Proton pump inhibitors ( PPI ) are a group of drugs whose primary action is a reduction in prolonged and pronounced stomach acid production. In the drug class, there is no clear evidence that one agent works better than the other.
They are the most potent acid-secretory inhibitors available. This group of drugs is followed and most are replaced by other drug groups with the same effect, but different mode of action, called H 2 receptor antagonists.
PPI is one of the most widely sold drugs in the world, and the first, omeprazole, is on the WHO Essential Drugs List. The costs between different agents vary significantly.
Video Proton-pump inhibitor
Medical use
These medications are used in the treatment of various conditions, such as:
- Dispepsia
- Peptic ulcer disease is included after endoscopic treatment for bleeding
- As part of Helicobacter pylori eradication therapy
- Gastroesophageal reflux disease (GERD or GORD) includes endoscopic reflux disease-symptomatic reflux and
-
- associated laryngopharyngeal reflux causes laryngitis and chronic cough
- Barrett's esophagus
- Eosinophilic esophagitis
- Stress gastritis and prevention of ulcers on critical care
- Gastrinomas and other conditions that cause acid hypersecretion include Zollinger-Ellison syndrome (often 2-3x regular dosing is required)
Specialized professional organizations recommend that people take the lowest effective PPI dose to achieve the desired therapeutic results when used to treat long-term gastroesophageal reflux disease. In the United States, the Food and Drug Administration has suggested that no more than three 14-day treatment courses should be used within a year.
Despite its extensive use, the quality of evidence supporting its use in some of these conditions varies. The effectiveness of PPI has not been proven for each case. For example, although they reduce the incidence of esophageal adenocarcinoma in Barrett's esophagus, they do not alter the affected length.
Maps Proton-pump inhibitor
Adverse effects
In general, proton pump inhibitors are well tolerated, and the incidence of short-term adverse effects is relatively low. The range and occurrence of side effects are similar for all PPIs, although they have been reported more frequently with omeprazole. This may be due to its longer availability and, therefore, clinical experience.
Common side effects include headache, nausea, diarrhea, abdominal pain, fatigue, and dizziness. Rare side effects include rash, itching, flatulence, constipation, anxiety, and depression. Also rarely, the use of PPIs may be associated with the occurrence of myopathy, including serious reaction rhabdomyolysis.
The long-term use of PPIs requires an assessment of the balance of benefits and therapeutic risks. Various adverse outcomes have been linked to long-term use of PPI in some major reports, but reviews assess the overall quality of evidence in this study as "low" or "very low". They illustrate insufficient evidence to establish a causal relationship between PPI therapy and many of the proposed associations, due to the study design and small effect size estimates. Benefits outweigh the risks when PPIs are used appropriately, but when used improperly, simple risks become important. They recommend that PPIs should be used at the lowest effective dose in people with proven indications, but prevent further doses and advanced chronic therapy in people unresponsive to initial empirical therapy.
Nutrition
Gastric acid is important for food breakdown and micronutrient release, and several studies have demonstrated the possibility for impaired iron, calcium, magnesium, and vitamin B 12 absorption. With respect to iron and vitamin B 12 , weak data and several confounding factors have been identified.
Low levels of magnesium can be found in people taking PPI therapy and this may reverse when they switch to the H 2 -receptor antagonist drug.
High doses and/or long-term use of PPIs may lead to an increased risk of fractures not found with short-term low-dose use; The FDA included a warning regarding this on the PPI drug label in 2010.
Gastrointestinal
Several studies have shown a correlation between the use of PPI and infection Clostridium difficile . While contradictory and controversial data, the FDA has sufficient attention to include warnings about this adverse effect on PPI drug labels. Concern has also been raised about spontaneous bacterial peritonitis in older people taking PPI and in people with irritable bowel syndrome taking PPIs; both types of infections appear in this population because of underlying conditions and it is unclear whether this is a PPI class effect. PPI can affect a person to develop the growth of small intestinal bacteria that is too fast or overgrowth of the fungus.
The long-term use of PPIs is associated with the development of benign polyps from the fundus gland (which is different from the polyposis of the fundis gland); These polyps do not cause cancer and heal when the PPI is stopped. There is no association between the use of PPI and cancer or pre-cancer. There is concern that the use of PPIs may mask stomach cancer or other serious gastric problems and doctors should be aware of these effects.
The use of PPI has also been linked to the development of microscopic colitis.
There is also evidence that PPIs use to alter the composition of bacterial populations that inhabit the gut. Although the mechanism by which PPIs cause these changes has not been determined, they may have a role in increasing the risk of bacterial infection with the use of PPIs.
Cardiovascular
Association of PPI use and cardiovascular events have also been studied extensively but clear conclusions have not been made because these relative risks are confounded by other factors. PPI is commonly used in cardiovascular patients for gastric protection when aspirin is administered for its antiplatelet action. An interaction between PPI and clopidogrel inhibitor inhibitor metabolism is known and this drug is also frequently used in patients with heart disease.
One of the recommended mechanisms for cardiovascular effects is that PPI binds and inhibits dimethylargininase, an enzyme that degrades asethmetric dimethylarginine (ADMA), resulting in higher ADMA levels and reduced nitrogen oxide available.
More
Associations have been demonstrated between the use of PPIs and an increased risk of pneumonia, especially within 30 days after initiation of therapy, where it was found to be 50% higher in community use. Other very weak PPI associations have been found, such as with chronic kidney disease and dementia. Since these results come from observational studies, it remains uncertain whether the association is a causal relationship.
Action mechanism
Proton pump inhibitors work by blocking the enzyme system of potassium adenosine adenosine triphosphate (H /K ATPase, or, more commonly, gastric proton pumps) of gastric parietal cells. The proton pump is the terminal stage in gastric acid secretion, which is directly responsible for secreting H ions to the gastric lumen, making it an ideal target for inhibiting acid secretion.
Targeting terminal steps in acid production, as well as irreversible inhibitory properties, results in a class of drugs significantly more effective than H 2 antagonists and reduces gastric acid secretion by up to 99%..
Reducing acids in the stomach can help the healing of duodenal ulcers and reduce the pain of indigestion and heartburn. However, stomach acid is needed to digest proteins, vitamin B 12 , calcium, and other nutrients, and too little stomach acid causes hypochlorhidria.
PPI is given in the inactive form, which is neutral (lipophilic) and readily passes through the cell membrane into intracellular compartments (such as parietal cell canales) with acidic environments. In an acid environment, the inactive drug is protonated and rearranged into its active form. As described above, the active form will be covalent and irreversibly bind to the gastric proton pump, disabling it.
Pharmacokinetics
Omeprazole absorption rate decreases with intake of food at the same time. In addition, the absorption of lansoprazole and esomeprazole decreases and is delayed by food. It has been reported, however, that this pharmacokinetic effect has no significant effect on efficacy.
PPI has a half life in human blood plasma of only 60-90 minutes, but because they covalently bind to the pump, the half-life of their gastric acid secretion inhibition lasts about 24 hours. The dissociation of inhibitory complexes may be due to endogenous antioxidant glutathione effects leading to the release of omeprazole sulfide and enzyme reactivation.
Example
Penghambat pompa proton yang digunakan secara medis:
- Omeprazole (OTC di AS)
- Lansoprazole (OTC di AS)
- Dexlansoprazole
- Esomeprazole
- Pantoprazole
- Rabeprazole
- Ilaprazole (tidak disetujui FDA sejak Mei 2017)
Histori
PPI was developed in 1980 with omeprazole launched in 1988. Most of these drugs are benzimidazole derivatives, associated with omeprazole, but imidazopirin derivatives such as tenatoprazole have also been developed. Potassium-competitive inhibitors such as revaprazan are reversibly blocking the potassium binding sites from proton pumps, acting faster, but not available in most countries.
Society and culture
Cost
In British Columbia, Canada the cost of PPI varies significantly from 0.20 CAD to 2.38 CAD per dose while all the agents in the class seem more or less equally effective.
Regulatory approval
The FDA approved indication comparison table for PPIs is shown below.
References
External links
- MedlinePlus Encyclopedia
Source of the article : Wikipedia
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