Propranolol#Idropranolol

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Image:Propranolol tablets.png

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Propranolol is used for treating various conditions, including:

• Hypertension
• Angina pectoris (with the exception of variant angina)
• Myocardial infarction
• Tachycardia (and other sympathetic nervous system symptoms, such as muscle tremor) associated with various conditions, including anxiety, panic, hyperthyroidism, and lithium therapy
• Portal hypertension, to lower portal vein pressure
• Prevention of esophageal variceal bleeding and ascites
• Anxiety
• Hypertrophic cardiomyopathy

While once a first-line treatment for hypertension, the role of beta blockers was downgraded in June 2006 in the United Kingdom to fourth-line, as they do not perform as well as other drugs, particularly in the elderly, and evidence is increasing that the most frequently used beta blockers at usual doses carry an unacceptable risk of provoking type 2 diabetes.{{cite web | vauthors = Ladva S | title=NICE and BHS launch updated hypertension guideline | url=http://www.nice.org.uk/download.aspx?o=335988 | date=28 June 2006 | publisher=National Institute for Health and Clinical Excellence | access-date=11 October 2009 | archive-url=https://web.archive.org/web/20060924003311/http://www.nice.org.uk/download.aspx?o=335988 | archive-date=24 September 2006 | df=dmy-all }}

Propranolol is not recommended for the treatment of high blood pressure by the Eighth Joint National Committee (JNC 8) because a higher rate of the primary composite outcome of cardiovascular death, myocardial infarction, or stroke compared to an angiotensin receptor blocker was noted in one study.{{cite journal | vauthors = James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC, Svetkey LP, Taler SJ, Townsend RR, Wright JT, Narva AS, Ortiz E | title = 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8) | journal = JAMA | volume = 311 | issue = 5 | pages = 507–520 | date = February 2014 | pmid = 24352797 | doi = 10.1001/jama.2013.284427 | df = dmy-all | doi-access = free }}

{{See also|Beta blocker#Anxiety}}

Propranolol is occasionally used to treat performance anxiety, although evidence to support its use in any anxiety disorders is poor.{{cite journal | vauthors = Steenen SA, van Wijk AJ, van der Heijden GJ, van Westrhenen R, de Lange J, de Jongh A | title = Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis | journal = Journal of Psychopharmacology | volume = 30 | issue = 2 | pages = 128–139 | date = February 2016 | pmid = 26487439 | pmc = 4724794 | doi = 10.1177/0269881115612236 }} Its efficacy in managing panic disorder appears similar to benzodiazepines, while carrying lower risks for addiction or abuse. Although beta-blockers such as propranolol have been suggested to be beneficial in managing physical symptoms of anxiety, its efficacy in treating generalized anxiety disorder and panic disorder remain unestablished.{{cite journal | title = Beta-blockers in anxiety disorders | vauthors = Peggy H, Charles S | doi = 10.1016/0165-0327(87)90017-6 | url = https://www.sciencedirect.com/science/article/abs/pii/0165032787900176 | journal = Journal of Affective Disorders | volume = 13 | issue = 2 | date = October 1987 | pages = 119–130| pmid = 2890677 | url-access = subscription }} It is thought that beta blockers do not directly treat psychological symptoms of anxiety, but can help control physical symptoms such as palpitations, and this may interfere with a positive feedback loop to indirectly reduce psychological anxiety.

A 2025 systematic review and meta-analysis found widespread prescription of beta blockers, namely propranolol, for treatment anxiety disorders, but found no evidence of a beneficial effect relative to placebo or benzodiazepines in people with social phobia or panic disorder.{{cite journal | vauthors = Archer C, Wiles N, Kessler D, Turner K, Caldwell DM | title = Beta-blockers for the treatment of anxiety disorders: A systematic review and meta-analysis | journal = J Affect Disord | volume = 368 | issue = | pages = 90–99 | date = January 2025 | pmid = 39271062 | doi = 10.1016/j.jad.2024.09.068 | url = }} However, the quality of evidence, including both numbers of studies and patients as well as quality and risk of bias of those studies, was limited. Findings were similar in a previous 2016 systematic review and meta-analysis.{{cite journal | vauthors = Steenen SA, van Wijk AJ, van der Heijden GJ, van Westrhenen R, de Lange J, de Jongh A | title = Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis | journal = J Psychopharmacol | volume = 30 | issue = 2 | pages = 128–139 | date = February 2016 | pmid = 26487439 | pmc = 4724794 | doi = 10.1177/0269881115612236 | url = }}

Other beta blockers that have been used to treat anxiety disorders besides propranolol include atenolol, betaxolol, nadolol, oxprenolol, and pindolol.{{cite journal | vauthors = Boyce TG, Ballone NT, Certa KM, Becker MA | title = The Use of β-Adrenergic Receptor Antagonists in Psychiatry: A Review | journal = J Acad Consult Liaison Psychiatry | volume = 62 | issue = 4 | pages = 404–412 | date = 2021 | pmid = 34210401 | doi = 10.1016/j.jaclp.2020.12.009 | url = }}

Some experimentation has been conducted in other psychiatric areas:{{cite journal | vauthors = Kornischka J, Cordes J, Agelink MW | title = 40 years beta-adrenoceptor blockers in psychiatry | language = de | journal = Fortschritte der Neurologie-Psychiatrie | volume = 75 | issue = 4 | pages = 199–210 | date = April 2007 | pmid = 17200914 | doi = 10.1055/s-2006-944295 | s2cid = 260156607 | url = https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-2006-944295| url-access = subscription }}

• Post-traumatic stress disorder (PTSD) and specific phobias
• Aggressive behavior of patients with brain injuries{{cite journal | vauthors = Thibaut F, Colonna L | title = [Anti-aggressive effect of beta-blockers] | language = fr | journal = L'Encephale | volume = 19 | issue = 3 | pages = 263–267 | year = 1993 | pmid = 7903928 }}
• Treating the excessive drinking of fluids in psychogenic polydipsia{{cite journal | vauthors = Vieweg V, Pandurangi A, Levenson J, Silverman J | title = The consulting psychiatrist and the polydipsia-hyponatremia syndrome in schizophrenia | journal = International Journal of Psychiatry in Medicine | volume = 24 | issue = 4 | pages = 275–303 | year = 1994 | pmid = 7737786 | doi = 10.2190/5WG5-VV1V-BXAD-805K | s2cid = 22703210 }}{{cite journal | vauthors = Kishi Y, Kurosawa H, Endo S | title = Is propranolol effective in primary polydipsia? | journal = International Journal of Psychiatry in Medicine | volume = 28 | issue = 3 | pages = 315–325 | year = 1998 | pmid = 9844835 | doi = 10.2190/QPWL-14H7-HPGG-A29D | s2cid = 25222454 }}

Propranolol is being investigated as a potential treatment for PTSD.{{cite web |url=http://www.nbcnews.com/id/10806799 |archive-url=https://web.archive.org/web/20131112233001/http://www.nbcnews.com/id/10806799/ |url-status=dead |archive-date=12 November 2013 |title=Doctors test a drug to ease traumatic memories - Mental Health - NBC News |website=NBC News |access-date=30 June 2007 }}{{cite journal | vauthors = Brunet A, Orr SP, Tremblay J, Robertson K, Nader K, Pitman RK | title = Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder | journal = Journal of Psychiatric Research | volume = 42 | issue = 6 | pages = 503–506 | date = May 2008 | pmid = 17588604 | doi = 10.1016/j.jpsychires.2007.05.006 }}{{Cite book | vauthors = Young C, Butcher R |url=http://www.ncbi.nlm.nih.gov/books/NBK562942/ |title=Propranolol for Post-Traumatic Stress Disorder: A Review of Clinical Effectiveness |date=2020 |publisher=Canadian Agency for Drugs and Technologies in Health |series=CADTH Rapid Response Reports |location=Ottawa (ON) |pmid=33074615}} Propranolol works to inhibit the actions of norepinephrine (noradrenaline), a neurotransmitter that enhances memory consolidation.{{Cite web |title=DocFilm – DW |url=https://www.dw.com/en/docfilm/program-294010 |access-date=2 August 2023 |website=dw.com |language=en}} In one small study, individuals given propranolol immediately after trauma experienced fewer stress-related symptoms and lower rates of PTSD than respective control groups who did not receive the drug.{{cite journal | vauthors = Vaiva G, Ducrocq F, Jezequel K, Averland B, Lestavel P, Brunet A, Marmar CR | title = Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma | journal = Biological Psychiatry | volume = 54 | issue = 9 | pages = 947–949 | date = November 2003 | pmid = 14573324 | doi = 10.1016/s0006-3223(03)00412-8 | s2cid = 3064619 }} Due to the fact that memories and their emotional content are reconsolidated in the hours after they are recalled/re-experienced, propranolol can also diminish the emotional impact of already formed memories; for this reason, it is also being studied in the treatment of specific phobias, such as arachnophobia, dental fear, and social phobia. It has also been found to be helpful for some individuals with misophonia.{{cite journal | vauthors = Webb J | title = β-Blockers for the Treatment of Misophonia and Misokinesia | journal = Clinical Neuropharmacology | volume = 45 | issue = 1 | pages = 13–14 | date = Jan–Feb 2022 | pmid = 35029865 | doi = 10.1097/WNF.0000000000000492 | s2cid = 245932937 }}

Ethical and legal questions have been raised surrounding the use of propranolol-based medications for use as a "memory damper", including altering memory-recalled evidence during an investigation, modifying the behavioral response to past (albeit traumatic) experiences, the regulation of these drugs, and others.{{cite journal| vauthors = Kolber AJ | title=Therapeutic Forgetting: The Legal and Ethical Implications of Memory Dampening |journal=Vanderbilt Law Review, San Diego Legal Studies Paper No. 07-37. |volume=59 |page=1561 |year=2006}} However, Hall and Carter have argued that many such objections are "based on wildly exaggerated and unrealistic scenarios that ignore the limited action of propranolol in affecting memory, underplay the debilitating impact that PTSD has on those who suffer from it, and fail to acknowledge the extent to which drugs like alcohol are already used for this purpose".{{cite journal | vauthors = Hall W, Carter A | title = Debunking alarmist objections to the pharmacological prevention of PTSD | journal = The American Journal of Bioethics | volume = 7 | issue = 9 | pages = 23–25 | date = September 2007 | pmid = 17849333 | doi = 10.1080/15265160701551244 | s2cid = 27063524 }}

• Essential tremor. Evidence for use for akathisia however is insufficient{{cite journal | vauthors = Lima AR, Bacalcthuk J, Barnes TR, Soares-Weiser K | title = Central action beta-blockers versus placebo for neuroleptic-induced acute akathisia | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD001946 | date = October 2004 | volume = 2004 | pmid = 15495022 | pmc = 6599862 | doi = 10.1002/14651858.CD001946.pub2 }}
• Migraine and cluster headache prevention{{cite journal | vauthors = Shields KG, Goadsby PJ | title = Propranolol modulates trigeminovascular responses in thalamic ventroposteromedial nucleus: a role in migraine? | journal = Brain | volume = 128 | issue = Pt 1 | pages = 86–97 | date = January 2005 | pmid = 15574468 | doi = 10.1093/brain/awh298 | doi-access = free }}{{cite book |title=The Biochemistry of Migraine | vauthors = Eadie M, Tyrer JH |year=1985 |publisher=Springer |location=New York |isbn=9780852007310 |page=148 |oclc=11726870 |url= https://books.google.com/books?id=JYeyCc9M6acC&q=Propranolol+migraine+mechanism%2C&pg=PA148 |url-status=live |archive-url=https://web.archive.org/web/20170324030406/https://books.google.com/books?id=JYeyCc9M6acC&pg=PA148&lpg=PA148&dq=Propranolol+migraine+mechanism,&source=bl&ots=Ep2oSjxpAo&sig=7H_KHF3xoIP0nBKJJaqsDl_IhAs&hl=en&ei=TXVPTuu6DKHE4gT6gLnXBw&sa=X&oi=book_result&ct=result&resnum=4&ved=0CCoQ6AEwAzgK#v=onepage&q=Propranolol%20migraine%20mechanism%2C&f=false |archive-date=24 March 2017 }} and in primary exertional headache{{cite web | vauthors = Chan C, Goadsby PJ | veditors = Silberstein SD | date = 26 September 1996 | title = Primary exercise headache | work = MedLink | url = https://www.medlink.com/articles/primary-exercise-headache }}
• Hyperhidrosis (excessive sweating){{cn|date=June 2023}}
• Infantile hemangioma{{cite journal | vauthors = Chen T, Gudipudi R, Nguyen SA, Carroll W, Clemmens C | title = Should Propranolol Remain the Gold Standard for Treatment of Infantile Hemangioma? A Systematic Review and Meta-Analysis of Propranolol Versus Atenolol | journal = The Annals of Otology, Rhinology, and Laryngology | pages = 332–340 | date = April 2022 | volume = 132 | issue = 3 | pmid = 35466712 | doi = 10.1177/00034894221089758 | s2cid = 248375711 }}
• Glaucoma{{cn|date=June 2023}}
• Thyrotoxicosis by deiodinase inhibition{{cn|date=June 2023}}

Propranolol may be used to treat severe infantile hemangiomas (IHs). This treatment shows promise as being superior to corticosteroids when treating IHs. Extensive clinical case evidence and a small controlled trial support its efficacy.{{cite journal |journal= Current Dermatology Reports |year= 2012 |doi= 10.1007/s13671-012-0026-6 |title= Propranolol for Infantile Hemangiomas: A Review | vauthors = Hogeling M |page= Online-first |volume=1|issue= 4 |doi-access= free }}

Propranolol is useful in the treatment of acute cardiovascular toxicity (e.g. in overdose) caused by sympathomimetics like amphetamine, methamphetamine, cocaine, ephedrine, and pseudoephedrine, including reducing elevations in heart rate and blood pressure caused by these agents.{{cite journal | vauthors = Richards JR, Albertson TE, Derlet RW, Lange RA, Olson KR, Horowitz BZ | title = Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review | journal = Drug Alcohol Depend | volume = 150 | issue = | pages = 1–13 | date = May 2015 | pmid = 25724076 | doi = 10.1016/j.drugalcdep.2015.01.040 | url = }}{{cite journal | vauthors = Richards JR, Hollander JE, Ramoska EA, Fareed FN, Sand IC, Izquierdo Gómez MM, Lange RA | title = β-Blockers, Cocaine, and the Unopposed α-Stimulation Phenomenon | journal = J Cardiovasc Pharmacol Ther | volume = 22 | issue = 3 | pages = 239–249 | date = May 2017 | pmid = 28399647 | doi = 10.1177/1074248416681644 | url = }} Other beta blockers are also used. However, the controversial yet possible phenomenon of "unopposed α-stimulation" with administration of selective beta blockers to block non-selective sympathomimetics potentially makes dual alpha-1 and beta blockers like labetalol and carvedilol more favorable for such purposes than selective beta blockers like propranolol. The rate of unopposed α-stimulation with selective beta blockers has been reported to be 0.4%, whereas no cases of unopposed α-stimulation have been reported with dual alpha and beta blockers like labetalol.

Propranolol is available in the form of 10, 20, 40, 60, and 80{{nbsp}}mg (as propranolol hydrochloride) oral tablets, among other formulations.

{{See also|Beta blocker#Contraindications}}

Contraindications of propranolol include cardiogenic shock, sinus bradycardia (slow heart rate; <60 beats/minute), heart block greater than first degree, bronchial asthma, overt heart failure, and known hypersensitivity to propranolol. Other contraindications include reversible airway diseases, particularly asthma or chronic obstructive pulmonary disease (COPD), sick sinus syndrome, atrioventricular block (second- or third-degree), circulatory shock, and severe hypotension (low blood pressure).

Propranolol should be used with caution in people with:{{cite book | veditors = Rossi S | title = Australian Medicines Handbook | date = 2006 | location = Adelaide | publisher = Australian Medicines Handbook }}

• Diabetes mellitus or hyperthyroidism, since signs and symptoms of hypoglycemia may be masked
• Peripheral artery disease and Raynaud syndrome, which may be exacerbated
• Phaeochromocytoma, as hypertension may be aggravated without prior alpha blocker therapy
• Myasthenia gravis, which may be worsened
• Other drugs with bradycardic effects

{{See also|Beta blocker#Adverse effects}}

Propranolol, like other beta-blockers, is classified as pregnancy category C in the United States and ADEC category C in Australia. β-blocking agents in general reduce perfusion of the placenta, which may lead to adverse outcomes for the neonate, including lung or heart complications, or premature birth. The newborn may experience additional adverse effects such as low blood sugar and a slower than normal heart rate.{{Cite book| veditors = Sweetman SC |chapter=Cardiovascular Drugs|title=Martindale: The complete drug reference |edition=36th |year=2009|pages=1226–1381|publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1|title-link=Martindale: The complete drug reference}}

Most β-blocking agents appear in the milk of lactating women. However, propranolol is highly bound to proteins in the bloodstream and is distributed into breast milk at very low levels.[No authors listed] (2007). "Propranolol". In: Drugs and Lactation Database. U.S. National Library of Medicine Toxicology Data Network. Retrieved 25 February 2013. These low levels are not expected to pose any risk to the breastfeeding infant, and the American Academy of Pediatrics considers propranolol therapy "generally compatible with breastfeeding."{{cite journal |author=Committee on Drugs | title = Transfer of drugs and other chemicals into human milk | journal = Pediatrics | volume = 108 | issue = 3 | pages = 776–789 | date = September 2001 | pmid = 11533352 | doi = 10.1542/peds.108.3.776| s2cid = 27763768 | doi-access = free }}{{cite journal | vauthors = Spencer JP, Gonzalez LS, Barnhart DJ | title = Medications in the breast-feeding mother | journal = American Family Physician | volume = 64 | issue = 1 | pages = 119–126 | date = July 2001 | pmid = 11456429 }}

Propranolol overdose has been associated with symptoms including bradycardia and hypotension. These symptoms may be managed by drugs including glucagon, isoprenaline (isoproterenol), medication, phosphodiesterase inhibitors, or atropine, whereas epinephrine may provoke uncontrolled hypertension due to unopposed alpha stimulation and is not indicated. Propranolol overdose has also been associated with seizures.{{cite journal | vauthors = Reith DM, Dawson AH, Epid D, Whyte IM, Buckley NA, Sayer GP | title = Relative toxicity of beta blockers in overdose | journal = Journal of Toxicology. Clinical Toxicology | volume = 34 | issue = 3 | pages = 273–278 | date = 1996 | pmid = 8667464 | doi = 10.3109/15563659609013789 }} Cardiac arrest may occur in propranolol overdose due to sudden ventricular arrhythmias, or cardiogenic shock which may ultimately culminate in bradycardic PEA.{{cite journal | vauthors = Holstege CP, Eldridge DL, Rowden AK | title = ECG manifestations: the poisoned patient | journal = Emergency Medicine Clinics of North America | volume = 24 | issue = 1 | pages = 159–77, vii | date = February 2006 | pmid = 16308118 | doi = 10.1016/j.emc.2005.08.012 }}

Since beta blockers are known to relax the cardiac muscle and constrict the smooth muscle, they have an additive effect with other drugs that decrease blood pressure or decrease cardiac contractility or conductivity. Pharmacodynamic interactions may occur with other drugs affecting the cardiovascular system including propafenone, quinidine, amiodarone, cardiac glycosides, calcium channel blockers like verapamil and diltiazem, ACE inhibitors, alpha blockers like prazosin, catecholamine-depleting drugs like reserpine, ergot alkaloids, and adrenergic receptor agonists including epinephrine (adrenaline), isoprenaline (isoproterenol), dobutamine, β₂-adrenergic receptor agonists like salbutamol, levosalbutamol, formoterol, salmeterol, and clenbuterol, and α₂-adrenergic receptor agonists like clonidine. Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) have hypotensive side effects and these may be exacerbated by propranolol. Hypotension and cardiac arrest have been reported with the combination of propranolol and haloperidol. Nonsteroidal anti-inflammatory drugs (NSAIDs), which include drugs like ibuprofen, naproxen, and aspirin, have been reported to blunt the antihypertensive effects of beta blockers like propranolol. The NSAID indomethacin specifically may reduce the efficacy of propranolol in decreasing heart rate and blood pressure.

Propranolol is metabolized by cytochrome P450 enzymes including CYP2D6, CYP1A2, and CYP2C19.{{cite journal | vauthors = Kalam MN, Rasool MF, Rehman AU, Ahmed N | title = Clinical Pharmacokinetics of Propranolol Hydrochloride: A Review | journal = Curr Drug Metab | volume = 21 | issue = 2 | pages = 89–105 | date = 2020 | pmid = 32286940 | doi = 10.2174/1389200221666200414094644 | url = }} Levels of propranolol may be increased by CYP2D6 inhibitors such as amiodarone, bupropion, cimetidine, duloxetine, fluoxetine, paroxetine, propafenone, quinidine, and ritonavir, by CYP1A2 inhibitors such as imipramine, cimetidine, ciprofloxacin, fluvoxamine, isoniazid, ritonavir, theophylline, zileuton, zolmitriptan, and rizatriptan, and by CYP2C19 inhibitors such as fluconazole, cimetidine, fluoxetine, fluvoxamine, teniposide, and tolbutamide.{{cite journal | vauthors = Shin J, Hills NK, Finley PR | title = Combining Antidepressants with β-Blockers: Evidence of a Clinically Significant CYP2D6 Drug Interaction | journal = Pharmacotherapy | volume = 40 | issue = 6 | pages = 507–516 | date = June 2020 | pmid = 32342526 | doi = 10.1002/phar.2406 | url = }} No interactions with propranolol were observed with ranitidine, lansoprazole, or omeprazole. Propranolol levels may be reduced by inducers of hepatic metabolism including rifampin, alcohol, phenytoin, phenobarbital, and cigarette smoking.

The CYP2D6 inhibitor quinidine has been found to increase propranolol levels by 2- to 3-fold. The CYP1A2 inhibitor fluvoxamine has been found to increase propranolol levels by 5-fold.{{cite journal | vauthors = van Harten J | title = Overview of the pharmacokinetics of fluvoxamine | journal = Clinical Pharmacokinetics | volume = 29 | issue = Suppl 1 | pages = 1–9 | year = 1995 | pmid = 8846617 | doi = 10.2165/00003088-199500291-00003 | s2cid = 71812133 }} The calcium channel blocker nisoldipine increased peak levels of propranolol by 1.5-fold and area-under-the-curve levels by 1.3-fold, while nicardipine increased propranolol peak levels by 1.8-fold and area-under-the-curve levels by 1.5-fold. Conversely, verapamil does not affect the pharmacokinetics of propranolol and vice-versa. The CYP1A2 inhibitor zolmitriptan increased peak propranolol levels by 1.4-fold and area-under-the-curve levels by 1.56-fold, while the CYP1A2 inhibitor rizatriptan increased propranolol peak levels by 1.8-fold and area-under-the-curve levels by 1.7-fold. Chlorpromazine has been found to increase propranolol levels by 1.7-fold. The non-selective CYP450 inhibitor cimetidine has been found to increase preak propranolol levels by 1.4-fold and area-under-the-curve levels by 1.5-fold. Cigarette smoking, which induces CYP1A2, has been found to reduce the clearance of propranolol by 77%, in turn resulting in decreased propranolol concentrations. The lipid-lowering drug cholestyramine or colestipol decreased propranolol levels by up to 50%. Aluminum hydroxide gel may decrease propranolol levels. Alcohol may increase propranolol levels.

Propranolol has been found to increase propafenone area-under-the-curve levels by more than 3-fold. It has been found to increase lidocaine levels by 1.3-fold. The drug has been found to increase peak and area-under-the-curve levels of nifedipine by 1.6-fold and 1.8-fold, respectively. Propranolol decreases theophylline clearance by 30 to 52%. Propranolol inhibits the metabolism of the benzodiazepine diazepam and can increase exposure to diazepam. Conversely, propranolol does not affect various other benzodiazepines including oxazepam, triazolam, lorazepam, and alprazolam. High-dose long-acting propranolol has been found to increase thioridazine levels by 1.6- to 4.7-fold and levels of its metabolite mesoridazine by 1.3- to 3.1-fold. Propranolol decreased lovastatin or pravastatin area-under-the-curve levels by 18 to 23% but did not affect fluvastatin. It may decrease triiodothyronine (T₃) levels when taken with thyroxine (T₄). Propranolol has been found to increase the bioavailability and effects of warfarin.

Propranolol is classified as a competitive non-cardioselective sympatholytic beta blocker that crosses the blood–brain barrier. It is lipid soluble and also has sodium channel-blocking effects. Propranolol is a non-selective β-adrenergic receptor antagonist, or beta blocker;{{cite book | vauthors = Al-Majed AA, Bakheit AH, Abdel Aziz HA, Alajmi FM, AlRabiah H | title = Propranolol | journal = Profiles of Drug Substances, Excipients, and Related Methodology | series = Profiles of Drug Substances, Excipients and Related Methodology | volume = 42 | pages = 287–338 | date = 2017 | pmid = 28431779 | doi = 10.1016/bs.podrm.2017.02.006 | isbn = 9780128122266 }} that is, it blocks the action of epinephrine (adrenaline) and norepinephrine (noradrenaline) at both β₁- and β₂-adrenergic receptors. It has little intrinsic sympathomimetic activity, but has strong membrane stabilizing activity (only at high blood concentrations, e.g. overdose).{{cite book| vauthors = Naish J, Court DS |title=Medical sciences|date=2014|isbn=978-0702052491|page=150|publisher=Elsevier Health Sciences |edition=Second}} Propranolol can cross the blood–brain barrier and exert effects in the central nervous system in addition to its peripheral activity.

In addition to blockade of adrenergic receptors, propranolol has very weak inhibitory effects on the norepinephrine transporter and/or weakly stimulates norepinephrine release (i.e., the concentration of norepinephrine is increased in the synapse).{{cite journal | vauthors = Young R, Glennon RA | title = S(-)Propranolol as a discriminative stimulus and its comparison to the stimulus effects of cocaine in rats | journal = Psychopharmacology | volume = 203 | issue = 2 | pages = 369–382 | date = April 2009 | pmid = 18795268 | doi = 10.1007/s00213-008-1317-2 | doi-access = free }} Since propranolol blocks β-adrenoceptors, the increase in synaptic norepinephrine only results in α-adrenoceptor activation, with the α₁-adrenoceptor being particularly important for effects observed in animal models. Therefore, it can be looked upon as a weak indirect α₁-adrenoceptor agonist in addition to potent β-adrenoceptor antagonist. In addition to its effects on the adrenergic system, there is evidence that indicates that propranolol may act as a relatively weak antagonist of certain serotonin receptors, namely the 5-HT_1A, 5-HT_1B, and 5-HT_2B receptors.{{cite journal | vauthors = Glennon RA | title = Central serotonin receptors as targets for drug research | journal = J Med Chem | volume = 30 | issue = 1 | pages = 1–12 | date = January 1987 | pmid = 3543362 | doi = 10.1021/jm00384a001 | url = | quote = Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites}}{{cite journal | vauthors = Davids E, Lesch KP | title = [The 5-HT1A receptor: a new effective principle in psychopharmacologic therapy?] | language = de | journal = Fortschritte der Neurologie-Psychiatrie | volume = 64 | issue = 11 | pages = 460–472 | date = November 1996 | pmid = 9064274 | doi = 10.1055/s-2007-996592 | s2cid = 147793142 }}{{cite journal | vauthors = Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP | title = International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin) | journal = Pharmacological Reviews | volume = 46 | issue = 2 | pages = 157–203 | date = June 1994 | doi = 10.1016/S0031-6997(25)06783-3 | pmid = 7938165 }} The latter may be involved in the effectiveness of propranolol in the treatment of migraine at high doses.

Both enantiomers of propranolol have a local anesthetic (topical) effect, which is normally mediated by blockade of voltage-gated sodium channels. Studies have demonstrated propranolol's ability to block cardiac, neuronal, and skeletal voltage-gated sodium channels, accounting for its known membrane stabilizing effect and antiarrhythmic and other central nervous system effects.{{cite journal | vauthors = Wang DW, Mistry AM, Kahlig KM, Kearney JA, Xiang J, George AL | title = Propranolol blocks cardiac and neuronal voltage-gated sodium channels | journal = Frontiers in Pharmacology | volume = 1 | pages = 144 | year = 2010 | pmid = 21833183 | pmc = 3153018 | doi = 10.3389/fphar.2010.00144 | doi-access = free }}{{cite journal | vauthors = Bankston JR, Kass RS | title = Molecular determinants of local anesthetic action of beta-blocking drugs: Implications for therapeutic management of long QT syndrome variant 3 | journal = Journal of Molecular and Cellular Cardiology | volume = 48 | issue = 1 | pages = 246–253 | date = January 2010 | pmid = 19481549 | pmc = 2813422 | doi = 10.1016/j.yjmcc.2009.05.012 }}{{cite journal | vauthors = Desaphy JF, Pierno S, De Luca A, Didonna P, Camerino DC | title = Different ability of clenbuterol and salbutamol to block sodium channels predicts their therapeutic use in muscle excitability disorders | journal = Molecular Pharmacology | volume = 63 | issue = 3 | pages = 659–670 | date = March 2003 | pmid = 12606775 | doi = 10.1124/mol.63.3.659 | url = http://pdfs.semanticscholar.org/20af/2edd8d1cb9f3874aee83a478c5af152298c0.pdf | s2cid = 631197 | archive-url = https://web.archive.org/web/20190220073326/http://pdfs.semanticscholar.org/20af/2edd8d1cb9f3874aee83a478c5af152298c0.pdf | archive-date = 20 February 2019 }}

Propranolol is a non-selective beta receptor antagonist. This means that it does not have preference to β₁ or β₂ receptors. It competes with sympathomimetic neurotransmitters for binding to receptors, which inhibits sympathetic stimulation of the heart. Blockage of neurotransmitter binding to β₁ receptors on cardiac myocytes inhibits activation of adenylate cyclase, which in turn inhibits cAMP synthesis leading to reduced Protein kinase A (PKA) activation. This results in less calcium influx to cardiac myocytes through voltage-gated L-type calcium channels meaning there is a decreased sympathetic effect on cardiac cells, resulting in antihypertensive effects including reduced heart rate and lower arterial blood pressure. Blockage of neurotransmitter binding to β₂ receptors on smooth muscle cells will increase contraction, which will increase hypertension.

Propranolol is rapidly and completely absorbed, with peak plasma levels achieved about 2{{nbsp}}hours (range 1–3{{nbsp}}hours) after ingestion. Its oral bioavailability is approximately 25%. Despite complete absorption, propranolol has a variable bioavailability due to extensive first-pass metabolism. Hepatic impairment therefore increases its bioavailability. Effective plasma concentrations are between 10 and 100 mg/L.{{Citation needed|date=September 2017}} Toxic levels are associated with plasma concentrations above 2000 mg/L.{{Citation needed|date=September 2017}} Coadministration with food appears to enhance bioavailability but does not hasten its time to peak levels.{{cite book| vauthors = Rang HP |title=Rang & Dale's pharmacology|date=2011|publisher=Churchill Livingstone |location=Edinburgh |isbn=9780702034718 |page=106 |edition=7th }} Propranolol can be absorbed along the whole intestine with the main absorption site being the colon,{{cite journal | vauthors = Nagare N, Damre A, Singh KS, Mallurwar SR, Iyer S, Naik A, Chintamaneni M | title = Determination of site of absorption of propranolol in rat gut using in situ single-pass intestinal perfusion | journal = Indian Journal of Pharmaceutical Sciences | volume = 72 | issue = 5 | pages = 625–629 | date = September 2010 | pmid = 21694996 | pmc = 3116309 | doi = 10.4103/0250-474X.78533 | doi-access = free }} which means people who have lost their colon due to surgery may absorb less propranolol. Propranolol shows marked interindividual variability in pharmacokinetics, with propranolol levels varying 20-fold in different individuals.{{cite journal | vauthors = Shand DG | title = Pharmacokinetics of propranolol: a review | journal = Postgrad Med J | volume = 52 Suppl 4 | issue = | pages = 22–25 | date = 1976 | pmid = 787953 | doi = | url = }}

The volume of distribution of propranolol is 4{{nbsp}}L/kg or 320{{nbsp}}L. The plasma protein binding of propranolol is approximately 90%, with a range of 85 to 96% in different studies. Propranolol is a highly lipophilic drug achieving high concentrations in the brain.{{cite journal | vauthors = Heel RC, Brogden RN, Speight TM, Avery GS | title = Atenolol: a review of its pharmacological properties and therapeutic efficacy in angina pectoris and hypertension | journal = Drugs | volume = 17 | issue = 6 | pages = 425–460 | date = June 1979 | pmid = 38096 | doi = 10.2165/00003495-197917060-00001 | url = }} The brain-to-blood ratio of propranolol was 33:1 in one study, whereas the ratio for the peripherally selective beta blocker atenolol was 0.2:1 in the same study.

Propranolol undergoes metabolism via aromatic hydroxylation (mainly 4-hydroxylation), N-dealkylation, side-chain oxidation, and glucuronidation. The metabolism of propranolol involves cytochrome P450 enzymes including CYP2D6, CYP1A2, and CYP2C19. CYP1A2 and CYP2D6 have a major role, while CYP2C19 and CYP3A4 have a minor role.{{Citation needed|date=June 2025}} The main metabolite 4-hydroxypropranolol, which has a longer elimination half-life than propranolol, is also pharmacologically active.

Propranolol is eliminated in urine.{{cite web |title=Propranolol |url=https://www.drugbank.ca/drugs/DB00571 |website=www.drugbank.ca |access-date=31 January 2019}} Approximately 91% of an oral dose of propranolol is eliminated in urine as 12{{nbsp}}metabolites.

The elimination half-life of propranolol is 3 to 8{{nbsp}}hours. The duration of action of a single oral dose is longer than the half-life and may be up to 12{{nbsp}}hours if the single dose is high enough (e.g., 80 mg).{{cite web |title=Propranolol |url=https://pubchem.ncbi.nlm.nih.gov/compound/propranolol |website=pubchem.ncbi.nlm.nih.gov |access-date=31 January 2019 |language=en}}

There were no significance differences in area-under-the-curve levels of propranolol in CYP2D6 poor metabolizers versus extensive metabolizers.{{cite journal | vauthors = Zhou SF | title = Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I | journal = Clin Pharmacokinet | volume = 48 | issue = 11 | pages = 689–723 | date = 2009 | pmid = 19817501 | doi = 10.2165/11318030-000000000-00000 | url = }} However, area-under-the-curve propranolol levels were ~2.5-fold higher in Caucasian CYP2D6 poor metabolizers or Chinese people with a non-functional CYP2D6 gene. The contribution of CYP2D6 to the metabolism of propranolol is less than with metoprolol and is described as only "marginal".

Propranolol is highly lipophilic. The experimental log P of propranolol is 3.48 and its predicted log P ranges from 2.58 to 3.10.{{cite web | title=b-Propranolol | website=ChemSpider | date=10 June 2024 | url=https://www.chemspider.com/Chemical-Structure.4777.html | access-date=22 June 2025}}

{{Main|Discovery and development of β-adrenergic receptor antagonists (beta-blockers)}}

Scottish scientist James W. Black developed propranolol in the 1960s.{{cite journal | vauthors = Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC | title = A New Adrenergic Beta-Receptor Antagonist | journal = Lancet | volume = 1 | issue = 7342 | pages = 1080–1081 | date = May 1964 | pmid = 14132613 | doi = 10.1016/S0140-6736(64)91275-9 }} It was the first beta-blocker effectively used in the treatment of coronary artery disease and hypertension.{{Cite book|title=Basic & Clinical Pharmacology| vauthors = Benowitz NL |publisher=McGraw-Hill|year=2017|isbn=9781259641152| veditors = Katzung BG |edition=14th|chapter=Antihypertensive Agents}}

Newer, more cardio-selective beta blockers (such as bisoprolol, nebivolol, carvedilol, or metoprolol) are used preferentially in the treatment of hypertension.

In a 1987 study by the International Conference of Symphony and Opera Musicians, it was reported that 27% of interviewed members said they used beta blockers such as propranolol for musical performances.{{cite journal |vauthors=Fishbein M, Middlestadt SE, Ottati V, Straus S, Ellis A | year = 1988 | title = Medical problems among ICSOM musicians: overview of a national survey | journal = Med Probl Perform Artist | volume = 3| pages = 1–8}} For about 10–16% of performers, their degree of stage fright is considered pathological.{{cite journal |vauthors=Steptoe A, Malik F, Pay C, Pearson P, Price C, Win Z | year = 1995 | title = The impact of stage fright on student actors | journal = Br J Psychol | volume = 86| pages = 27–39 | doi=10.1111/j.2044-8295.1995.tb02544.x}} Propranolol is used by musicians, actors, and public speakers for its ability to treat anxiety symptoms activated by the sympathetic nervous system.{{cite journal | vauthors = Lockwood AH | title = Medical problems of musicians | journal = The New England Journal of Medicine | volume = 320 | issue = 4 | pages = 221–227 | date = January 1989 | pmid = 2643048 | doi = 10.1056/nejm198901263200405 }} It has also been used as a performance-enhancing drug in sports where high accuracy is required, including archery, shooting, golf,{{cite news |author=Tim Glover |url=https://www.independent.co.uk/sport/golf-ogrady-says-players-use-betablockers-drugs-helped-win-majors-1368307.html |title=Golf: O'Grady says players use beta-blockers: Drugs 'helped win majors' |newspaper=The Independent |access-date=28 March 2017 |url-status=live |archive-url=https://web.archive.org/web/20150925223906/http://www.independent.co.uk/sport/golf-ogrady-says-players-use-betablockers-drugs-helped-win-majors-1368307.html |archive-date=25 September 2015 }} and snooker. In the 2008 Summer Olympics, 50-metre pistol silver medalist and 10-metre air pistol bronze medalist Kim Jong-su tested positive for propranolol and was stripped of his medals.{{cite web| vauthors = Scott M |title=Olympics: North Korea's Kim Jong-su loses medals after positive drugs test |url= https://www.theguardian.com/sport/2008/aug/15/olympics2008.drugsinsport |website=The Guardian |publisher=Guardian News and Media Limited |access-date=7 March 2018 |date=15 August 2008}}

Propranolol was first marketed under the brand name Inderal, manufactured by ICI Pharmaceuticals (now AstraZeneca), in 1965. "Inderal" is a quasi-anagram of "Alderlin", the trade name of pronethalol (which propranolol replaced); both names are an homage to Alderley Park, the ICI headquarters where the drugs were first developed.{{cite journal |vauthors=Quirke V |title=Putting theory into practice: James Black, receptor theory and the development of the beta-blockers at ICI, 1958-1978 |journal=Med Hist |volume=50 |issue=1 |pages=69–92 |date=January 2006 |pmid=16502872 |pmc=1369014 |doi=10.1017/s0025727300009455}}

Propranolol is also marketed under brand names Avlocardyl, Deralin, Dociton, Inderalici, InnoPran XL, Indoblok,{{Cite web |title=Indoblok Tablet - Product - TabletWise.com |url=https://www.tabletwise.com/southafrica/indoblok-tablet |access-date=15 October 2022 |website=www.tabletwise.com |language=en}} Sumial, Anaprilin, and Bedranol SR (Sandoz). In India, it is marketed under brand names such as Ciplar and Ciplar LA by Cipla. Hemangeol, a 4.28 mg/mL solution of propranolol, is indicated for the treatment of proliferating infantile hemangioma.{{cite web|title=Hemangeol - Food and Drug Administration|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205410s000lbl.pdf|access-date=23 March 2015|date=1 March 2014|url-status=live|archive-url=https://web.archive.org/web/20150402113709/https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205410s000lbl.pdf|archive-date=2 April 2015}}

{{Reflist}}

• {{cite journal | vauthors = Stapleton MP | title = Sir James Black and propranolol. The role of the basic sciences in the history of cardiovascular pharmacology | journal = Texas Heart Institute Journal | volume = 24 | issue = 4 | pages = 336–342 | year = 1997 | pmid = 9456487 | pmc = 325477 }}

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