Proton pump inhibitors belong to a group of drugs that are among the strongest sellers worldwide. The drugs inhibit the proton-potassium pump, an enzyme that acts as a proton pump in the occupant cells of the stomach to produce and release stomach acid. The drugs are therefore used primarily to treat complaints and diseases that may be associated with increased gastric acid production.
What are proton pump inhibitors?
Proton pump inhibitors, also called proton pump inhibitors (PPIs) or simply acid blockers, inhibit the proton-potassium pump in the occupant cells of the stomach lining. This is the enzyme H+/K+-ATPase, which is responsible for the expulsion of protons (H+) and the introduction of K+ ions in the gastric vestibular cells. The protons combine with negative chloride ions to form hydrochloric acid (HCl). The required energy is obtained from the conversion of ATP (adenosine triphosphate) to ADP (adenosine diphosphate). By inhibiting or blocking this process, most of the hydrochloric acid production in the stomach is prevented. The so-called vestibular cells or parietal cells are located in certain areas of the gastric mucosa. In addition to hydrochloric acid, they also release the important intrinsic factor that binds acid-sensitive vitamin B12 to itself in the stomach and carries the vitamin to the terminal part of the small intestine, where it is released and subsequently reabsorbed.
Pharmacological effects on the body and organs
Proton pump inhibitors provide blockade of H+/K+-ATPases in the gastric mucosal vestibular cells. The specific ATPases are transmembrane proteins that excrete positively charged hydrogen ions (protons) from the cytoplasm against an electrochemical gradient and introduce positive K+ ions into the cytoplasm. The “transmembrane lock enzyme” obtains the necessary energy via a hydrolytic cleavage of a phosphate residue from ATP, which thereby becomes ADP with only two phosphate residues. Since all known proton pump inhibitors are acid-sensitive, they are offered in enteric-coated form. The drugs are not released and absorbed until they reach the small intestine. Via the bloodstream, the active ingredient of the PPIs enters the vestibular cells and blocks the H+/K+-ATPases directly in the secretory outflow tracts of the vestibular cells. Because of the long distance that the drug has to travel via the stomach, small intestine and bloodstream before it can take effect in the occupant cells, it takes about one and a half hours after taking the preparation for the effect to set in. The irreversible blockade of the enzyme causes a sharp reduction in hydrochloric acid production in the stomach, which can even come to a complete standstill. As a result, the pH of the digestive juices in the stomach rises sharply and loses its aggressiveness. On the one hand, this is intentional in order to achieve certain effects; on the other hand, the higher pH influences digestion. For example, it makes it more difficult to break down long-chain proteins and absorb certain minerals such as calcium and magnesium. Another effect of the acid blockers occurs in the vestibular cells themselves. In addition to acid production, they are also responsible for the secretion of intrinsic factor. This is a special glycoprotein that binds the acid-sensitive vitamin B12 (cobalamin) from the food pulp and carries it to the lower section of the small intestine, where it is released and reabsorbed. PPIs also – unintentionally – decrease the release of intrinsic factor, so that long-term use can lead to problems caused by an undersupply of vitamin B12.
Medical use and use for treatment and prevention.
Primarily, proton pump inhibitors are used to treat esophageal reflux and gastric mucosal problems. Frequent reflux of acidic stomach contents into the esophagus often results in inflammation there, and in some cases even in the pharynx. Curbing acid production can provide relief. Individuals who react particularly strongly to stressful situations tend to produce a pathologically increased amount of stomach acid due to an increased concentration of stress hormones. For this reason, PPIs are also commonly used to prevent reflux into the esophagus (food pipe). In the case of gastritis or gastric ulcers, a less acidic environment of gastric juices supports healing.PPIs are also used to support the treatment of duodenal ulcers. Another main area of application is gastroprotection in the long-term use of non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs contain anti-inflammatory agents whose main effect is based on the inhibition of cyclooxygenases (COX), which play an important role in pain sensations. Inhibition of the tissue hormone COX therefore has an analgesic effect, among other things. However, NSAIDs also have inhibitory effects on the formation of mucus in the gastric mucosa, so that the protective effect of gastric mucus is reduced. Therefore, the additional intake of PPIs serves to protect the gastric mucosa by increasing the pH.
Risks and side effects
Short-term use of PPIs is associated with few risks. In rare cases, there are nonspecific symptoms such as abdominal pain, diarrhea, or dizziness and headache, which subside after some time to get used to them. The actual risks occur mainly with long-term therapies. A general problem comes from the higher pH in the stomach. This makes it more difficult to break down large-molecule proteins and to dissolve out minerals and trace elements from the food pulp. Another problem area is the reduction of intrinsic factor due to PPI intake. This is a special glycoprotein that binds the acid-sensitive vitamin B12 (cobalamin) to itself from the food pulp in the stomach and can thus protect it against hydrochloric acid. In the long term, this can lead to a deficiency of vitamin B12 with the development of corresponding deficiency symptoms such as mild to severe neurological problems or arteriosclerosis.
