Penbutolol

4.15

3.61

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

Pharmaceuticals

Mild-to-moderate elevations in serum aminotransferase levels occur in less than 2% of patients on penbutolol and are usually transient and asymptomatic, resolving even with continuation of therapy. Despite its wide spread use, penbutolol has not been convincingly linked to instances of clinically apparent liver injury. Other beta-blockers have been linked to rare instances of acute liver injury with a latency to onset of 4 to 24 weeks, a hepatocellular pattern of serum enzyme elevations and a rather mild, self-limiting course without evidence of hypersensitivity or autoimmune reactions.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

penbutolol

Levatol®

Beta blockers

Not Applicable

no-DILI-concern

C - Cardiovascular system

QC - Cardiovascular system

Penbutolol is a ß-1, ß-2 (nonselective) adrenergic receptor antagonist. Experimental studies showed a dose-dependent increase in heart rate in reserpinized (norepinephrine-depleted) rats given penbutolol intravenously at doses of 0.25 to 1.0 mg/kg, suggesting that penbutolol has some intrinsic sympathomimetic activity. In human studies, however, heart rate decreases have been similar to those seen with propranolol.

Penbutolol acts on the β1 adrenergic receptors in both the heart and the kidney. When β1 receptors are activated by catecholamines, they stimulate a coupled G protein that leads to the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). The increase in cAMP leads to activation of protein kinase A (PKA), which alters the movement of calcium ions in heart muscle and increases the heart rate. Penbutolol blocks the catecholamine activation of β1 adrenergic receptors and decreases heart rate, which lowers blood pressure.

78W62V43DY

PENBUTOLOL

Mechanisms of Action [MoA] - Adrenergic beta-Antagonists

Established Pharmacologic Class [EPC] - beta-Adrenergic Blocker

Penbutolol is a beta-Adrenergic Blocker. The mechanism of action of penbutolol is as an Adrenergic beta-Antagonist.

Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.

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.

>90%.

The metabolites are excreted principally in the urine.

Approximately 90% of the metabolites are excreted in the urine.