|Systematic (IUPAC) name|
|Licence data||US FDA:|
|Pregnancy cat.||C (AU) C (US)|
|Legal status||Prescription Only (S4) (AU) POM (UK) ℞-only (US)|
|Routes||Oral, anal, IV|
|Mol. mass||259.34 g/mol|
|Y (what is this?)|
Propranolol (INN) is a sympatholytic non-selective beta blocker. Sympatholytics are used to treat hypertension, anxiety and panic. It was the first successful beta blocker developed. Propranolol is available in generic form as Propranolol Hydrochloride; marketed in India under brand names like Ciplar and Ciplar LA by Cipla, also other brands from AstraZeneca and Wyeth under brand names Inderal, Inderal LA, Avlocardyl, Deralin, Dociton, Inderalici, InnoPran XL, Sumial, Anaprilinum, Bedranol SR (Sandoz).
- 1 Medical uses
- 1.1 Off-label and investigational use
- 2 Precautions and contraindications
- 3 Adverse effects
- 3.1 Pregnancy and lactation
- 4 Pharmacokinetics
- 5 Mechanism of action
- 6 Interactions
- 7 Chemistry
- 8 History
- 9 References
- 10 External links
Propranolol is indicated for the management of various conditions including:
- Angina pectoris
- Myocardial infarction
- Control of tachycardia/tremor associated with anxiety, hyperthyroidism or lithium therapy.
- Essential tremor
- Sex Change
- Migraine prophylaxis
- Cluster headaches prophylaxis
- Tension headache (Off label use)
- Shaky hands
- There has been some experimentation in psychiatric areas:
- Treating the excessive drinking of fluids in psychogenic polydipsia,
- Antipsychotic-induced akathisia,
- Aggressive behavior of patients with brain injuries
- Post-traumatic stress disorder
- Calming down individuals with phobias via sedative effects
- Performance anxiety
- Thyrotoxicosis via deiodinase inhibition
- Primary exertional headache
While once 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 also used to lower portal vein pressure in portal hypertension and prevent esophageal variceal bleeding and ascites.
Off-label and investigational use
Propranolol is often used by musicians and other performers to prevent stage fright. It has been taken by surgeons to reduce their own innate hand tremors during surgery.
Propranolol is currently being investigated as a potential treatment for post-traumatic stress disorder. Propranolol works to inhibit the actions of norepinephrine (noradrenaline), a neurotransmitter that enhances memory consolidation. Studies have shown that individuals given propranolol immediately after a traumatic experience show less severe symptoms of PTSD compared to their respective control groups that did not receive the drug (Vaiva et al., 2003)[full citation needed]. Propranolol reduces the effects of nightmare-related cardiac activity by keeping sinus rhythm low during nightmares, as a higher pulse and increased adrenaline are associated with severe nightmares. However, results remain inconclusive as to the success of propranolol in treatment of PTSD, including nightmares experienced by those with PTSD.
Ethical and legal questions have been raised surrounding the use of Propranolol-based medications for use as a "memory dampener," including: altering (memory-recalled) evidence during an investigation, modifying behavioral response to past (albeit traumatic) experiences, the regulation of these drugs, and others. 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." 
Propranolol in combination with etodolac is currently being investigated in a Phase 3 trial of 400 colorectal cancer patients as a potential treatment for prevention of colorectal cancer recurrence. The aim of this study is to assess the use of perioperative medical intervention using a combination of a propranolol and etodolac in order to attenuate the surgically induced immunosuppression and other physiological perturbations, aiming to reduce the rate of tumor recurrence and distant metastatic disease.
Starting in 2008, reports of successful use of propranolol to treat severe infantile hemangiomas (IHs) began to emerge. This treatment shows promise as being superior to corticosteroids when treating IHs. Extensive clinical case evidence and a small controlled trial support its efficacy.
Propranolol was investigated for possible effects on resting energy expenditure and muscle catabolism in patients with severe burns. In children with burns, treatment with propranolol during hospitalization attenuated hypermetabolism and reversed muscle wasting.
Propranolol along with a number of other membrane-acting drugs have been investigated for possible effects on Plasmodium falciparum and so the treatment of malaria. In vitro positive effects until recently had not been matched by useful in vivo anti-parasite activity against P. vinckei, or P. yoelii nigeriensis. However, a single study from 2006 has suggested that propranolol may reduce the dosages required for existing drugs to be effective against P. falciparum by 5- to 10-fold, suggesting a role for combination therapies.
Oxford researcher Sylvia Terbeck gave volunteers the beta-blocker propranolol. The volunteers scored lower on a range of psychological tests designed to reveal any racist attitudes than a group who took a placebo. The region of the brain called the amygdala is involved in processing emotion, including fear, and many psychologists think racist feelings are driven by the fear center. Propranolol inhibits the amygdala.
In 2011, a small study conducted in two French allergy practices suggested that low doses of propranolol (10–40 mg daily) were effective in the treatment of aquagenic pruritus.
Studies have found propranolol effectively decreases many of the side effects of marijuana.
Precautions and contraindications
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, may be worsened
- Other drugs with bradycardic effects
Propranolol is contraindicated in patients with:
- Reversible airways disease, particularly asthma or chronic obstructive pulmonary disease (COPD)
- Bradycardia (<60 beats/minute)
- Sick sinus syndrome
- Atrioventricular block (second or third degree)
- Severe hypotension
- Cocaine toxicity [per American Heart Association guidelines, 2005]
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 (ADRs) associated with propranolol therapy are similar to other lipophilic beta blockers (see beta blocker).
Pregnancy and lactation
Propranolol, like other beta blockers, is classified as pregnancy category C in the United States and ADEC Category C in Australia. Beta-blocking agents in general reduce perfusion of the placenta which may lead to adverse outcomes for the neonate, including pulmonary or cardiac complications, or premature birth. The newborn may experience additional adverse effects such as hypoglycemia and bradycardia.
Most beta-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. 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."
Propranolol is rapidly and completely absorbed, with peak plasma levels achieved approximately 1–3 hours after ingestion. Co-administration with food appears to enhance bioavailability. Despite complete absorption, propranolol has a variable bioavailability due to extensive first-pass metabolism. Hepatic impairment will therefore increase 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 10–100 ng/mL.
Toxic levels are associated with plasma concentrations above 2000 ng/ml.
Mechanism of action
Propranolol is a non-selective beta blocker, that is, it blocks the action of epinephrine and norepinephrine on both β1- and β2-adrenergic receptors. It has little intrinsic sympathomimetic activity (ISA) but has strong membrane stabilizing activity (only at high blood concentrations, e.g. overdosage). Research has also shown that propranolol has inhibitory effects on the norepinephrine transporter and/or stimulates norepinephrine release (present experiments have shown that the concentration of norepinephrine is increased in the synapse but do not have the ability to discern which effect is taking place). Since propranolol blocks β-adrenoceptors, the increase in synaptic norepinephrine only results in α-adrenergic activation, with the α1-adrenoceptor being particularly important for effects observed in animal models. Therefore, some have suggested that it be looked upon as an indirect α1 agonist as well as a β antagonist. Probably owing to the effect at the α1-adrenoceptor, the racemic and the individual enantiomers of propranolol have been shown to substitute for cocaine in rats, with the most potent enantiomer being S-(–)-propranolol. In addition, some evidence suggests that propranolol may function as a partial agonist at one or more serotonin receptors (possibly 5-HT1B).
Both enantiomers of the drug have a local anesthetic (topical) effect, which is normally mediated by blockade of voltage-gated sodium channels. Few studies have demonstrated propranolol's ability to block cardiac, neuronal, and skeletal voltage-gated sodium channels, accounting for its known "membrane stabilizing effect" and anti-arrhythmic and other central nervous system effects.
Since beta blockers are known to relax the cardiac muscle and to constrict the smooth muscle, these 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:
- β2-adrenergic receptor agonists
- Salbutamol, Levosalbutamol, Formoterol, Salmeterol, etc.
- ergot alkaloids
- non-steroidal anti-inflammatory drugs
- Fluvoxamine slows down the metabolism of propranolol significantly leading to increased blood levels of propranolol.
Propranolol is synthesized in two ways from the same initial substance. The first way consists of reacting 1-naphthol with epichlorohydrin. Opening of the epoxide ring gives 1-chloro-3-(1-naphthyloxy)-2-propanol, which is reacted further with isopropylamine, giving propranolol. The second method uses the same reagents in the presence of a base and consists of initially making 3-(1-naphthyloxy)propylenoxide, the subsequent reaction with isopropylamine which results in epoxide ring opening leading to the formation of propranolol.
British scientist James W. Black successfully developed propranolol in the 1960s. In 1988, he was awarded the Nobel Prize in Medicine for this discovery. Propranolol was derived from the early β-adrenergic antagonists dichloroisoprenaline and pronethalol. The key structural modification, which was carried through to essentially all subsequent beta blockers, was the insertion of an oxymethylene group into the arylethanolamine structure of pronethalol thus greatly increasing the potency of the compound. This also apparently eliminated the carcinogenicity found with pronethalol in animal models.
Newer, more selective beta-blockers (such as nebivolol, carvedilol, or metoprolol) are now used in the treatment of hypertension.
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- Propranolol (INN) is a sympatholytic nonselective beta blocker. It is used to treat high blood pressure, a number of heart dysrhythmias, thyrotoxicosis, and essential tremors.  It is used to prevent migraine headaches, and to prevent ...
- Inderal (Propranolol) インデラル(あがり症etc)海外より生活改善薬もお届け致します。 ... 商品No 商 品 名 濃度 / 数 量 価 格 PI-001 インデラルPropranolol HCL 北米で人気の高いポピュラーなブランド品を、お届けいたします。
|拡張検索||「insulin-propranolol test」「glucagon-propranolol test」「propranolol-glucagon test」「propranolol-insulin test」|
- drug entries
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|Ending of the drug name||Category||Example|
|～ane||Inhalatinal general anesthetic||halothane|
|～azine||Phenothiazine (neuroleptic, antiemetic)||chlorpromazine|
|～cycline||Antibiotic, protein syntlesis inhibitor||tetracycline|
|～operidol||Butyrophenone ( neuroleptic )||haloperidol|
|～oxin||Cardiac glycoside ( inotropic agent )||digoxin|
- 塩酸プロプラノロール propranolol hydrochloride
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