Proton pump inhibitors (PPIs) are among the most widely used drugs in the world. These drugs, called gastroprotectors, are used in the treatment of gastroesophageal reflux disease, but not only. Due to their ability to effectively reduce stomach acid secretion, they are used in many other acid-related conditions, such as therapy eradicating Helicobacter pylori infection, treatment for the prevention and healing of peptic ulcer disease and gastroprotection in patients taking for example non-steroidal anti-inflammatory drugs (NSAIDs) and anti-aggregants.
What are they
Proton pump inhibitors (PPIs) are drugs that serve to reduce the acidity of gastric juices.
In particular, they belong to the category of antisecretory drugs, so called because they act by blocking the secretion of hydrochloric acid by the stomach cells responsible for this task (parietal cells).
Other commonly used antisecretory drugs are H2 receptor antagonists, designed to block the action of histamine on the parietal cells of the stomach, decreasing the release of hydrochloric acid.
How they work
Proton pump inhibitors stably block the enzyme H+/K+-ATPase (hydrogen-potassium adenosine triphosphatase), known as “proton pump”, on whose action depends the release of hydrochloric acid by the parietal cells of the gastric mucosa. The proton pump is a membrane protein present in the so-called secretory canaliculi of the membrane of the parietal cells of the stomach.
Proton pump inhibitors are actually “pro-drugs” as they require activation in an acidic environment. Their activated form binds to the enzyme H+/K+-ATPase, irreversibly inactivating the proton pump. Gastric acid secretion resumes only when new H+/K+-ATPase molecules are synthesized and expressed. In this way, despite the fact that proton pump inhibitors have a plasma half-life (a parameter that indicates the time required to reduce the plasma concentration of a drug by 50 percent) of less than two hours, they are able to suppress acid secretion for a prolonged time (24-48 hours).
Given their mechanism of action, these drugs block the proton pump regardless of the different stimuli that can activate it both in basal conditions (fasting) and following food intake, thus being very effective in counteracting gastric hyperacidity regardless of its causes.
Since an acidic pH is required in the canaliculi of parietal cells to activate the gastroprotector molecule, and since food stimulates the production of gastric acid, drugs of this class should be administered at least 30 minutes before meals.
Not all proton pumps or all parietal cells are active at the same time, so the maximum abolition of gastric acid secretion is achieved after repeated dosages of the drug. For example, it takes two to five days of full-dose therapy of the drug, taken once a day, to achieve a 70 percent inhibition. If, on the other hand, you take the drug twice a day, the time it takes to achieve complete inhibition decreases. However, it seems that this strategy does not improve the result, so generally we opt for a single daily administration.
What are they?
The molecules belonging to the group of proton pump inhibitors currently available in Italy are five: omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole.
There are also formulations that do not require a prescription and are therefore suitable for alutomedication.
These molecules have shown overlapping efficacy: the choice of the most suitable drug must therefore be evaluated from time to time based on the characteristics of the individual active ingredient. For example, the doctor may prefer the prescription of pantoprazole in patients who also take other therapies, since this drug has fewer drug interactions, while lansoprazole could be indicated in case of acute events since it is characterized by a greater rapidity in resolving symptoms.
Directions
Proton pump inhibitors are used in the treatment of various conditions and diseases related to gastric hyperacidity such as acid-related dyspepsia, gastroduodenal ulcer and Zollinger-Ellison syndrome. The latter is a serious pathology (fortunately rare) characterized by an increase in the secretion of gastric acids, peptic ulcerations and a high concentration of gastrin in the blood (secondary phenomena to the presence of a gastrin or gastrinoma secreting tumor).
These gastroprotectors are also used for the treatment and prevention of esophagitis associated with gastroesophageal reflux disease, for the treatment and prevention of gastroduodenal ulcer during therapies with non-steroidal anti-inflammatory drugs (NSAIDs), and in addition to antibiotics, in the treatment for the eradication of Helicobacter pylori. In addition, recent data suggest that high-dose proton pump inhibitor therapy may prevent the development of esophageal adenocarcinoma in patients with Barrett’s esophagus (a pathological form found in 8-20 percent of gastroesophageal reflux patients, considered a true precancerosis).
In selected cases, proton pump inhibitors can also be used, on the recommendation of the pediatrician, in children. Gastroesophageal reflux disease, in particular, is very frequent in children: about 70 percent of babies at the fourth month of life have a physiological reflux due to liquid feeding and immaturity of the cardia, the valve placed between the esophagus and stomach that should prevent the ascent of food. Typically, this problem resolves by the 12th-18th month with the introduction of solid foods and the maturation of the cardia. However, a minority of children may continue to have regurgitation and discomfort and develop gastroesophageal reflux disease. In these cases, treatment with proton pump inhibitors may be considered, while in healthy children under one year of age regurgitation and/or vomiting, in the absence of alarm symptoms, can be alleviated with postural and dietary measures without the need for drug therapy.
The only proton pump inhibitor approved in the pediatric age is omeprazole, while no drug of this class is expressly approved for use in pregnant women.
As mentioned, the power and effectiveness of the different proton pump inhibitors are very similar. When administered once daily at standard dosages, they allow healing, verified by endoscopy, in most patients (more than 90 percent) with duodenal ulcer, gastric ulcer and gastroesophageal reflux disease.
These drugs are available in different dosages. The optimal dosage to be used is typically between 20-40 mg in the treatment of peptic ulcer disease and moderate-to-severe gastroesophageal reflux disease and 15-20 mg in the prevention of gastropathy by nonsteroidal anti-inflammatory drugs (NSAIDs), in mild forms of gastroesophageal reflux disease and in maintenance therapy.
Effects
Typically, proton pump inhibitors are well-tolerated drugs, which infrequently give side effects. Among these the most common are headache, diarrhea, abdominal pain and nausea.
In recent years, however, their safety profile has been questioned by several studies that have linked their chronic use to major adverse reactions.
Some observational studies have suggested an association between their intake and the risk of pneumonia, diabetes, osteoporosis, intestinal infections, cerebrovascular events, chronic kidney failure and even dementia. Other studies have partially disproved these suspicions, indicating that when these drugs are prescribed appropriately, with the right indications, the benefits far outweigh the potential risks. There remains only the doubt about some forms of gastrointestinal infections (in particular those from Clostridium difficile), a topic worthy of further observation before drawing conclusive considerations.
Before prescribing them, sometimes superficially as often happens in the elderly, it must however be borne in mind that proton pump inhibitors reduce the acid secretion of the stomach, a useful function for example because it helps absorb some important substances, such as calcium and iron, and because it reduces the amount of bacteria we introduce with food, creating a kind of gastric barrier and thus reducing the risk of intestinal infections. Great caution is therefore required, especially if they are expected to be used for long periods of time.
To be taken into account during treatment with proton pump inhibitors is also the possibility that they interfere with the metabolism of other drugs (anticoagulants, contraceptives, antiepileptics, cardiotonics, antibiotics, psychotropic drugs, etc.) taken in the same period and that they can limit the intestinal absorption of some nutrients (in particular vitamin B12).
Finally, their use should be evaluated with caution in case of liver failure, renal failure, pregnancy and lactation.
Joycelyn Elders is the author and creator of EmpowerEssence, a health and wellness blog. Elders is a respected public health advocate and pediatrician dedicated to promoting general health and well-being.
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