Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Bismuth subsalicylate: Difference between pages

{{short description|Antacid medication}}

|Verifiedfields = changed

|Watchedfields = changed

|verifiedrevid = 476992845

|IUPAC_name = 2-Hydroxy-2''H'',4''H''-benzo[''d'']1,3-dioxa-2-bismacyclohexan-4-one

[[File:Bismuth subsalicylate molecular structure.svg|thumb|alt=Simplified molecular structure of bismuth subsalicylate. The material is layered and each layer consists of a bismuth-oxo-rod decorated with salicylic acid molecules that join the rods, giving a layered material.|Simplified molecular structure of bismuth subsalicylate.]]

|image = Bismuth subsalicylate molecular structure.svg

|tradename = Pepto-Bismol, BisBacter

|Drugs.com = {{Drugs.com|MTM|bismuth-subsalicylate}}

|MedlinePlus = a607040

|pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->

|pregnancy_US =

|pregnancy_category =

|legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->

|legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->

|legal_UK = P

|legal_US = OTC

|legal_status =

|routes_of_administration = Oral

|bioavailability =

|protein_bound =

|metabolism =

|elimination_half-life =

|excretion =

|CAS_number_Ref = {{cascite|correct|??}}

|CAS_number = 14882-18-9

|ATC_prefix = none

|ATC_suffix =

|PubChem = 16682734

|DrugBank_Ref = {{drugbankcite|correct|drugbank}}

|DrugBank = DB01294

|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

|ChemSpiderID = 17215772

|UNII_Ref = {{fdacite|correct|FDA}}

|UNII = 62TEY51RR1

|KEGG_Ref = {{keggcite|changed|kegg}}

|KEGG = D00728

|ChEBI_Ref = {{ebicite|correct|EBI}}

|ChEBI = 261649

|ChEMBL_Ref = {{ebicite|correct|EBI}}

|ChEMBL = 1120

|chemical_formula =

|C=7 | H=5 | Bi=1 | O=4

|smiles = O[Bi]1OC(=O)C2CCCCC2O1

|StdInChI_Ref = {{stdinchicite|correct|chemspider}}

|StdInChI = 1S/C7H6O3.Bi.H2O/c8-6-4-2-1-3-5(6)7(9)10;;/h1-4,8H,(H,9,10);;1H2/q;+3;/p-3

|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

|StdInChIKey = ZREIPSZUJIFJNP-UHFFFAOYSA-K

'''Bismuth subsalicylate''', sold generically as '''pink bismuth''' and under brand names including '''Pepto-Bismol''', '''Pepti-Calm''' and '''BisBacter''', is a medication used to treat temporary discomfort of the [[stomach]] and [[gastrointestinal tract]], such as [[nausea]], [[heartburn]], [[indigestion]], [[upset stomach]], and [[diarrhea]].

Bismuth subsalicylate has the empirical chemical formula C₇H₅BiO₄,<ref>''[[Merck Index]]'', 11th Edition, '''1299'''</ref> and is a [[colloid]]al substance obtained by [[hydrolysis]] of [[bismuth]] [[salicylate]] (Bi(C₆H₄(OH)CO₂)₃).

==Medical uses==

[[File:Bismuth Subsalicylate Bottle.png|thumb|left|upright=.5|A generic version of Pepto-Bismol, back view]]

As a derivative of [[salicylic acid]], bismuth subsalicylate displays [[anti-inflammatory]]<ref name="Madisch-2008">{{cite journal |vauthors=Madisch A, Morgner A, Stolte M, Miehlke S |date=December 2008 |title=Investigational treatment options in microscopic colitis |journal=Expert Opinion on Investigational Drugs |pmid=19012499 |doi=10.1517/13543780802514500 |volume=17 |issue=12 |pages=1829–37|s2cid=72294495 }}</ref> and [[Bactericide|bactericidal]] action.<ref name="DuPont-2005">{{cite journal |vauthors=DuPont HL |s2cid=10666532 |date=April 2005 |title=Travelers' diarrhea: antimicrobial therapy and chemoprevention |journal=Nature Clinical Practice. Gastroenterology & Hepatology |pmid=16265184 |doi=10.1038/ncpgasthep0142 |volume=2 |issue=4 |pages=191–8; quiz 1 p following 198 }}</ref> It also acts as an [[antacid]].

==Mechanism of action==

Bismuth subsalicylate is used as an antacid and [[diarrhea|antidiarrheal]], and to treat some other gastrointestinal symptoms, such as nausea. The means by which this occurs is still not well documented. It is thought to be some combination of the following:<ref name="drugbank">[http://www.drugbank.ca/drugs/DB01294 Bismuth subsalicylate], DrugBank.</ref>

*Stimulation of absorption of fluids and electrolytes by the intestinal wall (antisecretory action)

*As a [[salicylate]], reducing inflammation/irritation of stomach and intestinal lining through inhibition of prostaglandin G/H synthase 1/2

*Reduction in hypermotility of the stomach

*Inhibits adhesion and filmogenesis by ''Escherichia coli''

*Bactericidal action of a number of its subcomponents, including salicylic acid<ref name="ReferenceA">{{cite journal | vauthors = Sox TE, Olson CA | title = Binding and killing of bacteria by bismuth subsalicylate | journal = Antimicrobial Agents and Chemotherapy | volume = 33 | issue = 12 | pages = 2075–82 | date = December 1989 | pmid = 2694949 | pmc = 172824 | doi = 10.1128/AAC.33.12.2075 }}</ref>

*Bactericidal action via a so-called [[oligodynamic effect]] in which small amounts of heavy metals such as bismuth damage many different bacteria species.

*Weak antacid properties

''[[In vitro]]'' and ''[[in vivo]]'' data have shown that bismuth subsalicylate hydrolyzes in the gut to [[bismuth oxychloride]] and [[salicylic acid]] and less commonly [[bismuth hydroxide]]. In the stomach, this is likely an acid-catalyzed hydrolysis. The salicylic acid is absorbed and therapeutical concentrations of salicylic acid can be found in blood after bismuth subsalicylate administration. Bismuth oxychloride and bismuth hydroxide are both believed to have bactericidal effects, as is salicylic acid for [[enterotoxigenic Escherichia coli|enterotoxigenic ''E. coli'']] a common cause of "[[traveler's diarrhea]]."<ref name="ReferenceA"/>

Organobismuth compounds have historically been used in growth media for selective isolation of microorganisms. Such salts have been shown to inhibit proliferation of ''[[Helicobacter pylori]]'', other enteric bacteria, and some fungi.<ref name="ASM">{{cite journal | vauthors = Dodge AG, Wackett LP | title = Metabolism of bismuth subsalicylate and intracellular accumulation of bismuth by Fusarium sp. strain BI | journal = Applied and Environmental Microbiology | volume = 71 | issue = 2 | pages = 876–82 | date = February 2005 | pmid = 15691943 | pmc = 546758 | doi = 10.1128/AEM.71.2.876-882.2005 | bibcode = 2005ApEnM..71..876D }}</ref>

==Adverse effects==

There are some [[Adverse effect (medicine)|adverse effects]]. It can cause a [[black hairy tongue|black tongue]] and black [[Feces|stools]] in some users of the drug when it combines with trace amounts of [[sulfur]] in saliva and the colon to form [[bismuth sulfide]].<ref>{{cite web |title=Why does Pepto-Bismol sometimes darken the tongue/stool and how long does it last? |work=Pepto-Bismol FAQ |publisher=Pepto-Bismol |url=http://www.pepto-bismol.com/en-us/faq/black-stool-black-tongue}}</ref> Bismuth sulfide is a highly insoluble black salt, and the discoloration seen is temporary and harmless.

Long-term use (more than six weeks) may lead to accumulation and toxicity.<ref name="Gorbach-1990">{{cite journal | vauthors = Gorbach SL | title = Bismuth therapy in gastrointestinal diseases | journal = Gastroenterology | volume = 99 | issue = 3 | pages = 863–75 | date = September 1990 | pmid = 2199292 | doi = 10.1016/0016-5085(90)90983-8 | authorlink1 = Sherwood Gorbach }}</ref> High daily intake over a period of months can possibly cause severe fatigue, weakness and neurological symptoms that reverse with discontinuation.<ref>{{cite web|url=https://www.nytimes.com/2024/03/07/magazine/bismuth-toxicity-pepto-bismol.html|title=It Was Like the Vigor Had Suddenly Been Sucked Out of His Body. What Was It? (March 7, 2024) |publisher=[[New York Times]]}}</ref> Some of the risks of [[salicylism]] can apply to the use of bismuth subsalicylate.<ref>{{cite web|url=https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a607040.html|title=Bismuth Subsalicylate|work=MedlinePlus|publisher=[[National Institutes of Health]]}}</ref><ref name="pmid1812638">{{cite journal | vauthors = Sainsbury SJ | title = Fatal salicylate toxicity from bismuth subsalicylate | journal = The Western Journal of Medicine | volume = 155 | issue = 6 | pages = 637–9 | date = December 1991 | pmid = 1812638 | pmc = 1003120 }}</ref><ref name="pmid8092182">{{cite journal | vauthors = Vernace MA, Bellucci AG, Wilkes BM | title = Chronic salicylate toxicity due to consumption of over-the-counter bismuth subsalicylate | journal = The American Journal of Medicine | volume = 97 | issue = 3 | pages = 308–9 | date = September 1994 | pmid = 8092182 | doi = 10.1016/0002-9343(94)90017-5 }}</ref>

Children should not take medication with bismuth subsalicylate while recovering from [[influenza]] or [[chicken pox]], as epidemiologic evidence points to an association between the use of [[salicylate]]-containing medications during certain viral infections and the onset of [[Reye syndrome]].<ref>[http://www.reyessyndrome.org/pdfs/medicationscontainingaspirin.pdf Aspirin or Salicylate-Containing Medications], reyessyndrome.org</ref> For the same reason, it is typically recommended that nursing mothers not use medication containing bismuth subsalicylate because small amounts of the medication are excreted in human breast milk, and these pose a theoretical risk of Reye's syndrome to nursing children.<ref>{{cite web |title=Food-borne and Waterborne Illness - Breastfeeding – CDC |work=cdc.gov |url=https://www.cdc.gov/breastfeeding/disease/food_illness.htm}}</ref>

Salicylates are very toxic to cats, and thus bismuth subsalicylate should not be administered to cats.<ref>''Cat Owner's Home Veterinary Handbook'', Carlson and Giffin, page 390.</ref>

The [[British National Formulary]] does not recommend bismuth-containing antacids (unless [[chelation|chelated]]), cautioning that absorbed bismuth can be neurotoxic, causing encephalopathy, and that such antacids tend to be constipating.<ref>{{cite web |title=1.1.1 Antacids and simeticone |url=http://services2.ascribe.com:8080/bnf/view/page/bnf/PHP276-antacids-and-simeticone.htm |access-date=2018-06-17 |archive-date=2018-05-02 |archive-url=https://web.archive.org/web/20180502064500/http://services2.ascribe.com:8080/bnf/view/page/bnf/PHP276-antacids-and-simeticone.htm |url-status=dead }}</ref>

== Drug interactions ==

There is an increased risk of [[bleeding]] when using bismuth subsalicylate and anticoagulation therapy, like [[Warfarin|Coumadin (Warfarin)]].<ref>{{Cite web|title=Drug Interactions between Pepto-Bismol and warfarin|url=https://www.drugs.com/drug-interactions/pepto-bismol-with-warfarin-391-177-2311-0.html|url-status=live|archive-url=https://web.archive.org/web/20160206192805/http://www.drugs.com:80/drug-interactions/pepto-bismol-with-warfarin-391-177-2311-0.html |archive-date=2016-02-06 }}</ref><ref>{{Cite book| vauthors = Rose SR, Keystone JS |title=International Travel Health Guide 2006-2007|year=2006|isbn=978-0-323-04050-1|pages=89–103|publisher=Mosby }}</ref><ref>{{cite journal | vauthors = Bingham AL, Brown RO, Dickerson RN | title = Inadvertent exaggerated anticoagulation following use of bismuth subsalicylate in an enterally fed patient receiving warfarin therapy | journal = Nutrition in Clinical Practice | volume = 28 | issue = 6 | pages = 766–769 | date = December 2013 | pmid = 24163322 | doi = 10.1177/0884533613507606 }}</ref>

==History==

[[File:1957 Pepto Bismol ad.jpg|thumbnail|1957 ''Life'' magazine ad for the product]]

Bismuth salts were in use in Europe by the late 1700s. The combination of bismuth subsalicylate and zinc salts for astringency with [[salol]] (phenyl salicylate) appears to have begun in the US in the early 20th century as a remedy for life-threatening diarrhea in infants with [[cholera]]. At first sold directly to physicians, it was first marketed as ''Bismosal'' in 1918.<ref name="RID1">{{cite journal | vauthors = Bierer DW | title = Bismuth subsalicylate: history, chemistry, and safety | journal = Reviews of Infectious Diseases | volume = 12 Suppl 1 | issue = Supplement 1 | pages = S3-8 | date = January–February 1990 | pmid = 2406853 | doi = 10.1093/clinids/12.supplement_1.s3 | jstor = 4455445 }}</ref>

Pepto-Bismol was first sold in 1900<ref name="RID1"/> or 1901<ref>{{cite web |url=https://www.pepto-bismol.com/en-us/about/history |title=History of Pepto Bismol |website=Pepto Bismol |publisher=Procter & Gamble }}</ref> by a doctor in New York. It was originally sold as a remedy for infant diarrhea by [[Norwich Pharmacal Company]] under the name "Bismosal: Mixture Cholera Infantum".<ref name="RID1"/> It was renamed Pepto-Bismol in 1919. Norwich Eaton Pharmaceuticals was acquired by Procter and Gamble in 1982.<ref>{{cite book | vauthors = Dyer D, Dalzell F, Olegario R |date=May 1, 2004 |title=Rising Tide: Lessons from 165 Years of Brand Building at Procter and Gamble |publisher=Harvard Business Press |isbn=9781591391470 |pages=424 |url=https://books.google.com/books?id=ZyUwNAs43LcC&pg=PA424}}</ref>

As of 1946 and 1959, Canadian advertisements placed by Norwich show the product as Pepto-Besmal both in graphic and text.<ref>{{cite news |date=August 16, 1946 |title='Simple Diarrhea' ad |work=Toronto Daily Star |page=33}}</ref><ref>{{cite news |date=June 6, 1959 |title='Pepto-Besmal puts out the fire of an upset stomach' ad |work=Toronto Daily Star}}</ref>

Pepto-Bismol is an [[over-the-counter drug]] currently produced by the [[Procter & Gamble]] company in the United States, Canada and the United Kingdom. Pepto-Bismol is made in chewable tablets<ref>http://tess2.uspto.gov/bin/showfield?f=doc&state=b8i462.2.2 The trademark was extended to cover the tablets in 1973. Registration No. 0972198], November 6, 1973.</ref> and swallowable caplets,<ref>The capsules were introduced in 1983. Registration No. 1269605, March 13, 1984; cancelled July 16, 1990. http://tess2.uspto.gov/bin/showfield?f=doc&state=b8i462.2.1.</ref> but it is best known for its original formula, which is a thick liquid. This original formula is a medium pink in color, with a [[Gaultheria procumbens|teaberry]] ([[methyl salicylate]]) flavor.<ref>{{cite web | title = Pepto-Bismol Original Liquid | work = Material Safety Data Sheet |publisher=[[Procter & Gamble]] |url= https://www.pg.com/productsafety/msds/health_care/gastrointestinal/Pepto-Bismol_Original_Liquid.pdf | archive-url = https://web.archive.org/web/20180617215839/https://www.pg.com/productsafety/msds/health_care/gastrointestinal/Pepto-Bismol_Original_Liquid.pdf | archive-date = 17 June 2018 }}</ref>

Generic bismuth subsalicylate and other branded versions of the drug are widely available in pill and liquid form.

==Structure==

[[File:Bismuth_subsalicylate_layers.png|thumb|left|text-bottom| The crystal structure of bismuth subsalicylate.<ref name="BSSstructure" />]]

Despite its common usage and commercial significance, the exact structure of the pharmaceutical long remained undetermined, but was revealed, through the use of advanced [[electron crystallography]] techniques, to be a layered coordination polymer with the formula BiO(C₇H₅O₃).<ref name="BSSstructure">{{cite journal | vauthors = Svensson Grape E, Rooth V, Nero M, Willhammar T, Inge AK | title = Structure of the active pharmaceutical ingredient bismuth subsalicylate | journal = Nature Communications | volume = 13 | issue = 1984 | date = April 2022 | page = 1984 | doi = 10.1038/s41467-022-29566-0|pmid=35418171 | pmc = 9008038 | doi-access = free }}</ref> In the structure, both the carboxylate and phenol groups of the salicylate coordinate towards the bismuth cations. The determination of bismuth subsalicylate had long been hindered due to the small particle size as well as defects within the structure, arising from variations in the stacking arrangement of the bismuth subsalicylate layers, which could be observed as part of the structural investigation.<ref>{{cite journal |last1=Henry Arnaud |first1=Celia |title=Structure of Pepto-Bismol active ingredient solved |journal=[[Chemical & Engineering News]] |date=April 26, 2022 |volume=100 |issue=44 |pages=34–35 |doi=10.1021/cen-10044-cover6 |s2cid=254899845 |url=https://cen.acs.org/materials/inorganic-chemistry/Structure-Pepto-Bismol-active-ingredient/100/web/2022/04 |access-date=15 April 2023 |language=en |issn=0009-2347}}</ref>

{{Clear}}

== References ==

{{Reflist|2}}

== External links ==

{{Commons category|Bismuth subsalicylate}}

* {{cite journal | vauthors = Andrews PC, Deacon GB, Forsyth CM, Junk PC, Kumar I, Maguire M | title = Towards a structural understanding of the anti-ulcer and anti-gastritis drug bismuth subsalicylate | journal = Angewandte Chemie | volume = 45 | issue = 34 | pages = 5638–42 | date = August 2006 | pmid = 16865763 | doi = 10.1002/anie.200600469 }}

{{Salicylates}}

{{Bismuth compounds}}

[[Category:Antidiarrhoeals]]

[[Category:Drugs acting on the gastrointestinal system and metabolism]]

[[Category:Salicylates]]

[[Category:Bismuth compounds]]

[[Category:Antacids]]

[[Category:Heterocyclic compounds with 2 rings]]