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Drug Treatment of Gastric Acidity


Nimish Vakil

, MD, University of Wisconsin School of Medicine and Public Health

Last full review/revision Jun 2021| Content last modified Jun 2021

Drugs for decreasing acidity are used for peptic ulcer, gastroesophageal reflux disease (GERD), and many forms of gastritis. Some drugs are used in regimens for treating Helicobacter pylori infection. Drugs include

  • Proton pump inhibitors
  • H2 blockers
  • Antacids
  • Prostaglandins

(See also Overview of Acid Secretion.)

Proton pump inhibitors

These drugs are potent inhibitors of H+,K+-ATPase. This enzyme, located in the apical secretory membrane of the parietal cell, plays a key role in the secretion of H+ (protons). These drugs can completely inhibit acid secretion and have a long duration of action. They promote ulcer healing and are also key components of H. pylori eradication regimens. Proton pump inhibitors have replaced H2 blockers in most clinical situations because of efficacy.

Proton pump inhibitors include esomeprazole, lansoprazole, and pantoprazole, these are available orally and IV, and omeprazole and rabeprazole, available only orally in the US (see Table: Proton Pump Inhibitors). Oral and IV doses are the same. Omeprazole, esomeprazole, and lansoprazole are available without a prescription in the US. For uncomplicated duodenal ulcers, omeprazole 20 mg once a day or lansoprazole 30 mg once a day is given for 4 weeks. Complicated duodenal ulcers (ie, multiple ulcers, bleeding ulcers, those > 1.5 cm, or those occurring in patients with serious underlying illness) respond better to higher doses (omeprazole 40 mg once a day, lansoprazole 60 mg once a day or 30 mg 2 times a day). Gastric ulcers require treatment for 6 to 8 weeks. Gastritis and GERD require 8 to 12 weeks of therapy; GERD additionally often requires long-term maintenance.

Proton Pump Inhibitors


Most Conditions, Including Gastritis, GERD, and Uncomplicated Duodenal Ulcers

Gastric Ulcers and Complicated Duodenal Ulcers


40 mg once a day

40 mg 2 times a day


30 mg once a day

Pediatric dosages:

  • < 10 kg: 7.5 mg once a day
  • 10–20 kg: 15 mg once a day
  • ≥ 20 kg: 30 mg once a day*

30 mg 2 times a day


20 mg once a day

Pediatric dosage: 1 mg/kg/day in a single dose or divided 2 times a day*

40 mg once a day


40 mg once a day

40 mg 2 times a day


20 mg once a day

20 mg 2 times a day

* Representative dosages. Oral and IV doses are the same. Data are limited to the use of proton pump inhibitors in children.

GERD = gastroesophageal reflux disease.

Long-term proton pump inhibitor therapy produces elevated gastrin levels, which lead to enterochromaffin-like cell hyperplasia. However, there is no evidence of dysplasia or malignant transformation in patients receiving this treatment. Micronutrient deficiencies (eg, vitamin B12 and magnesium) have been reported in a small number of patients. The absolute excess risk is 0.3 to 0.4% per patient per year. Some studies suggest that the risk of enteric infections such as Clostridioides difficile may be higher in patients receiving long-term therapy, but other studies do not support this observation. The absolute excess risk varies from 0 to 0.09% per patient. Carefully conducted studies have shown no effect on bone health or the risk of dementia, Parkinson disease, heart disease, and pneumonia.

H2 blockers

These drugs (cimetidine, famotidine, available IV and orally; and nizatidine available orally) are competitive inhibitors of histamine at the H2 receptor, thus suppressing gastrin-stimulated acid secretion and proportionately reducing gastric juice volume. Histamine-mediated pepsin secretion is also decreased. Nizatidine, famotidine, and cimetidine are available without a prescription in the US.

H2 blockers are well absorbed from the gastrointestinal tract, with onset of action 30 to 60 minutes after ingestion and peak effects at 1 to 2 hours. IV administration produces a more rapid onset of action. Duration of action is proportional to dose and ranges from 6 to 20 hours. Doses should often be reduced in older patients.

For duodenal ulcers, once daily oral administration of cimetidine 800 mg, famotidine 40 mg, or nizatidine 300 mg given at bedtime or after dinner for 6 to 8 weeks is effective. Gastric ulcers may respond to the same regimen continued for 8 to 12 weeks, but because nocturnal acid secretion is less important, morning administration may be equally or more effective. Children ≥ 40 kg may receive adult doses. Below that weight, the oral dosage is cimetidine 10 mg/kg every 12 hours. For GERD, H2 blockers are now mostly used for pain management. These drugs have been replaced by proton pump inhibitors for most patients with ulcer disease. Gastritis heals with famotidine given 2 times a day for 8 to 12 weeks.

The H2 blocker ranitidine (oral, IV, and over the counter) has been removed from the market in the US and in many other countries because of unacceptable concentrations of N-nitrosodimethylamine (NDMA), a probable human carcinogen. Cimetidine and famotidine are alternatives and do not contain NDMA, nor do proton pump inhibitors.

Cimetidine has minor antiandrogen effects expressed as reversible gynecomastia and, less commonly, erectile dysfunction with prolonged use. Mental status changes, diarrhea, rash, drug fever, myalgias, thrombocytopenia, and sinus bradycardia and hypotension after rapid IV administration have been reported with all H2 blockers, generally in < 1% of treated patients but more commonly in older patients.

Cimetidine and, to a lesser extent, other H2 blockers interact with the P-450 microsomal enzyme system and may delay metabolism of other drugs eliminated through this system (eg, phenytoin, warfarin, theophylline, diazepam, lidocaine).


These agents neutralize gastric acid and reduce pepsin activity (which diminishes as gastric pH rises to > 4.0). In addition, some antacids adsorb pepsin. Antacids may interfere with the absorption of other drugs (eg, tetracycline, digoxin, iron).

Antacids relieve symptoms, promote ulcer healing, and reduce recurrence. They are relatively inexpensive but must be taken 5 to 7 times/day. The optimal antacid regimen for ulcer healing seems to be 15 to 30 mL of liquid or 2 to 4 tablets 1 and 3 hours after each meal and at bedtime. The total daily dosage of antacids should provide 200 to 400 mEq of neutralizing capacity. However, antacids have been superseded by acid-suppressive therapy in the treatment of peptic ulcer and are used only for short-term symptom relief.

In general, there are 2 types of antacids:

  • Absorbable
  • Nonabsorbable

Absorbable antacids (eg, sodium bicarbonate, calcium carbonate) provide rapid, complete neutralization but may cause alkalosis and should be used only briefly (1 or 2 days).

Nonabsorbable antacids (eg, aluminum or magnesium hydroxide) have fewer systemic adverse effects and are preferred.

Aluminum hydroxide is a relatively safe, commonly used antacid. With chronic use, phosphate depletion occasionally develops as a result of binding of phosphate by aluminum in the gastrointestinal tract. The risk of phosphate depletion increases in patients who have an alcohol use disorder, undernourished patients, and patients with renal disease (including those receiving hemodialysis). Aluminum hydroxide causes constipation.

Magnesium hydroxide is a more effective antacid than aluminum but may cause diarrhea. To limit diarrhea, many proprietary antacids combine magnesium and aluminum antacids. Because small amounts of magnesium are absorbed, magnesium preparations should be used with caution in patients with renal disease.


Certain prostaglandins (especially misoprostol) inhibit acid secretion by decreasing the generation of cyclic AMP that is triggered by histamine stimulation of the parietal cell, and enhance mucosal defense. Synthetic prostaglandin derivatives are used predominantly to decrease the risk of nonsteroidal anti-inflammatory drug (NSAID)-induced mucosal injury. Patients at high risk of NSAID-induced ulcers (ie, older patients, those with a history of ulcer or ulcer complication, those also taking corticosteroids) are candidates to take oral misoprostol 200 mcg 4 times a day with food along with their NSAID. Common adverse effects of misoprostol are abdominal cramping and diarrhea, which occur in 30% of patients. Misoprostol is a powerful abortifacient and is absolutely contraindicated in women of childbearing age who are not using contraception.


This drug is a sucrose-aluminum complex that dissociates in stomach acid and forms a physical barrier over an inflamed area, protecting it from acid, pepsin, and bile salts. It also inhibits pepsin-substrate interaction, stimulates mucosal prostaglandin production, and binds bile salts. It has no effect on acid output or gastrin secretion. Sucralfate seems to have trophic effects on the ulcerated mucosa, possibly by binding growth factors and concentrating them at an ulcer site. Systemic absorption of sucralfate is negligible. Constipation occurs in 3 to 5% of patients. Sucralfate may bind to other drugs and interfere with their absorption.

Drugs Mentioned In This Article

Drug Name Select Trade
sodium bicarbonate No US brand name
esomeprazole NEXIUM
pantoprazole PROTONIX
lansoprazole PREVACID
theophylline ELIXOPHYLLIN
tetracycline ACHROMYCIN V
rabeprazole ACIPHEX
misoprostol CYTOTEC
omeprazole PRILOSEC
nizatidine AXID
ranitidine ZANTAC
famotidine PEPCID
cimetidine TAGAMET
Sucralfate CARAFATE
lidocaine XYLOCAINE
phenytoin DILANTIN
warfarin COUMADIN
diazepam VALIUM
digoxin LANOXIN

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