Editing Propranolol

{{Short description|Beta blocker drug}}
{{Distinguish|Propanol|Propofol}}
{{Use dmy dates|date=February 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 464216937
| image = Propranolol.svg
| image_class = skin-invert-image
| width = 250
| alt =
| caption =
| image2 = Propranolol-from-1977-crystal-structure-3D-balls-side.png
| width2 = 250
| alt2 =
| chirality = [[Racemic mixture]]

<!--Clinical data-->| pronounce = {{IPAc-en|p|r|oʊ|ˈ|p|r|æ|n|ə|ˌ|l|ɒ|l}}
| tradename = Inderal, others
| Drugs.com = {{drugs.com|monograph|propranolol-hydrochloride}}
| DailyMedID = Propranolol
| MedlinePlus =
| pregnancy_AU = C
| pregnancy_category =
| routes_of_administration = [[Oral administration|By mouth]], [[rectal administration|rectal]], [[intravenous therapy|intravenous]]
| ATC_prefix = C07
| ATC_suffix = AA05
| legal_AU = S4
| legal_UK = POM
| legal_US = Rx-only
| legal_EU = Rx-only
| legal_CA = Rx-only
| legal_status = <!--Pharmacokinetic data-->
| bioavailability = 26%
| protein_bound = 90%
| metabolism = [[Liver]] (extensive) [[CYP1A2]], [[CYP2D6]]; minor: [[CYP2C19]], [[CYP3A4]]
| metabolites = N-desisopropylpropranolol, 4'-hydroxypropanolol
| elimination_half-life = 4–5 hours
| excretion = [[Kidney]] (<1%)

<!--Identifiers-->| class = [[Beta blocker]]
| index2_label = as HCl
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 525-66-6
| PubChem = 4946
| IUPHAR_ligand = 564
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00571
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4777
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9Y8NXQ24VQ
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08443
| KEGG2_Ref = {{keggcite|correct|kegg}}
| KEGG2 = D00483
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 8499
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 27

<!--Chemical data-->| IUPAC_name = (''RS'')-1-(propan-2-ylamino)-3-(1-naphthyloxy)propan-2-ol
| C = 16
| H = 21
| N = 1
| O = 2
| SMILES = OC(COC1=C2C=CC=CC2=CC=C1)CNC(C)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C16H21NO2/c1-12(2)17-10-14(18)11-19-16-9-5-7-13-6-3-4-8-15(13)16/h3-9,12,14,17-18H,10-11H2,1-2H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = AQHHHDLHHXJYJD-UHFFFAOYSA-N
| melting_point = 96
}}

<!-- Definition and medical uses -->
'''Propranolol''' is a medication of the [[beta blocker]] class.<ref name="AHFS2015" /> It is used to treat [[hypertension|high blood pressure]], some types of [[cardiac dysrhythmia|irregular heart rate]], [[thyrotoxicosis]], [[capillary hemangioma]]s, [[akathisia]], [[performance anxiety]], and [[essential tremor]]s,<ref name="AHFS2015" /><ref name="Dav2006">{{cite journal | vauthors = Davidson JR | title = Pharmacotherapy of social anxiety disorder: what does the evidence tell us? | journal = The Journal of Clinical Psychiatry | volume = 67 | issue = Suppl 12 | pages = 20–26 | date = 2006 | pmid = 17092192 | doi = 10.1016/j.genhosppsych.2005.07.002 }}</ref><ref name="Chinnadurai2016">{{cite journal | vauthors = Chinnadurai S, Fonnesbeck C, Snyder KM, Sathe NA, Morad A, Likis FE, McPheeters ML | title = Pharmacologic Interventions for Infantile Hemangioma: A Meta-analysis | journal = Pediatrics | volume = 137 | issue = 2 | pages = e20153896 | date = February 2016 | pmid = 26772662 | doi = 10.1542/peds.2015-3896 | s2cid = 30459652 | url = http://pediatrics.aappublications.org/content/pediatrics/137/2/e20153896.full.pdf | doi-access = free }}</ref><ref>{{Cite journal |last=Blaisdell |first=G. D. |date=July 1994 |title=Akathisia: A Comprehensive Review and Treatment Summary |url=https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2007-1014294 |journal=Pharmacopsychiatry |language=en |volume=27 |issue=4 |pages=139–146 |doi=10.1055/s-2007-1014294 |pmid=7972345 |issn=0176-3679|url-access=subscription }}</ref> as well to prevent [[migraine headaches]], and to prevent further heart problems in those with [[angina]] or previous [[myocardial infarction|heart attacks]].<ref name="AHFS2015">{{cite web | title = Propranolol hydrochloride | work = Monograph | url = https://www.drugs.com/monograph/propranolol-hydrochloride.html | publisher = The American Society of Health-System Pharmacists | access-date = 1 January 2015 | url-status = live | archive-url = https://web.archive.org/web/20150101152631/http://www.drugs.com/monograph/propranolol-hydrochloride.html | archive-date = 1 January 2015 | df = dmy-all }}</ref> It can be taken [[oral administration|orally]] or by [[intravenous injection]].<ref name="AHFS2015" /> The formulation that is taken orally comes in short-acting and long-acting versions.<ref name="AHFS2015" /> Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken orally.<ref name="AHFS2015" /><ref>{{cite book| vauthors = Bryson PD |title=Comprehensive review in toxicology for emergency clinicians|date=1997|publisher=Taylor & Francis|location=Washington, DC|isbn=9781560326120|page=167|edition=3|url=https://books.google.com/books?id=f7009NkJv70C&pg=PA167|url-status=live|archive-url=https://web.archive.org/web/20170324020627/https://books.google.com/books?id=f7009NkJv70C&pg=PA167|archive-date=24 March 2017}}</ref>

<!-- Side effects and mechanism-->
Common [[side effect]]s include [[nausea]], [[abdominal pain]], and [[constipation]].<ref name=AHFS2015/> It may worsen the symptoms of [[asthma]].<ref name=AHFS2015/> Propranolol may cause [[teratogen|harmful effect]]s for the baby if taken during [[pregnancy]];<ref>{{cite web|title=Prescribing medicines in pregnancy database|url=http://www.tga.gov.au/hp/medicines-pregnancy.htm|work=Australian Government|access-date=22 April 2014|date=3 March 2014|url-status=live|archive-url=https://web.archive.org/web/20140408040902/http://www.tga.gov.au/hp/medicines-pregnancy.htm#.U1Yw8Bc3tqw|archive-date=8 April 2014}}</ref> however, its use during [[breastfeeding]] is generally considered to be safe.<ref>{{cite book| vauthors = Briggs GG, Freeman RK, Yaffe SJ |title=Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk|date=2011|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |isbn=9781608317080 |page=1226|edition=9th|url=https://books.google.com/books?id=OIgTE4aynrMC&pg=PA1226|url-status=live|archive-url=https://web.archive.org/web/20170214212837/https://books.google.ca/books?id=OIgTE4aynrMC&pg=PA1226|archive-date=14 February 2017}}</ref> It is a non-selective beta blocker which works by blocking [[β-adrenergic receptors]].<ref name=AHFS2015/>

<!-- History, society and culture -->
Propranolol was patented in 1962 and approved for medical use in 1964.<ref>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=460 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA460 }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO }}</ref> Propranolol is available as a [[generic medication]].<ref name=AHFS2015/> In 2022, it was the 77th most commonly prescribed medication in the United States, with more than 8{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Propranolol Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Propranolol | access-date = 30 August 2024 }}</ref>

==Medical uses==
[[Image:Propranolol 80mg.png|thumb|right|An 80&nbsp;mg capsule of [[Time release technology|extended-release]] propranolol]]
[[Image:Propranolol tablets.png|thumb|right|A mixture of 20&nbsp;mg and 10&nbsp;mg extended-release propranolol tablets]]
[[File:Propranolol hci sandoz 10mg.jpg|thumb|Propranolol blister pack]]
Propranolol is used for treating various conditions, including:

===Cardiovascular===
* [[Hypertension]]
* [[Angina pectoris]] (with the exception of [[Prinzmetal's angina|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 pharmacology|lithium therapy]]
* [[Portal hypertension]], to lower [[Hepatic portal vein|portal vein]] pressure
* Prevention of [[esophageal varices|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 [[Diabetes mellitus type 2|type 2 diabetes]].<ref>{{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 }}</ref>

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.<ref>{{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 }}</ref>

===Psychiatric===
Propranolol is occasionally used to treat [[performance anxiety]],<ref name=Dav2006/> although evidence to support its use in any [[anxiety disorder]]s is poor.<ref name="Steenenvan Wijk2015">{{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 }}</ref> Its efficacy in managing [[panic disorder]] appears similar to [[benzodiazepine]]s, while carrying lower risks for addiction or abuse.<ref name="Steenenvan Wijk2015"/> Although beta-blockers such as propranolol have been suggested to be beneficial in managing [[Sympathetic nervous system|physical symptoms]] of anxiety, its [[efficacy#Medicine|efficacy]] in treating [[generalized anxiety disorder]] and panic disorder remain unestablished.<ref>{{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 }}</ref> Some experimentation has been conducted in other psychiatric areas:<ref name="pmid17200914">{{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 }}</ref>
* [[Post-traumatic stress disorder]] (PTSD) and [[specific phobia]]s
* [[Aggressive behavior]] of patients with [[acquired brain injury|brain injuries]]<ref name="pmid7903928">{{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 }}</ref>
* Treating the excessive drinking of fluids in [[psychogenic polydipsia]]<ref name="pmid7737786">{{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 }}</ref><ref name="pmid9844835">{{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 }}</ref>

====PTSD and phobias====
Propranolol is being investigated as a potential treatment for PTSD.<ref>{{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 }}</ref><ref>{{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 }}</ref><ref>{{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}}</ref> Propranolol works to inhibit the actions of [[norepinephrine]] (noradrenaline), a [[neurotransmitter]] that enhances [[memory consolidation]].<ref>{{Cite web |title=DocFilm – DW |url=https://www.dw.com/en/docfilm/program-294010 |access-date=2 August 2023 |website=dw.com |language=en}}</ref> 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.<ref>{{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 }}</ref> 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 phobia]]s, such as [[arachnophobia]], [[dental fear]], and [[social phobia]].<ref name="Steenenvan Wijk2015" />  It has also been found to be helpful for some individuals with [[misophonia]].<ref>{{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 }}</ref>

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.<ref>{{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}}</ref> 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 (drug)|alcohol]] are already used for this purpose".<ref>{{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 }}</ref>

===Other uses===
* [[Essential tremor]]. Evidence for use for [[akathisia]] however is insufficient<ref>{{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 }}</ref>
* [[Migraine]] and [[cluster headache]] prevention<ref>{{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 }}</ref><ref>{{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 }}</ref> and in primary exertional headache<ref name=AHFS2015/><ref>{{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 }}</ref>
* [[Hyperhidrosis]] (excessive sweating){{cn|date=June 2023}}
* [[Infantile hemangioma]]<ref>{{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 }}</ref>
* [[Glaucoma]]{{cn|date=June 2023}}
* [[Thyrotoxicosis]] by [[deiodinase]] inhibition{{cn|date=June 2023}}

Propranolol may be used to treat severe [[infantile hemangioma]]s (IHs). This treatment shows promise as being superior to [[corticosteroid]]s when treating IHs. Extensive clinical case evidence and a small controlled trial support its efficacy.<ref>{{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 }}</ref>

==Contraindications==
{{See also|Beta blocker#Contraindications}}
Propranolol may be contraindicated in people with:<ref name="Rossi" />
* Reversible airway diseases, particularly [[asthma]] or [[chronic obstructive pulmonary disease]] (COPD)
* [[Bradycardia|Slow heart rate]] (bradycardia) (<60 beats/minute)
* [[Sick sinus syndrome]]
* [[Atrioventricular block]] ([[Second-degree atrioventricular block|second-]] or [[Third-degree atrioventricular block|third-degree]])
* [[Shock (circulatory)|Shock]]
* Severe [[hypotension|low blood pressure]]

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

Propranolol should be used with caution in people with:<ref name="Rossi">{{cite book | veditors = Rossi S | title = [[Australian Medicines Handbook]] | date = 2006 | location = Adelaide | publisher = Australian Medicines Handbook }}</ref>
* [[Diabetes mellitus]] or [[hyperthyroidism]], since signs and symptoms of [[hypoglycemia]] may be masked
* [[Peripheral artery disease]] and [[Raynaud's syndrome|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 [[bradycardia|bradycardic]] effects

===Pregnancy and lactation===
Propranolol, like other beta-blockers, is classified as [[pregnancy category]] C in the United States and [[Australian Drug Evaluation Committee|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 [[human lung|lung]] or [[human heart|heart]] complications, or [[premature birth]]. The newborn may experience additional adverse effects such as [[hypoglycemia|low blood sugar]] and a [[bradycardia|slower than normal heart rate]].<ref name="Martindale">{{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}}</ref>

Most β-blocking agents appear in the milk of [[lactation|lactating]] women. However, propranolol is highly [[plasma protein binding|bound to proteins in the bloodstream]] and is distributed into breast milk at very low levels.<ref name="LactMed">[No authors listed] (2007). "Propranolol". In: ''Drugs and Lactation Database.'' U.S. [[National Library of Medicine]] Toxicology Data Network. Retrieved 25 February 2013.</ref> 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."<ref name="Martindale"/><ref name="LactMed"/><ref>{{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 }}</ref><ref>{{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 }}</ref>

==Overdose==
In [[Drug overdose|overdose]], propranolol is associated with [[seizure]]s.<ref>{{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 }}</ref> [[Cardiac arrest]] may occur in propranolol overdose due to sudden [[ventricular arrhythmias]], or [[cardiogenic shock]] which may ultimately culminate in bradycardic [[Pulseless electrical activity|PEA]].<ref>{{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 }}</ref>

== Interactions ==

Since beta blockers are known to relax the cardiac muscle and constrict the smooth muscle, beta-adrenergic antagonists, including propranolol, have an additive effect with other drugs that decrease blood pressure or decrease cardiac contractility or conductivity. Clinically significant interactions particularly occur with:<ref name="Rossi" />
* [[Verapamil]]
* [[Epinephrine]] (adrenaline)
* [[Beta2-adrenergic receptor agonist|β<sub>2</sub>-adrenergic receptor agonists]]
** [[Salbutamol]] (albuterol), [[levosalbutamol]], [[formoterol]], [[salmeterol]], [[clenbuterol]], others
* [[Clonidine]]
* [[Ergot alkaloid]]s
* [[Isoprenaline]] (isoproterenol)
* [[Nonsteroidal anti-inflammatory drug]]s (NSAIDs)
* [[Quinidine]]
* [[Cimetidine]]
* [[Lidocaine]]
* [[Phenobarbital]]
* [[Rifampicin]]
* [[Fluvoxamine]] (slows down the metabolism of propranolol significantly, leading to increased blood levels of propranolol)<ref>{{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 }}</ref>

==Pharmacology==
===Pharmacodynamics===
{| class="wikitable floatright" style="font-size:small;"
|+ Propranolol<ref name="PDSP">{{cite web | title = PDSP K<sub>i</sub> Database | work = Psychoactive Drug Screening Program (PDSP)|author1-link=Bryan Roth | vauthors = Roth BL, Driscol J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=propranolol&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}</ref>
|-
! Site !! K<sub>i</sub> (nM) !! Species !! Ref
|-
| [[5-HT1A receptor|5-HT<sub>1A</sub>]] || 55–272 || Human || <ref name="pmid2078271">{{cite journal | vauthors = Hamon M, Lanfumey L, el Mestikawy S, Boni C, Miquel MC, Bolaños F, Schechter L, Gozlan H | title = The main features of central 5-HT1 receptors | journal = Neuropsychopharmacology | volume = 3 | issue = 5–6 | pages = 349–360 | year = 1990 | pmid = 2078271 }}</ref><ref name="pmid9686407">{{cite journal | vauthors = Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS | title = Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications | journal = NIDA Research Monograph | volume = 178 | pages = 440–466 | date = March 1998 | pmid = 9686407 }}</ref>
|-
| [[5-HT1B receptor|5-HT<sub>1B</sub>]] || 56–85 || Rat || <ref name="pmid1968985">{{cite journal | vauthors = Tsuchihashi H, Nakashima Y, Kinami J, Nagatomo T | title = Characteristics of 125I-iodocyanopindolol binding to beta-adrenergic and serotonin-1B receptors of rat brain: selectivity of beta-adrenergic agents | journal = Japanese Journal of Pharmacology | volume = 52 | issue = 2 | pages = 195–200 | date = February 1990 | pmid = 1968985 | doi = 10.1254/jjp.52.195 | doi-access = free }}</ref><ref name="pmid2936965">{{cite journal | vauthors = Engel G, Göthert M, Hoyer D, Schlicker E, Hillenbrand K | title = Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 332 | issue = 1 | pages = 1–7 | date = January 1986 | pmid = 2936965 | doi = 10.1007/bf00633189 | s2cid = 5999838 }}</ref>
|-
| [[5-HT1D receptor|5-HT<sub>1D</sub>]] || 4,070 || Pig || <ref name="pmid2797214">{{cite journal | vauthors = Schlicker E, Fink K, Göthert M, Hoyer D, Molderings G, Roschke I, Schoeffter P | title = The pharmacological properties of the presynaptic serotonin autoreceptor in the pig brain cortex conform to the 5-HT1D receptor subtype | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 340 | issue = 1 | pages = 45–51 | date = July 1989 | pmid = 2797214 | doi = 10.1007/bf00169206 | s2cid = 2287040 }}</ref>
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 4,280 || Human || <ref name="pmid2723656">{{cite journal | vauthors = Elliott JM, Kent A | title = Comparison of [125I]iodolysergic acid diethylamide binding in human frontal cortex and platelet tissue | journal = Journal of Neurochemistry | volume = 53 | issue = 1 | pages = 191–196 | date = July 1989 | pmid = 2723656 | doi = 10.1111/j.1471-4159.1989.tb07313.x | s2cid = 25820829 }}</ref>
|-
| [[5-HT2B receptor|5-HT<sub>2B</sub>]] || 457–513 ({{abbr|+|(+)-propranolol}})<br />166–316 ({{abbr|–|(–)-propranolol}}) || Human || <ref name="pmid8743744">{{cite journal | vauthors = Schmuck K, Ullmer C, Kalkman HO, Probst A, Lubbert H | title = Activation of meningeal 5-HT2B receptors: an early step in the generation of migraine headache? | journal = The European Journal of Neuroscience | volume = 8 | issue = 5 | pages = 959–967 | date = May 1996 | pmid = 8743744 | doi = 10.1111/j.1460-9568.1996.tb01583.x | s2cid = 19578349 }}</ref>
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 61,700 ({{abbr|+|(+)-propranolol}})<br /> 5,010 ({{abbr|–|(–)-propranolol}})<br />736–2,457 || Human<br />Human<br />Rodent || <ref name="pmid8743744" /><br /><ref name="pmid8743744" /><br /><ref name="pmid4078623">{{cite journal | vauthors = Yagaloff KA, Hartig PR | title = 125I-lysergic acid diethylamide binds to a novel serotonergic site on rat choroid plexus epithelial cells | journal = The Journal of Neuroscience | volume = 5 | issue = 12 | pages = 3178–3183 | date = December 1985 | pmid = 4078623 | pmc = 6565215 | doi = 10.1523/JNEUROSCI.05-12-03178.1985 }}</ref><ref name="pmid9686407" />
|-
| [[5-HT3 receptor|5-HT<sub>3</sub>]] || >10,000 || Human || <ref name="pmid2809591">{{cite journal | vauthors = Barnes JM, Barnes NM, Costall B, Ironside JW, Naylor RJ | title = Identification and characterisation of 5-hydroxytryptamine 3 recognition sites in human brain tissue | journal = Journal of Neurochemistry | volume = 53 | issue = 6 | pages = 1787–1793 | date = December 1989 | pmid = 2809591 | doi = 10.1111/j.1471-4159.1989.tb09244.x | s2cid = 46356673 }}</ref>
|-
| [[Alpha-1 adrenergic receptor|α<sub>1</sub>]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}
|-
| [[Alpha-2 adrenergic receptor|α<sub>2</sub>]] || 1,297–2,789 || Rat || <ref name="pmid2885406">{{cite journal | vauthors = Boyajian CL, Leslie FM | title = Pharmacological evidence for alpha-2 adrenoceptor heterogeneity: differential binding properties of [3H]rauwolscine and [3H]idazoxan in rat brain | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 241 | issue = 3 | pages = 1092–1098 | date = June 1987 | doi = 10.1016/S0022-5347(25)00190-9 | pmid = 2885406 }}</ref>
|-
| [[Beta-1 adrenergic receptor|β<sub>1</sub>]] || 0.02–2.69 || Human || <ref name="pmid8935801">{{cite journal | vauthors = Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE | title = Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding | journal = Psychopharmacology | volume = 124 | issue = 1–2 | pages = 57–73 | date = March 1996 | pmid = 8935801 | doi = 10.1007/bf02245606 | s2cid = 12028979 }}</ref><ref name="pmid7915318">{{cite journal | vauthors = Fraundorfer PF, Fertel RH, Miller DD, Feller DR | title = Biochemical and pharmacological characterization of high-affinity trimetoquinol analogs on guinea pig and human beta adrenergic receptor subtypes: evidence for partial agonism | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 270 | issue = 2 | pages = 665–674 | date = August 1994 | doi = 10.1016/S0022-3565(25)22397-7 | pmid = 7915318 }}</ref>
|-
| [[Beta-2 adrenergic receptor|β<sub>2</sub>]] || 0.01–0.61 || Human || <ref name="pmid8935801" /><ref name="pmid7915318" />
|-
| [[Beta-3 adrenergic receptor|β<sub>3</sub>]] || 450 || Mouse || <ref name="pmid1718744">{{cite journal | vauthors = Nahmias C, Blin N, Elalouf JM, Mattei MG, Strosberg AD, Emorine LJ | title = Molecular characterization of the mouse beta 3-adrenergic receptor: relationship with the atypical receptor of adipocytes | journal = The EMBO Journal | volume = 10 | issue = 12 | pages = 3721–3727 | date = December 1991 | pmid = 1718744 | pmc = 453106 | doi = 10.1002/j.1460-2075.1991.tb04940.x }}</ref>
|-
| [[D1 receptor|D<sub>1</sub>]] || >10,000 || Human || <ref name="pmid9686407" />
|-
| [[D2 receptor|D<sub>2</sub>]] || >10,000 || Human || <ref name="pmid9686407" />
|-
| [[H1 receptor|H<sub>1</sub>]] || >10,000 || Human || <ref name="pmid6146381">{{cite journal | vauthors = Kanba S, Richelson E | title = Histamine H1 receptors in human brain labelled with [3H]doxepin | journal = Brain Research | volume = 304 | issue = 1 | pages = 1–7 | date = June 1984 | pmid = 6146381 | doi = 10.1016/0006-8993(84)90856-4 | s2cid = 45303586 }}</ref>
|-
| {{abbrlink|SERT|Serotonin transporter}} || 3,700 || Rat || <ref name="pmid2970277">{{cite journal | vauthors = Kovachich GB, Aronson CE, Brunswick DJ, Frazer A | title = Quantitative autoradiography of serotonin uptake sites in rat brain using [3H]cyanoimipramine | journal = Brain Research | volume = 454 | issue = 1–2 | pages = 78–88 | date = June 1988 | pmid = 2970277 | doi = 10.1016/0006-8993(88)90805-0 | s2cid = 9586842 }}</ref>
|-
| {{abbrlink|NET|Norepinephrine transporter}} || 5,000 ({{abbrlink|IC<sub>50</sub>|Half-maximal inhibitory concentration}}) || Rat || <ref name="pmid2872325">{{cite journal | vauthors = Tuross N, Patrick RL | title = Effects of propranolol on catecholamine synthesis and uptake in the central nervous system of the rat | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 237 | issue = 3 | pages = 739–745 | date = June 1986 | doi = 10.1016/S0022-3565(25)24861-3 | pmid = 2872325 }}</ref>
|-
| {{abbrlink|DAT|Dopamine transporter}} || 29,000 ({{abbr|IC<sub>50</sub>|Half-maximal inhibitory concentration}}) || Rat || <ref name="pmid2872325" />
|-
| {{abbrlink|VDCC|Voltage-dependent calcium channel}} || >10,000 || Rat || <ref name="pmid2338642">{{cite journal | vauthors = Zobrist RH, Mecca TE | title = [3H]TA-3090, a selective benzothiazepine-type calcium channel receptor antagonist: in vitro characterization | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 253 | issue = 2 | pages = 461–465 | date = May 1990 | doi = 10.1016/S0022-3565(25)12990-X | pmid = 2338642 }}</ref>
|- class="sortbottom"
| colspan="4" style="width: 1px;" | Values are K<sub>i</sub> (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.
|}

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]];<ref name="Propranolol">{{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 }}</ref> that is, it [[receptor antagonist|blocks]] the action of [[epinephrine]] (adrenaline) and [[norepinephrine]] (noradrenaline) at both [[Beta-1 adrenergic receptor|β<sub>1</sub>-]] and [[Beta-2 adrenergic receptor|β<sub>2</sub>-adrenergic receptor]]s. It has little [[Beta blocker#Intrinsic sympathomimetic activity|intrinsic sympathomimetic activity]], but has strong [[membrane stabilizing effect|membrane stabilizing activity]] (only at high blood concentrations, e.g. [[overdose]]).<ref>{{cite book| vauthors = Naish J, Court DS |title=Medical sciences|date=2014|isbn=978-0702052491|page=150|publisher=Elsevier Health Sciences |edition=Second}}</ref>   Propranolol can cross the blood-brain barrier and exert effects in the [[central nervous system]] in addition to its peripheral activity.<ref name="Steenenvan Wijk2015"/>

In addition to blockade of [[adrenergic receptor]]s, 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]]).<ref name="YoungGlennon2008">{{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 }}</ref><ref name="pmid2872325"/> Since propranolol blocks β-adrenoceptors, the increase in synaptic norepinephrine only results in α-adrenoceptor activation, with the [[Alpha-1 adrenergic receptor|α<sub>1</sub>-adrenoceptor]] being particularly important for effects observed in [[animal model]]s.<ref name="YoungGlennon2008" /><ref name="pmid2872325" /> Therefore, it can be looked upon as a weak indirect α<sub>1</sub>-adrenoceptor [[agonist]] in addition to potent β-adrenoceptor antagonist.<ref name="YoungGlennon2008" /><ref name="pmid2872325" /> In addition to its effects on the adrenergic system, there is evidence that indicates that propranolol may act as a weak [[receptor antagonist|antagonist]] of certain [[serotonin receptor]]s, namely the [[5-HT1A|5-HT<sub>1A</sub>]], [[5-HT1B receptor|5-HT<sub>1B</sub>]], and [[5-HT2B receptor|5-HT<sub>2B</sub> receptor]]s.<ref name="pmid9064274">{{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 }}</ref><ref name="pmid7938165">{{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 }}</ref><ref name="pmid8743744" /> The latter may be involved in the effectiveness of propranolol in the treatment of [[migraine]] at high doses.<ref name="pmid8743744" />

Both enantiomers of propranolol have a [[local anesthetic]] (topical) effect, which is normally mediated by blockade of [[voltage-gated sodium channel]]s. 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.<ref>{{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 }}</ref><ref>{{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 }}</ref><ref>{{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 }}</ref>

===Mechanism of action===
Propranolol is a non-selective beta receptor antagonist.<ref name="Propranolol"/> This means that it does not have preference to β<sub>1</sub> or β<sub>2</sub> receptors. It competes with sympathomimetic neurotransmitters for binding to receptors, which inhibits sympathetic stimulation of the heart. Blockage of neurotransmitter binding to β<sub>1</sub> receptors on cardiac myocytes inhibits activation of adenylate cyclase, which in turn inhibits [[Cyclic adenosine monophosphate|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.<ref name=drugbank /> Blockage of neurotransmitter binding to β<sub>2</sub> receptors on smooth muscle cells will increase contraction, which will increase hypertension.

===Pharmacokinetics===
Propranolol is rapidly and completely absorbed, with peak plasma levels achieved about 1–3 hours after ingestion. More than 90% of the drug is found bound to plasma protein in the blood.<ref name=drugbank/> Coadministration with food appears to enhance [[bioavailability]].<ref>{{cite book| vauthors = Rang HP |title=Rang & Dale's pharmacology|date=2011|publisher=Churchill Livingstone |location=Edinburgh |isbn=9780702034718 |page=106 |edition=7th }}</ref> Despite complete absorption, propranolol has a variable [[bioavailability]] due to extensive [[first-pass metabolism]]. [[Hepatic]] impairment therefore increases its bioavailability. Propranolol can be absorbed along the whole intestine with the main absorption site being the colon,<ref>{{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 }}</ref> which means people who have lost their colon due to surgery may absorb less propranolol. The main metabolite 4-hydroxypropranolol, with a longer [[half-life]] (5.2–7.5 hours) than the parent compound (3–4 hours), is also pharmacologically active. Most of the metabolites are excreted in the urine.<ref name=drugbank>{{cite web |title=Propranolol |url=https://www.drugbank.ca/drugs/DB00571 |website=www.drugbank.ca |access-date=31 January 2019}}</ref>

Propranolol is a highly [[lipophilic]] drug achieving high concentrations in the brain. The duration of action of a single oral dose is longer than the half-life and may be up to 12 hours if the single dose is high enough (e.g., 80&nbsp;mg).<ref>{{cite web |title=Propranolol |url=https://pubchem.ncbi.nlm.nih.gov/compound/propranolol#section=Top |website=pubchem.ncbi.nlm.nih.gov |access-date=31 January 2019 |language=en}}</ref> Effective plasma concentrations are between 10 and 100&nbsp;mg/L.{{Citation needed|date=September 2017}} Toxic levels are associated with plasma concentrations above 2000&nbsp;mg/L.{{Citation needed|date=September 2017}}

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

[[Scottish people|Scottish]] scientist [[James W. Black]] developed propranolol in the 1960s.<ref name="Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC 1964 1080–1081">{{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 }}</ref> It was the first beta-blocker effectively used in the treatment of [[coronary artery disease]] and [[hypertension]].<ref name=":0">{{Cite book|title=Basic & Clinical Pharmacology| vauthors = Benowitz NL |publisher=McGraw-Hill|year=2017|isbn=9781259641152| veditors = Katzung BG |edition=14th|chapter=Antihypertensive Agents}}</ref>

Newer, more cardio-selective beta blockers (such as [[bisoprolol]], [[nebivolol]], [[carvedilol]], or [[metoprolol]]) are used preferentially in the treatment of [[hypertension]].<ref name=":0" />

==Society and culture==
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.<ref name= Fishbein>{{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}}</ref> For about 10–16% of performers, their degree of stage fright is considered pathological.<ref name= Fishbein/><ref>{{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}}</ref> Propranolol is used by musicians, actors, and public speakers for its ability to treat anxiety symptoms activated by the sympathetic nervous system.<ref>{{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 }}</ref> It has also been used as a [[Performance-enhancing substance|performance-enhancing drug]] in sports where high accuracy is required, including [[Target archery|archery]], [[Shooting sports|shooting]], [[golf]],<ref name="ogrady">{{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 }}</ref> and [[snooker]].<ref name="ogrady"/> In the [[2008 Summer Olympics]], [[Shooting at the 2008 Summer Olympics – Men's 50 metre pistol|50-metre pistol]] silver medalist and [[Shooting at the 2008 Summer Olympics – Men's 10 metre air pistol|10-metre air pistol]] bronze medalist [[Kim Jong-su]] tested positive for propranolol and was stripped of his medals.<ref name="Guardian NK Doping">{{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}}</ref>

===Brand names===
Propranolol was first marketed under the brand name Inderal, manufactured by [[Imperial Chemical Industries|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.<ref name=Quirke>{{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}}</ref>

Propranolol is also marketed under brand names Avlocardyl, Deralin, Dociton, Inderalici, InnoPran XL, Indoblok,<ref>{{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}}</ref> 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&nbsp;mg/mL solution of propranolol, is indicated for the treatment of proliferating [[infantile hemangioma]].<ref>{{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}}</ref>

== References ==
{{Reflist}}

== Further reading ==
* {{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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