Acebutolol

Acebutolol

Acebutolol
Systematic (IUPAC) name
(RS)-N-{3-acetyl-4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl}butanamide
Clinical data
Trade names Sectral
AHFS/Drugs.com
MedlinePlus
Licence data US FDA:
Pregnancy
category
  • AU: C
  • US: B (No risk in non-human studies)
Legal status
Routes of
administration
oral, iv
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 Registry Number  YesY
ATC code C07
PubChem CID:
IUPHAR/BPS
DrugBank  YesY
ChemSpider  YesY
UNII  YesY
KEGG  YesY
ChEBI  YesY
ChEMBL  YesY
Chemical data
Formula C18H28N2O4
Molecular mass
Documentation

Physical data
Melting point 121 °C (250 °F)
 YesY   

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

Contents

  • Pharmacology 1
  • Pharmacokinetics 2
  • Indications 3
  • Contraindications 4
  • Contraindications and Precautions 5
  • Side effects 6
  • External links 7

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 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

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

Contraindications

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

Contraindications and Precautions

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

Side effects

The development of 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

  • AHFS Database