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INTRODUCTION — Eradication of Helicobacter pylori, withdrawal of nonsteroidal anti-inflammatory drugs, and antisecretory drugs are the mainstays of treatment for peptic ulcer disease.
The pharmacology of antiulcer drugs, excluding the antibiotics used to treat H. pylori, will be reviewed here. For detailed prescribing information, readers should refer to the individual drug information topics within UpToDate. Comprehensive information on drug-drug interactions can be determined using the drug interactions tool (Lexi-Interact online). This tool can be accessed from the UpToDate online search page or through the individual drug information topics in the section on drug interactions. Complete information on United States Food and Drug Administration (FDA) labeling for each drug can be accessed using the FDA searchable database.
Histamine-2 receptor antagonists
Mechanism of action — Histamine-2 receptor antagonists (H2RAs) (eg, cimetidine, ranitidine, famotidine, and nizatidine) inhibit acid secretion by blocking H2 receptors on the parietal cell (figure 1).
H2RAs are well absorbed after oral dosing; peak serum concentrations occur within one to three hours. Absorption is reduced 10 to 20 percent by concomitant antacid administration, but not by food.
H2RAs are eliminated by a combination of hepatic and renal metabolism . Their bioavailability is reduced 30 to 70 percent by first-pass hepatic metabolism . Renal clearance is generally greater than accounted for by glomerular filtration, reflecting the importance of renal tubular secretion . The dose of all the H2RAs is generally reduced by 50 percent in patients with severe renal failure [1-3]. The half-life of cimetidine is prolonged with liver failure, but dose reduction is necessary only if renal failure accompanies severe hepatic disease [1,4].
Adverse effects — Side effects of H2RAs are rare .
●Gynecomastia and impotence – Gynecomastia and impotence occur with cimetidine in a dose- and time-dependent fashion and resolve when discontinued . This effect is relatively specific for cimetidine and rarely occurs if treatment is limited to standard doses for eight weeks or less .
●Hematopoietic and immune effects – Long-term H2RA use is also associated with B12 deficiency . H2RAs have also been implicated in idiosyncratic cases of myelosuppression, thrombocytopenia, neutropenia, anemia, and pancytopenia [9-13]. Other rare diseases that have been associated with H2RAs include polymyositis and interstitial nephritis with cimetidine, an immune complex rash with ranitidine, and fever with both cimetidine and ranitidine [9,14,15]. Some immunomodulatory effects may reflect a unique action of the imidazole ring of cimetidine rather than actions at H2 receptors .
●Central nervous system (CNS) effects – H2RAs have been associated with CNS side-effects including confusion, restlessness, somnolence, agitation, headaches, dizziness, and, with prolonged therapy, hallucinations, focal twitching, and seizures [13,14,16]. Although these symptoms are generally reversible upon discontinuation of the drug, cases with more persistent CNS symptoms have been reported .
Mental status changes appear to be most common in older adults in the intensive care unit with renal or hepatic dysfunction and are rare in outpatients [16,18]. Cimetidine has been implicated as the most frequent cause of these CNS symptoms, but similar side effects have also been described with ranitidine and famotidine [14,16].
●Hepatic effects – H2RAs are metabolized in the liver by the cytochrome P450 system. Of the H2RAs, cimetidine is the most potent inhibitor of the P450 system (CYP1A2, 2C9, and 2D6) and can cause significant drug interactions. H2RAs can rarely cause acute hepatic injury [4,19,20]. The clinical presentation of the hepatic injury may be cholestatic, hepatocellular, or mixed with features of both cholestatic and hepatocellular injury . Patients may rarely have features of hypersensitivity with rash, fever, and/or eosinophilia. The acute hepatitis is rapidly reversible after withdrawal of the drug. Hepatotoxicity has recurred with rechallenge in a sufficient number of cases to firmly establish this rare, but important, association . (See "Drug-induced liver injury", section on 'Clinical manifestations'.)
●Cardiac effects – Sinus bradycardia, hypotension, atrioventricular block, prolongation of the QT interval, and sinus and cardiac arrest have occurred with the rapid infusion of an H2RA [1,21,22]. Oral therapy also has been reported to cause cardiac toxicity, although clinically significant effects upon sinus rhythm or conduction are rare. Possible risk factors for cardiac events include rapid intravenous infusion, high dose, conditions that would delay drug clearance (eg, renal or hepatic dysfunction), and underlying cardiac disease .
Proton pump inhibitors
Mechanism of action — The proton pump inhibitors (PPIs) (eg, omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, and esomeprazole) effectively block acid secretion by irreversibly binding to and inhibiting the hydrogen-potassium ATPase pump that resides on the luminal surface of the parietal cell membrane (figure 1). (See "Overview and comparison of the proton pump inhibitors for the treatment of acid-related disorders", section on 'Pharmacology of the proton pump inhibitors'.)
A complete discussion of the pharmacology, clinical efficacy, and safety of the PPIs is presented separately. (See "Overview and comparison of the proton pump inhibitors for the treatment of acid-related disorders".)
Adverse effects — Adverse effects of PPIs are discussed in detail, separately. (See "Overview and comparison of the proton pump inhibitors for the treatment of acid-related disorders", section on 'Safety'.)
Indications and comparative efficacy — As a result of stronger acid suppression as compared with H2RA, PPI use results in faster control of peptic ulcer disease symptoms and higher ulcer healing rates [23-25]. PPIs are also more effective in preventing nonsteroidal anti-inflammatory drug (NSAID)-induced gastroduodenal toxicity and in healing gastroduodenal ulcers associated with NSAIDs when they cannot be discontinued . PPIs are a component of H. pylori antibiotic regimens and are used in the treatment of hypersecretory states (eg, gastrinoma). (See "Overview and comparison of the proton pump inhibitors for the treatment of acid-related disorders", section on 'Treatment of acid-related disorders' and "Management and prognosis of the Zollinger-Ellison syndrome (gastrinoma)" and "Treatment regimens for Helicobacter pylori", section on 'Initial therapy' and "Treatment regimens for Helicobacter pylori".)
Unlike H2RAs, tolerance does not occur for PPIs, but variable PPI metabolism may account for some difference in efficacy. (See "Physiology of gastric acid secretion" and "Overview and comparison of the proton pump inhibitors for the treatment of acid-related disorders".)
ANTACIDS — Antacids usually contain a combination of magnesium trisilicate, aluminum hydroxide, or calcium carbonate.
Mechanism of action — Antacids can neutralize gastric acid and reduce acid delivery to the duodenum. The following are hypothesized mechanisms for the acid-independent actions of antacids; however it is unclear which, if any, of these actions facilitate peptic ulcer healing [27,28]:
●Aluminum hydroxide binds growth factors and enhances their binding to experimental ulcers, possibly serving to deliver growth factors to injured mucosa.
●Antacids promote angiogenesis in injured mucosa .
●Antacids bind bile acids and also inhibit peptic activity .
●Heavy metals are well known to suppress, but generally not eradicate, H. pylori.
Indication — Given the effectiveness of PPIs, antacids are not used in the treatment of peptic ulcer disease. The role of antacids is limited to the treatment of heartburn associated with mild intermittent gastroesophageal reflux disease. (See "Medical management of gastroesophageal reflux disease in adults", section on 'Antacids'.)
Adverse effects — Antacid side effects depend upon the quantity consumed and the duration of therapy. Magnesium-containing antacids cause diarrhea and hypermagnesemia; the latter only becomes important in patients with renal insufficiency. Some antacids may also contain sodium, and volume overload can occur in susceptible patients.
Ingestion of large amounts of calcium and absorbable alkali, particularly calcium carbonate, can lead to hypercalcemia, alkalosis, and acute or chronic renal injury, a constellation known as the milk-alkali syndrome . (See "The milk-alkali syndrome".)
Significant aluminum retention only occurs in patients with renal failure and may result in neurotoxicity and anemia following prolonged treatment with aluminum hydroxide. Aluminum hydroxide blocks intestinal absorption of phosphate; two weeks of therapy with moderate doses can result in significant hypophosphatemia, especially if the patient is on a low phosphate diet or is phosphate depleted for other reasons . (See "Aluminum toxicity in chronic kidney disease", section on 'Other medications'.)
Mechanism of action — Sucralfate is a sulfated polysaccharide, sucrose octasulfate, complexed with aluminum hydroxide. It prevents acute, chemically-induced mucosal damage and heals chronic ulcers without altering gastric acid or pepsin secretion or significantly buffering acid [27,33]. Similar to aluminum-containing antacids, sucralfate stimulates angiogenesis and the formation of granulation tissue, possibly due to growth factor binding . Sucralfate also binds to the injured tissue, thereby delivering growth factors and reducing access to pepsin and acid. Aluminum hydroxide mediates some of the actions of sucralfate, but the sucrose octasulfate moiety may also have a role by contributing sulfhydryl groups to reduce oxidant damage to epithelial cells.
Indication — Sucralfate has been reported to suppress H. pylori and inhibit acid secretion in infected patients with duodenal ulcers . However, sucralfate is not used to treat peptic ulcers as proton pump inhibitors heal ulcers more rapidly and to a greater extent. The use of sucralfate is limited to the initial management of gastroesophageal reflux disease in pregnancy. (See "Medical management of gastroesophageal reflux disease in adults", section on 'Pregnancy and lactation'.)
Adverse effects — Sucralfate has few adverse effects . It can bind to other drugs if taken simultaneously. Similar to antacids, significant aluminum retention only occurs in patients with renal failure [3,35,36]. Sucralfate can also bind to phosphate and lead to hypophosphatemia . Combining sucralfate and antacids can potentially amplify these effects. (See "Aluminum toxicity in chronic kidney disease" and "Causes of hypophosphatemia".)
Mechanism of action — Bismuth does not inhibit or neutralize gastric acid. The most dramatic action of bismuth salts is the suppression of H. pylori . Other actions that may promote ulcer healing include the following:
●Inhibition of peptic activity but not pepsin secretion .
●Bismuth from colloidal bismuth subcitrate (CBS) may bind to ulcer craters [40,41].
●Macrophages, recruited to the edge of the ulcer crater in CBS-treated rats, may promote healing .
●CBS may increase mucosal prostaglandin production and mucus and bicarbonate secretion.
Indication — The role of bismuth preparations (eg, bismuth subcitrate and bismuth subsalicylate [BSS]) is limited to part of a quadruple antibiotic therapy regimen in H. pylori-positive ulcers . (See "Treatment regimens for Helicobacter pylori", section on 'Quadruple therapy'.)
Adverse effects — In the colon, bismuth salts react with hydrogen sulfide to form bismuth sulfide, which blackens the stools .
Bismuth toxicity is rare with CBS or BSS [38,43]. Bismuth absorption varies with the specific form of bismuth; absorption is much greater with CBS than with BSS or bismuth subnitrate [44,45]. Coadministration of histamine-2 receptor antagonists increases bismuth absorption from CBS, but not from BSS or bismuth subnitrate . Bismuth should be avoided or serum bismuth concentrations monitored in patients with renal failure .
The subsalicylate moiety in BSS is converted to salicylic acid and absorbed; however, salicylate in the absence of the acetyl group does not inhibit platelet function or appear to share the same high risk of aspirin for gastrointestinal bleeding [47-50]. However, the salicylate from BSS will raise serum salicylate levels and can cause salicylate toxicity, and combination with other salicylate products should therefore be avoided.
Mechanism of action — Misoprostol is a 15-deoxy-15-hydroxy-16-methyl analogue of prostaglandin E1. Prostaglandins, particularly of the E and I group, inhibit acid secretion by selectively reducing the ability of the parietal cell to generate cyclic adenosine monophosphate in response to histamine . Prostaglandins also enhance mucosal defense mechanisms . (See "NSAIDs (including aspirin): Pathogenesis of gastroduodenal toxicity", section on 'Mechanisms of gastroduodenal protection by endogenous prostaglandins'.)
Indication — The role of misoprostol in peptic ulcer disease is limited to the prevention of nonsteroidal anti-inflammatory drug-induced gastroduodenal ulcers. It is contraindicated in women of childbearing potential who are not on contraception. (See "NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity", section on 'Misoprostol' and 'Pregnancy and lactation' below.)
Adverse effects — The most frequent side effects of misoprostol are dose-dependent cramping, abdominal pain, and diarrhea [53,54]. These side effects interfere with compliance in many patients. (See "NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity", section on 'Misoprostol'.)
POTASSIUM-COMPETITIVE ACID INHIBITORS — Potassium-competitive acid inhibitors (PCABs) work by competing for potassium on the luminal side of the parietal cell, and cause rapid and reversible inhibition of pumps and therefore acid secretion . After oral doses, PCABs rapidly achieve high plasma concentrations and have linear, dose-dependent pharmacokinetics; therefore, they have a rapid onset of action and achieve a full effect with the first dose. The effect is also seen with repeated doses.
PCABs are not available outside of Asia, and data on safety and comparative efficacy with antisecretory agents are limited [56,57]. The PCAB vonoprazan has been approved for the prevention of nonsteroidal anti-inflammatory drug-induced ulcers and treatment of peptic ulcer disease in Japan. Another PCAB, revaprazan, has been approved in Korea. Studies also suggest that vonoprazan may be effective in combination with antibiotics for the eradication of H. pylori . However, additional studies are needed to confirm these findings.
Pregnancy and lactation — All histamine-2 receptor antagonists (H2RAs) appear to be safe in pregnancy, with ranitidine and cimetidine having the most safety data available . Ranitidine and cimetidine are concentrated in breast milk but are compatible with breastfeeding.
Experience with proton pump inhibitors (PPIs) is more limited compared with H2RAs, but suggests that PPIs are probably safe in pregnancy [60-62]. Limited data are available on the secretion of PPIs in breast milk. Omeprazole and pantoprazole are secreted in low concentrations in breast milk [63,64]. However, a large portion of them is likely to be destroyed by gastric acid in the infant's stomach . (See "Medical management of gastroesophageal reflux disease in adults", section on 'Pregnancy and lactation'.)
Most antacids are considered safe in pregnancy and are compatible with breastfeeding . However, antacids containing sodium bicarbonate and magnesium trisilicate should be avoided in pregnancy . (See "Medical management of gastroesophageal reflux disease in adults", section on 'Antacids'.)
Prostaglandins of the E group are uterotropic. Misoprostol has been given with or without mifepristone to induce abortion [62,65]. As a result, it is contraindicated in women of childbearing potential who are not on contraception. All patients should be informed of this risk to minimize the drug being inadvertently given by the patient to a pregnant woman.
●Eradication of H. pylori, withdrawal of nonsteroidal anti-inflammatory drugs (NSAIDs), and antisecretory drugs are the mainstays of treatment for peptic ulcer disease. (See 'Introduction' above.)
●Histamine-2 receptor antagonists (H2RAs) inhibit acid secretion by blocking H2 receptors on the parietal cell (figure 1). Proton pump inhibitors (PPIs) effectively block acid secretion by irreversibly binding to and inhibiting the hydrogen-potassium ATPase pump that resides on the luminal surface of the parietal cell membrane. (See 'Histamine-2 receptor antagonists' above and 'Proton pump inhibitors' above.)
●PPI use results in faster control of peptic ulcer disease symptoms and higher ulcer healing rates as compared with H2RAs. PPIs are also more effective in preventing NSAID-induced gastroduodenal toxicity and in healing gastroduodenal ulcers associated with NSAIDs when they cannot be discontinued. PPIs are a component of H. pylori antibiotic regimens and are used in the management of hypersecretory states (eg, Zollinger-Ellison syndrome). The use of H2RAs is largely limited to the management of mild gastroesophageal reflux disease. (See 'Indications and comparative efficacy' above.)
●Antacids and sucralfate have no role in the treatment of peptic ulcer disease. The role of bismuth preparations (eg, bismuth subcitrate and bismuth subsalicylate) is as part of a quadruple antibiotic therapy regimen in H. pylori-positive ulcers. (See 'Antacids' above and 'Sucralfate' above and 'Bismuth' above.)
●Prostaglandin analogues (eg, misoprostol) are effective for preventing NSAID-induced ulcers, but they have no established role for healing ulcers. Misoprostol is contraindicated in women of childbearing potential who are not on contraception. (See 'Misoprostol' above.)
●Potassium-competitive acid inhibitors (PCABs) work by competing for potassium on the luminal side of the parietal cell, and cause rapid and reversible inhibition of pumps and therefore acid secretion. PCABs are not widely available outside of Asia, and data on safety and comparative efficacy with antisecretory agents are limited.
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Andrew H. Soll, MD, who contributed to an earlier version of this topic review.
- Feldman M, Burton ME. Histamine2-receptor antagonists. Standard therapy for acid-peptic diseases. 1. N Engl J Med 1990; 323:1672.
- Manlucu J, Tonelli M, Ray JG, et al. Dose-reducing H2 receptor antagonists in the presence of low glomerular filtration rate: a systematic review of the evidence. Nephrol Dial Transplant 2005; 20:2376.
- Gladziwa U, Koltz U. Pharmacokinetic optimisation of the treatment of peptic ulcer in patients with renal failure. Clin Pharmacokinet 1994; 27:393.
- Lewis JH. Hepatic effects of drugs used in the treatment of peptic ulcer disease. Am J Gastroenterol 1987; 82:987.
- Reynolds JC. The clinical importance of drug interactions with antiulcer therapy. J Clin Gastroenterol 1990; 12 Suppl 2:S54.
- Jensen RT, Collen MJ, Pandol SJ, et al. Cimetidine-induced impotence and breast changes in patients with gastric hypersecretory states. N Engl J Med 1983; 308:883.
- McCarthy DM. Ranitidine or cimetidine. Ann Intern Med 1983; 99:551.
- Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA 2013; 310:2435.
- Potter HP Jr, Byrne EB, Lebovitz S. Fever after cimetidine and ranitidine. J Clin Gastroenterol 1986; 8:275.
- Nakano T, Kuroiwa T, Tsumita Y, et al. Aplastic anemia associated with initiation of nizatidine therapy in a hemodialysis patient. Clin Exp Nephrol 2004; 8:160.
- Takami N, Yamamoto Y, Matsuo H, et al. Agranulocytosis possibly caused by ranitidine in a patient with renal failure. Int J Clin Pharmacol Ther 2002; 40:520.
- Ecker RD, Wijdicks EF, Wix K, McClelland R. Does famotidine induce thrombocytopenia in neurosurgical patients? J Neurosurg Anesthesiol 2004; 16:291.
- Feldman M, Burton ME. Histamine2-receptor antagonists. Standard therapy for acid-peptic diseases (2). N Engl J Med 1990; 323:1749.
- Smallwood RA, Berlin RG, Castagnoli N, et al. Safety of acid-suppressing drugs. Dig Dis Sci 1995; 40:63S.
- Kumar A. Cimetidine: an immunomodulator. DICP 1990; 24:289.
- Cantú TG, Korek JS. Central nervous system reactions to histamine-2 receptor blockers. Ann Intern Med 1991; 114:1027.
- von Einsiedel RW, Roesch-Ely D, Diebold K, et al. H(2)-histamine antagonist (famotidine) induced adverse CNS reactions with long-standing secondary mania and epileptic seizures. Pharmacopsychiatry 2002; 35:152.
- Hanlon JT, Landerman LR, Artz MB, et al. Histamine2 receptor antagonist use and decline in cognitive function among community dwelling elderly. Pharmacoepidemiol Drug Saf 2004; 13:781.
- Black M. Hepatotoxic and hepatoprotective potential of histamine (H2)-receptor antagonists. Am J Med 1987; 83:68.
- Fisher AA, Le Couteur DG. Nephrotoxicity and hepatotoxicity of histamine H2 receptor antagonists. Drug Saf 2001; 24:39.
- Hinrichsen H, Halabi A, Kirch W. Clinical aspects of cardiovascular effects of H2-receptor antagonists. Eur J Clin Invest 1995; 25 Suppl 1:47.
- Lee KW, Kayser SR, Hongo RH, et al. Famotidine and long QT syndrome. Am J Cardiol 2004; 93:1325.
- Burget DW, Chiverton SG, Hunt RH. Is there an optimal degree of acid suppression for healing of duodenal ulcers? A model of the relationship between ulcer healing and acid suppression. Gastroenterology 1990; 99:345.
- Howden CW, Hunt RH. The relationship between suppression of acidity and gastric ulcer healing rates. Aliment Pharmacol Ther 1990; 4:25.
- Walan A, Bader JP, Classen M, et al. Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. N Engl J Med 1989; 320:69.
- Agrawal NM, Campbell DR, Safdi MA, et al. Superiority of lansoprazole vs ranitidine in healing nonsteroidal anti-inflammatory drug-associated gastric ulcers: results of a double-blind, randomized, multicenter study. NSAID-Associated Gastric Ulcer Study Group. Arch Intern Med 2000; 160:1455.
- Tarnawski A, Tanoue K, Santos AM, Sarfeh IJ. Cellular and molecular mechanisms of gastric ulcer healing. Is the quality of mucosal scar affected by treatment? Scand J Gastroenterol Suppl 1995; 210:9.
- Konturek SJ. New aspects of clinical pharmacology of antacids. J Physiol Pharmacol 1993; 44:5.
- Tarnawski A, Hollander D, Gergely H. Antacids: new perspectives in cytoprotection. Scand J Gastroenterol Suppl 1990; 174:9.
- Weberg R, Berstad K, Berstad A. Acute effects of antacids on gastric juice components in duodenal ulcer patients. Eur J Clin Invest 1990; 20:511.
- Orwoll ES. The milk-alkali syndrome: current concepts. Ann Intern Med 1982; 97:242.
- Shields HM. Rapid fall of serum phosphorus secondary to antacid therapy. Gastroenterology 1978; 75:1137.
- Soll AH, Weinstein WM, Kurata J, McCarthy D. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med 1991; 114:307.
- Banerjee S, El-Omar E, Mowat A, et al. Sucralfate suppresses Helicobacter pylori infection and reduces gastric acid secretion by 50% in patients with duodenal ulcer. Gastroenterology 1996; 110:717.
- Robertson JA, Salusky IB, Goodman WG, et al. Sucralfate, intestinal aluminum absorption, and aluminum toxicity in a patient on dialysis. Ann Intern Med 1989; 111:179.
- Arieff AI, Cooper JD, Armstrong D, Lazarowitz VC. Dementia, renal failure, and brain aluminum. Ann Intern Med 1979; 90:741.
- Chines A, Pacifici R. Antacid and sucralfate-induced hypophosphatemic osteomalacia: a case report and review of the literature. Calcif Tissue Int 1990; 47:291.
- Gorbach SL. Bismuth therapy in gastrointestinal diseases. Gastroenterology 1990; 99:863.
- Baron JH, Barr J, Batten J, et al. Acid, pepsin, and mucus secretion in patients with gastric and duodenal ulcer before and after colloidal bismuth subcitrate (De-Nol). Gut 1986; 27:486.
- Koo J, Ho J, Lam SK, et al. Selective coating of gastric ulcer by tripotassium dicitrato bismuthate in the rat. Gastroenterology 1982; 82:864.
- Elder JB. Recent experimental and clinical studies on the pharmacology of colloidal bismuth subcitrate. Scand J Gastroenterol Suppl 1986; 122:14.
- Malfertheiner P, Bazzoli F, Delchier JC, et al. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet 2011; 377:905.
- Wagstaff AJ, Benfield P, Monk JP. Colloidal bismuth subcitrate. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in peptic ulcer disease. Drugs 1988; 36:132.
- Nwokolo CU, Gavey CJ, Smith JT, Pounder RE. The absorption of bismuth from oral doses of tripotassium dicitrato bismuthate. Aliment Pharmacol Ther 1989; 3:29.
- Nwokolo CU, Prewett EJ, Sawyer AM, et al. Lack of bismuth absorption from bismuth subnitrate (Roter) tablets. Eur J Gastroenterol Hepatol 1990; 2:433.
- Nwokolo CU, Prewett EJ, Sawyerr AM, et al. The effect of histamine H2-receptor blockade on bismuth absorption from three ulcer-healing compounds. Gastroenterology 1991; 101:889.
- Sweeney JD, Hoernig LA. Hemostatic effects of salsalate in normal subjects and patients with hemophilia A. Thromb Res 1991; 61:23.
- Danesh BJ, McLaren M, Russell RI, et al. Comparison of the effect of aspirin and choline magnesium trisalicylate on thromboxane biosynthesis in human platelets: role of the acetyl moiety. Haemostasis 1989; 19:169.
- Cohen A. Fecal blood loss and plasma salicylate study of salicylsalicylic acid and aspirin. J Clin Pharmacol 1979; 19:242.
- Torgyán S, Ady E, Wagner L, et al. Reduction of indomethacin-induced gastrointestinal blood loss by sodium salicylate in man. Int J Clin Pharmacol Biopharm 1978; 16:610.
- Chen MC, Amirian DA, Toomey M, et al. Prostanoid inhibition of canine parietal cells: mediation by the inhibitory guanosine triphosphate-binding protein of adenylate cyclase. Gastroenterology 1988; 94:1121.
- Feldman M. Prostaglandins and gastric ulcers: from seminal vesicle to misoprostol (Cytotec). Am J Med Sci 1990; 300:116.
- Bianchi Porro G, Parente F. Side effects of anti-ulcer prostaglandins: an overview of the worldwide clinical experience. Scand J Gastroenterol Suppl 1989; 164:224.
- Graham DY, Agrawal NM, Roth SH. Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial. Lancet 1988; 2:1277.
- Andersson K, Carlsson E. Potassium-competitive acid blockade: a new therapeutic strategy in acid-related diseases. Pharmacol Ther 2005; 108:294.
- Garnock-Jones KP. Vonoprazan: first global approval. Drugs 2015; 75:439.
- Simon WA, Herrmann M, Klein T, et al. Soraprazan: setting new standards in inhibition of gastric acid secretion. J Pharmacol Exp Ther 2007; 321:866.
- Murakami K, Sakurai Y, Shiino M, et al. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study. Gut 2016; 65:1439.
- Larson JD, Patatanian E, Miner PB Jr, et al. Double-blind, placebo-controlled study of ranitidine for gastroesophageal reflux symptoms during pregnancy. Obstet Gynecol 1997; 90:83.
- Pasternak B, Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects. N Engl J Med 2010; 363:2114.
- Gill SK, O'Brien L, Einarson TR, Koren G. The safety of proton pump inhibitors (PPIs) in pregnancy: a meta-analysis. Am J Gastroenterol 2009; 104:1541.
- Matok I, Levy A, Wiznitzer A, et al. The safety of fetal exposure to proton-pump inhibitors during pregnancy. Dig Dis Sci 2012; 57:699.
- Marshall JK, Thompson AB, Armstrong D. Omeprazole for refractory gastroesophageal reflux disease during pregnancy and lactation. Can J Gastroenterol 1998; 12:225.
- Plante L, Ferron GM, Unruh M, Mayer PR. Excretion of pantoprazole in human breast. J Reprod Med 2004; 49:825.
- National Health Service. Proton-pump-inhibitors for treatment of reflux in a breastfeeding mother: which is preferred? https://www.evidence.nhs.uk/search?q=%22Proton-pump-inhibitors+for+treatment+of+reflux+in+a+breastfeeding+mother%22 (Accessed on March 13, 2016).
- Hodgkinson R, Glassenberg R, Joyce TH 3rd, et al. Comparison of cimetidine (Tagamet) with antacid for safety and effectiveness in reducing gastric acidity before elective cesarean section. Anesthesiology 1983; 59:86.
- Witter FR, King TM, Blake DA. The effects of chronic gastrointestinal medication on the fetus and neonate. Obstet Gynecol 1981; 58:79S.
- Physician's Desk Reference, 46th ed, Physician's Desk Reference, Oradell, NJ 1992.