While once a first-line treatment for hypertension, the role of beta blockers was downgraded in June 2006 in theUnited 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 provokingtype 2 diabetes.[17]
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, orstroke compared to an angiotensin receptor blocker was noted in one study.[18]
Propranolol is occasionally used to treat performance anxiety,[7] although evidence to support its use in any anxiety disorders is poor.[19] Its efficacy in managingpanic disorder appears similar tobenzodiazepines, while carrying lower risks for addiction or abuse.[19] Although beta-blockers such as propranolol have been suggested to be beneficial in managingphysical symptoms of anxiety, itsefficacy in treatinggeneralized anxiety disorder and panic disorder remain unestablished.[20] It is thought that beta blockers do not directly treat psychological symptoms of anxiety, but can help control physical symptoms such aspalpitations, and this may interfere with a positive feedback loop to indirectly reduce psychological anxiety.[21]
A 2025systematic review andmeta-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 orbenzodiazepines in people withsocial phobia or panic disorder.[21] However, thequality of evidence, including both numbers of studies and patients as well as quality and risk ofbias of those studies, was limited.[21] Findings were similar in a previous 2016 systematic review and meta-analysis.[22]
Propranolol is being investigated as a potential treatment for PTSD.[28][29][30] Propranolol works to inhibit the actions ofnorepinephrine (noradrenaline), aneurotransmitter that enhancesmemory consolidation.[31] 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.[32] 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 ofspecific phobias, such asarachnophobia,dental fear, andsocial phobia.[19] It has also been found to be helpful for some individuals withmisophonia.[33]
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.[34] 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 likealcohol are already used for this purpose".[35]
Propranolol may be used to treat severeinfantile hemangiomas (IHs). This treatment shows promise as being superior tocorticosteroids when treating IHs. Extensive clinical case evidence and a small controlled trial support its efficacy.[41]
Propranolol is useful in the treatment of acutecardiovasculartoxicity (e.g. inoverdose) caused bysympathomimetics likeamphetamine,methamphetamine,cocaine,ephedrine, andpseudoephedrine, including reducing elevations inheart rate andblood pressure caused by these agents.[42][43] Other beta blockers are also used.[42][43] However, the controversial yet possible phenomenon of "unopposed α-stimulation" with administration of selective beta blockers to block non-selective sympathomimetics potentially makes dualalpha-1 and beta blockers likelabetalol andcarvedilol more favorable for such purposes than selective beta blockers like propranolol.[42][43] The rate of unopposed α-stimulation with selective beta blockers has been reported to be 0.4%,[42] whereas no cases of unopposed α-stimulation have been reported with dual alpha and beta blockers like labetalol.[43]
The CYP2D6 inhibitor quinidine has been found to increase propranolol levels by 2- to 3-fold.[1][53] The CYP1A2 inhibitor fluvoxamine has been found to increase propranolol levels by 5-fold.[54] Thecalcium channel blockernisoldipine increased peak levels of propranolol by 1.5-fold and area-under-the-curve levels by 1.3-fold, whilenicardipine increased propranolol peak levels by 1.8-fold and area-under-the-curve levels by 1.5-fold.[1] Conversely,verapamil does not affect thepharmacokinetics of propranolol and vice-versa.[1] 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 inhibitorrizatriptan increased propranolol peak levels by 1.8-fold and area-under-the-curve levels by 1.7-fold.[1]Chlorpromazine has been found to increase propranolol levels by 1.7-fold.[1] Thenon-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.[1] Cigarette smoking, which induces CYP1A2, has been found to reduce theclearance of propranolol by 77%, in turn resulting in decreased propranolol concentrations.[1][51] The lipid-lowering drugcholestyramine orcolestipol decreased propranolol levels by up to 50%.[1]Aluminum hydroxide gel may decrease propranolol levels.[1] Alcohol may increase propranolol levels.[1]
Propranolol has been found to increasearea-under-the-curve levels ofpropafenone by more than 3-fold.[1] It has been found to increaselidocaine levels by 1.3-fold.[1] 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.[1] Propranolol decreasestheophylline clearance by 30 to 52%.[1] Propranolol inhibits the metabolism of the benzodiazepinediazepam and can increase exposure to diazepam.[1] Conversely, propranolol does not affect various otherbenzodiazepines, includingoxazepam,triazolam,lorazepam, andalprazolam.[1] High-dose long-acting propranolol has been found to increasethioridazine levels by 1.6- to 4.7-fold and levels of its metabolitemesoridazine by 1.3- to 3.1-fold.[1] Propranolol decreasedlovastatin orpravastatin area-under-the-curve levels by 18 to 23% but did not affectfluvastatin.[1] It may decreasetriiodothyronine (T3) levels when taken withthyroxine (T4).[1] Propranolol has been found to increase thebioavailability and effects ofwarfarin.[1]
In addition to blockade ofadrenergic receptors, propranolol has very weak inhibitory effects on thenorepinephrine transporter and/or weakly stimulates norepinephrine release (i.e., the concentration of norepinephrine is increased in thesynapse).[77][71] Since propranolol blocks β-adrenoceptors, the increase in synaptic norepinephrine only results in α-adrenoceptor activation, with theα1-adrenoceptor being particularly important for effects observed inanimal models.[77][71] Therefore, it can be looked upon as a weak indirect α1-adrenoceptoragonist in addition to potent β-adrenoceptor antagonist.[77][71] In addition to its effects on the adrenergic system, there is evidence that indicates that propranolol may act as a relatively weakantagonist of certainserotonin receptors, namely the5-HT1A,5-HT1B, and5-HT2B receptors.[78][79][80][62] The latter may be involved in the effectiveness of propranolol in the treatment ofmigraine at high doses.[62] (–)-Propranolol is not asilent antagonist of the serotonin 5-HT1A receptor but is instead a very weakpartial agonist of the receptor.[57]
Both enantiomers of propranolol have alocal anesthetic (topical) effect, which is normally mediated by blockade ofvoltage-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.[81][82][83]
Propranolol is a non-selective beta receptor antagonist.[75] This means that it does not have preference to β1 or β2 receptors. It competes with sympathomimetic neurotransmitters for binding to receptors, which inhibitssympathetic stimulation of the heart. Blockage of neurotransmitter binding to β1 receptors oncardiac myocytes inhibits activation of adenylate cyclase, which in turn inhibitscAMP synthesis leading to reducedProtein kinase A (PKA) activation. This results in lesscalcium influx to cardiac myocytes throughvoltage-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.[4] Blockage of neurotransmitter binding to β2 receptors on smooth muscle cells will increase contraction, which will increase hypertension.
Propranolol is rapidly and completelyabsorbed, with peak plasma levels achieved about 2hours (range 1–3hours) after ingestion.[4][2] Its oralbioavailability is approximately 25%.[1][3] Despite complete absorption, propranolol has a variablebioavailability due to extensivefirst-pass metabolism.[2]Hepatic impairment therefore increases its bioavailability.[2] Effective plasma concentrations are between 10 and 100mg/L.[citation needed] Toxic levels are associated with plasma concentrations above 2,000mg/L.[citation needed] Coadministration with food appears to enhance bioavailability but does not hasten its time to peak levels.[4][84] Propranolol can be absorbed along the whole intestine with the main absorption site being the colon,[85] which means people who have lost their colon due to surgery may absorb less propranolol. Propranolol shows markedinterindividual variability inpharmacokinetics, with propranolol levels varying 20-fold in different individuals.[86]
Theelimination half-life of propranolol ranges from 2.8 to 8hours in different studies, with a typical half-life of around 4hours.[1][4][2] Theduration of action of a single oral dose is longer than the half-life and may be up to 12hours if the single dose is high enough (e.g., 80 mg).[5]
There were no significance differences in area-under-the-curve levels of propranolol inCYP2D6poor metabolizers versusextensive metabolizers.[53] However, area-under-the-curve propranolol levels were ~2.5-fold higher inCaucasian CYP2D6 poor metabolizers orChinese people with a non-functional CYP2D6 gene.[53] The contribution of CYP2D6 to the metabolism of propranolol is less than withmetoprolol and is described as only "marginal".[53]
Propranolol is highlylipophilic.[3][2] The experimentallog P of propranolol is 3.0 to 3.48 and its predicted log P ranges from 2.20 to 3.10.[2][4][5][89][90]
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.[93] For about 10 to 16% of performers, their degree of stage fright is considered pathological.[93][94] Propranolol is used by musicians, actors, and public speakers for its ability to treat anxiety symptoms activated by the sympathetic nervous system.[95] It has also been used as aperformance-enhancing drug in sports where high accuracy is required, includingarchery,shooting,golf,[96] andsnooker.[96] In the2008 Summer Olympics,50-metre pistol silver medalist and10-metre air pistol bronze medalistKim Jong-su tested positive for propranolol and was stripped of his medals.[97]
Propranolol was first marketed under the brand name Inderal, manufactured byICI Pharmaceuticals (nowAstraZeneca), in 1965. "Inderal" is a quasi-anagram of "Alderlin", the trade name of pronethalol (which propranolol replaced); both names are an homage toAlderley Park, the ICI headquarters where the drugs were first developed.[98]
Propranolol is also marketed under brand names Avlocardyl, Deralin, Dociton, Inderalici, InnoPran XL, Indoblok,[99] Sumial, Anaprilin, and Bedranol SR (Sandoz). In India, it is marketed under brand names such as Ciplar and Ciplar LA byCipla. Hemangeol, a 4.28 mg/mL solution of propranolol, is indicated for the treatment of proliferatinginfantile hemangioma.[100]
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