Bismuth subsalicylate

Bismuth subsalicylate

Systematic (IUPAC) name
2-hydroxy-2H,4H-benzo[d]1,3-dioxa-2-bismacyclohexan-4-one
Clinical data
Trade names	Pepto-bismol and others
AHFS/Drugs.com	Multum Consumer Information
MedlinePlus	a607040
Pregnancy cat.	?
Legal status	OTC (US)
Routes	Oral
Identifiers
CAS number	14882-18-9 Y
ATC code	None
PubChem	CID 16682734
DrugBank	DB01294
ChemSpider	17215772 Y
UNII	62TEY51RR1 Y
KEGG	D00728 N
ChEBI	CHEBI:261649 Y
ChEMBL	CHEMBL1120 Y
Chemical data
Formula	C7H5BiO4
Mol. mass	362.093 g/mol
SMILES	eMolecules & PubChem
InChI InChI=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 Y Key:ZREIPSZUJIFJNP-UHFFFAOYSA-K Y
N (what is this?)  (verify)

Bismuth subsalicylate, with a nominal 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, 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

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

Structure

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. The crystal structure of the molecule is available here, which shows an octahedral cluster. 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

Bismuth subsalicylate is used as an antidiarrheal and to treat some other gastro-intestinal diseases (oligodynamic effect). 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:^[2]

• 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
• Weak antacid properties

In vitro and in vivo data has shown that bismuth subsalicylate hydrolyzes in the gut to bismuth oxychloride and salicylic acid. In the stomach, this is likely an acid-catalyzed hydrolysis. Links to the hydrolysis products can be found below.

Salicylic acid

Bismuth Oxychloride

Additionally, Bismuth hydroxide is a side product produced. Bismuth oxychloride and bismuth hydroxide are both believed to have bactericidal effects.

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.^[3]

Adverse effects and contraindications

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.

Some of the risks of salicylism can apply to the use of bismuth subsalicylate.^[5][6][7]

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.^[8] 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.^[9]

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

Decomposition

Bismuth slag from decomposition of Pepto-Bismol

Bismuth subsalicylate is the only active ingredient in an over the counter medication that will leave a shiny metal oxide slag behind after being completely burnt with a blow torch.^[10]

References