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.

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.

toxicity

Symptoms of overdose include cardiac arrest, bradycardia, hypotension, electromechanical dissociation and loss of consciousness.

biotransformation

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.

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.

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.

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.

drug interactions

Acetohexamide: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Chlorpropamide: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Clonidine: Increased hypertension when clonidine stopped

Dihydroergotamine: Ischemia with risk of gangrene

Dihydroergotoxine: Ischemia with risk of gangrene

Disopyramide: The beta-blocker, esmolol, may increase the adverse effects of disopyramide.

Epinephrine: Hypertension, then bradycardia

Ergonovine: Ischemia with risk of gangrene

Ergotamine: Ischemia with risk of gangrene

Fenoterol: Antagonism

Formoterol: Antagonism

Gliclazide: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Glipizide: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Glisoxepide: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Glyburide: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Glycodiazine: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Ibuprofen: Risk of inhibition of renal prostaglandins

Indomethacin: Risk of inhibition of renal prostaglandins

Insulin Aspart: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Insulin Detemir: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Insulin Glargine: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Insulin Glulisine: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Insulin Lispro: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Isoproterenol: Antagonism

Lidocaine: The beta-blocker, esmolol, may increase the effect and toxicity of lidocaine.

Methysergide: Ischemia with risk of gangrene

Orciprenaline: Antagonism

Pipobroman: Antagonism

Pirbuterol: Antagonism

Piroxicam: Risk of inhibition of renal prostaglandins

Prazosin: Risk of hypotension at the beginning of therapy

Procaterol: Antagonism

Repaglinide: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Salbutamol: Antagonism

Salmeterol: Antagonism

Terazosin: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Terbutaline: Antagonism

Tolazamide: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Tolbutamide: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Verapamil: Increased effect of both drugs