Proton Pump Inhibitors (PPIs)

Millions of people across the world suffer from stomach acid-related health conditions.

Proton pump inhibitors are one of the most frequently used medications in the world. The FDA estimates that one in 14 American adults takes PPIs.

Millions of people take PPIs for short-term relief with no health complications. However, the risk of taking PPIs only appears when they’re taken long-term.

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Jump to topic
  • What Are Proton Pump Inhibitors?
    • What Kinds of Proton Pump Inhibitors Are There?
    • How Do Proton Pump Inhibitors Work?
  • What Do Proton Pump Inhibitors Treat?
    • What Is Acid Reflux?
    • What Is Heartburn?
      • What Are the Symptoms of Heartburn?
      • When Should I See a Doctor?
    • What Is GERD?
      • What Are the Symptoms of GERD?
    • What Is Esophagitis?
      • What Are the Symptoms of Esophagitis?
    • What Are Peptic Ulcers?
      • What Are the Symptoms of Peptic Ulcers?
    • What Is Zollinger-Ellison Syndrome?
      • What Are the Symptoms of Zollinger-Ellison Syndrome?
  • What Are the Side Effects of Taking PPIs?
    • What Are the Risks of Taking Proton Pump Inhibitors?
  • How are PPI Manufacturers Responsible?

What Are Proton Pump Inhibitors?

Proton pump inhibitors are a type of medication prescribed to treat health conditions related to stomach acid, particularly those involving an excess of stomach acid. They’re the most popularly prescribed drug for stomach acid-related woes, outstripping the sales of H2 blockers and other medications that are prescribed to treat similar conditions.

Proton pump inhibitors were first approved by the FDA in 1988. The first one to be approved was omeprazole, the generic name for Prilosec. PPIs were developed throughout the 1980s after it was discovered in the 1970s that it was the gastric proton pump on the gastric parietal cells that was the final step in the process of stomach acid production. Once the process of how gastric acid was made had been discovered, drug manufacturers began to develop medications that could reduce the amount of stomach acid by blocking the final step in its production.

What Kinds of Proton Pump Inhibitors Are There?

There are several different types of proton pump inhibitors. They include:

  • Dexlansoprazole (Dexilant)
  • Esomeprazole (Nexium)
  • Lansoprazole (Prevacid)
  • Omeprazole (Prilosec)
    • Immediate release version of omeprazole (Zegerid)
  • Pantoprazole (Protonix)
  • Rabeprazole (Aciphex)

Of these, the most common are Nexium, Prevacid, and Prilosec. Some of the brand names are available in their generic forms as well. The generic names end in -prazole, while the brand names do not. Some of the brand names, such as Prilosec OTC, are available for purchase over the counter, while others may require a prescription from a doctor.

How Do Proton Pump Inhibitors Work?

Proton pump inhibitors work differently from antacids. While antacids work by neutralizing acid that already exists in the stomach, proton pump inhibitors prevent the acid from being produced in the first place.

Proton pump inhibitors work by reducing the amount of stomach acid the body produces. PPIs block the H+/K+ ATPase (hydrogen/potassium adenosine triphosphatase) enzyme system from producing more stomach acid. Another name for H+/K+ ATPase is the gastric proton pump. This enzyme is located on the gastric parietal cells, which are the cells in the stomach that are responsible for the production of hydrochloric acid (HCl), which is one of the gastric acids the stomach produces. By binding to the gastric parietal cells and blocking this enzyme, proton pump inhibitors stop the production of hydrochloric acid in the stomach.

What Do Proton Pump Inhibitors Treat?

Proton pump inhibitors are intended to treat health conditions caused by excess stomach acid. These conditions can include:

  • Acid reflux
  • Heartburn
  • GERD
  • Esophagitis
  • Peptic ulcers
  • Zollinger-Ellison syndrome

PPIs are most commonly take to ease the symptoms of heartburn, acid reflux, and GERD, all of which are caused by excess stomach acid backing up into the esophagus and irritating the esophageal lining. Both esophagitis and peptic ulcers can form when the lining of the esophagus, stomach, or intestines is exposed to excess gastric acid over time.

What Is Acid Reflux?

Acid reflux occurs when stomach acid backs up the esophagus instead of remaining in the stomach. This happens because the lower esophageal sphincter doesn’t fully close or is abnormally relaxed. Normally, the lower esophageal sphincter stays tight, keeping the end of the esophagus where it meets the stomach closed so that food and drink can’t get through. When you eat or drink, the sphincter relaxes, allowing food and drink to pass through, and then closes again afterward.

However, sometimes the lower esophageal sphincter doesn’t close as it should and acid washes back up from the stomach into the esophagus. This process is called acid reflux. Acid reflux is the cause of heartburn, which is the burning sensation in the chest felt because of the acid irritating the lining of the esophagus. Acid reflux occurring more than twice a week is known as GERD.

What Is Heartburn?

Heartburn is the burning feeling in the chest, behind the breastbone, that occurs when stomach acid washing back up the esophagus. Typically, the pain from heartburn is worse under these circumstances:

  • In the evening
  • When lying down
  • When bending over
  • After eating

Most of the time, heartburn can be treated with over the counter medication or by making lifestyle changes. If heartburn is only occasional and isn’t interfering with living a normal life, then there’s no cause for worry. However, if heartburn is so frequent or so intense that it’s making daily activities difficult, then it’s time to seek medical attention because it could be a sign of a more serious health condition.

What Are the Symptoms of Heartburn?

The symptoms of heartburn can include the following:

  • A burning pain located in the chest that occurs after eating
  • Burning pain in the chest at night
  • Pain in the chest that worsens when bending over or lying down
  • An acidic or bitter taste in the mouth
When Should I See a Doctor?

Heartburn can be a sign of a more serious health condition if it’s frequent or severe. Any of the following symptoms are signs that it’s time to seek medical attention:

  • Heartburn more frequent than twice weekly
  • Difficulty swallowing
  • Persistent nausea
  • Persistent vomiting
  • Weight loss because of:
    • Poor appetite
    • Difficulty eating
  • Over the counter medication doesn’t ease the symptoms

Regardless of other symptoms, anyone experiencing severe chest pain or pressure, especially when it’s combined with pain or numbness in the arm or jaw or if breathing is difficult. These can be signs of a heart attack rather than heartburn.

What Is GERD?

GERD is gastrointestinal reflux disease. Acid reflux becomes GERD when it occurs frequently or more severely rather than only every once in a while. Milder acid reflux is considered GERD if it occurs twice or more weekly. Acid reflux can still be considered GERD if it occurs only once a week if the symptoms are more severe.

For those experiencing more mild forms of GERD, it may be manageable with lifestyle changes. However, some people may require over the counter medication to manage the symptoms. Others with more severe GERD may need to consult a doctor and get a prescription.

What Are the Symptoms of GERD?

The most common symptoms of GERD can be similar to those of heartburn. However, typically GERD is worse because it occurs more frequently. The potential symptoms of GERD can include:

  • Heartburn
    • Typically worse at night or after eating
  • Regurgitation of food
  • Regurgitation of sour liquid
  • Trouble swallowing
  • Chest pain
  • A sensation of a lump in the throat

People who experience acid reflux at night may experience additional symptoms. These can include:

  • Sleep disruption
  • Asthma
    • New if no prior asthma
    • Worsening if prior asthma
  • Laryngitis
  • Chronic coughing

Sometimes chest pain can be a sign of a heart attack, so if chest pain is severe, patients should seek medical attention. Patients should also make an appointment with a medical professional if they experience any of the following:

  • Severe GERD symptoms
  • Frequent GERD symptoms
  • Taking over the counter medications to treat GERD symptoms more than twice weekly

What Is Esophagitis?

Esophagitis is the inflammation of the esophagus. It can occur because of medication, allergies, or an infection, but is also commonly caused by frequent acid reflux. If acid is frequently backing up from the stomach into the esophagus, over time that acid will irritate the esophageal lining. The lining of the stomach is designed to protect the stomach wall from the gastric acid produced in the stomach. The esophagus doesn’t and so is susceptible to irritation and inflammation over time if acid consistently is present in the esophagus.

If esophagitis isn’t treated quickly, it can, over time, result in permanent damage to the esophageal lining. This damage can include the narrowing of the esophagus due to scar tissue forming and difficulty swallowing food.

What Are the Symptoms of Esophagitis?

Symptoms of esophagitis typically include the following:

  • Heartburn
  • Chest pain while eating
  • Acid regurgitation
  • Food impaction (food gets stuck in the esophagus)
  • Difficulty swallowing
  • Pain while swallowing

Esophagitis doesn’t just occur in adults. It can also occur in children who are too young to explain what they’re feeling. Symptoms to keep an eye out for in young children include:

  • Failure to thrive
  • Difficulty eating

People experiencing esophagitis symptoms should consider seeing a doctor if:

  • Symptoms persist for more than a few days
  • Over the counter medications don’t ease symptoms
  • Symptoms are severe enough that it is difficult to eat
  • Esophagitis symptoms are accompanied by symptoms of the flu:
    • Fever
    • Headache
    • Muscle aches

It’s important to see a doctor right away or seek emergency medical care if you experience any of the following symptoms:

  • Chest pain:
    • Lasting longer than a few minutes
    • If you have a history of heart disease
    • That occurs after eating
  • Food is lodged in your esophagus
  • Throat or mouth pain during eating
  • Shortness of breath after eating
  • Vomiting
    • Forceful vomiting
    • Large amounts or vomit
    • Difficulty breathing after vomiting
    • Yellow or green vomit
    • Vomit that looks like coffee grounds
    • Bloody vomit

What Are Peptic Ulcers?

An ulcer is an open sore that develops within an organ of the body. Peptic ulcers are open sores that develop in the stomach or the upper small intestine. There are two types of peptic ulcer:

  • Gastric ulcers
  • Duodenal ulcers

Gastric ulcers occur in the stomach and duodenal ulcers occur in the duodenum, which is the upper part of the small intestine. Peptic ulcers are most frequently caused by a bacterium called H. pylori but can be caused by other factors, including medication. Ulcers can form when there is a thinning in the stomach or intestinal lining, allowing stomach acid to reach the organ wall, where the open sore can form.

Some factors can make ulcers worse, even though they don’t cause them. These can include:

  • Spicy foods
  • Stress
  • Smoking
  • Alcohol

What Are the Symptoms of Peptic Ulcers?

Stomach pain is the most common symptom of a peptic ulcer. That’s not the only symptom, however. Signs of a peptic ulcer can include:

  • Heartburn
  • Nausea
  • Burning pain in the stomach
  • Fatty food intolerance
  • Feeling full
  • Bloating
  • Belching

Most people, if they experience symptoms of an ulcer at all, experience only the stomach pain. Sometimes, people can have peptic ulcers and experience no symptoms, not even realizing that they have an ulcer. However, others experience severe symptoms, which can include:

  • Vomiting
  • Vomiting blood
  • Feeling faint
  • Difficulty breathing
  • Nausea
  • Changes in appetite
  • Inexplicable weight loss

Anyone experiencing the severe symptoms of an ulcer should seek medical attention.

What Is Zollinger-Ellison Syndrome?

Zollinger-Ellison syndrome is a rare condition. In patients with the syndrome, tumors form can form on the pancreas or in the duodenum, or upper small intestine. These tumors aren’t fatal, but they cause the body to start secreting too much gastric acid. The extra acid can cause ulcers, diarrhea, and more. Typically, the syndrome is treated with medication, such as proton pump inhibitors, to decrease the amount of stomach acid the body can produce.

What Are the Symptoms of Zollinger-Ellison Syndrome?

Zollinger-Ellison syndrome can occur at any age but is most common between the ages of 20 and 60. Symptoms to keep an eye out for can include:

  • Acid reflux
  • Heartburn
  • Diarrhea
  • Nausea
  • Vomiting
  • Burping
  • Decreased appetite
  • Unintentional weight loss
  • Digestive tract bleeding
  • A feeling in the upper abdomen of:
    • Gnawing
    • Discomfort
    • Burning
    • Aching

It’s time to see a doctor if a burning, aching feeling in the upper abdomen is persistent, especially if it’s accompanied by nausea, diarrhea, and vomiting. It’s important to inform your doctor if you’ve been treating your symptoms with over the counter medication since they can mask some of the symptoms. It may delay a diagnosis or cause a misdiagnosis if the doctor doesn’t know how truly severe the symptoms are.

What Are the Side Effects of Taking PPIs?

Just like any drug, proton pump inhibitors carry a risk of side effects. The side effects can range from mild to severe. The more common, mild side effects of taking PPIs can include:

  • Dizziness
  • Headache
  • Joint pain
  • Muscle pain
  • An unpleasant aftertaste
  • Stomach pain
  • Nausea
  • Diarrhea
  • Rash or other skin disruption
  • Anxiety

The more severe side effects can include:

  • Erythema multiforme (a severe skin rash)
  • Low magnesium levels
  • Arrhythmia
  • Seizures
  • Muscle spasms
  • Osteoporosis
  • Birth defects
  • Speech disorders
  • Cardiac effects
  • Kidney effects
  • Liver toxicity
  • Hematologic laboratory abnormalities

Anyone experiencing any of the severe side effects should immediately see a medical professional.

What Are the Risks of Taking Proton Pump Inhibitors?

The risks of taking proton pump inhibitors typically appear when the drugs are taken over a longer period of time. The FDA has warned about the following risks:

  • Fractures
  • Hypomagnesemia
  • difficile infection
  • Acute interstitial nephritis
    • Which can lead to kidney failure
  • Interactions with diagnostic investigations into neuroendocrine tumors
  • Vitamin B12 deficiency

There have been studies that have linked PPIs to the following health conditions:

  • Iron deficiency
  • B12 deficiency
  • Heart attack
  • Stroke
  • Pneumonia
  • difficile infection
  • Chronic kidney disease
  • Kidney failure
  • Dementia

Despite the FDA warnings on some of these risks, there has been no black box warning issued by the FDA for proton pump inhibitors. Nor has the FDA issued warnings for such risks as heart attacks, chronic kidney disease, or kidney failure.

How are PPI Manufacturers Responsible?

Manufacturers of proton pump inhibitors are facing lawsuits for a failure to adequately warn patients and doctors about the known risks of taking the medication. They’re also accused of failing to adequately test proton pump inhibitor medications before releasing them on the market. Some PPI manufacturers are also accused of putting profits over patient health and safety by using aggressive marketing techniques.

AstraZeneca, the manufacturer of both Nexium and Prilosec, was sued in 2015 by plaintiffs alleging that the company had introduced Nexium as an improvement to Prilosec for the purpose of maintaining profits after the patent on Prilosec had expired. That lawsuit resulted in a $20 million settlement for the plaintiffs.

There are thousands of other lawsuits ongoing against PPI manufacturers that have not yet been settled. Many of these have been combined into an MDL, or multi-district litigation. The first of these cases will be heard in November of 2020.

Notwithstanding claims relating to this product, the drug/medical device remains approved by the U.S. FDA. 

View Sources

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  3. “Gastroesophageal Reflux Disease (GERD).” Mayo Clinic, Mayo Foundation for Medical Education and Research, 22 May 2020,
  4. “Heartburn.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 17 Apr. 2020,
  5. “Peptic Ulcer.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 6 Aug. 2020,
  6. “Proton Pump Inhibitors: Use in Adults.” Centers for Medicare & Medicaid Services, Centers for Medicare & Medicaid Services Medicaid Integrity Group , Oct. 2015,
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  8. Publishing, Harvard Health. “What You Should Know about: PPIs.” Harvard Health, Feb. 2013,
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