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Pharmacology: Pharmacodynamics: Bismuth subsalicylate is an insoluble salt of trivalent bismuth and salicylic acid, with each molecule containing 42% salicylate and 58% bismuth. Bismuth compounds have been demonstrated to exert numerous actions in the gastrointestinal tract, including antibacterial activity, protective effects on the gastric mucosa, binding of the ulcer base and mucus, and binding of bile acids.
Bismuth subsalicylate appears to have antisecretory and antimicrobial effects in vitro and may give some anti-inflammatory effects. The salicylate moiety provides the antisecretory and anti-inflammatory effects, while the bismuth moiety may exert direct antimicrobial effects against bacterial and viral enteropathogens.
Therapeutic effects of bismuth subsalicylate in gastritis and gastric and duodenal ulcer have been primarily attributed to demulcent and cytoprotective properties. Bismuth subsalicylate interferes with the integrity of the Helicobacter pylori cell and prevents adhesion of the organism to the gastric epithelium. Another mechanism by which bismuth compounds interferes with H. pylori is by inhibiting its urease, phospholipase and proteolytic activity. By eliminating H. pylori associated with peptic ulcers, the esophageal lesion healing rate is improved and the chance of recurrence is decreased. The in vitro minimum inhibitory concentration (MIC) of bismuth subsalicylate for H. pylori ranges from 2-32 mcg/mL, and these concentrations are achieved locally in the gastric mucosa.
The antidiarrheal effects of bismuth subsalicylate appear to be mediated via both antimicrobial and antisecretory properties. Direct antimicrobial activity against numerous diarrheal pathogens has been reported, including E. coli, salmonella, Clostridium difficile, Campylobacter jejuni and shigella. Other aerobic and anaerobic bacteria in the normal microflora are also inhibited in vitro, although the overall composition of normal flora of the stomach or feces does not appear altered.
Pharmacokinetics: Time to peak concentration (tmax): Oral: 1.8-5 hrs. With a dose regimen of 524 mg bismuth subsalicylate (30 mL suspension) every 30 min for a total of 8 doses in 3.5 hrs, peak salicylate serum level of 137 mcg/mL were observed; peak levels occurred 5 hrs after administration of the 1st dose. Steady-state salicylate plasma level of 24 mcg/mL were reported after 2 weeks of therapy during administration of bismuth subsalicylate 30 mL (1 tablet) 4 times daily for 3 weeks (daily dose 2.1 g).
Absorption: Bioavailability: Gastro-Bismol: Less than 1% (bismuth), >80% (salicylic acid) bismuth serum level following oral administration of bismuth subsalicylate are characteristically low due to poor gastrointestinal absorption. Normal bismuth plasma levels are <10 mcg/L.
In contrast, the salicylate moiety of bismuth subsalicylate is almost completely absorbed, with 95% of salicylate in each dose being recovered in the urine after 72 hrs.
Gastro-Bismol L: Bismuth subsalicylate undergoes chemical dissociation in the gastrointestinal tract. One (1) tablet of Gastro-Bismol L yields salicylate 408 mg. Following ingestion, salicylate is absorbed with >90% recovered in the urine; plasma levels are similar to levels achieved after a comparable dose of aspirin. Absorption of bismuth is negligible.
Distribution: Bismuth is 90% bound to plasma proteins. Absorbed bismuth is sequestered in multiple tissue site and slowly excreted over a period of several months. Bismuth has a half-life (t½) ranging from 5-11 days.
Metabolism: Bismuth subsalicylate is hydrolyzed in the stomach to form bismuth oxychloride and salicylic acid. A portion of unchanged bismuth subsalicylate passed into the duodenum, and reacts with other anions; salicylate continues to be released from these reactions. Salicylate is primary absorbed in the small intestine.
In the colon, bismuth oxychloride, undissociated bismuth subsalicylate, bismuth subcarbonate and bismuth phosphate react with hydrogen sulfite to form bismuth sulfide; this salt is black and insoluble and accounts for the harmless darkening of the stool associated with the use of bismuth subsalicylate.
Excretion: Salicylate absorbed from bismuth subsalicylate appears in breast milk. Renal excretion (in urine): Salicylate 95%. Greater than 99% of bismuth present in a dose of bismuth subsalicylate is excreted in the feces.
Toxicology: Salicylate plasma levels of 200-390 mcg/mL are associated with adverse effects (eg, tinnitus, hyperventilation, dehydration), and acute salicylate toxicity occurs with levels exceeding 400 mcg/mL.
"Safe" serum bismuth levels during bismuth salt therapy are considered to be <50 mcg/L. Most patients with bismuth encephalopathy have had blood bismuth level in excess of 100 mcg/L (more commonly, >500 mcg/L). In one case of encephalopathy associated with bismuth salicylate administration, the blood bismuth level on admission was 72 mcg/mL; this declined to 10 mcg/mL after 2 weeks.
