Propranolol

Propranolol

Clinical data
Pronunciation	/proʊˈprænəˌlɒl/
Trade names	Inderal, others
Other names	AY-20694; AY20694
AHFS/Drugs.com	Monograph
License data	US DailyMed: Propranolol
Pregnancy category	AU: C
Antihypertensive agent; Anxiolytic
ATC code	C07AA05 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only EU: Rx-only
oxidation, glucuronidation[1][2]
Metabolites	N-Desisopropylpropranolol; 4'-Hydroxypropanolol[2]
Elimination half-life	~4 hours (range 3–8 hours)[1][4][2]
Duration of action	Up to 12 hours[5]
Excretion	Urine: 91%[4][2]
Identifiers
IUPAC name (RS)-1-(propan-2-ylamino)-3-(1-naphthyloxy)propan-2-ol
JSmol)	Interactive image
Chirality	Racemic mixture
Melting point	96 °C (205 °F)
SMILES OC(COC1=C2C=CC=CC2=CC=C1)CNC(C)C
InChI InChI=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 Y Key:AQHHHDLHHXJYJD-UHFFFAOYSA-N Y
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Propranolol is a medication of the

Propranolol is used for treating various conditions, including:

• Hypertension
• variant angina
  )
• Myocardial infarction
• lithium therapy
• portal vein
  pressure
• Prevention of esophageal variceal bleeding and ascites
• Anxiety
• Hypertrophic cardiomyopathy

While once a first-line treatment for

Propranolol is occasionally used to treat

Other beta blockers that have been used to treat anxiety disorders besides propranolol include atenolol, betaxolol, nadolol, oxprenolol, and pindolol.^[21][23]

Some experimentation has been conducted in other psychiatric areas:^[24]

• Post-traumatic stress disorder (PTSD) and specific phobias
• Aggressive behavior of patients with brain injuries^[25]
• Treating the excessive drinking of fluids in
  psychogenic polydipsia^[26][27]

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 like alcohol are already used for this purpose".^[35]

• Essential tremor. Evidence for use for akathisia however is insufficient^[36]
• Migraine and cluster headache prevention^[37][38] and in primary exertional headache^[6][39]
• Hyperhidrosis (excessive sweating)^{[citation needed]}
• Infantile hemangioma^[40]
• Glaucoma^{[citation needed]}
• Thyrotoxicosis by deiodinase inhibition^{[citation needed}
  ]

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.^[41]

Propranolol is useful in the treatment of acute

Propranolol is available in the form of 10, 20, 40, 60, and 80 mg (as propranolol hydrochloride) oral tablets, among other formulations.^[1][4]

Propranolol should be used with caution in people with:[44]

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

Propranolol, like other beta-blockers, is classified as

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.^[46] 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."^{[45][46][47][48]}

Propranolol

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.^[80][81][82]

Propranolol is a non-selective beta receptor antagonist.^[74] 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.^[4] Blockage of neurotransmitter binding to β₂ receptors on smooth muscle cells will increase contraction, which will increase hypertension.

Propranolol is rapidly and completely

Propranolol is eliminated in urine.^[4][2] Approximately 91% of an oral dose of propranolol is eliminated in urine as 12 metabolites.^[4][2] Only about 1 to 4% of propranolol is excreted unchanged in urine or feces.^[2]

The

Newer, more cardio-selective beta blockers (such as bisoprolol, nebivolol, carvedilol, or metoprolol) are used preferentially in the treatment of hypertension.^[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.^[91] For about 10 to 16% of performers, their degree of stage fright is considered pathological.^[91][92] Propranolol is used by musicians, actors, and public speakers for its ability to treat anxiety symptoms activated by the sympathetic nervous system.^[93] It has also been used as a performance-enhancing drug in sports where high accuracy is required, including archery, shooting, golf,^[94] and snooker.^[94] 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.^[95]

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.^[96]

Propranolol is also marketed under brand names Avlocardyl, Deralin, Dociton, Inderalici, InnoPran XL, Indoblok,^[97] 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.^[98]