Bismuth subsalicylate

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Bismuth subsalicylate
Bismuth subsalicylate.png
Bismuth-subsalicylate-3D-balls.png
Systematic (IUPAC) name
2-Hydroxy-2H,4H-benzo[d]1,3-dioxa-2-bismacyclohexan-4-one
Clinical data
Trade names Pepto-Bismol
AHFS/Drugs.com Multum Consumer Information
MedlinePlus a607040
Legal status OTC (US)
Routes Oral
Identifiers
CAS number 14882-18-9 YesY
ATC code None
PubChem CID 16682734
DrugBank DB01294
ChemSpider 17215772 YesY
UNII 62TEY51RR1 YesY
KEGG D00728 N
ChEBI CHEBI:261649 YesY
ChEMBL CHEMBL1120 YesY
Chemical data
Formula C7H5BiO4 
Mol. mass 362.093 g/mol
 N (what is this?)  (verify)

Bismuth subsalicylate, with the empirical chemical formula of C7H5BiO4,[1] is a colloidal substance obtained by hydrolysis of bismuth salicylate (Bi{C6H4(OH)CO2}3). The actual structure is unknown and the formulation is only approximate. Recent evidence indicates that it is composed of a bismuth oxide core structure with salicylate ions attached to the surface. A model structure has recently been published having the composition Bi38O44{C6H3(OH)CO2}26. It is a drug used to treat temporary discomforts of the stomach and gastrointestinal tract, such as diarrhea, indigestion, heartburn and nausea. Commonly known as pink bismuth, it is the active ingredient in popular medications such as Pepto-Bismol and, since 2003, in Kaopectate.

Pharmacology[edit]

A generic version of Pepto-Bismol, back view.

As a derivative of salicylic acid, bismuth salicylate displays anti-inflammatory[2] and bactericidal action,[3] and also acts as an antacid.

Adverse effects[edit]

There are some adverse effects. It can cause a black tongue and black stools in some users of the drug, when it combines with trace amounts of sulfur in saliva and the colon to form bismuth sulfide.[4] Bismuth sulfide is a highly insoluble black salt, and the discoloration seen is temporary and harmless.

Long-term use (greater than 6 weeks) may lead to accumulation and toxicity.[5] Some of the risks of salicylism can apply to the use of bismuth subsalicylate.[6][7][8]

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's syndrome.[9] For the same reason, it is typically recommended that nursing mothers not use medication containing bismuth subsalicylate (such as Pepto-Bismol) because small amounts of the medication are excreted in breast milk and pose a theoretical risk of Reye's syndrome to nursing children.[10]

Salicylates are very toxic to cats, and thus bismuth subsalicylate should not be administered to cats.[11]

Structure[edit]

The term "sub" refers to the high oxygen content in the molecule and the presence of Bi-O moieties.

Characterization of the properties of bismuth subsalicylate has been difficult due to its insolubility and its partial hydrolysis. Two crystal structures are observed, them being:

  • [Bi38O44(HSal)26(Me2CO)16(H2O)2] with a Bi38O44 core
  • [Bi9O7(HSal)13(Me2CO)5] with a Bi9O7 core

It is believed that the latter cluster gives rise to the former, leading researchers to believe that they may be extrapolated to form larger clusters. This may be the basis for bismuth subsalicylate's extreme insolubility.

Other bismuth carboxylates have typically been trapped using chelating amines such as bipyridine. Attempts to do so with bismuth subsalicylate have typically led to a loss of the "sub" portion of the molecule.

Mechanism of action[edit]

Bismuth subsalicylate is used as an antacid and antidiarrheal, and to treat some other gastro-intestinal diseases, such as nausea. It is the active ingredient in various stomach-settling medications, including Pepto-Bismol.
The means by which this occurs is still not well documented. It is thought to be some combination of the following:[12]

  • Retarding the expulsion of fluids into the digestive system by irritated tissues, by "coating" them.
  • Stimulation of absorption of fluids and electrolytes by the intestinal wall (antisecretory action)
  • Reducing inflammation/irritation of stomach and intestinal lining through inhibition of prostaglandin G/H Synthase 1/2
  • Reduction in hypermotility of the stomach
  • Binding of toxins produced by E. coli
  • Bactericidal action of a number of its subcomponents, including salicylic acid[13]
  • Bactericidal action via a so-called oligodynamic effect in which small amounts of heavy metals such as bismuth are toxic for a number of microbes.
  • Weak antacid properties

In vitro and in vivo data has 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 concentration 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 a common cause of "traveler's diarrhea."[13]

Organobismuth compounds have historically been used in growth media for selective isolation of microorganisms. Such salts have been shown to inhibit proliferation of H. pylori, other enteric bacteria, and some fungi.[14]

Decomposition[edit]

Bismuth slag from decomposition of Pepto-Bismol

Bismuth subsalicylate is the only active ingredient in an over the counter drug that can leave a shiny metal oxide slag behind after being completely burnt with a blow torch.[15]

History[edit]

While bismuth salts were in use in Europe by the late 1700s, the combination of bismuth subsalicylate and zinc salts for astringency with salol (phenyl salicilate) appears to have begun in the US in the early 1900s 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.[16]

References[edit]

  1. ^ Merck Index, 11th Edition, 1299
  2. ^ Madisch, A.; Morgner, A.; Stolte, M.; Miehlke, S. (Dec 2008). "Investigational treatment options in microscopic colitis.". Expert Opin Investig Drugs 17 (12): 1829–37. doi:10.1517/13543780802514500. PMID 19012499. 
  3. ^ DuPont, HL. (Apr 2005). "Travelers' diarrhea: antimicrobial therapy and chemoprevention.". Nat Clin Pract Gastroenterol Hepatol 2 (4): 191–8; quiz 1 p following 198. doi:10.1038/ncpgasthep0142. PMID 16265184. 
  4. ^ "I noticed that Pepto-Bismol sometimes darkens the tongue/stool...". Pepto-Bismol FAQ. Pepto-Bismol. 
  5. ^ Gorbach, SL. (Sep 1990). "Bismuth therapy in gastrointestinal diseases.". Gastroenterology 99 (3): 863–75. PMID 2199292. 
  6. ^ "Bismuth Subsalicylate". MedlinePlus. National Institutes of Health. 
  7. ^ Sainsbury, S. J. (December 1991). "Fatal salicylate toxicity from bismuth subsalicylate". The Western Journal of Medicine 155 (6): 637–639. PMC 1003120. PMID 1812638. 
  8. ^ Vernace, M. A.; Bellucci, A. G; Wilkes B. M. (September 1994). "Chronic salicylate toxicity due to consumption of over-the-counter bismuth subsalicylate". The American Journal of Medicine 97 (3): 308–309. doi:10.1016/0002-9343(94)90017-5. PMID 8092182. 
  9. ^ Aspirin or Salicylate-Containing Medications, reyessyndrome.org
  10. ^ CDC warning about breastfeeding while taking bismuth subsalicylate compounds
  11. ^ Cat Owner's Home Veterinary Handbook, Carlson and Giffin, page 390
  12. ^ Bismuth subsalicylate, DrugBank
  13. ^ a b Sox, TE; Olson, CA (December 1989). "Binding and killing of bacteria by bismuth subsalicylate". Antimicrob. Agents Chemother. 33 (12): 2075–82. doi:10.1128/AAC.33.12.2075. PMC 172824. PMID 2694949. 
  14. ^ Dodge, A. G.; Wackett, L. P. (2005). "Metabolism of Bismuth Subsalicylate and Intracellular Accumulation of Bismuth by Fusarium sp. Strain BI". Applied and Environmental Microbiology 71 (2): 876–82. doi:10.1128/AEM.71.2.876-882.2005. PMC 546758. PMID 15691943. 
  15. ^ Wesołowski, M. (1982). "Thermal decomposition of pharmaceutical preparations containing inorganic components". Microchimica Acta (Vienna) 77 (5–6): 451–464. doi:10.1007/BF01197125. 
  16. ^ Bierer, Douglas Ws. (Jan–Feb 1990). "Bismuth Subsalicylate: History, Chemistry, and Safety". Reviews of Infectious Diseases (Oxford University Press) 12 (Supplement 1): S3–S8. doi:10.1093/clinids/12.Supplement_1.S3. JSTOR 4455445. 

External links[edit]

  • Andrews, Philip C.; Deacon, Glen B.; Forsyth, Craig M.; Junk, Peter C.; Kumar, Ish; Maguire, Melissa (2006). "Towards a Structural Understanding of the Anti-Ulcer and Anti-Gastritis Drug Bismuth Subsalicylate". Angewandte Chemie International Edition 45 (34): 5638. doi:10.1002/anie.200600469.