Active ingredient: Esmolol - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Adrenergic beta-Antagonists

Dosage Forms

• Liquid

Brands / Synonyms

Brevibloc; Esmolol HCL; Esmolol Hydrochloride

Indications

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.

Pharmacology

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.

Toxicity

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

Biotrnasformation / Drug 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.

Contraindications

BREVIBLOC (esmolol HCl) is contraindicated in patients with sinus bradycardia, heart block greater than first degree, cardiogenic shock or overt heart failure.

Drug Interactions

Catecholamine-depleting drugs, e.g., reserpine, may have an additive effect when given with beta blocking agents. Patients treated concurrently with BREVIBLOC (esmolol HCl) and a catecholamine depletor should therefore be closely observed for evidence of hypotension or marked bradycardia, which may result in vertigo, syncope, or postural hypotension.

A study of interaction between BREVIBLOC and warfarin showed that concomitant administration of BREVIBLOC and warfarin does not alter warfarin plasma levels. BREVIBLOC concentrations were equivocally higher when given with warfarin, but this is not likely to be clinically important.

When digoxin and BREVIBLOC were concomitantly administered intravenously to normal volunteers, there was a 10-20% increase in digoxin blood levels at some time points. Digoxin did not affect BREVIBLOC pharmacokinetics. When intravenous morphine and BREVIBLOC were concomitantly administered in normal subjects, no effect on morphine blood levels was seen, but BREVIBLOC steady-state blood levels were increased by 46% in the presence of morphine. No other pharmacokinetic parameters were changed.

The effect of BREVIBLOC on the duration of succinylcholine-induced neuromuscular blockade was studied in patients undergoing surgery. The onset of neuromuscular blockade by succinylcholine was unaffected by BREVIBLOC, but the duration of neuromuscular blockade was prolonged from 5 minutes to 8 minutes.

Although the interactions observed in these studies do not appear to be of major clinical importance, BREVIBLOC should be titrated with caution in patients being treated concurrently with digoxin, morphine, succinylcholine or warfarin.

While taking beta blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

Caution should be exercised when considering the use of BREVIBLOC and verapamil in patients with depressed myocardial function. Fatal cardiac arrests have occurred in patients receiving both drugs. Additionally, BREVIBLOC should not be used to control supraventricular tachycardia in the presence of agents which are vasoconstrictive and inotropic such as dopamine, epinephrine, and norepinephrine because of the danger of blocking cardiac contractility when systemic vascular resistance is high.