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| {{Drugbox|
| | #REDIRECT [[Propranolol#Pharmacology]] |
| | image = Propranolol-2D-skeletal.png
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| | image2 = Propranolol-3D-balls.png
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| | IUPAC_name = 1-(isopropylamino)-<br />3-(naphthalen-1-yloxy)propan-2-ol
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| | ATC_prefix=C07
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| | ATC_suffix=AA05
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| | PubChem=4946
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| | DrugBank=APRD00194
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| | CAS_number = 525-66-6
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| | C=16 | H=21 | N=1 | O=2
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| | molecular_weight = 259.34 g/mol
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| | bioavailability = 26%
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| | metabolism = [[hepatic]] (extensive)
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| | elimination_half-life = 4-5 hours
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| | excretion = [[renal]] <1%
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| | pregnancy_AU = C
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| | pregnancy_US = C
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| | pregnancy_category =
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| | legal_AU = S4
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| | legal_UK = POM
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| | legal_US = Rx-only
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| | routes_of_administration = oral, [[intravenous|iv]]
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| }}
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| {{CMG}}
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| {{Editor Join}}
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| ==[[Propranolol oral (patient information)|For patient information, click here]]==
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| '''Propranolol''' ([[International Nonproprietary Name|INN]]) ([[International Phonetic Alphabet|IPA]]: {{IPA|[proˈprænəloʊl]}}) is a non-selective [[beta blocker]] mainly used in the treatment of [[hypertension]]. It was the first successful beta blocker developed. Propranolol is available in generic form as propranolol hydrochloride, as well as an [[AstraZeneca]] product under the trade names Inderal, Inderal LA, Avlocardyl, Avlocardyl retard, Dociton, Inderalici, Sumial (depending on marketplace and release rate). It is also marketed by [[Wyeth]].
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| == History and development==
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| Scottish scientist [[James W. Black]] successfully developed propranolol in the late 1950s. He was awarded the [[Nobel Prize in Medicine]] for this discovery in 1988.
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| Propranolol developed 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 bridge 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.
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| == Pharmacology ==
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| {{dablink|Main article: [[Beta blocker]]}}
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| Propranolol is a [[beta blocker|non-selective beta blocker]], that is, it blocks the action of [[epinephrine]] on both β<sub>1</sub>- and β<sub>2</sub>-[[adrenergic receptor]]s. It has little intrinsic sympathomimetic activity (ISA) but has strong membrane stabilizing activity (only at high blood concentrations, eg overdosage).
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| == Pharmacokinetics ==
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| 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.
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| 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 indicates 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.
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| Toxic levels are associated with plasma concentrations above 2000 ng/ml
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| == Clinical use ==
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| {{dablink|Main article: [[Beta blocker]]}}
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| === Indications ===
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| Propranolol is indicated for the management of various conditions including:<ref name="Rossi">Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006.</ref>
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| *[[Hypertension]]
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| *[[Angina pectoris]]
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| *[[Tachyarrhythmia]]s
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| *[[Myocardial infarction]]
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| *Control of [[tachycardia]]/tremor associated with [[anxiety]] and [[hyperthyroidism]]
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| *[[Essential tremor]]
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| *[[Migraine]] prophylaxis
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| *[[Tetralogy of Fallot]]
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| *[[Phaeochromocytoma]] (along with [[alpha blocker|α blocker]])
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| *[[Post Traumatic Stress Disorder]] (experimental)
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| 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 perform less well than 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 [[Diabetes mellitus type 2|type 2 diabetes]]. <ref>{{cite web | author= Sheetal Ladva | title=NICE and BHS launch updated hypertension guideline | url=http://www.nelm.nhs.uk/Record%20Viewing/viewRecord.aspx?id=567178 | date=28/06/2006 | publisher=[[National Institute for Health and Clinical Excellence]]}}</ref>
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| Propranolol is also used to lower [[portal vein]] pressure in [[portal hypertension]] and prevent [[esophageal varices|oesophageal variceal]] bleeding.
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| Propranolol is often used by musicians and other performers to prevent [[stage fright]].
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| Propranolol is currently being investigated as a potential treatment for [[post-traumatic stress disorder]]. <ref>{{cite web |url=http://www.msnbc.msn.com/id/10806799/ |title=Doctors test a drug to ease traumatic memories - Mental Health - MSNBC.com |format= |work=}}</ref><ref>{{cite journal |author=Brunet A, Orr SP, Tremblay J, Robertson K, Nader K, Pitman RK |title=Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder |journal= |volume= |issue= |pages= |year=2007 |pmid=17588604 |doi=10.1016/j.jpsychires.2007.05.006}}</ref><ref>{{cite web|url=http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T8T-4P1G931-2&_user=10&_coverDate=06%2F22%2F2007&_alid=594818882&_rdoc=1&_fmt=summary&_orig=search&_cdi=5095&_sort=d&_docanchor=&view=c&_ct=1&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=cff0ee031b688b5fbc74a7de54915c38 |title=Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder}}</ref>
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| === Precautions/contraindications ===
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| Propranolol should be used with caution in patients with:<ref name="Rossi">Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006.</ref>
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| *[[Diabetes mellitus]] or [[hyperthyroidism]], since signs and symptoms of [[hypoglycaemia]] may be masked
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| *[[Peripheral vascular disease]] and [[Raynaud's syndrome]], which may be exacerbated
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| *[[Phaeochromocytoma]], as [[hypertension]] may be aggravated without prior [[alpha blocker]] therapy
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| *[[Myasthenia gravis]], may be worsened
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| *Other drugs with [[bradycardia|bradycardic]] effects
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| Propranolol is contraindicated in patients with:<ref name="Rossi"> </ref>
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| *Reversible airways disease, particularly [[asthma]] or [[chronic obstructive pulmonary disease]] (COPD)
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| *[[Bradycardia]] (<50 beats/minute)
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| *[[Sick sinus syndrome]]
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| *[[Atrioventricular block]] (second or third degree)
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| *[[Shock (medical)|Shock]]
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| *Severe [[hypotension]]
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| *Uncontrolled [[congestive heart failure]]
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| *Cocaine toxicity [per American Heart Association guidelines, 2005]
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| === Adverse effects ===
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| [[Adverse drug reaction]]s (ADRs) associated with propranolol therapy are similar to other lipophilic beta blockers (''see [[beta blocker]]'').
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| === Pregnancy and Lactation ===
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| Propranolol, like other beta blockers, is classified as [[Pregnancy category]] C in the United States and [[Australian Drug Evaluation Committee|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]].
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| Most beta-blocking agents appear in the milk of [[lactation|lactating]] women. This is especially the case for a [[lipophilic]] drug like propranolol. Breastfeeding is not recommended in patients receiving propranolol therapy.
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| === Interactions ===
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| Beta blockers, 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:<ref name="Rossi"> </ref>
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| *[[verapamil]]
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| *[[epinephrine]]
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| *[[Beta2-adrenergic receptor agonist|β<sub>2</sub>-adrenergic receptor agonists]]
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| *[[clonidine]]
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| *[[ergot alkaloid]]s
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| *[[isoprenaline]]
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| *[[non-steroidal anti-inflammatory drug]]s
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| *[[quinidine]]
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| *[[cimetidine]]
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| *[[lidocaine]]
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| *[[phenobarbital]]
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| *[[rifampicin]]
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| === Dosage ===
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| The usual maintenance dose ranges for oral propranolol therapy vary by indication:
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|
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| *Hypertension, angina, essential tremor
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| **120–320 mg daily in divided doses.
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| **Sustained-release formulations are available in some markets.
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| *Tachyarrhythmia, anxiety, hyperthyroidism
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| **10–40 mg 3–4 times daily
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| Intravenous ([[intravenous|IV]]) propranolol may be used in acute [[arrhythmia]] or [[Hyperthyroidism|thyrotoxic crisis]].<ref>*Joint Formulary Committee. British National Formulary, 47th edition. London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2004.</ref>
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| ===Research into role against malaria===
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| Propranolol along with a number of other membrane-acting drugs have been investigated for possible effects on ''[[Plasmodium falciparum|P. 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 ''Plasmodium vinckei'',<ref>{{cite journal |author=Ohnishi S, Sadanaga K, Katsuoka M, Weidanz W |title=Effects of membrane acting-drugs on plasmodium species and sickle cell erythrocytes |journal=Mol Cell Biochem |volume=91 |issue=1-2 |pages=159-65 |year=1990 |id=PMID 2695829}}</ref> or ''[[Plasmodium yoelii|P. yoelii nigeriensis]]''.<ref>{{cite journal |author=Singh N, Puri S |title=Interaction between chloroquine and diverse pharmacological agents in chloroquine resistant Plasmodium yoelii nigeriensis |journal=Acta Trop |volume=77 |issue=2 |pages=185-93 |year=2000 |id=PMID 11080509}}</ref> 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.<ref>{{cite journal |author=Murphy S, Harrison T, Hamm H, Lomasney J, Mohandas N, Haldar K |title=Erythrocyte G protein as a novel target for malarial chemotherapy |journal=PLoS Med |volume=3 |issue=12 |pages=e528 |year=2006 | month=Dec | id=PMID 17194200 | url=http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030528}}</ref>
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| ==Media==
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| *Propranolol as an experimental treatment for [[Post Traumatic Stress Disorder]] was a subject of the television show ''Boston Legal'', Season 3, Episode 14, ''Selling Sickness''.
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| * Propanonol was used by one of the criminals in the TV show ''CSI: NY'' episode titled "Some buried bones" , Season 3 Episode 15 (2004-02-17).
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| *Propranolol was referenced on the Late Show With David Letterman on May 4, 2007 in a mock-advertisement.
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| == References ==
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| {{Reflist|2}}
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| == External links==
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| *[http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202087.html Beta-adrenergic blocking agents (systemic)] – information from USP DI Advice for the Patient
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| * [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9456487&dopt=Abstract Historical Remarks about Propranolol and its inventor]
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| * [http://www.sciam.com/article.cfm?chanID=sa004&articleID=0006783F-2CFE-1FE2-ACFE83414B7FFE9F&pageNumber=1&catID=4 Scientific American Interview with James McGaugh]
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| *[http://www.cbsnews.com/stories/2006/11/22/60minutes/main2205629.shtml CBS NEWS 60 Minutes: A Pill To Forget]
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| {{beta blockers}}
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| [[Category:Antiarrhythmic agents]]
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| [[Category:Anxiolytics]]
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| [[Category:Beta blockers]]
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