Acebutolol

Acebutolol
Names
Trade namesSectral, Prent, others
IUPAC name
  • (RS)-N-{3-acetyl-4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl}butanamide
Clinical data
Drug classBeta blocker[1]
Main usesHigh blood pressure, angina, heart arrhythmias[1]
Side effectsTiredness, lightheadedness, shortness of breath, constipation, swelling, depression[1]
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Pregnancy
category
    Routes of
    use    		By mouth, iv
    Onset of actionWithin 90 min[1]
    Duration of actionUp to 24 hr[1]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa687003
    Legal
    License data
    Legal status
    • UK: POM (Prescription only)
    • In general: ℞ (Prescription only)
    Pharmacokinetics
    Bioavailability40% (range 35 to 50%)
    MetabolismHepatic
    Elimination half-life3-4 hours (parent drug)
    8-13 hours (active metabolite)
    ExcretionKidney: 30%
    Biliary: 60%
    Chemical and physical data
    FormulaC18H28N2O4
    Molar mass336.432 g·mol−1
    3D model (JSmol)
    Melting point121 °C (250 °F)
    SMILES
    • O=C(Nc1ccc(OCC(O)CNC(C)C)c(c1)C(=O)C)CCC
    InChI
    • InChI=1S/C18H28N2O4/c1-5-6-18(23)20-14-7-8-17(16(9-14)13(4)21)24-11-15(22)10-19-12(2)3/h7-9,12,15,19,22H,5-6,10-11H2,1-4H3,(H,20,23) checkY
    • Key:GOEMGAFJFRBGGG-UHFFFAOYSA-N checkY

    Acebutolol, sold under the brand names Sectral among others, is a beta blocker used for the treatment of high blood pressure, heart related chest pain, and heart arrhythmias.[1] They are not generally the initially recommended medication for high blood pressure.[1] It is taken by mouth.[1] Onset is within 90 minutes and may last up to 24 hours.[1]

    Common side effects include tiredness, lightheadedness, shortness of breath, constipation, swelling, and depression.[1] Other side effects may include sexual dysfunction, heart failure, and liver problems.[1][2] Use is not recommended when breastfeeding.[1] It works by blocking β1-adrenergic receptors.[1]

    Acebutolol was patented in 1967 and approved for medical use in 1973.[3] It is available as a generic medication.[4] In the United Kingdom it costs the NHS about 20£ per month.[2] In the United States this amount is about 18 USD per month as of 2021.[4]

    Medical uses

    Dosage

    Commonly started at 400 mg once per day or 200 mg twice per day.[2] The maximum dose is 1,200 mg per day.[2]

    Side effects

    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.

    Pharmacology

    Acebutolol is a cardioselective beta-1 blocker which also considered a partial agonist due to its intrinsic sympathomimetic activity (ISA); this means it provides low-grade beta stimulation at rest but acting as typical beta-blockers when sympathetic activity is high.[5] Due to its cardioselectivity, Acebutolol is more suitable than non-cardioselective beta-blockers, in a patient with asthma or chronic obstructive pulmonary disease (COPD) who 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 800 mg 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 800 mg/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.

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 "Acebutolol Monograph for Professionals". Drugs.com. Archived from the original on 26 January 2021. Retrieved 18 July 2021.
    2. 1 2 3 4 BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 163. ISBN 978-0-85711-369-6.{{cite book}}: CS1 maint: date format (link)
    3. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 461. ISBN 9783527607495. Archived from the original on 2017-09-08. Retrieved 2020-09-19.
    4. 1 2 "Acebutolol Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 19 July 2021.
    5. ↑ Kannam JP, Gersh BJ (9 April 2019). Beta blockers in the management of chronic coronary syndrome. Waltham, MA: UpToDate.
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