An Overview of H2 Receptor Antagonists for Reflux
Histamine type 2 receptor antagonists — also known as H2 blockers — are used to treat gastroesophageal reflux disease (GERD) and ulcers. Up to 60% of the US population experiences pain and discomfort from acid reflux. GERD symptoms may commonly include:
- Difficulty swallowing;
- Gas and bloating;
- Pain and discomfort;
- Intolerance of certain foods or liquids.
Atypical symptoms may include:
- Hoarseness or laryngitis;
- Asthma or asthma-like symptoms;
- Chronic dry or irritated throat;
- Persistent cough;
- Burning in the mouth or throat;
- Discomfort in the ears or nose;
- Trouble sleeping.
What Are H2 Blockers?
H2 blockers treat duodenal and gastric ulcers, gastroesophageal reflux disease, acid indigestion, sour stomach, and common heartburn. Histamine type 2 receptor antagonists were developed in the early 1990s and have been made available as both over-the-counter and prescription medications.
How Do H2 Blockers Work?
H2 blockers decrease the amount of acid produced in the stomach by binding to the histamine type 2 receptors on the surface of gastric cells. After a meal, gastrin stimulates the release of histamine and begins the cycle of gastric acid release to help the body breakdown and digest food and to kill germs and bacteria.
For some, the causes of GERD may be reflux chemistry or physical anatomy. Symptoms may be exacerbated by an excess of stomach acid, which can break down the barrier protecting the rest of the body from damage caused by stomach acid, causing irritation and pain through heartburn or ulcers. By binding to the cells, the histamine type 2 receptor antagonists interfere with and suppress gastric production and secretion and can reduce secretion by 70% in 24 hours.
Types of H2 Blockers
There are four types of H2 receptor blockers that are acknowledged by the Food and Drug Administration for treatments of gastric ulcers, gastroesophageal reflux disease, acid-peptic disease, and the prevention of stress ulcers and heartburn.
- Cimetidine is the H2 blocker that was the first introduced to clinical practice. Cimetidine is available by prescription and over-the-counter under differing generic and brand names such as Tagamet or Tagamet HB, as well as intravenous and intramuscular forms.
- Ranitidine is the second H2 blocker that was introduced into clinical practice.
Ranitidine has historically been available by prescription and over the counter formulas under differing generic and brand names such as Zantac, Zantac 75, Zantac syrup, etc., as well as intravenous and intramuscular forms. However, in April of 2020, the FDA requested the removal of all ranitidine products from the market due to ongoing investigations of a human carcinogen contaminate in ranitidine medications. The FDA advises consumers of medicines that contain ranitidine to speak with their healthcare professionals about discontinuing treatments with ranitidine and switching to an approved medication.
- Famotidine is the third H2 blocker that was introduced to clinical practice. Lower doses are commonly used for heartburn and indigestion therapy. Famotidine is typically less likely to cause drug-to-drug interactions than cimetidine. Famotidine is available by prescription and over-the-counter under different generic and brand names, such as Pepcid AC or Pepcid Oral, as well as intravenous and intramuscular forms.
- Nizatidine is the fourth H2 blocker that was introduced to clinical practice.
Nizatidine is available by prescription and over the counter formulas under differing generic and brand names such as Axid AR, Axid Capsules, Nizatidine Capsules.
H2 Blocker Side Effects
While H2 blockers have generally been well-tolerated there are some side effects that may include:
- Abdominal pain;
- Muscle aches.
For those with renal impairment, hepatic impairment, or who are over 50, there may be some nervous system side effects such as:
- Slurred speech.
Some symptoms require immediate medical attention and the user should cease taking any H2 blockers abruptly. These include:
- Trouble or pain when swallowing food,
- Vomiting with blood;
- Bloody or black stool.
There are also some drug-to-drug interactions that may occur from the administration of H2 blockers, including digoxin, warfarin, oral contraceptives, isoniazid, and phenytoin. It is important to consult with your healthcare provider before taking cimetidine to ensure that cimetidine is safe for use. There have also been some clinical cases of liver injury reported by patients using H2 blockers which vary by H2 blocker type:
- Cimetidine: highly likely cause of clinically apparent liver injury.
- Ranitidine: a very likely but rare cause of clinically apparent liver injury.
- Famotidine: a probably rare cause of clinically apparent liver injury.
- Nizatidine: a possible rare cause of clinically apparent liver injury.
What Are the Benefits of H2 Blockers?
H2 blockers are easily available over-the-counter at most pharmacies, making them an easy solution for heartburn relief, indigestion, or acid indigestion. H2 blocker medications are most often taken orally with the first meal of the day. It may take only 30-90 minutes for the H2 blocker to start working, and the benefits may up to 24 hours after dosage. Healthcare providers may prescribe H2 blockers alongside other medications during treatment for peptic ulcers.
What Are the Risks of H2 Blockers?
While some may experience mild to moderate symptoms associated with H2 blockers, there may be safety issues relating to long-term treatment. High doses of cimetidine may cause reversible impotence or gynecomastia and may interact with many other medical drug prescriptions. Long-term use of H2 blockers for acid suppression may include the risk of proliferation of gastric flora and hyperplasia which may result in gastric malignancy.
Alternatives to H2 Blockers for Treating GERD
Treatment options for GERD vary by case and severity of symptoms. Some patients may experience relief from changes in lifestyle and eating habits. This may include discovering what foods to limit or avoid, or changing sleeping positions to keep the head elevated.
Medication therapy, such as H2 blockers or proton pump inhibitors, limits the production of acid in the stomach and is commonly used to treat acid reflux, ulcers, heartburn, and inflammation. While taking medication can relieve symptoms, they are sometimes accompanied by side effects, or may not be available to patients who are breastfeeding or have underlying liver issues.
Surgical options for GERD are available for patients that do not wish to take acid suppression medications for extended periods or as a life long treatment. A transoral incisionless fundoplication — TIF procedure reconstructs the antireflux valve. The procedure of TIF typically takes less than an hour, is often covered by insurance, and has clinical results that show improved quality of life and removal of dependence on medical therapies.
All therapy options for GERD should be consulted with your doctor or health care provider. Making changes to your lifestyle, taking medication, or considering surgery may all have impacts on your health that should be addressed with a medical professional.