MSD Manual

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Professional Version

Gastrointestinal Drugs (Toxicity)


Safdar A. Khan

, DVM, MS, PhD, DABVT, ASPCA Animal Poison Control Center, Urbana, Illinois

Reviewed/Revised Aug 2014 | Modified Nov 2022

H2-Receptor Antagonists

H2-receptor antagonists are structural analogues of histamine, commonly used to treat GI ulcers, erosive gastritis, esophagitis, and gastric reflux. They act at the H2 receptors of parietal cells to competitively inhibit histamine, reducing gastric acid secretions during basal conditions and when stimulated by food, amino acids, pentagastrin, histamine, or insulin. Cimetidine, famotidine, nizatidine, and ranitidine are examples of this group, also commonly referred to as H2 blockers. These drugs are rapidly absorbed, reaching peak plasma concentrations within 1–3 hr. Ranitidine is widely distributed throughout the body. H2 blockers are primarily metabolized in the liver. Nizatidine, famotidine, and ranitidine are excreted in the urine as metabolites and unchanged drug, whereas cimetidine is eliminated in feces. The elimination half-life for these drugs is short (~2.2 hr). Because cimetidine may inhibit the hepatic microsomal enzyme system, ingestion of an H2 blocker may result in reduced metabolism of certain drugs, including β blockers, calcium channel blockers, diazepam, metronidazole, and theophylline.

H2 blockers have a wide margin of safety, with acute oral overdoses typically resulting in minor effects such as vomiting, diarrhea, anorexia, and dry mouth. Serious adverse effects, such as tremors, hypotension, and bradycardia, are more likely to occur with IV H2-blocker overdoses. The minimum lethal dose of famotidine in dogs is >2 g/kg, PO, and 300 mg/kg, IV. Single oral doses of nizatidine at 800 mg/kg in dogs were not lethal. Most exposures require only monitoring for development of GI signs and supportive care, although massive overdoses may also warrant decontamination.


Antacids come in pill and liquid forms and are frequently used to treat GI upset. Common antacids include calcium carbonate, aluminum hydroxide, and magnesium hydroxide (milk of magnesia). These agents are poorly absorbed orally. Calcium- and aluminum-containing antacids generally cause constipation, whereas magnesium-containing antacids tend to cause diarrhea. Some products contain both aluminum and magnesium salts in an attempt to balance their constipating and laxative effects. Acute single ingestion of calcium salts may cause transient hypercalcemia but is unlikely to be associated with significant systemic effects. Induction of emesis within 2–3 hr of exposure may help prevent severe GI upset.

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