| Indication |
For the rapid control of ventricular rate in patients with atrial
fibrillation or atrial flutter in perioperative, postoperative, or other
emergent circumstances where short term control of ventricular rate
with a short-acting agent is desirable. Also used in noncompensatory
sinus tachycardia where the rapid heart rate requires specific
intervention. |
| Pharmacodynamics |
Not Available |
| Mechanism of action |
Similar to other beta-blockers, esmolol blocks the agonistic
effect of the sympathetic neurotransmitters by competing for receptor
binding sites. Because it predominantly blocks the beta-1 receptors in
cardiac tissue, it is said to be cardioselective. In general, so-called
cardioselective beta-blockers are relatively cardioselective; at lower
doses they block beta-1 receptors only but begin to block beta-2
receptors as the dose increases. At therapeutic dosages, esmolol does
not have intrinsic sympathomimetic activity (ISA) or
membrane-stabilizing (quinidine-like) activity. Antiarrhythmic activity
is due to blockade of adrenergic stimulation of cardiac pacemaker
potentials. In the Vaughan Williams classification of antiarrhythmics,
beta-blockers are considered to be class II agents. |
| Absorption |
Rapidly absorbed, steady-state blood levels for dosages from
50-300 µg/kg/min (0.05-0.3 mg/kg/mm) are obtained within five minutes. |
| Volume of distribution |
Not Available |
| Protein binding |
55% bound to human plasma protein, while the acid metabolite is 10% bound. |
| Metabolism |
Rapidly metabolized by hydrolysis of the ester linkage, chiefly
by the esterases in the cytosol of red blood cells and not by plasma
cholinesterases or red cell membrane acetylcholinesterase. Mainly in red
blood cells to a free acid metabolite (with 1/1500 the activity of
esmolol) and methanol. |
| Route of elimination |
Consistent with the high rate of blood-based metabolism of esmolol
hydrochloride, less than 2% of the drug is excreted unchanged in the
urine. The acid metabolite has an elimination half-life of about 3.7
hours and is excreted in the urine with a clearance approximately
equivalent to the glomerular filtration rate.
Excretion of the acid metabolite is significantly decreased in patients
with renal disease, with the elimination half-life increased to about
ten-fold that of normals, and plasma levels considerably elevated. |
| Half life |
Rapid distribution half-life of about 2 minutes and an elimination
half-life of about 9 minutes. The acid metabolite has an elimination
half-life of about 3.7 hours. |
| Clearance |
|
| Toxicity |
Symptoms of overdose include cardiac arrest, bradycardia, hypotension, electromechanical dissociation and loss of consciousness. |
