrated that esmolol has minimal sympathomimetic activity and does not alter the transmembrane action potential at thera peutic concentrations. In addition, in vivo studies have confirmed that esmolol lacks local anesthetic effects at therapeutic con centrations characteristic of class I antiarrhythmic drugs [5],…”

“…Esmolol is a new cardioselective betablocker with unique pharmacologic proper ties [5], Except for the presence of an ester group in the para-position of the phenoxypropranolamine nucleus, it is structurally similar to metoprolol. Because esmolol is rapidly metabolized by plasma esterases present in the red blood cell cytosol into an inactive metabolite, it has a half-life of 9.5 min.…”

“…It is assumed that physiologic or pharmacologic interventions that alter the VFT will produce a similar directional change in the vulnera bility of the ventricles to spontaneous fibril lation [I], The method most widely em-ployed to measure the VFT involves scan ning the ventricular vulnerable period with either a single electrical pulse or a train of electrical pulses. It has been suggested that antiadrenergic interventions may have a more pronounced effect on the VFT mea sured with the train-of-pulses technique than the single-pulse technique because of the greater release of local catecholamines with the train-of-pulses method [2][3][4], Esmolol is a new ultrashort-acting betaantagonist with a half-life of 9'h min [5]. Its major advantage over longer acting betablockers is that its ultrashort half-life en hances the safety margin of the drug.…”