What Are Bismuth Compounds?
Bismuth compounds are chemical compounds that contain bismuth as one of their elements. Bismuth is a heavy metal often used in various applications, including medicine, cosmetics, and electronics. Some common bismuth compounds include bismuth subsalicylate, used in medications for treating digestive issues, and bismuth oxychloride, used in cosmetics for its pearly appearance.
Bismuth compounds also have interesting electronic and thermal conductivity properties, making them useful in specific electronic applications. Additionally, bismuth compounds have been studied for their potential in various fields, including catalysis and materials science.
In the stomach’s acidic environment, poorly soluble bismuth compounds are converted mainly to insoluble bismuth oxide, hydroxide, and oxychloride. Most of the bismuth compounds included in this monograph are thus only slightly absorbed. Increased gastric pH may increase bismuth absorption. Unabsorbed bismuth is excreted in the feces. Absorbed bismuth is distributed throughout body tissues, including bone, and is slowly excreted in the urine and bile. It has a plasma half-life of about 5 days and continues to be excreted for about 12 weeks after stopping therapy.
Bismuth compounds have been used for their astringent and antidiarrhoeal properties in various gastrointestinal disorders and have been applied topically in skin disorders and anorectal disorders such as hemorrhoids. Certain salts are active against Helicobacter pylori and are used to treat peptic ulcer disease.
Dosage and Administration
Some insoluble bismuth salts are given orally for their supposed antacid and mildly astringent action in various gastrointestinal disorders, including diarrhea and dyspepsia. Such salts include the aluminate, salicylate, subcarbonate, and subnitrate. Bismuth salicylate, which is given as an antidiarrhoeal and weak antacid in doses up to about 4 g daily in divided doses, possesses, in addition, the properties of the salicylates.
Tripotassium dicitratobismuthate is active against Helicobacter pylori and has been used as triple therapy (with metronidazole and either tetracycline or amoxicillin) to eradicate this organism and thereby prevent relapse of duodenal ulcer. It is also used as a mucosal protectant to treat peptic ulcer disease. Bismuth subcitrate potassium and bismuth salicylate are also active against H. pylori and have been used similarly in eradication regimens.
The usual oral dose of tripotassium dicitratobismuthate in benign gastric and duodenal ulceration is 240 mg twice daily or 120 mg four times daily before food. Treatment is for a period of 4 weeks, extended to 8 weeks if necessary. Maintenance therapy with tripotassium dicitratobismuthate is not recommended, although treatment may be repeated after a drug-free interval of one month. When used as part of triple therapy, the usual dose of tripotassium dicitratobismuthate has been 120 mg four times daily for two weeks. The usual dose of bismuth salicylate as part of triple therapy is 525 mg four times daily for two weeks. Appropriate antisecretory treatment with a histamine H2-antagonist or a proton pump inhibitor is usually added to these regimens.
A complex of bismuth citrate with ranitidine, ranitidine bismuth citrate, is also used to treat peptic ulcer disease.
Some insoluble bismuth salts have been used topically in treating skin disorders, wounds, and burns. Some have been used as ingredients of ointments or suppositories (sometimes containing more than one bismuth salt) in treating hemorrhoids and other anorectal disorders. Bismuth compounds that have been used topically and/or rectally include the oxide, subgallate, and subnitrate bismuth resorcinol compounds have also been used.
Numerous other salts and compounds of bismuth have been promoted for various therapeutic purposes. Gly-cobiarsol was formerly given orally as an amoebicide.
Adverse Effects, Treatment, and Precautions
The bismuth compounds listed above are insoluble or poorly soluble, and bismuth toxicity does not occur if used for limited periods. However, excessive or prolonged dosage may produce symptoms of bismuth poisoning, so long-term systemic therapy is not recommended. Reversible encephalopathy was once a problem in some countries, notably France and Australia; bone and joint toxicity had also occurred, sometimes associated with the encephalopathy. This led to restrictions on bismuth salts and a virtual disappearance of these toxic effects. Nausea and vomiting have been reported. Darkening or blackening of the feces and tongue may occur due to conversion to bismuth sulfide in the gastrointestinal tract.
The effects of acute bismuth intoxication include gastrointestinal disturbances, skin reactions, stomatitis, and discoloration of mucous membranes; a characteristic blue line may appear on the gums. There may be renal failure and liver damage. Other adverse effects may not be related to the bismuth content. With bismuth subnitrate given orally, there is a risk of the nitrate being reduced in the intestines to nitrite and the development of methemoglobinemia. Absorption of salicylate occurs from oral bismuth salicylate; therefore, the adverse effects, treatment of adverse effects, and precautions of aspirin should be considered.
Gastric lavage should be considered in overdosage-activated charcoal orally, and a chelating agent such as dimercaprol, succimer, or unithiol has been recommended. Renal function should be monitored for 10 days after acute overdosage.
Bismuth compounds should not be given to patients with moderate to severe renal impairment.
Many of the original reports implicated bismuth subgallate or subnitrate, in most but not all cases, at high doses or for prolonged periods, toxicity has also occurred with other salts. Patients receiving the subcitrate (480 mg daily) or the subnitrate (1.8 g daily) for 8 weeks in treating Helicobacter pylori infection showed no evidence of neurological changes compared with a control group.
TOPICAL APPLICATION. Encephalopathy has been associated with using bismuth iodoform paraffin paste (BIPP) to pack wound cavities after surgery to the head and neck. However, there is some debate about whether the bismuth or the iodoform component is responsible.
Bismuth salicylate or tripotassium dicitratobismuthate in recommended doses are rarely associated with severe adverse effects, but there are reports of renal failure, encephalopathy, and neurotoxicity in acute or chronic overdose. Bismuth has been detected in these patients’ blood, urine, stools, and kidneys; a blood concentration of 1.6 micrograms/mL was found 4 hours after an oral dose of 9.6 g.
The optimal treatment of bismuth overdosage is unknown. Gastric lavage, purgation, and hydration should be considered, even if the patient presents late, as bismuth may be absorbed from the colon. Chelating agents may be effective; unithiol has been reported to increase the renal clearance of bismuth with a reduction in the blood concentration. Hemodialysis may be necessary,” but whether this hastens tissue clearance is uncertain. Hemodialysis plus unithiol treatment has been reported to eliminate bismuth successfully. Peritoneal dialysis has also been effectively used in pediatric patients.
Prolonged ingestion of bismuth salicylate in excessive doses by an elderly diabetic was associated with hearing disturbances, vertigo, acid-base abnormalities, and mild clotting disturbances. The toxicity was thought to be due to the salicylate component.
Toxicity from Non-Conventional Use
The FDA has warned against using an injectable product called bismacine or chromacine, which contains large amounts of bismuth. There are reports of death or serious adverse effects associated with its use. Although unlicensed, bismacine has been used in alternative medicine to treat Lyme disease.
Bismuth salts, given orally, reduce the absorption of tetracyclines, possibly by chelation or by reducing tetracycline solubility due to increasing gastric pH. This interaction can be minimized by separating doses of the two drugs by a couple of hours. The clinical significance of this interaction to the use of bismuth salts for peptic ulcer disease is unclear. tripotassium dicitratobismuthate, or bismuth salicylate, have been given at the same time as tetracycline as part of triple therapy for eradicating Helicobacter pylori.
Pretreatment with omeprazole resulted in about a threefold increase in the absorption of bismuth from tripotassium dicitratobismuthate in 6 healthy subjects. The mean peak plasma concentration of bismuth after a single dose of 240 mg of tripotassium dicitratobismuthate was increased from 36.7 to 86.7 nanograms/mL after omeprazole, suggesting an increased risk of toxicity from combined therapy.
The mechanism was thought to be the increase in gastric pH produced by the antisecretory drug, as similar results had been reported with ranitidine. However, the clinical significance of these interactions to the use of antisecretory drugs with bismuth compounds to eradicate Helicobacter pylori is unclear. Bismuth compounds have been combined with proton pump inhibitors or H2 antagonists in short-term regimens as part of triple or quadruple therapy.
(US Adopted Name)
Pharmacopoeias. In China, and France.
Note. Do not confuse with bismuth subcitrate potassium or tripotassium dicitratobismuthate (colloidal bismuth subcitrate).
Pharmacopoeias. In US.
The United States Pharmacopeia 31, 2008 (Bismuth Citrate). A white, amorphous or crystalline powder. Insoluble in water and in alcohol soluble in dilute ammonia solution and in solutions of alkali citrates. Store in airtight containers. Protect from light. Prevent exposure to temperatures above 40°.
Pharmacopoeias. In Europe and US.
European Pharmacopoeia, 6th ed. (Bismuth Subsalicylate). A complex of bismuth and salicylic acid. It contains not less than 56% and not more than 59.4% of Bi, calculated with reference to the dried substance. A white or almost white powder. Practically insoluble in water and in alcohol dissolves in mineral acids with decomposition. Protect from light.
The United States Pharmacopeia 31, 2008 (Bismuth Subsalicylate). A basic salt corresponding to C7H5Bi04 and containing not less than 56.0% and not more than 59.4% of Bi and not less than 36.5% and not more than 39.3% of total salicylates. It is a fine, odourless, white to off-white micro-crystalline powder. Practically insoluble in water, in alcohol, and in ether. It reacts with alkalis and mineral acids. Store in airtight containers. Protect from light.
(US Adopted Name)
Pharmacopoeias. In China, Europe, and US.
European Pharmacopoeia, 6th ed. (Bismuth Subcarbonate). A white or almost white powder. Practically insoluble in water and in alcohol. It dissolves in mineral acids with effervescence. Protect from light.
The United States Pharmacopeia 31, 2008 (Bismuth Subcarbonate). A white or almost white powder. Practically insoluble in water, in alcohol, and in ether dissolves in dilute acids with effervescence. Protect from light.
Bismuth Subcitrate Potassium
(US Adopted Name)
Note. Do not confuse with bismuth citrate or tripotassium dicitratobismuthate (colloidal bismuth subcitrate).
(US Adopted Name)
Pharmacopoeias. In Europe, Japan, and US.
European Pharmacopoeia, 6th ed. (Bismuth Subgallate). A complex of bismuth and gallic acid. It contains not less than 48% and not more than 51 % of Bi, calculated with reference to the dried substance. A yellow powder. Practically insoluble in water and in alcohol dissolves in mineral acids with decomposition and in alkali hydroxides, producing a reddish-brown liquid. Protect from light.
The United States Pharmacopeia 31, 2008 (Bismuth Subgallate). A basic salt containing 52 to 57% of Bi203 when dried at 105° for 3 hours. It is an odourless amorphous bright yellow powder. Practically insoluble in water, in alcohol, in chloroform, and in ether insoluble in very dilute mineral acids dissolves readily with decomposition in warm, moderately dilute hydrochloric, nitric, or sulfuric acids readily dissolves in solutions of alkali hydroxides to form a clear yellow liquid which rapidly becomes deep red. Store in airtight containers. Protect from light.
Pharmacopoeias. In Europe, Japan, and US. France also includes Bismuth (Sous-Nitrate de) Leger (Bismuthi Subnitras Levis) which is described as a variable mixture of bismuth hydroxide, carbonate, and subnitrate.
European Pharmacopoeia, 6th ed. (Bismuth Subnitrate, Heavy). It contains not less than 71 % and not more than 74% of Bi, calculated with reference to the dried substance. A white or almost white powder. Practically insoluble in water and in alcohol dissolves in mineral acids with decomposition.
The United States Pharmacopeia 31, 2008 (Bismuth Subnitrate). A basic salt containing not less than 79% of Bi203 calculated on the dried basis. It is a white, slightly hygroscopic powder. Practically insoluble in water and in alcohol readily dissolves in nitric and hydrochloric acids.
Note. Do not confuse with bismuth citrate or bismuth subcitrate potassium.
Bismuth has been used in homeopathic medicines under the following names: Bismuth-um Bismutum metallicum.
Bismuth oxide has been used in homeopathic medicines under the following names: Bismuthum oxydatum; Bis. ox.
Bismuth subnitrate has been used in homeopathic medicines under the following names: Heavy bismuth subnitrate, Bismuthi subnitrate ponderosus, Bismutum subnitricum, Bism. sub.
BPC 1954: Bismuth Subnitrate and Iodoform Paste
The United States Pharmacopeia 31, 2008: Bismuth Subsalicylate Magma Bismuth Subsalicylate Oral Suspension Bismuth Subsalicylate Tablets Compound Resorcinol Ointment Milk of Bismuth.
Argentina: Re-Dux, Sesamoil
Brazil: Pepto-Bismol, Peptosan, Peptulan, Senophile
Canada: Bismed, Maalox, Multi-action, Neo-Laryngobis, Pepto-Bismol, Personnel
Czech Republic: De-Nol Jatrox
Germany: Angass S, Dermatol, Haemo-Exhirud, Bufexamac, Katuldn-R, Stryphnasal N, Telen
Hong Kong: De-Nol
Israel: Kalbeten Pink Bismuth
Mexico: Biselicf, Bismed, Bismofarma, Bisval, Facidmol, Itamol, Pepto-Bismol, Siparox, Sucrato
The Netherlands: De-Nol
New Zealand: De-Nol
South Africa: De-Nol
Spain: Gastrodenol Rectamigdol
Turkey: De-Nol Dermatol
UK: De-Noltab Pepto-Bismol
USA: Bismatrol Children’s Kaopectate Devrom K-Pek Kao-Tin Kaopectate Kapectolin Maalox Total Stomach Relief Peptic Relief Pepto-Bismol
Argentina: Anusol Anusol Duo S Benitol Bismuto con Pectina Colistop Colistoral Crema De Bismuto Cutidermin Gastop Gastranil Gastricur Histidanol Lemil Mabis
Belgium: Gastrofilm Procto-Synalar Rectovasol
Brazil: Aftine Anusol-HC Bismu-Jet Bisuisanf Claudemor Colutoide Cutisanol Magnesia Bisurada Neoseptil Salicilato de Bismuto Composto Senophile
Canada: Bismutal Onrectal Pepto-Bismol Thunas Pile
Czech Republic: Carbocit Mastu S Sagittaproct Spofax Suspensio Visnevski cum Pice Liquida Herbacos
France: Anoreine Anusol Cutiphile Paps Pholcones Bismuth
Germany: Angass Anisan Bismolan H Corti Bismolan N Bismolan Combustin Heilsalbe Duoventrin Eulatin N Eulatin NN Faktu akut Friosmin N Hamo-ratiopharm N Hamoagil plus Mastu S Nervogastrol N Pascomag Spasmo-Nervogastrol Tamposit N Ventricon N Wismut comp
Hong Kong: Anusol Anusol-HC Haemoral Mastu S Rowatanal
Hungary: Bolus Adstringens Dermaforine Mastu S Nilacid
Indonesia: Anusol Anusol-HC
Ireland: Anugesic-HC Anusol Anusol-HC Rowatanal
Italy: Antiemorroidali Anusol
Mexico: Estomacurol Heliton
The Netherlands: Anaesthetica Roteroblong Maagtabletten Theranal
Poland: Gastro Hemo rectal
Portugal: Claudemor Servetinal Synalar Rectal
Russia: Anaesthesol Anusol Neo-Anusol Proctosan Simetrid
South Africa: Anugesic Anusol Arola Rosebalm Biskapect Bisma Rex Chloropect Enterodyne Kantrexil Sentinel Ulcer Mixture
Spain: Grietalgen Grietalgen Hidrocort Hemodren Compuesto Nasopomada Pomada Infantil Vera Sabanotropico Synalar Rectal
Switzerland: Bismorectal Cicafissan Euproctol N Fissan Furodermal Haemocortin Haemolan La pommade du Dr Brand Leucen Magenpulver Hafter Magentabletten Hafter Rectoseptal-Neo bismuthe
Turkey: Dermikolin Hemoralgine Kortos Metamorfoz
UK: Anugesic-HC Anusol Anusol-HC, Plus HC Bisma-Rex Hemocane Moorland OxBipp Stomach Mixture
USA: Anumed Anumed HC BFI Calmol Helidac Hem-Prep Hemril K-C Kao-Paverin Kaodene Non-Narcotic Mammol Fylera Rectagene Medicated Rectal Balm
Venezuela: Claudemorf Klincosal Polantac.