ESmOlo1hydrochloride (ASL-80S2) is a ~-adrenoreceptor antagonist
with a very short duration of action. It is the first in a series of compounds
that contains an ester group on the aromatic ring, the basic structure of~-
adrenoreeeptor blockers, since certain esters are known to be
metabolically labile, it was thought that the short duration of esmolol ~-
blocking effect is due to the incorporation of this ester group into the
moecule. Esmolol is rapidly hydrolyzed byesterases found in the cytosole
of red blood cells.
The pharmacokinetic properties of esmolol are distinct, following
intravenous administration, it is rapidly distributed from the ceatral to
peripheral compartment with a distribution half life of 2.03 min. Due to its
leak of lipophilicity the drug is not accessible to the eNS. Esmolol is a
relatively cardioselective (3-blocker. It possess neither (3-adrenoreceptor
parital agonist nor local anaesthetic activity at clinically relevant
concentrations.
In perioperative settings, esmolol attenuates tachycardia induced by
a variety of surgical stimull such as endotracneal intubation, sternotomy
aortic dissection suggesting a clinical use of the drug to prevent potentially
serious complications in surgical patients with cardiovascular diseases. It
has been successfully used for control of supraventricular
tachyarrhythmias (SVT) with response rates favourably compared with
this achieved with propranolol. Preliminary studies has reported that
esmolol exerts significant antihypertensive effects in patients with postoperative
hypertension and beneficial effects in patients with myocardial ischemia and infatction. It has no significant effect on intrammial pressure
or oerebral blood tlow, its apparent lack of effect on cerebrovascular
~.•..•-..
dynamics and intracranial pressure makes it an attractive choice for
management of hypertension in neurosurgical patients.
Laryngoscopy and tracheal intubation are well known to be
accompanied by increase in heart rate and arterial blood pressure. These
changes are transient and well tolerated by most of the patients, but certain
groups of patients who are at risk of developing arterial hypertension,
myocardial ischemia or cardiac dysrrhytbmias, such changes may be
determintal. So, many authors considered the intubation period is one of
periods of greatest risk for those patients.
Deliberate or controlled hypotension is an anaesthetic technique dtat
permits the. clinician to lower arterial blood pressure electively in order to
decrease blood loss during surgery, thereby decreasing the need for blood
transfusion with its potential risks. It also provides a relatively dry surgical
field, thus improving operating conditions at the surgical site and allowing
the surgeon to accomplish successful operations which previously could be
performed only with difficulty and with high rate of mortality.
Several methods and pharmacological agents have been described to
acheive deliberate hypotension. These include: controlled haemorrhage,
high spinal and epidural anaesthesia, inhaled anaesthetics as well as
intravenous drugs. A wide range of intravenous drugs has been used, and
they differ greatly in their mode of action. These include SNP,
nitroglycerin, hydralazine and labetalol.
Whatever the technique, or the pharmacological agent used to
achieve deliberate hypotension, ideally it should allow for rapid and easy modulation of. arterial blood pressure, should not adversely affect the
physiologic responsiveness of differentparts oftbe circulation especially
of vital organs. Moreover, it should not be toxic to the patient or produce
toxic metabolites.
The aim of this work is evaluation of the safety and efficacy of
esmoIol hydrochloride in attneuation of sympathetic response to
endotracheal intubation and as a primary agent for the induction of
controlled hypotension. Also experimentalevaluation of the effects of the
drug in anesthetized animals.
Experimental studeis were done on intact anesthetized rates for
evaluation of the effect of gradually increasingdoses of esmolol, effect of
esmolol on isoprenaline induced hypotension and tachycardia, effect of
esmolol on adrenaline induced anbythmias and drug interaction between
esmolol and morphine. In all experiments heart rate and blood pressure
were recorded.
The results of these experiments revealed that esmolol possessed a
significant dose-related reduction of blood pressure and heart rate when
given by bolus injection, as well as esmololwas effective in controlling
adrenaline induced arrhysthmia, also there was interaction between
morphine and esmolol where morphinepotentiateeffects of esmolol.
In clinical work, the safety and efficacy of esmolol hydrochloride in
attenuation of symptomathetic response to endotracheal intubation was
investigated on 100 patients of both sexe~,ASA I & IT aged 20-40 years,
divided into 5 equal groups, |
