Propranolol

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Template:Short description Template:Distinguish Template:Use dmy dates Template:Cs1 config Template:Infobox drug Propranolol is a medication of the beta blocker class.<ref name="Srinivasan2019">Template:Cite journal</ref><ref name="AHFS2015" /><ref name="Inderal-Label">Template:Cite web</ref> It is used to treat high blood pressure, some types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, and essential tremors,<ref name="AHFS2015" /><ref name="Dav2006">Template:Cite journal</ref><ref name="Chinnadurai2016">Template:Cite journal</ref><ref>Template:Cite journal</ref> as well as to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks.<ref name="AHFS2015">Template:Cite web</ref> It can be taken orally, rectally, or by intravenous injection.<ref name="AHFS2015" /><ref name="KalamRasoolRehman2020" /> 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>Template:Cite book</ref>

Common side effects include nausea, abdominal pain, and constipation.<ref name=AHFS2015/> It may worsen the symptoms of asthma.<ref name=AHFS2015/> Propranolol may cause harmful effects for the baby if taken during pregnancy;<ref>Template:Cite web</ref> however, its use during breastfeeding is generally considered to be safe.<ref>Template:Cite book</ref> It is a non-selective beta blocker which works by blocking β-adrenergic receptors.<ref name=AHFS2015/>

Propranolol was patented in 1962 and approved for medical use in 1964.<ref>Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">Template:Cite book</ref> Propranolol is available as a generic medication.<ref name=AHFS2015/> In 2023, it was the 69th most commonly prescribed medication in the United States, with more than 9Template:Nbspmillion prescriptions.<ref name="Top300Drugs">Template:Cite web</ref><ref>Template:Cite web</ref>

Medical uses

An 80 mg capsule of extended-release propranolol
A mixture of 20 mg and 10 mg extended-release propranolol tablets
Propranolol blister pack

Propranolol is used for treating various conditions, including:

Cardiovascular

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.<ref>Template:Cite web</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>Template:Cite journal</ref>

Template:See also

Propranolol is occasionally used to treat performance anxiety,<ref name=Dav2006/> although evidence to support its use in any anxiety disorders is poor.<ref name="Steenenvan Wijk2015">Template:Cite journal</ref> Its efficacy in managing panic disorder appears similar to benzodiazepines, 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 physical symptoms of anxiety, its efficacy in treating generalized anxiety disorder and panic disorder remain unestablished.<ref>Template:Cite journal</ref> 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.<ref name="ArcherWilesKessler2025" />

A 2025 systematic review and meta-analysis found widespread prescription of beta blockers, namely propranolol, for treatment of anxiety disorders, but found no evidence of a beneficial effect relative to placebo or benzodiazepines in people with social phobia or panic disorder.<ref name="ArcherWilesKessler2025">Template:Cite journal</ref> 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.<ref name="ArcherWilesKessler2025" /> Findings were similar in a previous 2016 systematic review and meta-analysis.<ref name="SteenenvanWijkvanderHeijden2016">Template:Cite journal</ref>

Other beta blockers that have been used to treat anxiety disorders besides propranolol include atenolol, betaxolol, nadolol, oxprenolol, and pindolol.<ref name="ArcherWilesKessler2025" /><ref name="BoyceBalloneCerta2021">Template:Cite journal</ref>

Some experimentation has been conducted in other psychiatric areas:<ref name="pmid17200914">Template:Cite journal</ref>

Post-traumatic stress disorder and phobias

Propranolol is being investigated as a potential treatment for PTSD.<ref>Template:Cite web</ref><ref>Template:Cite journal</ref><ref>Template:Cite book</ref> Propranolol works to inhibit the actions of norepinephrine (noradrenaline), a neurotransmitter that enhances memory consolidation.<ref>Template:Cite web</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>Template:Cite journal</ref> Due to the fact that memories and their emotional content are reconsolidated in the hours after they are recalled or 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.<ref name="Steenenvan Wijk2015" /> It has also been found to be helpful for some individuals with misophonia.<ref>Template:Cite journal</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>Template:Cite journal</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 are already used for this purpose".<ref>Template:Cite journal</ref>

Other uses

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.<ref>Template:Cite journal</ref>

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.<ref name="RichardsAlbertsonDerlet2015">Template:Cite journal</ref><ref name="RichardsHollanderRamoska2017">Template:Cite journal</ref> Other beta blockers are also used.<ref name="RichardsAlbertsonDerlet2015" /><ref name="RichardsHollanderRamoska2017" /> 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.<ref name="RichardsAlbertsonDerlet2015" /><ref name="RichardsHollanderRamoska2017" /> The rate of unopposed α-stimulation with selective beta blockers has been reported to be 0.4%,<ref name="RichardsAlbertsonDerlet2015" /> whereas no cases of unopposed α-stimulation have been reported with dual alpha and beta blockers like labetalol.<ref name="RichardsHollanderRamoska2017" />

Available forms

Propranolol is available in the form of 10, 20, 40, 60, and 80Template:Nbspmg (as propranolol hydrochloride) oral tablets, among other formulations.<ref name="Inderal-Label" /><ref name="DrugBank" />

Contraindications

Template:See also

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.<ref name="Inderal-Label" /> 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).<ref name="Rossi" />

Propranolol should be used with caution in people with:<ref name="Rossi">Template:Cite book</ref>

Side effects

Template:See also

Pregnancy and lactation

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.<ref name="Martindale">Template:Cite book</ref>

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.<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>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Overdose

Propranolol overdose has been associated with symptoms including bradycardia and hypotension.<ref name="Inderal-Label" /> 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.<ref name="Inderal-Label" /> Propranolol overdose has also been associated with seizures.<ref>Template:Cite journal</ref> Cardiac arrest may occur in propranolol overdose due to sudden ventricular arrhythmias, or cardiogenic shock which may ultimately culminate in bradycardic PEA.<ref>Template:Cite journal</ref>

Interactions

Pharmacodynamic interactions

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.<ref name="Inderal-Label" /><ref name="MaideenRajkapoorMuthusamy2021">Template:Cite journal</ref> 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.<ref name="Inderal-Label" /><ref name="Rossi" /> Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) have hypotensive side effects and these may be exacerbated by propranolol.<ref name="Inderal-Label" /> Hypotension and cardiac arrest have been reported with the combination of propranolol and haloperidol.<ref name="Inderal-Label" /> 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.<ref name="Inderal-Label" /> The NSAID indomethacin specifically may reduce the efficacy of propranolol in decreasing heart rate and blood pressure.<ref name="Inderal-Label" />

Effects of drugs on propranolol

Propranolol is metabolized by cytochrome P450 enzymes including CYP2D6, CYP1A2, and CYP2C19.<ref name="Inderal-Label" /><ref name="KalamRasoolRehman2020" /><ref name="MaideenRajkapoorMuthusamy2021" /> 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, theophylline, zileuton, zolmitriptan, and rizatriptan, and by CYP2C19 inhibitors such as fluconazole, cimetidine, fluoxetine, fluvoxamine, teniposide, and tolbutamide.<ref name="Inderal-Label" /><ref name="KalamRasoolRehman2020" /><ref name="MaideenRajkapoorMuthusamy2021" /><ref name="ShinHillsFinley2020">Template:Cite journal</ref><ref name="Zhou2009" /> No interactions with propranolol were observed with ranitidine, lansoprazole, or omeprazole.<ref name="Inderal-Label" /> Propranolol levels may be reduced by inducers of hepatic metabolism including rifampin, alcohol, phenytoin, phenobarbital, and cigarette smoking.<ref name="Inderal-Label" /><ref name="MaideenRajkapoorMuthusamy2021" />

The CYP2D6 inhibitor quinidine has been found to increase propranolol levels by 2- to 3-fold.<ref name="Inderal-Label" /><ref name="Zhou2009" /> The CYP1A2 inhibitor fluvoxamine has been found to increase propranolol levels by 5-fold.<ref name="vanHarten1995">Template:Cite journal</ref> 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.<ref name="Inderal-Label" /> Conversely, verapamil does not affect the pharmacokinetics of propranolol and vice-versa.<ref name="Inderal-Label" /> 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.<ref name="Inderal-Label" /> Chlorpromazine has been found to increase propranolol levels by 1.7-fold.<ref name="Inderal-Label" /> The non-selective CYP450 inhibitor cimetidine has been found to increase peak propranolol levels by 1.4-fold and area-under-the-curve levels by 1.5-fold.<ref name="Inderal-Label" /> Cigarette smoking, which induces CYP1A2, has been found to reduce the clearance of propranolol by 77%, in turn resulting in decreased propranolol concentrations.<ref name="Inderal-Label" /><ref name="MaideenRajkapoorMuthusamy2021" /> The lipid-lowering drug cholestyramine or colestipol decreased propranolol levels by up to 50%.<ref name="Inderal-Label" /> Aluminum hydroxide gel may decrease propranolol levels.<ref name="Inderal-Label" /> Alcohol may increase propranolol levels.<ref name="Inderal-Label" />

Effects of propranolol on other drugs

Propranolol has been found to increase area-under-the-curve levels of propafenone by more than 3-fold.<ref name="Inderal-Label" /> It has been found to increase lidocaine levels by 1.3-fold.<ref name="Inderal-Label" /> 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.<ref name="Inderal-Label" /> Propranolol decreases theophylline clearance by 30 to 52%.<ref name="Inderal-Label" /> Propranolol inhibits the metabolism of the benzodiazepine diazepam and can increase exposure to diazepam.<ref name="Inderal-Label" /> Conversely, propranolol does not affect various other benzodiazepines, including oxazepam, triazolam, lorazepam, and alprazolam.<ref name="Inderal-Label" /> 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.<ref name="Inderal-Label" /> Propranolol decreased lovastatin or pravastatin area-under-the-curve levels by 18 to 23% but did not affect fluvastatin.<ref name="Inderal-Label" /> It may decrease triiodothyronine (T3) levels when taken with thyroxine (T4).<ref name="Inderal-Label" /> Propranolol has been found to increase the bioavailability and effects of warfarin.<ref name="Inderal-Label" />

Pharmacology

Pharmacodynamics

Propranolol activities
Site Ki (nM) Species Ref
5-HT1A 55–272 (Ki)
29 (Template:Abbr) (Ki)
128 (Template:Abbr) (Template:Abbrlink)
15% (Template:Abbr) (Template:Abbrlink)		 Human
Human
Human
Human		 <ref name="pmid2078271">Template:Cite journal</ref><ref name="pmid9686407">Template:Cite journal</ref>
<ref name="Newman-TancrediConteChaput1997" />
<ref name="Newman-TancrediConteChaput1997" />
<ref name="Newman-TancrediConteChaput1997" />
5-HT1B 56–85 Rat <ref name="pmid1968985">Template:Cite journal</ref><ref name="pmid2936965">Template:Cite journal</ref>
5-HT1D 4,070 Pig <ref name="pmid2797214">Template:Cite journal</ref>
5-HT2A 4,280 Human <ref name="pmid2723656">Template:Cite journal</ref>
5-HT2B 457–513 (Template:Abbr)
166–316 (Template:Abbr)		 Human
Human		 <ref name="pmid8743744">Template:Cite journal</ref>
<ref name="pmid8743744" />
5-HT2C 61,700 (Template:Abbr)
5,010 (Template:Abbr)
736–2,457		 Human
Human
Rodent		 <ref name="pmid8743744" />
<ref name="pmid8743744" />
<ref name="pmid4078623">Template:Cite journal</ref><ref name="pmid9686407" />
5-HT3 >10,000 Human <ref name="pmid2809591">Template:Cite journal</ref>
α1 Template:Abbr Template:Abbr Template:Abbr
α2 1,297–2,789 Rat <ref name="pmid2885406">Template:Cite journal</ref>
β1 0.02–2.69 Human <ref name="pmid8935801">Template:Cite journal</ref><ref name="pmid7915318">Template:Cite journal</ref>
β2 0.01–0.61 Human <ref name="pmid8935801" /><ref name="pmid7915318" />
β3 450 Mouse <ref name="pmid1718744">Template:Cite journal</ref>
D1 >10,000 Human <ref name="pmid9686407" />
D2 >10,000 Human <ref name="pmid9686407" />
H1 >10,000 Human <ref name="pmid6146381">Template:Cite journal</ref>
Template:Abbrlink 3,700 Rat <ref name="pmid2970277">Template:Cite journal</ref>
Template:Abbrlink 5,000 (Template:Abbrlink) Rat <ref name="pmid2872325">Template:Cite journal</ref>
Template:Abbrlink 29,000 (Template:Abbr) Rat <ref name="pmid2872325" />
Template:Abbrlink >10,000 Rat <ref name="pmid2338642">Template:Cite journal</ref>
Notes: Values are Ki (nM), unless otherwise noted. The smaller the value, the more avidly the drug binds to the site. Refs: <ref name="PDSPKiDatabase">Template:Cite web</ref><ref name="BindingDB">Template:Cite web</ref>

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">Template:Cite book</ref> 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).<ref>Template:Cite book</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 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).<ref name="YoungGlennon2008">Template:Cite journal</ref><ref name="pmid2872325"/> 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.<ref name="YoungGlennon2008" /><ref name="pmid2872325" /> Therefore, it can be looked upon as a weak indirect α1-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 relatively weak antagonist of certain serotonin receptors, namely the 5-HT1A, 5-HT1B, and 5-HT2B receptors.<ref name="Glennon1987">Template:Cite journal</ref><ref name="pmid9064274">Template:Cite journal</ref><ref name="pmid7938165">Template:Cite journal</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" /> (–)-Propranolol is not a silent antagonist of the serotonin 5-HT1A receptor but is instead a very weak partial agonist of the receptor.<ref name="Newman-TancrediConteChaput1997">Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Mechanism of action

Propranolol is a non-selective beta receptor antagonist.<ref name="Propranolol"/> 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.<ref name="DrugBank" /> Blocking neurotransmitter activity at β2 receptors in vascular smooth muscle cells causes vasoconstriction, leading to hypertension.

Pharmacokinetics

Absorption

Propranolol is rapidly and completely absorbed, with peak plasma levels achieved about 2Template:Nbsphours (range 1–3Template:Nbsphours) after ingestion.<ref name="DrugBank" /><ref name="KalamRasoolRehman2020">Template:Cite journal</ref> Its oral bioavailability is approximately 25%.<ref name="Inderal-Label" /><ref name="Srinivasan2019" /> Despite complete absorption, propranolol has a variable bioavailability due to extensive first-pass metabolism.<ref name="KalamRasoolRehman2020" /> Hepatic impairment therefore increases its bioavailability.<ref name="KalamRasoolRehman2020" /> Effective plasma concentrations are between 10 and 100Template:Nbspmg/L.Template:Citation needed Toxic levels are associated with plasma concentrations above 2,000Template:Nbspmg/L.Template:Citation needed Coadministration with food appears to enhance bioavailability but does not hasten its time to peak levels.<ref name="DrugBank" /><ref>Template:Cite book</ref> Propranolol can be absorbed along the whole intestine with the main absorption site being the colon,<ref>Template:Cite journal</ref> 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.<ref name="Shand1976">Template:Cite journal</ref>

Distribution

The volume of distribution of propranolol is about 4Template:NbspL/kg or 320Template:NbspL.<ref name="DrugBank" /><ref name="KalamRasoolRehman2020" /> The plasma protein binding of propranolol is approximately 90%, with a range of 85 to 96% in different studies.<ref name="DrugBank" /><ref name="KalamRasoolRehman2020" /> Propranolol is a highly lipophilic drug achieving high concentrations in the brain.<ref name="Srinivasan2019" /><ref name="HeelBrogdenSpeight1979">Template:Cite journal</ref> The brain-to-blood ratio of propranolol in humans ranges from 15:1 to 33:1, whereas the ratio for the peripherally selective beta blocker atenolol has been found to be 0.2:1.<ref name="Drayer1987">Template:Cite journal</ref><ref name="HeelBrogdenSpeight1979" />

Metabolism

Propranolol undergoes metabolism via aromatic hydroxylation (mainly 4-hydroxylation), N-dealkylation, side-chain oxidation, and glucuronidation.<ref name="Inderal-Label" /><ref name="DrugBank" /><ref name="KalamRasoolRehman2020" /> The metabolism of propranolol involves cytochrome P450 enzymes including CYP2D6, CYP1A2, and CYP2C19.<ref name="Inderal-Label" /><ref name="KalamRasoolRehman2020" /><ref name="MaideenRajkapoorMuthusamy2021" /> CYP1A2 and CYP2D6 have a major role, while CYP2C19 and CYP3A4 have a minor role.<ref name="MaideenRajkapoorMuthusamy2021" />Template:Additional citation needed The main metabolite 4-hydroxypropranolol, which has a longer elimination half-life than propranolol, is also pharmacologically active.<ref name="DrugBank" /><ref name="KalamRasoolRehman2020" />

Elimination

Propranolol is eliminated in urine.<ref name="DrugBank">Template:Cite web</ref><ref name="KalamRasoolRehman2020" /> Approximately 91% of an oral dose of propranolol is eliminated in urine as 12Template:Nbspmetabolites.<ref name="DrugBank" /><ref name="KalamRasoolRehman2020" /> Only about 1 to 4% of propranolol is excreted unchanged in urine or feces.<ref name="KalamRasoolRehman2020" />

The elimination half-life of propranolol ranges from 2.8 to 8Template:Nbsphours in different studies, with a typical half-life of around 4Template:Nbsphours.<ref name="Inderal-Label" /><ref name="DrugBank" /><ref name="KalamRasoolRehman2020" /> The duration of action of a single oral dose is longer than the half-life and may be up to 12Template:Nbsphours if the single dose is high enough (e.g., 80 mg).<ref name="PubChem">Template:Cite web</ref>

Pharmacogenomics

There were no significance differences in area-under-the-curve levels of propranolol in CYP2D6 poor metabolizers versus extensive metabolizers.<ref name="Zhou2009">Template:Cite journal</ref> 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.<ref name="Zhou2009" /> The contribution of CYP2D6 to the metabolism of propranolol is less than with metoprolol and is described as only "marginal".<ref name="Zhou2009" />

Chemistry

Propranolol is highly lipophilic.<ref name="Srinivasan2019" /><ref name="KalamRasoolRehman2020" /> The experimental log P of propranolol is 3.0 to 3.48 and its predicted log P ranges from 2.20 to 3.10.<ref name="KalamRasoolRehman2020" /><ref name="DrugBank" /><ref name="PubChem" /><ref name="TekesSzegiHashemi2013">Template:Cite journal</ref><ref name="ChemSpider">Template:Cite web</ref>

History

Template:See also

Scottish scientist James W. Black developed propranolol in the 1960s.<ref name="Srinivasan2019" /><ref name="Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC 1964 1080–1081">Template:Cite journal</ref> It was the first beta-blocker effectively used in the treatment of coronary artery disease and hypertension.<ref name=":0">Template:Cite book</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

Performance enhancement

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>Template:Cite journal</ref> For about 10 to 16% of performers, their degree of stage fright is considered pathological.<ref name= Fishbein/><ref>Template:Cite journal</ref> Propranolol is used by musicians, actors, and public speakers for its ability to treat anxiety symptoms activated by the sympathetic nervous system.<ref>Template:Cite journal</ref> It has also been used as a performance-enhancing drug in sports where high accuracy is required, including archery, shooting, golf,<ref name="ogrady">Template:Cite news</ref> and snooker.<ref name="ogrady"/> 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.<ref name="Guardian NK Doping">Template:Cite web</ref>

Brand names

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.<ref name=Quirke>Template:Cite journal</ref>

Propranolol is also marketed under brand names Avlocardyl, Deralin, Dociton, Inderalici, InnoPran XL, Indoblok,<ref>Template:Cite web</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 mg/mL solution of propranolol, is indicated for the treatment of proliferating infantile hemangioma.<ref>Template:Cite web</ref>

References

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Further reading

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