What are H2 blockers

H2 blockers also called H2 histamine blockers or H2 antagonists, are medicines that work by reducing the amount of stomach acid secreted by glands in the lining of your stomach. H2 blockers block histamine-induced gastric acid secretion from the parietal cells of the gastric mucosa (lining of the stomach).

H2 blockers are FDA-approved for short-term use in the treatment of uncomplicated gastroesophageal reflux disease (GERD), gastric or duodenal ulcers, gastric hypersecretion, and for mild to infrequent heartburn or indigestion ¹.

H2 blockers may also be used off-label for stress ulcer prophylaxis, esophagitis, gastritis, gastrointestinal hemorrhage, or urticaria ¹. H2 blockers are also sometimes included in a multidrug regimen for Helicobacter pylori eradication ². Although antacids are generally considered first-line agents for heartburn during pregnancy, H2 blockers are pregnancy category B with no known teratogenic effects and may be used if needed ³. H2 blockers have also been shown to be safe for use in children or adolescents with mild or infrequent heartburn symptoms that do not respond to lifestyle changes ⁴. The overall therapeutic effectiveness of H2 blockers greatly depends on the severity of gastric disease, dosage regimen, and duration of therapy.

There are currently four FDA-approved H2 blockers for use in the United States available either over-the-counter (OTC) or by prescription only. Famotidine, ranitidine, and cimetidine are all available either OTC or by prescription, depending on the dose. Nizatidine is available by prescription only.

H2 blockers are used to:

• Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This is a condition where food or liquid moves up from the stomach into the esophagus (the tube from the mouth to the stomach).
• Treat a peptic or stomach ulcer.

H2 blockers are most often taken by mouth. You can get them in the form of tablets, liquids, or capsules.

• H2 blocker medicines are most often taken with the first meal of the day. In some cases, you may also take them before your evening meal.
• It takes 30 to 90 minutes for the medicines to work. The benefits will last several hours. People often take the drugs at bedtime, as well.
• Symptoms may improve for up to 24 hours after taking a H2 blocker.

H2 blockers may be bought in lower doses at the store without a prescription. If you find yourself taking these most days for 2 weeks or more for acid reflux symptoms, make sure you see your health care provider about your symptoms.

If you have a peptic ulcer, your doctor may prescribe H2 blockers along with 2 or 3 other medicines for up to 2 weeks.

If your doctor prescribed these H2 blockers for you:

• Take all of your medicines as your doctor told you to. Try to take them at the same time each day.
• DO NOT stop taking your medicines without talking to your doctor first. Follow up with your provider regularly.
• Plan ahead so that you do not run out of medicine. Make sure you have enough with you when you travel.

H2 blockers types

There are different names and brands of H2 blockers. All are available over the counter (OTC) without a prescription. Most work equally as well. Side effects may vary from drug to drug.

• Famotidine (Pepcid AC, Pepcid Oral)
• Cimetidine (Tagamet, Tagamet HB)
• Ranitidine (Zantac, Zantac 75, Zantac Efferdose, Zantac injection, and Zantac Syrup)
• Nizatidine Capsules (Axid AR, Axid Capsules, Nizatidine Capsules)

H2 blockers mechanism of action

H2 blockers decrease gastric acid secretion by reversibly binding to histamine H2 receptors located on gastric parietal cells, thereby inhibiting the binding and action of the endogenous ligand histamine. Normally, after a meal, gastrin stimulates the release of histamine, which then binds to histamine H2 receptors and leads to gastric acid release. H2 blockers suppress both stimulated and basal gastric acid secretion that is induced by histamine ⁵. The onset of gastric relief provided by H2 blockers is approximately 60 minutes with a duration of action that ranges from 4 to 10 hours, making them useful for the on-demand treatment of occasional symptoms. All H2 blockers have similar efficacy in decreasing gastric acid secretion ⁶.

Proton pump inhibitors vs H2 blockers

Proton pump inhibitors are like H2 blockers, but stronger. They include omeprazole and pantoprazole. Compared to proton pump inhibitors, H2 blockers pose a minor risk for the development of bacterial overgrowth and infections ⁷.

H2 blockers side effects

H2 blockers are generally well-tolerated. Mild side effects may include headache, drowsiness, fatigue, abdominal pain, constipation, or diarrhea ⁸. The use of H2 blockers in patients with renal impairment, hepatic impairment, or who are greater than 50 years of age has been associated with central nervous system side effects such as delirium, confusion, hallucinations, or slurred speech. Cimetidine has been linked as the most frequent cause of these symptoms, although similar effects have also been seen with ranitidine and famotidine ⁹.

Side effects from H2 blockers are rare.

• Famotidine. The most common side effect is headache.
• Cimetidine. Side effects are rare. But diarrhea, dizziness, rashes, headaches, and gynecomastia may occur.
• Ranitidine. The most common side effect is headache.
• Nizatidine. Side effects are rare.

Drug interactions with H2 blockers may occur. As a result of the therapeutic increase in gastric pH, absorption of drugs requiring an acidic environment for dissolution may be altered. Cimetidine is a potent cytochrome P450 (CYP450) enzyme inhibitor and should be avoided with other drugs that are metabolized by CYP450 enzymes such as theophylline, selective serotonin reuptake inhibitors, or warfarin. Prolonged, high doses of cimetidine have also been linked to gynecomastia, reduced sperm count, and impotence in men and galactorrhea in women. This typically resolves with drug discontinuation. Today, cimetidine is generally avoided as a therapeutic recommendation for gastric symptoms ¹⁰.

The use of H2 blockers on a scheduled basis may result in tachyphylaxis or tolerance, which may limit their use as maintenance therapy for GERD symptoms. Tolerance to the effects of H2 blockers can occur within 7 to 14 days of continued treatment. Intermittent, or as needed, use of H2 blockers may help prevent the development of tachyphylaxis ¹¹.

If you are breastfeeding or pregnant, talk to your doctor before taking these medicines. If you have kidney problems, DO NOT use famotidine without talking to your doctor.

Tell your doctor about other medicines you are taking. H2 blockers may change the way certain drugs work. This problem is less likely with cimetidine and nizatidine.

H2 blockers are eliminated by a combination of hepatic and renal metabolism. Famotidine, ranitidine, and nizatidine all require dose adjustment for patients with a creatine clearance less than 50 mL/min, while cimetidine doses should be reduced for patients with a creatine clearance less than 30 mL/min. The half-life of cimetidine may be prolonged in patients with hepatic impairment, but for all H2 blockers, no dose adjustments are required for hepatic impairment unless also accompanied by renal impairment.

Rarely, QT-prolongation or central nervous system effects have been observed in patients with impaired renal function whose dose was not properly adjusted. Famotidine should be used with caution during renal impairment and in combination with other QT-prolonging medications or conditions. Elderly patients should also be monitored for central nervous system side effects such as dizziness or confusion that may result from decreased drug clearance ¹².

H2 receptor antagonists overdose

Symptoms of an H2 receptor antagonist overdose are:

• Abnormal heartbeat, including rapid or slow heartbeat
• Drowsiness, confusion
• Diarrhea
• Difficulty breathing
• Dilated pupils
• Flushing
• Low blood pressure
• Nausea, vomiting
• Slurred speech
• Sweating

What to expect at the emergency room

Take the container with you to the hospital, if possible.

You doctor will measure and monitor the person’s vital signs, including temperature, pulse, breathing rate, and blood pressure. Symptoms will be treated. The person may receive:

• Activated charcoal
• Blood and urine tests
• Breathing support, including oxygen
• Chest x-ray
• ECG (electrocardiogram, or heart tracing)
• Intravenous fluids (through a vein)
• A laxative
• Medicine to treat symptoms
• Tube through the mouth into the stomach to empty the stomach (gastric lavage)

Prognosis

Serious complications are rare. These are generally safe medicines, even when taken in large doses.

References

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