Acebutolol

Pharmacology

Acebutolol is a cardioselective beta blocker with ISA (Intrinsic Sympathomimetic Activity, see article on Pindolol). It is therefore more suitable than non cardioselective beta blockers, if a patient with Asthma bronchiale or chronic obstructive pulmonary disease (COPD) needs treatment with a beta blocker. In doses lower than 800mg daily its constricting effects on the bronchial system and smooth muscle vessels are only 10% to 30% of those observed under Propranolol treatment, but there is experimental evidence that the cardioselective properties diminish at doses of 800mg/day or more. The drug has lipophilic properties, and therefore crosses the Blood-Brain Barrier. Acebutolol has no negative impact on serum lipids (cholesterol and triglycerides). No HDL decrease has been observed. In this regard, it is unlike many other beta blockers which have this unfavourable property. The drug works in hypertensive patients with high, normal, or low renin plasma concentrations, although acebutolol may be more efficient in patients with high or normal renin plasma concentrations. In clinically relevant concentrations, a membrane-stabilizing effect does not appear to play an important role.

Pharmacokinetics

Acebutolol is well absorbed from the GI tract, but undergoes substantial first-pass-metabolization, leading to a bioavailability of only 35% to 50%. Peak plasma levels of acebutolol are reached within 2 to 2. 5 hours after oral dosing. Peak levels of the main active metabolite, diacetolol, are reached after 4 hours. Acebutolol has a halflife of 3 to 4 hours, and diacetolol a halflife of 8 to 13 hours. Acebutolol undergoes extensive hepatic metabolization resulting in the desbutyl amine acetolol which is readily converted into diacetolol. Diacetolol is as active as acebutolol (equipotency) and appears to have the same pharmacologic profile. Geriatric patients tend to have higher peak plasma levels of both acebutolol and diacetolol and a slightly prolonged excretion. Excretion is substantially prolonged in patients with renal impairment, and so a dose reduction may be needed. Liver cirrhosis does not seem to alter the pharmacokinetic profile of the parent drug and metabolite.

Indications

*hypertension*ventricular and atrial cardiac arrhythmia*acute myocardial infarction in high-risk patients*Smith-Magenis syndrome

Contraindications

*Stable or Unstable Angina (due to its partial agonist or ISA activity)

Contraindications and Precautions

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Propranolol