Acebutolol

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Acebutolol
Acebutolol structure.svg
Acebutolol ball-and-stick.png
Clinical data
Trade names Sectral
AHFS/Drugs.com Monograph
MedlinePlus a687003
License data
Pregnancy
category
  • AU: C
  • US: B (No risk in non-human studies)
Routes of
administration
oral, iv
ATC code C07AB04 (WHO)
Legal status
Legal status
  • UK: POM (Prescription only)
  • ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 40% (range 35 to 50%)
Metabolism Hepatic
Biological half-life 3-4 hours (parent drug)
8-13 hours (active metabolite)
Excretion Renal: 30%
Biliary: 60%
Identifiers
CAS Number 37517-30-9 YesY
PubChem (CID) 1978
IUPHAR/BPS 7107
DrugBank DB01193 YesY
ChemSpider 1901 YesY
UNII 67P356D8GH YesY
KEGG D02338 YesY
ChEBI CHEBI:2379 YesY
ChEMBL CHEMBL642 YesY
ECHA InfoCard 100.048.654
Chemical and physical data
Formula C18H28N2O4
Molar mass 336.426 g/mol
3D model (Jmol) Interactive image
Melting point 121 °C (250 °F)
  (verify)

Acebutolol (trade names Sectral, Prent) is a beta blocker for the treatment of hypertension and arrhythmias.

Pharmacology[edit]

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 or chronic obstructive pulmonary disease (COPD) needs treatment with a beta blocker. (For these reasons, it may be a beta-blocker of choice in inclusion in Polypill strategies). 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[edit]

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 half-life of 3 to 4 hours, and diacetolol a half-life 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[edit]

Contraindications[edit]

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

Contraindications and Precautions[edit]

Further information: Propranolol

Acebutolol may not be suitable in patients with Asthma bronchiale or COPD due to its bronchoconstricting (β2 antagonistic) effects.

Side effects[edit]

Further information: Propranolol

The development of anti-nuclear antibodies (ANA) has been found in 10 to 30% of patients under treatment with acebutolol. A systemic disease with arthralgic pain and myalgias has been observed 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 are more likely to develop these symptoms than male patients. Some 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. When possible, the treatment should be discontinued gradually in order to avoid a withdrawal syndrome with increased frequency of angina and even precipitation of myocardial infarction.

External links[edit]