Esmolol pharmacokinetics

Elestolol sulfate is a nonselective, ultrashort acting P-adrenoceptor blocker. It has no ISA and produces weak inhibition of the fast sodium channel. The dmg is under clinical investigation for supraventricular tachyarrhythmias, unstable angina, and acute MI. In humans, flestolol has hemodynamics and electrophysiologic effects similar to those of other P-adrenoceptor blockers. The pharmacokinetics of flestolol are similar to those of esmolol. It is 50 times more potent than esmolol and the elimination half-life is 7.2 min. Recovery from P-adrenoceptor blockade is 30—45 min after stopping iv infusions. The dmg is hydrolyzed by tissue esterases and no active metabohtes of flestolol have been identified (41). 

Pharmacokinetics. For long-term use, any of the oral preparations of P-blocker is suitable. In emergencies, esmolol may be given i.v. (see Table 24.1). Esmolol has a t) of 9 min, which justifies adininistration by infusion with rapid alterations in dose, possibly titrated against response. 

Benfield P, Sorkin EM. Esmolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs 1987 33(4) 392-412. 

In the case of remifentanil it was also proved that, as predicted by the basic principles used in soft drug design, the possibility of drug interactions could be minimized by building metabolic considerations into the structure. Clearance, volume of distribution, and terminal half-life data indicated that coadministration of esmolol has no significant (P < 0.05) effect on the pharmacokinetics (or pharmacodynamics) of remifentanil in rats, despite both drugs being metabolized by nonspecific esterases (99,100). 

Compare the pharmacokinetics of propranolol, atenolol, esmolol. and nadolol. 

Pharmacokinetics Most of the systemic agents have been developed for chronic oral use, but bioavailability and duration of action vary widely (Table 10-2). Esmolol is a shortacting ester beta-blocker that is only used parenterally. Nadolol is the longest-acting beta-blocker. Acebutolol and atenolol are less lipid-soluble than the older beta-blockers and probably enter the CNS to a lesser extent. 

A) Esmolol s pharmacokinetics are compatible with chronic oral use Metoprolol blocks p2 receptors selectively Nadolol lacks p2 blocking action... 

D. Pharmacokinetics. Peak absorption occurs within 1-4 hours but may be much longer with sustained-release preparations. Volumes of distribution are generally large. Elimination of most agents is by hepatic metabolism, although nadolol is excreted unchanged in the urine and esmolol is rapidly inactivated by red blood cell esterases. (See also Table 11-59, p 381.)... 

Several studies have similarly found that the use of esmolol reduced the required dose of isoflurane or propofol, or resulted in a deeper anaesthesia (as measured by BIS), but only in the presence of an opioid. " As there appears to be no pharmacokinetic interaction between esmolol and propofol it has been suggested that esmolol could be interacting with the opioid. ... 

In 6 patients stabilised on warfarin, acebutolol 300 mg three times daily for 3 days had no effect on prothrombin time response. Similarly, in one patient taking warfarin, neither atenolol 100 mg daily nor metoprolol 100 mg twice daily for 3 weeks had any effect on prothrombin time. Similarly, in studies in healthy subjects the following beta blockers had no clinically relevant effects on the pharmacokinetics and/or anticoagulant response to warfarin atenolol 100 mg daily, betaxolol 20 mg daily, bisoprolol 10 mg daily, esmolol, or metoprolol 100 mg twice daily. In contrast, the minimum steady state plasma warfarin levels of 6 healthy subjects rose by 15% when they took propranolol 80 mg twice daily in one study." Similarly, in another study in 6 healthy subjects given propranolol 80 mg twice daily for 7 days with a single dose of warfarin on day 4, the AUC of warfarin was increased by 16.3% and the in maximum serum level was increased by 23%, but there was no change in the prothrombin time. A patient stabilised on warfarin had a rise in his Brit-... 

In a study in 10 healthy men a 3-mg injeetion of morphine sulfate inereased the steady-state levels of a 300 mierogram/kg per minute infusion of esmolol, given over 4 hours. However, the inereases were only sta-tistieally signifieant in 2 of the subjeets (inerease of 46%), and were considered to be of no clinical importance. The pharmacokinetics of morphine were unchanged. ... 

Mscellaneous. A single dose of intravenous esmolol did not affect the pharmacokinetics of multiple-dose digoxin, except that a small increase was seen in the AUC of digoxin. The pharmacokinetics of multiple-dose digoxin have been shown to be unaffected by acebutolol, bevan-tolol 200 mg daily, bisoprolol 10 mg daily, nebivolol 10 mg daily, or sotalol 80 to 320 mg daily. 

Tabbutt S, Nicolson SC, Adamson PC, Zhang X, Hofhnan ML, Wells W, Backer CL, McGowan FX, Tweddell JS, Bokesch P, Schreiner M. The safety, efficacy, and pharmacokinetics of esmolol for blood pressure control immediately after repair of coarctation of the aorta in infants and... 

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