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9780521704632c13 CUFX213A/Peck 9780521618168 December 28, 2007 12:27
13 Adrenoceptor antagonistsKinetics
Esmolol is only available intravenously and is 60% protein bound. Its volume of
distribution is 3.5 l.kg−^1 .Itisrapidly metabolized by red blood cell esterases to an
essentially inactive acid metabolite (with a long half-life) and methyl alcohol. Its
rapid metabolism ensures a short half-life of 10 minutes. The esterases responsible
for its hydrolysis are distinct from plasma cholinesterase so that it does not prolong
the actions of suxamethonium.
Like otherβ-blockers it may also precipitate heart failure and bronchospasm,
although its short duration of action limits these side effects.
Itis irritant to veins and extravasation may lead to tissue necrosis.Metoprolol
Metoprolol is a relatively cardioselectiveβ-blocker with no intrinsic sympath-
omimetic activity. Early use of metoprolol in myocardial infarction reduces infarct
size and the incidence of ventricular fibrillation. It is also used in hypertension, as an
adjunct in thyrotoxicosis and for migraine prophylaxis. The dose is 50–200 mg daily.
Upto 5 mg may be given intravenously for arrhythmias and in myocardial infarction.Kinetics
Absorption is rapid and complete, but due to hepatic first-pass metabolism, its oral
bioavailability is only 50%. However, this increases to 70% during continuous admin-
istration and is also increased when given with food. Hepatic metabolism may exhibit
genetic polymorphism resulting in two different half-life profiles of 3 and 7 hours. Its
high lipid solubility enables it to cross the blood–brain barrier and also into breast
milk. Only 20% is plasma protein bound.Propranolol
Propranolol is a non-selectiveβ-blocker without intrinsic sympathomimetic activity.
Itexhibits the full range of effects described above at therapeutic concentrations. It is
aracemic mixture, the S-isomer conferring most of its effects, although the R-isomer
is responsible for preventing the peripheral conversion of T 4 to T 3.Uses
Propranolol is used to treat hypertension, angina, essential tremor and in the pro-
phylaxis of migraine. It is theβ-blocker of choice in thyrotoxicosis as it not only
inhibits the effects of the thyroid hormones, but also prevents the peripheral con-
version of T 4 to T 3 .Intravenous doses of 0.5 mg (up to 10 mg) are titrated to effect.
The oral dose ranges from 160 mg to 320 mg daily, but due to increased clearance in
thyrotoxicosis even higher doses may be required.