Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Beta-blocking agents, selective ATC code: C07AB09 Esmolol is a parenteral administered, cardioselective beta- inhibitor.
In therapeutic doses Esmolol does not have intrinsic sympathicomimetic activity (ISA) of importance and no membrane stabilising (local anaesthetic) properties.
Based on the pharmacological properties Esmolol has a fast and short action by which the dose can be quickly adjusted: After a high starting dose a steady state plasma concentration is reached within 5 minutes (without starting dose in 30 minutes). However, the therapeutic effect is sooner obtained than the stabile plasma concentration. The infusion rate can then be adjusted to obtain the desired pharmacological effect.
Esmolol hydrochloride has the known hemodynamic andelectrophysiologic effect of beta-blockers: –   Reduction of the heart frequency during rest and exercise
–   Reduction of the isoprenaline caused increase of the heart frequency –   Increase of the recovering time of the SA-node
–   Delay of the AV-conductance
–   Prolonging the AV-interval with normal sinus rhythm and during atrium stimulation without delay in the His-Purkinje tissue –   Prolonging of PQ time, induction of AV block grade II
-   Prolonging the functional refractory period of atria and ventricles Negative inotrope effect with decreased ejection fraction Decrease in blood pressure 

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
The kinetics of Esmolol are linear in healthy adults, the plasma concentration is proportional to the dose. If a loading dose is not used then steady-state blood concentrations are reached within 30 minutes with doses of 50 to 300 micro-grams/kg per minute.
The distribution half-life of Esmolol hydrochloride is very fast, about 2 minutes. The volume of distribution is 3.4 l/kg.
Esmolol hydrochloride is metabolised by esterases into an acid metabolite (ASL-8123) and methanol. This occurs through hydrolysis of the ester group by esterases in the redblood cells.
The metabolism of Esmolol hydrochloride is independent when the dose is between 50 and 300 micrograms/kg/min.
Esmolol hydrochloride is 55% bound to human plasma protein compared with only 10% for the acid metabolite.
The elimination half-life after intravenous administrationis approximately 9 minutes. The total clearance is285 ml/kg/min; this is independent of the circulation of the liver or any other organ. Esmolol hydrochloride is excreted by the kidneys, partly unchanged (less than 2% of the administered amount), partly as acid metabolite that hasa weak (less than 0.1% of Esmolol) beta-blocking activity. The acid metabolite is excreted in the urine and has a half-life of about 3.7 hours.