Acebutolol

1.7

1.71

Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents; Adrenergic Beta-Antagonists; Antiarrhythmics

Pharmaceuticals

136-138

119 - 123 °C

9.52

9.67

187.43 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

190.2 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

H362 (100%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]

P203, P260, P263, P264, P270, and P318 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Acebutolol is associated with a low rate of mild-to-moderate elevations of serum aminotransferase levels during treatment. These enzyme elevations are usually asymptomatic and transient and resolve even with continuation of therapy. There have been few documented cases of clinically apparent, acute liver injury attributed to acebutolol. The time to onset of injury was typically between 1 and 6 weeks of starting. The pattern of liver enzyme elevations was usually hepatocellular with an acute hepatitis-like presentation, although some cases present with a mixed pattern of enzymes. Fever commonly accompanied the liver injury, but usually without rash and eosinophia. Acebutolol is known to induce autoantibodies such as antinuclear antibody in 10% to 30% of patients, some of whom develop a lupus-like syndrome with fatigue, skin rash and arthralgias. Serum enzyme elevations may accompany this syndrome, but jaundice and symptoms of liver injury are uncommon. The published cases of hepatotoxicity due to acebutolol were relatively mild, self-limited and recovery was rapid upon stopping. Rechallenge resulted in rapid recurrence of injury.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

acebutolol

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

Acebutolol

4.7

19.7

An optimal response is usually achieved with dosages of 400 to 800 mg per day, although some patients have been maintained on as little as 200 mg per day.

Data used to generate the benchmarks include the following: Lowest Daily Dose (LDD): 200 mg/day, Lowest Therapeutic Dose (LTD): 2.5 mg/kg-day, and Screening Dose: 0.001 mg/kg-day.

27-Dec-20

C07AB04

C - Cardiovascular system

QC - Cardiovascular system

Acebutolol is a cardioselective, beta-adrenoreceptor blocking agent, which possesses mild intrinsic sympathomimetic activity (ISA) in its therapeutically effective dose range. In general, beta-blockers reduce the work the heart has to do and allow it to beat more regularly. Acebutolol has less antagonistic effects on peripheral vascular ß2-receptors at rest and after epinephrine stimulation than nonselective beta-antagonists. Low doses of acebutolol produce less evidence of bronchoconstriction than nonselective agents like propranolol but more than atenolol.

Acebutolol is a selective β1-receptor antagonist. Activation of β1-receptors by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Acebutolol blocks these receptors, lowering the heart rate and blood pressure. This drug then has the reverse effect of epinephrine. In addition, beta blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels.

67P356D8GH

ACEBUTOLOL

Mechanisms of Action [MoA] - Adrenergic beta-Antagonists

Established Pharmacologic Class [EPC] - beta-Adrenergic Blocker

Acebutolol is a beta-Adrenergic Blocker. The mechanism of action of acebutolol is as an Adrenergic beta-Antagonist.

Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.

Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters.

Drugs that bind to and block the activation of ADRENERGIC BETA-1 RECEPTORS.

Well absorbed from the Gl tract with an absolute bioavailability of approximately 40% for the parent compound.

Elimination via renal excretion is approximately 30% to 40% and by non-renal mechanisms 50% to 60%, which includes excretion into the bile and direct passage through the intestinal wall.