Acebutolol chemical structure
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Acebutolol

Acebutolol is a beta blocker. more...

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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 lung disease (COLD) 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, this means that it crosses the Blood Brain Barrier. Acebutolol has no negative impact on serum lipids (cholesterol and triglycerides), in particular no HDL decrease has been observed. In this regard it is unlike to many other beta blockers which have this unfavourable property. The drug works in hypertensive patients with high or normal and low renin plasma concentrations, although acebutolol may be more efficient in patients with high or normal renin plasma concentrations. It seems that in clinical relevant concentrations a membrane stabilizing effect does not 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, those of the active main metabolite diacetolol after 4 hours. Acebutolol has a halflife of 3 to 4 hours, diacetolol one 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 aktive as acebutolol (equipotency) and appears to have the same pharmakologic 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; a dose reduction may be needed. Liver cirrhosis does not seem to alter the pharmakokinetic profile of parent drug and metabolite.

Uses

  • hypertension
  • angina pectoris, including instable angina
  • ventricular and atrial cardiac arrhythmias
  • acute myocardial infarction in high risk patients

Contraindications and Precautions

See article on Propranolol. Acebutolol may be suitable in patients with Asthma bronchiale or COLD.

Side Effects

See article on Propranolol. The development of ANA (Anti-Nuclear-Antibodies) has been found in 10 to 30% of patients under treatment with acebutolol. A systemic disease with arthralgic pain and myalgias has been developed in 1%. A lupus erythematosus like syndrome with skin rash and multiforme organ involvement is even less frequent. The incidence of both ANA and symptomatic disease under acebutolol is higher than under Propranolol. Female patients develop these symptoms more likely than male patients. Also, a few cases of hepatotoxicity with increased liver enzymes (ALT, AST) have been seen. Altogether, 5 to 6% of all patients treated have to discontinue acebutolol due to intolerable side effects. The treatment should be, if possible, discontinued gradually in order to avoid a withdrawal syndrome with increased frequency of angina and even precipitation of myocardial infarction.

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