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Proton pump inhibitors – The most important information about gastric acid blockers at a glance

Dr. med. Andre Sommer

Dr. med. Andre Sommer

Proton pump inhibitors (PPI) inhibit stomach acid formation and are used for heartburn, acid regurgitation and gastric mucosal injuries. For this reason, they are colloquially referred to as gastric acid blockers. Their use has grown steadily since their introduction in 1989. Today proton pump inhibitors are among the most prescribed drugs worldwide. Proton pump inhibitors have also been available over the counter in pharmacies for almost 10 years. But with the increasing use, the critical demand and the need for education also increases. This article summarizes the mechanisms of action and indications and presents current research results on attempts at omission and possible side effects.

How do proton pump inhibitors (PPI) work?

Proton pump inhibitors work on our gastric mucosa: we swallow the tablet through our mouth, it passes through the esophagus and gets into the stomach. The stomach wall consists of different cell types with different tasks:

  • Main cells: Breakdown of proteins ingested with food
  • In addition to cells: Formation of mucus on the stomach wall
  • Parietal cells: Formation of hydrochloric acid and release of a factor for Vit B12 intake

Release of the active ingredient in the stomach

Gastric acid blockers do not work directly, but must first be activated with the help of acid. It is particularly acidic in the vicinity of the parietal cells, so the PPI becomes the pharmacologically active sulfenamide.

The hydrochloric acid in gastric juice consists of hydrogen and chloride. The parietal cells of our stomach provide the two ions. A pump sits in the cell wall, which releases hydrogen in exchange with potassium. It is called H+/K+-ATPase.Proton pump inhibitors irreversibly inhibit this pump. The effect lasts until the cell has created new pumps in its wall. Depending on the dose, the effects last about 24-48 hours.

When the parietal cells pump less hydrogen ions into the stomach, less hydrochloric acid forms. The gastric juice becomes less acidic and the pH increases. A pH of three is sought for ulcer healing, and a pH of four for reflux disease.

Better effectiveness of antibiotics

When eliminating the Helicobacter Pylori bacterium, the less acidic gastric juice is capitalized on. The proton pump inhibitors increase the stability and availability of other drugs that have a hard time in the acidic environment of the stomach. In the fight against Helicobacter, proton pump inhibitors increase the local effects of antibiotics.

What diseases are proton pump inhibitors prescribed for?

Proton pump inhibitor for reflux disease

Typical symptoms of reflux disease are:

  • Heartburn
  • Regurgitation of stomach acid

Gastroesophageal reflux disease is by far the the most important and most common Indication for acute and long-term therapy with proton pump inhibitors. In the case of non-erosive reflux disease, proton pump inhibitors can also be used as therapy for symptoms. Symptoms such as coughing, clearing the throat and laryngitis are not among the classic reflux symptoms and are only an indication for gastric acid blockers in exceptional cases or in special patient groups.

Proton pump inhibitor against ulcer disease

An ulcer in the stomach or duodenum is a mucosal defect with ulceration that occurs when there is an imbalance of aggressive stomach acid and protective factors such as mucus and mediators. Proton pump inhibitors are the most effective therapy for ulcer diseases in the gastrointestinal tract. Most ulcer diseases are caused by a bacterial infection with Helicobacter Pyloris or by taking medication.

Proton pump inhibitors to protect against side effects from other medications

Non-steroidal anti-inflammatories are commonly used drugs, including:

  • Aspirin
  • Voltaren
  • Ibuprofen
  • Aaproxen

The side effects of these anti-inflammatories are upper abdominal pain and damage to the mucous membrane in the stomach. Combined therapy with gastric acid blockers therefore makes sense for high-risk patients, but must be weighed individually by the doctor. There is no recommendation for general accompanying therapy with proton pump inhibitors.

Proton pump inhibitor for the elimination of the Helicobacter Pylori bacterium

The bacteria lives in the stomach and must be treated with medication for:

  • Inflammation of the stomach with ulcer
  • Mucosa-associated lymphoma
  • B-cell lymphoma of the stomach
  • Surgical removal of gastric cancer

To eradicate the bacterium, the patient takes proton pump inhibitors and two different antibiotics for one to two weeks. The therapy lasts one to two weeks and is called triple therapy.

Two standard therapies have become established in Germany for Helicobacter pylori eradication:

French scheme: Proton pump inhibitor + clarithromycin + amoxicillin

Italian scheme: Proton pump inhibitor + clarithromycin + metronidazole

Proton pump inhibitor with irritable bowel syndrome

Scientists are still discussing how sensible it is to use proton pump inhibitors for irritable bowel syndrome. In short-term studies, proton pump inhibitors show little therapeutic effects compared to placebos. They work better in patients who complain of upper abdominal pain than those with symptoms such as feeling of fullness. The efficacy for long-term therapies has also not been sufficiently demonstrated.

Rare indications for proton pump inhibitors

Proton pump inhibitors are the first choice medication for Zollinger-Ellison syndrome, a hormone-producing tumor of the pancreas or duodenum. In addition, doctors use proton pump inhibitors in special disease constellations such as weakness of the pancreas or eosinophilic esophagitis.

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For which disease are over-the-counter proton pump inhibitors suitable?

Omeprazole, pantoprazole and esomerazole are available** over the counter in the pharmacy for the treatment of reflux symptoms**. If the symptoms do not improve after two weeks or if the medication has been taken continuously for four weeks, a doctor should be contacted.

Overview of important information about over-the-counter proton pump inhibitors

  • Area of application: heartburn and acid regurgitation
  • Use 1x daily, in the morning before breakfast (preferably at the same time)
  • Use for at least two to three days
  • With complete freedom from symptoms: no further intake
  • The symptoms did not improve after two weeks -> doctor
  • Continuous intake for 4 weeks -> doctor
  • Children and adolescents under the age of 18
  • Pregnant woman
  • Breastfeeding

Please inform your doctor or pharmacist if you are taking the following medications:

  • Warfarin or phenprocoumon (blood thinner)
  • Ketoconazole (against fungal infection)
  • Methotrexate (use in rheumatoid arthritis, psoriasis, cancer)
  • Atazanavir (when treating HIV infection)

Consult with a doctor before taking if the following are present:

  • 4-week treatment (or longer) of heartburn or indigestion in the past
  • Older than 55 years and new **or recently **changed reflux symptoms
  • Older than 55 years and daily **indigestion **that are treated with non-prescription drugs
  • Stomach ulcer or stomach operation in the past
  • Presence of liver problems or jaundice (Yellowing of the eyes or skin)
  • Planned endoscopy
  • Planned urea test for the detection of Helicobacter pyloris

Immediately contact a doctor with the following symptoms, which may indicate a serious medical condition:

  • Accidental loss of weight
  • Vomiting
  • Vomiting blood
  • Blood in the stool
  • Difficulties swallowing
  • Pallor and weakness
  • Chest pain
  • Stomach pain
  • Persistent diarrhea

What are the side effects of proton pump inhibitors?

According to the package leaflets frequent side effects (in one to ten percent of those treated):

  • Stomach pain
  • Diarrhea
  • Vomiting
  • Bloating
  • Constipation
  • Nausea
  • Headache

Similar side effects are also seen in studies with placebos, so they are probably not substance-specific effects.

Broken bones and pneumonia

The question of an increased risk of bone fractures and pneumonia from PPI is not yet finally clarified. Scientists are discussing whether the acid blockage in the stomach reduces the absorption of calcium and vitamin D and thus promotes fractures. Some studies suggest a** slightly increased risk of broken bones. **The same applies to pneumonia, The proton pump inhibitors may only be an indicative marker, since the risk of broken bones and pneumonia is increased in many patients.

Heart attack and kidney failure

Here, too, there are studies speculating on an increased risk. The interpretation of the available data is currently being discussed very critically. **Heart attack and kidney failure could be associated with taking **proton pump inhibitors. However, this does not mean that gastric acid blockers contribute to the development of the disease.

Dementia

A Bonn study from 2016 linked proton pump inhibitor therapy to dementia. The worldwide sensation and the letters from the readers prompted a supplementary article that warned against overly rapid reactions. A removal of **proton pump inhibitors from use for therapy would not be justified at the moment**. In the meantime, there has been a large Finnish study that was unable to establish a connection between taking proton pumps and dementia. In addition, several studies examined the cognitive abilities of patients after long-term proton pump inhibitor use. They also found no restrictions in the patients.

Can you stop long-term proton pump inhibitor therapy?

Observations in recent years show that proton pump inhibitor therapies that were started in the hospital are sometimes continued uncritically by the family doctor. Proton pump inhibitor therapy can also be discontinued or the dose reduced after long-term use. In patients with gastric mucosal ulcers, permanent withdrawal is more successful than in patients with reflux disease. Around 50 percent can stop stomach acid blockers in the long term without relapses. If the symptoms start again, then usually after a week. It is unclear whether a slow discontinuation is better than an abrupt termination of therapy.

Possible strategy for ending proton pump inhibitor therapy

  • Day 1-7: Halve the dose
  • Day 7-14: Take only every other day
  • Day 15: no further intake

Note: Discontinuation of long-term proton pump inhibitor therapy should only be started after consulting a doctor

What alternative is there to proton pump inhibitors?

H2 antihistamines are the second-line medication for reflux and gastric mucosal ulcer. They act on a histamine receptor on the parietal cells of our stomach and reduce the production of hydrochloric acid. Their side effect profile is less favorable than gastric acid blockers.

The probably most effective and low side effect alternative is nutritional therapy. In such therapy the patient finds out which foods they tolerate best. The causes of the symptoms can of course be combated in this way. Statutory health insurance companies in Germany reimburse such therapy in many cases.

Mössner, J. (2016). Indikationen, Nutzen und Risiken von Protonenpumpeninhibitoren. Eine Bestandsaufnahme nach, 25, 477-483. Downloaded on 19.05.2018 from https://www.aerzteblatt.de/archiv/180624/Indikationen-Nutzen-und-Risiken-von-Protonenpumpeninhibitoren

Koop, H. (2018). Verordnungspraxis und Risiken von Protonenpumpenblockern–Fiktion und Fakten. Zeitschrift für Gastroenterologie, 56(03), 264-274. Download on 19.05.2018 from https://www.thieme-connect.com/DOI/DOI?10.1055/s-0043-125340

Klotz, U. (2005). Pharmakologie der Protonenpumpenhemmer: Aus der Sicht eines klinischen Pharmakologen. Pharmazie in unserer Zeit, 34(3), 200-204. Downloaded on 22.05.2018 from: https://onlinelibrary.wiley.com/doi/abs/10.1002/pauz.200500119

Dr. med. Andre Sommer

Dr. med. Andre Sommer

I’m André, a medical doctor from Berlin. Together with a team of medical doctors, nutritionists and data scientists we empower people to understand digestive issues with our app Cara Care.

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