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{{Propranolol}}
{{Drugbox| verifiedrevid = 464216937
| IUPAC_name = (''RS'')-1-(1-methylethylamino)-3-(1-naphthyloxy)propan-2-ol
| drug_name = Propranolol
<!--Clinical data-->
| brand = Inderal
| Drugs.com = {{drugs.com|monograph|propranolol-hydrochloride}}
| licence_US = Propranolol
| pregnancy_AU = C
| pregnancy_US = C
| legal_AU = S4
| legal_UK = POM
| legal_US = Rx-only
| routes_of_administration = Oral, anal, [[intravenous|IV]]
<!--Pharmacokinetic data-->
| bioavailability = 26%
| metabolism = [[hepatic]] (extensive)
| elimination_half-life = 4–5 hours
| excretion = [[renal]] <1%
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 525-66-6
| ATC_prefix = C07
| ATC_suffix = AA05
| PubChem = 4946
| IUPHAR_ligand = 564
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00571
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4777
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9Y8NXQ24VQ
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08443
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 8499
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 27
<!--Chemical data-->
| C=16 | H=21 | N=1 | O=2
| molecular_weight = 259.34 g/mol
| smiles = CC(C)NCC(COc1cccc2c1cccc2)O
| InChI = 1/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
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = AQHHHDLHHXJYJD-UHFFFAOYSA-N
}}
__NOTOC__
__NOTOC__
{{CMG}}
{{CMG}}; {{AE}} {{Alonso}}


'''''For patient information about Propranolol, click [[Propranolol (patient information)|here]].'''''
Infobox goes here


{{SB}} Inderal LA<sup>®</sup>, InnoPran XL<sup>®</sup>
<nowiki>{{SI}}</nowiki>


==Overview==
'''''Synonyms and keywords:'''''


'''Propranolol''' ([[International Nonproprietary Name|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.<ref name="Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC 1964 1080–1081">{{cite journal|author=Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC |title=A new adrenergic betareceptor antagonist | journal=[[The Lancet]] |volume=283 |issue=7342 |pages=1080–1081 |year=1964 |pmid=14132613 |doi=10.1016/S0140-6736(64)91275-9}}</ref>  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]]).
== Overview ==
'''Body dysmorphic disorder (BDD)''' is a mental disorder that involves a disturbed [[body image]]. It is generally diagnosed in those who are extremely critical of their physique or self-image, despite the fact there may be no noticeable disfigurement or defect.


==Category==
Most people wish they could change or improve some aspect of their physical appearance, but people suffering from BDD, generally considered of normal appearance, believe that they are so unspeakably hideous that they are unable to interact with others or function normally for fear of ridicule and humiliation at their appearance. They tend to be very secretive and reluctant to seek help because they are afraid others will think them vanity|vain or they may feel too embarrassed to do so.


Beta-blockers, Antimigraine drugs
Ironically, BDD is often misunderstood as a vanity driven obsession, whereas it is quite the opposite; people with BDD believe themselves to be irrevocably ugly or defective.


==FDA Package Insert==
BDD combines obsessive and compulsive aspects, which links it to the [[Obsessive-Compulsive Disorder|OCD]] spectrum disorders among psychologists. People with BDD may engage in compulsive mirror checking behaviors or mirror avoidance, typically think about their appearance for more than one hour a day, and in severe cases may drop all social contact and responsibilities as they become homebound. The disorder is linked to an unusually high [[suicide]] rate among all mental disorders.


====INDERAL LA (propranolol hydrochloride) capsule, extended release====
A German study has shown that 1-2% of the population meet all the diagnostic criteria of BDD, with a larger percentage showing milder symptoms of the disorder (''Psychological Medicine'', vol 36, p 877). Chronically low self-esteem is characteristic of those with BDD due to the value of oneself being so closely linked with their perceived appearance. The prevalence of BDD is equal in men and women, and causes chronic social [[anxiety]] for those suffering from the disorder[http://www.lipo.com/Health_Articles/Lifestyle_Articles/When_the_mirror_lies_-_Body_dysmorphic_disorder_(dysmorphophobia)_on_the_rise_and_taking_lives./].


'''  [[Propranolol indications and usage|Indications and Usage]]'''
Phillips & Menard (2006) found the completed suicide rate in patients with BDD to be 45 times higher than in the general US population. This rate is more than double that of those with [[Clinical depression]] and three times as high as those with [[bipolar disorder]]<ref>http://ajp.psychiatryonline.org/cgi/content/full/163/7/1280</ref>. There has also been a suggested link between undiagnosed BDD and a higher than average suicide rate among people who have undergone cosmetic surgery<ref>http://www.newscientist.com/channel/health/mg19225745.200-cosmetic-surgery-special-when-looks-can-kill.html</ref>.
'''| [[Propranolol dosage and administration|Dosage and Administration]]'''
'''| [[Propranolol contraindications|Contraindications]]'''
'''| [[Propranolol warnings and precautions|Warnings and Precautions]]'''
'''| [[Propranolol adverse reactions|Adverse Reactions]]'''
'''| [[Propranolol drug interactions|Drug Interactions]]'''
'''| [[Propranolol use in specific populations|Use in Specific Populations]]'''
'''| [[Propranolol overdosage|Overdosage]]'''
'''| [[Propranolol description|Description]]'''
'''| [[Propranolol clinical pharmacology|Clinical Pharmacology]]'''
'''| [[Propranolol nonclinical toxicology|Nonclinical Toxicology]]'''
'''| [[Propranolol how supplied storage and handling|How Supplied/Storage and Handling]]'''
'''| [[Propranolol labels and packages|Labels and Packages]]'''


== Medical uses ==
==Historical Perspective==
 
BDD was first documented in 1886 by the researcher Morselli, who called the condition simply "'''Dysmorphophobia'''". BDD was first recorded/formally recognized in 1997 as a disorder in the [[Diagnostic and Statistical Manual of Mental Disorders|DSM]]; however, in 1987 it was first truly recognized by the [[American Psychiatric Association]].  
Propranolol is indicated for the management of various conditions including:
 
* [[Hypertension]]
* [[Angina pectoris]]
* [[Tachyarrhythmia]]s
* [[Myocardial infarction]]
* Control of [[tachycardia]]/tremor associated with [[anxiety]], [[hyperthyroidism]] or [[Lithium pharmacology|lithium therapy]]
* [[Essential tremor]]
* [[Migraine]] prophylaxis<ref>{{cite journal |last1=Shields |first1=Kevin G. |coauthors=Peter J. Goadsby |date=January 2005 |title=Propranolol modulates trigeminovascular responses in thalamic ventroposteromedial nucleus: a role in migraine? |journal=[[Brain (journal)|Brain]]|volume=128 |issue=1 |pages=86–97 |doi=10.1093/brain/awh298 |url=http://brain.oxfordjournals.org/content/128/1/86.full |accessdate=17 August 2012}}</ref><ref>{{cite book |title=The Biochemistry of Migraine |last=Eadie |first=M. |coauthors=J. H. Tyrer |year=1985 |publisher=Springer |location=New York |isbn=9780852007310 |page=148 |oclc=11726870 |url=http://books.google.com/books?id=JYeyCc9M6acC&pg=PA148&lpg=PA148&dq=Propranolol+migraine+mechanism,&source=bl&ots=Ep2oSjxpAo&sig=7H_KHF3xoIP0nBKJJaqsDl_IhAs&hl=en&ei=TXVPTuu6DKHE4gT6gLnXBw&sa=X&oi=book_result&ct=result&resnum=4&ved=0CCoQ6AEwAzgK#v=onepage&q=Propranolol%20migraine%20mechanism%2C&f=false}}{{dead link|date=August 2012}}</ref>
* [[Cluster headaches]] prophylaxis
* [[Tension headache]] (Off label use)
* Shaky hands
* Hyperhidrosis
 
There has been some experimentation in psychiatric areas:<ref name="pmid17200914">{{cite journal |author=Kornischka J, Cordes J, Agelink MW |title=[40 years beta-adrenoceptor blockers in psychiatry] |language=German |journal=Fortschritte Der Neurologie-Psychiatrie |volume=75 |issue=4 |pages=199–210 |date=April 2007 |pmid=17200914 |doi=10.1055/s-2006-944295}}</ref> 
 
* Treating the excessive drinking of fluids in [[psychogenic polydipsia]]<ref name="pmid7737786">{{cite journal |doi=10.2190/5WG5-VV1V-BXAD-805K |author=Vieweg V, Pandurangi A, Levenson J, Silverman J |title=The consulting psychiatrist and the polydipsia-hyponatremia syndrome in schizophrenia |journal=International Journal of Psychiatry in Medicine |volume=24 |issue=4 |pages=275–303 |year=1994 |pmid=7737786}}</ref><ref name="pmid9844835">{{cite journal |doi=10.2190/QPWL-14H7-HPGG-A29D |author=Kishi Y, Kurosawa H, Endo S |title=Is propranolol effective in primary polydipsia? |journal=International Journal of Psychiatry in Medicine |volume=28 |issue=3 |pages=315–25 |year=1998 |pmid=9844835}}</ref>
 
* [[Antipsychotic]]-induced [[akathisia]]<ref name="pmid2577308">{{cite journal |author=Kramer MS, Gorkin R, DiJohnson C |title=Treatment of neuroleptic-induced akathisia with propranolol: a controlled replication study |journal=The Hillside Journal of Clinical Psychiatry |volume=11 |issue=2 |pages=107–19 |year=1989 |pmid=2577308}}</ref>
 
* [[Aggressive behavior]] of patients with [[Acquired brain injury|brain injuries]]<ref name="pmid7903928">{{cite journal |author=Thibaut F, Colonna L |title=[Anti-aggressive effect of beta-blockers] |language=French |journal=L'Encéphale |volume=19 |issue=3 |pages=263–7 |year=1993 |pmid=7903928}}</ref>
 
* [[Post-traumatic stress disorder]]
* Calming down individuals with [[phobias]] via sedative effects
* Performance anxiety
* [[Glaucoma]]
* [[Thyrotoxicosis]]  via deiodinase inhibition
* Primary exertional headache<ref>[http://www.medlink.com/medlinkcontent.asp Clinical summary]</ref>
 
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 [[Diabetes mellitus type 2|type 2 diabetes]].<ref>{{cite web | author= Sheetal Ladva | title=NICE and BHS launch updated hypertension guideline | url=http://www.nice.org.uk/download.aspx?o=335988 | date=2006-06-28 | publisher=[[National Institute for Health and Clinical Excellence]] | accessdate=2009-10-11}}</ref>
 
Propranolol is also used to lower [[Hepatic portal vein|portal vein]] pressure in [[portal hypertension]] and prevent [[esophageal varices|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 [[tremor|hand tremors]] during surgery.<ref>{{cite journal |author=Elman MJ, Sugar J, Fiscella R, ''et al.'' |title=The effect of propranolol versus placebo on resident surgical performance |journal=Transactions of the American Ophthalmological Society |volume=96 |issue= |pages=283–91; discussion 291–4 |year=1998 |pmid=10360293 |pmc=1298399}}</ref>
 
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 |accessdate=2007-06-30 |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=Journal of Psychiatric Research |volume=42 |issue=6 |pages=503–6 |date=May 2008 |pmid=17588604 |doi=10.1016/j.jpsychires.2007.05.006}}</ref><ref>[http://www.cbsnews.com/stories/2006/11/22/60minutes/main2205629.shtml?tag=contentMain;contentBody A pill to forget]</ref> 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|date=November 2012}}. 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.<ref>{{cite journal| author=Kolber, Adam J.| title=Therapeutic Forgetting: The Legal and Ethical Implications of Memory Dampening |journal=Vanderbilt Law Review, San Diego Legal Studies Paper No. 07-37. |volume=59 |page=1561 |year=2006}}</ref> 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." <ref>{{cite journal|last=Hall|first=Wayne|coauthors=Carter, Adrian | title=Debunking Alarmist Objections to the Pharmacological Prevention of PTSD |journal=American Journal of Bioethics|year=2007|volume=7|issue=9|pages=23 -25|doi=10.1080/15265160701551244|accessdate=8 December 2013}}</ref>   
 
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.<ref>{{cite web |url=http://clinicaltrials.gov/ct2/show/NCT00888797|title=β-adrenergic Blocker and a COX2 Inhibitor for Prevention of Colorectal Cancer Recurrence |accessdate=2010-07-19 |work=}}</ref> 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.<ref>{{cite journal |journal= Current Dermatology Reports |year= 2012 |doi= 10.1007/s13671-012-0026-6 |title= Propranolol for Infantile Hemangiomas: A Review |first1= M. |last1= Hogeling |page= Online-first }}</ref>
 
Propranolol was investigated for possible effects on resting energy expenditure and muscle catabolism in patients with severe burns.<ref>{{cite journal |author=Herndon DN et al. |title=Reversal of Catabolism by Beta-Blockade after Severe Burns|journal=New England Journal of Medicine |volume=345 |issue=17 |pages=1223–1229 |date=October 2001 |pmid=11680441 |doi=10.1056/NEJMoa010342}}</ref> 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 ''[[Plasmodium vinckei|P. 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 |pmid=2695829 |doi=10.1007/BF00228091}}</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 |pmid=11080509 |doi=10.1016/S0001-706X(00)00133-9}}</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 |date=December 2006 | pmid=17194200 | doi= 10.1371/journal.pmed.0030528 |pmc=1716186}}</ref>
 
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.<ref>{{cite web | author= Sheetal Ladva | title=Drug 'reduces implicit racial bias,' study suggests | url=http://www.ox.ac.uk/media/news_stories/2012/120803.html | date=2012-03-15 | publisher=[[Oxford Medical School]] | accessdate=2012-03-16}}</ref> 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.<ref>[http://www.kplctv.com/story/17144764/medical-headliners-racism-pill-springing-forward-school-menus?clienttype=printable Pill for Racism]</ref>


In 2011, a small study conducted in two French allergy practices suggested that low doses of propranolol (10–40&nbsp;mg daily) were effective in the treatment of [[aquagenic pruritus]].<ref>Journal of Allergy and Clinical Immunology, May 2011</ref>
In his practice, [[Sigmund Freud|Freud]] eventually had a patient who would today be diagnosed with the disorder; Russian [[aristocrat]] [[Sergei Pankejeff]], nicknamed "The Wolf Man" by Freud himself in order to protect Pankejeff's identity, had a preoccupation with his nose to an extent that greatly limited his functioning.


Studies have found propranolol effectively decreases many of the side effects of [[marijuana]].<ref>{{cite pmid|403557}}</ref><ref>{{cite pmid|15131000}}</ref><ref>[http://archives.drugabuse.gov/pdf/monographs/68.pdf#page=117 Hollister, Leo E. "Interactions of cannabis with other drugs in man." Strategies for research on the interactions of drugs of abuse. National Institute on Drug Abuse Research monograph 68 (1986): 110-116.]</ref>
==Classification==


==Precautions and contraindications==
==Pathophysiology==
BDD usually develops in adolescence, a time when people are generally most sensitive about their appearance. However, many patients suffer for years before seeking help. When they do seek help through mental health professionals, patients often complain of other symptoms such as depression, social anxiety or obsessive compulsive disorder, but do not reveal their real concern over body image. Most patients cannot be convinced that they have a distorted view of their body image, due to the very limited knowledge of the disorder as compared to OCD or others.


Propranolol should be used with caution in people with:<ref name="Rossi">Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006.</ref>
An absolute cause of body dysmorphic disorder is unknown. However research shows that a number of factors may be involved and that they can occur in combination, including:


*[[Diabetes mellitus]] or [[hyperthyroidism]], since signs and symptoms of [[hypoglycaemia]] may be masked.
'''A chemical imbalance in the brain.''' An insufficient level of [[serotonin]], one of the brain's [[neurotransmitter]]s involved in mood and pain, may contribute to body dysmorphic disorder. Although such an imbalance in the brain is unexplained, it may be hereditary.
*[[Peripheral vascular disease]] and [[Raynaud's syndrome]], which may be exacerbated
*[[Phaeochromocytoma]], as [[hypertension]] may be aggravated without prior [[alpha blocker]] therapy
'''Obsessive-compulsive disorder.''' BDD often occurs with OCD, where the patient uncontrollably practices ritual behaviors that may literally take over their life. A history of, or [[gene]]tic predisposition to, OCD may make people more susceptible to BDD.
*[[Myasthenia gravis]], may be worsened
*Other drugs with [[bradycardia|bradycardic]] effects


Propranolol is contraindicated in patients with:<ref name="Rossi" />
'''Generalized anxiety disorder.''' Body dysmorphic disorder may co-exist with generalized anxiety disorder. This condition involves excessive worrying that disrupts the patient's daily life, often causing exaggerated or unrealistic anxiety about life circumstances, such as a perceived flaw or defect in appearance, as in BDD.


*Reversible airways disease, particularly [[asthma]] or [[chronic obstructive pulmonary disease]] (COPD)
==Causes==
*[[Bradycardia]] (<60 beats/minute)
*[[Sick sinus syndrome]]
*[[Atrioventricular block]] (second or third degree)
*[[shock (circulatory)|Shock]]
*Severe [[hypotension]]
*Cocaine toxicity [per American Heart Association guidelines, 2005]


==Adverse effects==
==Differentiating type page name here from other Diseases==


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.<ref name="pmid21180298">{{cite journal |author=Cruickshank JM |title=Beta-blockers and heart failure |journal=Indian Heart J |volume=62 |issue=2 |pages=101–10 |year=2010 |pmid=21180298 }}</ref>
== Epidemiology and Demographics ==
''According to Dr Katharine Phillips (2004) :''


[[Adverse drug reaction]]s (ADRs) associated with propranolol therapy are similar to other lipophilic beta blockers (''see [[beta blocker]]'').
Although large [[epidemiology|epidemiologic]] surveys of BDD's prevalence have not been done, studies to date indicate that BDD is relatively common in both nonclinical and clinical settings (Phillips & Castle, 2002). Studies in community samples have reported current rates of 0.7% and 1.1%, and studies in nonclinical student samples have reported rates of 2.2%, 4%, and 13% (Phillips & Castle, 2002). A study in a general inpatient setting found that 13% of patients had BDD (Grant, Won Kim, Crow, 2001). Studies in outpatient settings have reported rates of 8%-37% in patients with OCD, 11%-13% in social phobia, 26% in trichotillomania, 8% in major depression, and 14%-42% in atypical major depression (Phillips & Castle, 2002). In one study of atypical depression, BDD was more than twice as common as OCD (Phillips, Nierenberg, Brendel et al 1996), and in another (Perugi, Akiskal, Lattanzi et al, 1998) it was more common than many other disorders, including OCD, social phobia, simple phobia, generalized anxiety disorder, [[bulimia nervosa]], and substance abuse or dependence. In a [[dermatology]] setting, 12% of patients screened positive for BDD, and in [[cosmetic surgery]] settings, rates of 6%-15% have been reported (Phillips & Castle, 2002).


===Pregnancy and lactation===
BDD is underdiagnosed, however. Two studies of inpatients (Phillips, McElroy, Keck et al, 1993, and Grant, Won Kim, Crow, 2001), as well as studies in general outpatients (Zimmerman & Mattia, 1998) and depressed outpatients (Phillips, Nierenberg, Brendel et al 1996), systematically assessed a series of patients for the presence of BDD and then determined whether clinicians had made the diagnosis in the clinical record. All four studies found that BDD was missed by the clinician in every case in which it was present. Thus, underdiagnosis of BDD appears common.
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 [[human lung|pulmonary]] or [[human heart|cardiac]] complications, or premature birth. The newborn may experience additional adverse effects such as [[hypoglycemia]] and [[bradycardia]].<ref name="Martindale">{{Cite book|editor=Sweetman, Sean C. |chapter=Cardiovascular Drugs|title=[[Martindale: The complete drug reference]] |edition=36th |year=2009|pages=1226–1381|publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1}}</ref>


Most beta-blocking agents appear in the milk of [[lactation|lactating]] women. However, propranolol is highly [[plasma protein binding|bound to proteins in the bloodstream]] and is distributed into breast milk at very low levels.<ref name="LactMed">[No authors listed] (2007). "Propranolol". In: ''Drugs and Lactation Database.'' U.S. [[National Library of Medicine]] Toxicology Data Network. Retrieved 2013-02-25.</ref> 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."<ref name="LactMed"/><ref name="Martindale"/><ref>{{cite journal |author=[No authors listed] |title=Transfer of drugs and other chemicals into human milk |journal=Pediatrics |volume=108 |issue=3 |pages=776–89 |date=September 2001 |pmid=11533352}}</ref><ref>{{cite journal |author=Spencer JP, Gonzalez LS, Barnhart DJ |title=Medications in the breast-feeding mother |journal=Am Fam Physician |volume=64 |issue=1 |pages=119–26 |date=July 2001 |pmid=11456429}}</ref>
== Risk Factors ==


==Pharmacokinetics==
== Screening ==


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.
== Natural History, Complications, and Prognosis==


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&nbsp;mg). Effective plasma concentrations are between 10–100&nbsp;ng/mL.
== Diagnosis ==


Toxic levels are associated with plasma concentrations above 2000&nbsp;ng/ml.
=== Symptoms ===
*Compulsive mirror checking, glancing in reflective doors, windows and other reflective surfaces.
*Alternatively, an inability to look at one's own reflection or photographs of oneself; often the removal of mirrors from the home.
*Compulsive skin-touching, especially to measure or feel the perceived defect.
*Reassurance-seeking from loved ones.
*Social withdrawal and co-morbid depression.
*Obsessive viewing of favorite celebrities or models the person suffering from BDD may wish to resemble.
*Excessive grooming behaviors: combing hair, plucking eyebrows, shaving, etc.
*Obsession with [[plastic surgery]] or multiple plastic surgeries with little satisfactory results for the patient.
*In obscure cases patients have performed plastic surgery on themselves, including [[liposuction]] and various implants with disastrous results.


==Mechanism of action==
===Location of imagined defects===
In research carried out by Dr. Katharine Philips, involving over 500 patients, the percentage of patients concerned with the most common locations were as follows:
{{col-begin}}
{{col-break}}
*skin (73%)
*hair (56%)
*nose (37%)
*weight (22%)
*stomach (22%)
*breasts/chest/nipples (21%)
*eyes (20%)
*thighs (20%)
*teeth (20%)
*legs (overall) (18%)
*body build / bone structure (16%)
*ugly face (general) (14%)
*lips (12%)
*buttocks (12%)
*chin (11%)
*fingers
*eyebrows (11%)


Propranolol is a [[beta blocker|non-selective beta blocker]], that is, it blocks the action of [[epinephrine]] and [[norepinephrine]] 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, 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).<ref>{{cite journal |author=Young R, Glennon RA |title=S(-)Propranolol as a discriminative stimulus and its comparison to the stimulus effects of cocaine in rats |journal=Psychopharmacology (Berl.) |volume=203 |issue=2 |pages=369–82 |date=April 2009 |pmid=18795268 |doi=10.1007/s00213-008-1317-2 }}</ref> 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-HT<sub>1B</sub>).
''source: '''The Broken Mirror''', Katharine A Philips, Oxford University Press, 2005 ed, p56 ''


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.<ref>{{cite journal | author = Wang D. W., Mistry A. M., Kahlig K. M., Kearney J. A., Xiang J., George A. L. Jr | year = 2010 | title = Propranolol blocks cardiac and neuronal voltage-gated sodium channels | url = | journal = Front. Pharmacol | volume = 1 | issue = | page = 144 | doi = 10.3389/fphar.2010.00144 }}</ref><ref>{{cite journal | author = Bankston J. R., Kass R. S. | year = 2010 | title = Molecular determinants of local anesthetic action of beta-blocking drugs: implications for therapeutic management of long QT syndrome variant 3 | url = | journal = J. Mol. Cell. Cardiol | volume = 48 | issue = | pages = 246–253 }}</ref><ref>{{cite journal | author = Desaphy J. F., Pierno S., De Luca A., Didonna P., Camerino D. C. | year = 2003 | title = Different ability of clenbuterol and salbutamol to block sodium channels predicts their therapeutic use in muscle excitability disorders | url = | journal = Mol. Pharmacol | volume = 63 | issue = | pages = 659–670 }}</ref>
People with BDD often have more than one area of concern.


==Interactions==
==The Disabling Effects of BDD==
BDD can be anywhere from slightly to severely debilitating. It can make normal employment or family life impossible. Those who are in regular employment or who have family responsibilities would almost certainly find life more productive and satisfying if they did not have the symptoms. The partners of sufferers of BDD may also become involved and suffer greatly, sometimes losing their loved one to [[suicide]].


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:<ref name="Rossi" />
==Prognosis==
Many individuals with BDD have repeatedly sought treatment from dermatologists or cosmetic surgeons with little satisfaction before finally accepting psychiatric or psychological help. Treatment can improve the outcome of the illness for most people. Other patients may function reasonably well for a time and then relapse, while others may remain chronically ill. Research on outcome without therapy is not known but it is thought the symptoms persist unless treated.  


*[[verapamil]]
== Treatment ==
*[[epinephrine]]
Typically the [[psychodynamic]] approach to therapy does not seem to be effective in battling BDD while in some patients it may even be countereffective.
*[[Beta2-adrenergic receptor agonist|β<sub>2</sub>-adrenergic receptor agonists]]
**[[Salbutamol]], [[Levosalbutamol]], [[Formoterol]], [[Salmeterol]], etc.
*[[clonidine]]
*[[ergot alkaloid]]s
*[[isoprenaline]]
*[[non-steroidal anti-inflammatory drug]]s
*[[quinidine]]
*[[cimetidine]]
*[[lidocaine]]
*[[phenobarbital]]
*[[rifampicin]]
*[[Fluvoxamine]] slows down the metabolism of propranolol significantly leading to increased blood levels of propranolol.<ref>{{cite journal |author=van Harten J |title=Overview of the pharmacokinetics of fluvoxamine |journal=Clinical Pharmacokinetics |volume=29 |issue=Suppl 1 |pages=1–9 |year=1995 |pmid=8846617 |doi=10.2165/00003088-199500291-00003}}</ref>
 
==Chemistry==
 
Propranolol is synthesized in two ways from the same initial substance.<ref>A.F. Crowther, L.H. Smith, {{US Patent|3337628}} (1967)</ref><ref>A.F. Crowther, L.H. Smith, {{US Patent|3520919}} (1970)</ref><ref>A.F. Crowther, L.H. Smith, {{Cite patent|GB|994918}} (1963)</ref><ref>A.F. Crowther, L.H. Smith, {{Cite patent|DE|1493897}} (1963)</ref><ref>A.F. Crowther, L.H. Smith, {{Cite patent|BE|640312}} (1964)</ref><ref>A.F. Crowther, L.H. Smith, {{Cite patent|BE|640313}} (1964)</ref> 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.
 
==Historical Perspective==


[[British people|British]] scientist [[James W. Black]] successfully developed propranolol in the 1960s.<ref name="Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC 1964 1080–1081"/> 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 [[aryl]][[ethanolamine]] structure of pronethalol thus greatly increasing the potency of the compound. This also apparently eliminated the [[carcinogenicity]] found with pronethalol in animal models.
CBT ([[Cognitive Behavioral Therapy]]) coupled with [[exposure therapy]] has been shown effective in the treatment of BDD. Low levels or insufficient use of serotonin in the brain has been implicated with the disorder and so [[SSRI]] drugs are commonly used, and with some success, in the treatment of Body Dysmorphic Disorder. Drug treatment will sometimes also include the use of an [[anxiolytic]].


Newer, more selective beta-blockers (such as [[nebivolol]], [[carvedilol]], or [[metoprolol]]) are now used in the treatment of [[hypertension]].
BDD tends to be chronic; current information suggests that symptoms do not subside, but rather worsen through time. Indeed in most patients, the symptoms and concerns diversify and social contacts may further deteriorate. As so, treatment should be initiated as early as possible following the diagnoses.


==References==
==References==
{{reflist|2}}


{{Reflist|2}}
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[[Category:Drugs]]
[[Category:Disease]]
[[Category:Cardiovascular Drugs]]
[[Category:FLK]]
[[Category:Beta blockers]]

Latest revision as of 01:53, 14 October 2014

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2]

Infobox goes here

{{SI}}

Synonyms and keywords:

Overview

Body dysmorphic disorder (BDD) is a mental disorder that involves a disturbed body image. It is generally diagnosed in those who are extremely critical of their physique or self-image, despite the fact there may be no noticeable disfigurement or defect.

Most people wish they could change or improve some aspect of their physical appearance, but people suffering from BDD, generally considered of normal appearance, believe that they are so unspeakably hideous that they are unable to interact with others or function normally for fear of ridicule and humiliation at their appearance. They tend to be very secretive and reluctant to seek help because they are afraid others will think them vanity|vain or they may feel too embarrassed to do so.

Ironically, BDD is often misunderstood as a vanity driven obsession, whereas it is quite the opposite; people with BDD believe themselves to be irrevocably ugly or defective.

BDD combines obsessive and compulsive aspects, which links it to the OCD spectrum disorders among psychologists. People with BDD may engage in compulsive mirror checking behaviors or mirror avoidance, typically think about their appearance for more than one hour a day, and in severe cases may drop all social contact and responsibilities as they become homebound. The disorder is linked to an unusually high suicide rate among all mental disorders.

A German study has shown that 1-2% of the population meet all the diagnostic criteria of BDD, with a larger percentage showing milder symptoms of the disorder (Psychological Medicine, vol 36, p 877). Chronically low self-esteem is characteristic of those with BDD due to the value of oneself being so closely linked with their perceived appearance. The prevalence of BDD is equal in men and women, and causes chronic social anxiety for those suffering from the disorder[3].

Phillips & Menard (2006) found the completed suicide rate in patients with BDD to be 45 times higher than in the general US population. This rate is more than double that of those with Clinical depression and three times as high as those with bipolar disorder[1]. There has also been a suggested link between undiagnosed BDD and a higher than average suicide rate among people who have undergone cosmetic surgery[2].

Historical Perspective

BDD was first documented in 1886 by the researcher Morselli, who called the condition simply "Dysmorphophobia". BDD was first recorded/formally recognized in 1997 as a disorder in the DSM; however, in 1987 it was first truly recognized by the American Psychiatric Association.

In his practice, Freud eventually had a patient who would today be diagnosed with the disorder; Russian aristocrat Sergei Pankejeff, nicknamed "The Wolf Man" by Freud himself in order to protect Pankejeff's identity, had a preoccupation with his nose to an extent that greatly limited his functioning.

Classification

Pathophysiology

BDD usually develops in adolescence, a time when people are generally most sensitive about their appearance. However, many patients suffer for years before seeking help. When they do seek help through mental health professionals, patients often complain of other symptoms such as depression, social anxiety or obsessive compulsive disorder, but do not reveal their real concern over body image. Most patients cannot be convinced that they have a distorted view of their body image, due to the very limited knowledge of the disorder as compared to OCD or others.

An absolute cause of body dysmorphic disorder is unknown. However research shows that a number of factors may be involved and that they can occur in combination, including:

A chemical imbalance in the brain. An insufficient level of serotonin, one of the brain's neurotransmitters involved in mood and pain, may contribute to body dysmorphic disorder. Although such an imbalance in the brain is unexplained, it may be hereditary.

Obsessive-compulsive disorder. BDD often occurs with OCD, where the patient uncontrollably practices ritual behaviors that may literally take over their life. A history of, or genetic predisposition to, OCD may make people more susceptible to BDD.

Generalized anxiety disorder. Body dysmorphic disorder may co-exist with generalized anxiety disorder. This condition involves excessive worrying that disrupts the patient's daily life, often causing exaggerated or unrealistic anxiety about life circumstances, such as a perceived flaw or defect in appearance, as in BDD.

Causes

Differentiating type page name here from other Diseases

Epidemiology and Demographics

According to Dr Katharine Phillips (2004) :

Although large epidemiologic surveys of BDD's prevalence have not been done, studies to date indicate that BDD is relatively common in both nonclinical and clinical settings (Phillips & Castle, 2002). Studies in community samples have reported current rates of 0.7% and 1.1%, and studies in nonclinical student samples have reported rates of 2.2%, 4%, and 13% (Phillips & Castle, 2002). A study in a general inpatient setting found that 13% of patients had BDD (Grant, Won Kim, Crow, 2001). Studies in outpatient settings have reported rates of 8%-37% in patients with OCD, 11%-13% in social phobia, 26% in trichotillomania, 8% in major depression, and 14%-42% in atypical major depression (Phillips & Castle, 2002). In one study of atypical depression, BDD was more than twice as common as OCD (Phillips, Nierenberg, Brendel et al 1996), and in another (Perugi, Akiskal, Lattanzi et al, 1998) it was more common than many other disorders, including OCD, social phobia, simple phobia, generalized anxiety disorder, bulimia nervosa, and substance abuse or dependence. In a dermatology setting, 12% of patients screened positive for BDD, and in cosmetic surgery settings, rates of 6%-15% have been reported (Phillips & Castle, 2002).

BDD is underdiagnosed, however. Two studies of inpatients (Phillips, McElroy, Keck et al, 1993, and Grant, Won Kim, Crow, 2001), as well as studies in general outpatients (Zimmerman & Mattia, 1998) and depressed outpatients (Phillips, Nierenberg, Brendel et al 1996), systematically assessed a series of patients for the presence of BDD and then determined whether clinicians had made the diagnosis in the clinical record. All four studies found that BDD was missed by the clinician in every case in which it was present. Thus, underdiagnosis of BDD appears common.

Risk Factors

Screening

Natural History, Complications, and Prognosis

Diagnosis

Symptoms

  • Compulsive mirror checking, glancing in reflective doors, windows and other reflective surfaces.
  • Alternatively, an inability to look at one's own reflection or photographs of oneself; often the removal of mirrors from the home.
  • Compulsive skin-touching, especially to measure or feel the perceived defect.
  • Reassurance-seeking from loved ones.
  • Social withdrawal and co-morbid depression.
  • Obsessive viewing of favorite celebrities or models the person suffering from BDD may wish to resemble.
  • Excessive grooming behaviors: combing hair, plucking eyebrows, shaving, etc.
  • Obsession with plastic surgery or multiple plastic surgeries with little satisfactory results for the patient.
  • In obscure cases patients have performed plastic surgery on themselves, including liposuction and various implants with disastrous results.

Location of imagined defects

In research carried out by Dr. Katharine Philips, involving over 500 patients, the percentage of patients concerned with the most common locations were as follows: