Propranolol

Other Uses -> Pharmaceuticals

Pharmaceutical

Pharmaceuticals -> Antihypertensive drugs

Pharmaceuticals -> Used in Switzerland

Pharmaceuticals

3.48

3.09

Antidepressants -> Beta blockers

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

EMA approved medicines: Human medicine

Pharmaceuticals

Antianginal medicines

Positive

3.75

2.7

Agilent XCT

Electrospray ionization

formic acid (5.3nM)

9.53

9.45

9.42

162.5 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: APCI+; Dataset: TOXCAST; Source Identifier: DTXSID3021198]

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

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

155.55 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2 reports by companies from 1 notifications to the ECHA C&L Inventory.

Status: Active Update: 13-09-2017 https://echa.europa.eu/registration-dossier/-/registered-dossier/20584

Propranolol: Does not have an individual approval but may be used under an appropriate group standard

Mild-to-moderate elevations in serum aminotransferase levels occur in less than 2% of patients on propranolol and are usually transient and asymptomatic, resolving even with continuation of therapy. Despite its widespread use, propranolol has not been convincingly linked to instances of clinically apparent liver injury; the few cases reported have generally occurred in patients who were receiving other well known hepatotoxic agents or were associated with elevations in serum enzymes only without jaundice.

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

Common side effects of using propranolol include bradycardia, gastrointestinal issues, abdominal pain, nausea, erectile dysfunction, and wheezing/bronchospasms. Propranolol use can also cause drowsiness, fatigue, and cold extremities. Some extreme side effects to be aware of include allergic reactions, insulin resistance, and hallucinations. Prescribers need to explain and discuss all of the side effects before giving patients a prescription for propranolol.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

propranolol

Inderal®

Beta blockers

3

less-DILI-concern drugs

◉ Summary of Use during Lactation

◈ What is propranolol?

Propranolol

Pharmaceutical

Smith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP

C07AA05

C - Cardiovascular system

QC - Cardiovascular system

C07AA05

Propranolol is a beta-adrenergic receptor antagonist used to treat hypertension. Propranolol has a long duration of action as it is given once or twice daily depending on the indication. When patients abruptly stop taking propranolol, they may experience exacerbations of angina and myocardial infarctions.

Propranolol is a nonselective β-adrenergic receptor antagonist. Blocking of these receptors leads to vasoconstriction, inhibition of angiogenic factors like vascular endothelial growth factor (VEGF) and basic growth factor of fibroblasts (bFGF), induction of apoptosis of endothelial cells, as well as down regulation of the renin-angiotensin-aldosterone system.

Propranolol undergoes side chain oxidation to α-naphthoxylactic acid, ring oxidation to 4’-hydroxypropranolol, or glucuronidation to propranolol glucuronide. It can also be N-desisopropylated to become N-desisopropyl propranolol. 17% of a dose undergoes glucuronidation and 42% undergoes ring oxidation.

Propranolol has known human metabolites that include (2S,3S,4S,5R)-3,4,5-Trihydroxy-6-[1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-yl]oxyoxane-2-carboxylic acid.

9Y8NXQ24VQ

PROPRANOLOL

Mechanisms of Action [MoA] - Adrenergic beta-Antagonists

Established Pharmacologic Class [EPC] - beta-Adrenergic Blocker

Propranolol is a beta-Adrenergic Blocker. The mechanism of action of propranolol is as an Adrenergic beta-Antagonist.

PROPRANOLOL

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.

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 used to cause dilation of the blood vessels.

Patients taking doses of 40mg, 80mg, 160mg, and 320mg daily experienced Cmax values of 18±15ng/mL, 52±51ng/mL, 121±98ng/mL, and 245±110ng/mL respectively. Propranolol has a Tmax of approximately 2 hours, though this can range from 1 to 4 hours in fasting patients. Taking propranolol with food does not increase Tmax but does increase bioavailability.

91% of an oral dose of propranolol is recovered as 12 metabolites in the urine.

The volume of distribution of propranolol is approximately 4L/kg or 320L.

The clearance of propranolol is 2.7±0.03L/h/kg in infants <90 days and 3.3±0.35L/h/kg in infants >90 days. Propranolol clearance increases linearly with hepatic blood flow. Propranolol has a clearance in hypertensive adults of 810mL/min.

Used as a beta-blocking agent (antihypertensive drug); [Kanerva, p. 1830]

Use (kg) in Switzerland (2009): >750