LACTOLOGY FOUNDATION

Anti-ulcer Drugs and Antacids

1. Introduction

Peptic ulcers (gastric and duodenal) and gastroesophageal reflux disease (GERD) are common conditions resulting from an imbalance between aggressive factors (hydrochloric acid, pepsin, Helicobacter pylori) and mucosal defensive mechanisms (mucus barrier, bicarbonate secretion, prostaglandins).
The main pharmacological groups used include antacids, proton pump inhibitors (PPIs), H₂‑antihistamines, cytoprotective agents and anti‑Helicobacter pylori regimens.

From a lactation standpoint, most anti‑ulcer medicines can be used during breastfeeding with individual risk assessment, careful choice of drug within the class, and monitoring for possible gastrointestinal adverse effects in the nursing infant.

2. Antacids

Mechanism of action

Antacids neutralize gastric hydrochloric acid and increase intragastric pH to approximately 2–4.
Some formulations may stimulate bicarbonate secretion and contribute to protection of the gastric mucosa.

Main representatives

• Almagel (aluminum hydroxide + magnesium hydroxide) – balanced combination with relatively few systemic adverse effects.
• Maalox (aluminum hydroxide + magnesium hydroxide) – very similar to Almagel in composition and clinical use.
• Calcium carbonate – fast onset of action, but associated with a risk of “rebound hyperacidity” after the effect wears off.
• Sodium bicarbonate – rapid but short‑lasting relief with a potential risk of metabolic alkalosis when used excessively.

Adverse effects in adults and considerations in breastfeeding

• Aluminum hydroxide: constipation and hypophosphatemia.
• Magnesium hydroxide: osmotic diarrhea.
• Calcium carbonate: hypercalcemia, milk‑alkali syndrome.

In lactating women, short‑term use of non‑systemic antacids is generally considered compatible with breastfeeding, because systemic absorption of aluminum and magnesium from modern preparations is low; nevertheless, prolonged high‑dose use should be avoided and bowel habits of the infant (constipation or diarrhea) should be observed. Sodium bicarbonate‑containing products are usually reserved for occasional use only due to systemic alkalinizing potential and high sodium load, which may be undesirable in mothers with cardiovascular or renal comorbidity.

Clinical use

Antacids are suitable for symptomatic relief of acid dyspepsia and mild GERD, but their effect is relatively short‑lived, and they do not heal ulcers.

3. Proton Pump Inhibitors (PPIs)

Mechanism of action and pharmacokinetics

PPIs irreversibly block the H⁺/K⁺‑ATPase (proton pump) in gastric parietal cells, producing profound and sustained inhibition of gastric acid secretion (intragastric pH often around 6).
Common agents are omeprazole, esomeprazole, pantoprazole, lansoprazole and rabeprazole.
They are prodrugs activated in an acidic environment and therefore should be taken before meals to ensure optimal accumulation in the canaliculi of parietal cells. Esomeprazole has higher bioavailability compared with racemic omeprazole.

Clinical indications

• Treatment and prophylaxis of peptic ulcers.
• GERD and erosive esophagitis.
• Part of Helicobacter pylori eradication regimens in combination with antibiotics.

Adverse effects and lactation aspects

Typical adverse reactions include headache, diarrhea and hypomagnesemia during long‑term therapy, as well as an increased risk of intestinal infections such as Clostridium difficile due to reduced gastric acidity.

In breastfeeding, PPIs are often preferred for sustained acid suppression, and available clinical experience suggests that omeprazole and pantoprazole produce very low levels in breast milk, with low expected exposure of the infant; nonetheless, therapy should be individualized, using the lowest effective dose and regular reassessment of the indication. Monitoring for loose stools, colic or irritability in the infant is advisable, especially in premature or low‑birth‑weight babies, who may be more sensitive to changes in gastric pH and microbiota.

4. H₂‑Antihistamines

Mechanism and representatives

H₂‑antihistamines block H₂‑receptors on gastric parietal cells and thereby reduce secretion of hydrochloric acid.
Ranitidine has been withdrawn from the market in several countries due to contamination with N‑nitrosodimethylamine (NDMA), a probable carcinogen.
Famotidine remains a widely used and generally safer alternative within this class.

Clinical use and safety

They are indicated in the treatment of ulcers and GERD, though they are less potent than PPIs, and for prophylaxis of stress ulcers in hospitalized patients.
Adverse effects include headache, fatigue and, rarely, thrombocytopenia.

In lactating women, famotidine is often considered a suitable option for mild to moderate acid‑related symptoms, as limited data and pharmacokinetic properties suggest low milk transfer; even so, PPIs are usually preferred for long‑term control of severe GERD or complicated ulcers.

5. Cytoprotective Agents

A. Misoprostol (PGE₁ analogue)

Misoprostol is a prostaglandin E₁ analogue that enhances mucosal blood flow and stimulates secretion of mucus and bicarbonate, thus improving the defensive barrier.
Its main indication is the prevention of NSAID‑induced gastric and duodenal ulcers.
Adverse effects include diarrhea and pronounced uterotonic activity, leading to an abortifacient effect; consequently, misoprostol is contraindicated in pregnancy.

From a lactological perspective, use of misoprostol in breastfeeding women must be strictly justified, because prostaglandin analogues may reach breast milk; when prescribed for gastrointestinal protection, dosing should be minimal and duration short, with close monitoring for diarrhea and abdominal cramps in the infant.

B. Sucralfate

Sucralfate forms a protective, adhesive barrier over ulcerated mucosa, shielding lesions from acid and pepsin.
It is used in the treatment of gastric and duodenal ulcers and gastritis.
Adverse effects include constipation; in addition, sucralfate can bind concomitant oral medications in the gastrointestinal tract and reduce their absorption.

Because sucralfate is minimally absorbed systemically, it is generally considered compatible with breastfeeding, with a low theoretical risk for the infant; however, separation of sucralfate and other oral drugs by at least 2 hours is recommended in breastfeeding women receiving multiple medications, to avoid reduced efficacy of concurrent therapies.

6. Anti‑Helicobacter pylori Therapy

Standard regimens

There are around 40 therapeutic protocols described in the literature; however, a limited number of standard triple and quadruple regimens are most commonly used.

Triple therapy (7–14 days):

• PPI (e.g. omeprazole) + clarithromycin + amoxicillin or metronidazole.

Quadruple therapy (for resistant strains or after failure of triple therapy):

• PPI + bismuth + tetracycline + metronidazole.

The main goal is complete eradication of H. pylori in patients with peptic ulcers and chronic gastritis.

Lactation‑related notes

In breastfeeding women, eradication therapy requires careful assessment of the necessity and timing, because multiple antibiotics are involved and some, such as tetracycline, are not recommended during lactation.
When eradication cannot be postponed, regimens based on amoxicillin and clarithromycin combined with a PPI are usually preferred over tetracycline‑containing quadruple therapy, with attention to possible alterations in the infant’s gut flora (diarrhea, candidiasis) and temporary monitoring of breastfeeding tolerance.

7. Clinical Recommendations

• Acute peptic ulcer: PPI (e.g. pantoprazole 40 mg/day) plus H. pylori eradication if infection is confirmed.
• GERD: PPI therapy for 4–8 weeks, followed by individualized maintenance treatment (continuous, on‑demand or step‑down to H₂‑antihistamines), taking into account the breastfeeding status and severity of symptoms.
• NSAID‑induced ulcers: prophylaxis with misoprostol or PPIs in high‑risk patients; in lactating women, PPIs are generally preferred over misoprostol due to a more favorable safety profile for the infant.

Antacids provide useful short‑term symptomatic relief but do not replace PPIs for ulcer healing and long‑term control of GERD. PPIs are considered the gold standard for treatment of peptic ulcers and GERD, while H₂‑blockers remain an alternative for mild cases or in patients who cannot tolerate PPIs.
Combination therapy is essential for successful eradication of H. pylori and long‑term remission of ulcer disease, and in lactating women, regimen choice must balance eradication efficacy with antibiotic safety in breastfeeding.