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Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class.
Common side effects include nausea, abdominal pain, and constipation.
Propranolol was discovered in 1964.
Contents
1 Medical uses
1.1 Cardiovascular
1.2 Psychiatric
1.2.1 PTSD and phobias
1.3 Others
2 Contraindications
3 Adverse effects
3.1 Pregnancy and lactation
4 Overdose
5 Interactions
6 Pharmacology
6.1 Pharmacodynamics
6.2 Pharmacokinetics
7 History
8 Society and culture
8.1 Brand names
9 Research
10 References
11 External links
Medical uses
An 80 mg capsule of extended-release propranolol
A mixture of 20 mg and 10 mg propranolol tablets
Propranolol
Propranolol is used for treating various conditions, including:
Cardiovascular
Hypertension
Angina pectoris (with the exception of variant angina )
Tachyarrhythmia
Myocardial infarction
Tachycardia (and other sympathetic nervous system symptoms, such as muscle tremor ) associated with various conditions, including anxiety, panic, hyperthyroidism, and lithium therapy
Portal hypertension, to lower portal vein pressure
Prevention of esophageal variceal bleeding and ascites
Anxiety
Hypertrophic cardiomyopathy
While once a first-line treatment for hypertension, the role for 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.
Propranolol is not recommended for the treatment of hypertension 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.
Psychiatric
Propranolol is occasionally used to treat performance anxiety.
Post-traumatic stress disorder (PTSD) and specific phobias (see subsection below)
Aggressive behavior of patients with brain injuries
Treating the excessive drinking of fluids in psychogenic polydipsia
PTSD and phobias
Propranolol is being investigated as a potential treatment for PTSD.
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 behavioral response to past (albeit traumatic) experiences, the regulation of these drugs, and others.
Others
Essential tremor. Evidence for use for akathisia however is insufficient
Migraine and cluster headache prevention
Hyperhidrosis (excessive sweating)
Proliferating infantile hemangioma
Glaucoma
Thyrotoxicosis by deiodinase inhibition
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.
Contraindications
See also: Beta blocker § Contraindications
Propranolol may be contraindicated in people with:
Reversible airways diseases, particularly asthma or chronic obstructive pulmonary disease (COPD)
Slow heart rate (bradycardia) (<60 beats/minute)
Sick sinus syndrome
Atrioventricular block ( second- or third-degree )
Shock
Severe low blood pressure
Cocaine toxicity
Adverse effects
See also: Beta blocker § Adverse effects
Propranolol should be used with caution in people with:
Diabetes mellitus or hyperthyroidism, since signs and symptoms of hypoglycaemia may be masked
Peripheral vascular disease and Raynaud’s 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
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.
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.
Due to the high penetration across the blood–brain barrier, lipophilic beta blockers such as propranolol and metoprolol are more likely than other less lipophilic beta blockers to cause sleep disturbances such as insomnia and vivid dreams, and nightmares.
Adverse drug reactions associated with propranolol therapy are similar to other lipophilic beta blockers.
Overdose
In overdose propranolol is associated with seizures.
Interactions
Since beta blockers are known to relax the cardiac muscle and to constrict the smooth muscle, beta-adrenergic antagonists, including propranolol, have an additive effect with other drugs which decrease blood pressure, or which decrease cardiac contractility or conductivity. Clinically significant interactions particularly occur with:
Verapamil
Epinephrine (adrenalin)
β 2 -adrenergic receptor agonists
Salbutamol, levosalbutamol, formoterol, salmeterol, clenbuterol etc.
Clonidine
Ergot alkaloids
Isoprenaline (isoproterenol)
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Quinidine
Cimetidine
Lidocaine
Phenobarbital
Rifampicin
Fluvoxamine (slows down the metabolism of propranolol significantly, leading to increased blood levels of propranolol)
Pharmacology
Pharmacodynamics
Propranolol
Site
K i (nM)
Species
Ref
5-HT 1A
55–272
Human
5-HT 1B
56–85
Rat
5-HT 1D
4,070
Pig
5-HT 2A
4,280
Human
5-HT 2B
457–513 ( + ) 166–316 ( – )
Human
5-HT 2C
61,700 ( + ) 5,010 ( – ) 736–2,457
Human Human Rodent
5-HT 3
>10,000
Human
α 1
ND
ND
ND
α 2
1,297–2,789
Rat
β 1
0.02–2.69
Human
β 2
0.01–0.61
Human
β 3
450
Mouse
D 1
>10,000
Human
D 2
>10,000
Human
H 1
>10,000
Human
SERT
3,700
Rat
NET
5,000 ( IC 50 )
Rat
DAT
29,000 ( IC 50 )
Rat
VDCC
>10,000
Rat
Values are K i (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.
Propranolol is classified as a 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 beta blocker ; that is, it blocks the action of epinephrine (adrenaline) and norepinephrine (noradrenaline) at both β 1 – and β 2 -adrenergic receptors. It has little intrinsic sympathomimetic activity, but has strong membrane stabilizing activity (only at high blood concentrations, e.g. overdose ).
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 ).
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.
Pharmacokinetics
Propranolol is rapidly and completely absorbed, with peak plasma levels achieved about 1–3 hours after ingestion. Coadministration with food appears to enhance bioavailability. Despite complete absorption, propranolol has a variable bioavailability due to extensive first-pass metabolism. Hepatic impairment therefore increases its bioavailability. 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.
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 mg). Effective plasma concentrations are between 10 and 100 mg/l.
History
Main article: Discovery and development of β-adrenergic receptor antagonists (beta-blockers)
British scientist James W. Black developed propranolol in the 1960s. In 1988, he was awarded the Nobel Prize in Medicine for this discovery. Propranolol was inspired by the early β-adrenergic antagonists dichloroisoprenaline and pronethalol. The key difference, which was carried through to essentially all subsequent beta blockers, was the inclusion of an oxymethylene group (-O-CH 2 -) between the aryl and ethanolamine moieties of pronethalol, greatly increasing the potency of the compound. This also apparently eliminated the carcinogenicity found with pronethalol in animal models.
Newer, more cardio-selective beta blockers (such as bisoprolol, nebivolol, carvedilol, or metoprolol ) are now used in the treatment of hypertension.
Society and culture
In a 1987 study by the International Conference of Symphony and Opera Musicians, it was shown that 27% of interviewed members admitted to using beta blockers such as propranolol for musical performances.
Brand names
Original propranolol was marketed in 1965 under the brand name Inderal and manufactured by ICI Pharmaceuticals (now AstraZeneca ). Propranolol is also marketed under brand names Avlocardyl, Deralin, Dociton, Inderalici, InnoPran XL, 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.
Research
Clinical research has been conducted to learn if propranolol could be useful in the treatment of some cancers.

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