Lansoprazole pantoprazole omeprazole
Proton pump inhibitors (PPIs) are one of the most commonly used drugs in the treatment of routine gastroenterology diseases. Do we really understand the mechanism of action, side effects, and duration of treatment when we apply PPIs in clinical work? The purpose of this article is to help you understand PPI more deeply and regulate the clinical application of PPI.
Mechanism of action of PPI
PPI, i.e. H+-K+-ATPase inhibitor, has strong acid-suppressive effect, high specificity and long duration. The last step of gastric acid secretion is in the proton pump-driven cells in the gastric wall cells, PPI blocks the last channel of gastric acid secretion, and has different action sites and different characteristics compared with the traditional gastric acid inhibiting drugs, i.e. good nocturnal acid inhibiting effect, fast onset of action, strong acid inhibiting effect, long duration, easy to take, and can inhibit the secretion of basal gastric acid and acid secretion caused by histamine, acetylcholine, gastrin and food stimulation. It can inhibit basal gastric acid secretion and acid secretion caused by histamine, acetylcholine, gastrin and food stimulation.
Different types of PPI and their usage
There are 5 types of PPI available, the following is a detailed introduction of PPI usage for peptic ulcer as an example.
1.Omeprazole: It was the first PPI to be marketed in 1988.
(1) Duodenal ulcer: 20 mg/d, PO, usually heals in 2-4 weeks;
(2) Gastric ulcer: 20 mg, qd, po, usually healing in 4-8 weeks.
2. Lansoprazole: marketed in 1992, it is the second PPI marketed.
(1) Duodenal ulcer: 15-30 mg, qd, po, for 4-6 weeks;
(2) Gastric ulcer: 30 mg, qd, po, for 6-8 weeks.
3. Pantoprazole: the 3rd PPI developed by Germany and marketed in 1995.
(1) Duodenal ulcer: 40 mg, qd, po, for 2-4 weeks;
(2) Gastric ulcer: 40 mg, qd, po, for 4-8 weeks; a course of treatment beyond 8 weeks is not recommended.
4. Rabeprazole: the 4th PPI introduced by Japan in 1998.
(1) Duodenal ulcer: 10 mg, qd, po, for 6 weeks;
(2) gastric ulcer: 10 mg, qd, po, for 8 weeks.
5.Esomeprazole: It is the latest PPI, developed and marketed by Germany in 2000.
(1) Duodenal ulcer: 20-40 mg, qd, po, for 4-6 weeks;
(2) Gastric ulcer: 20-40 mg, qd, po, for 6-8 weeks.
The standard of diagnosis and treatment of peptic ulcer disease recommends: 4 weeks for duodenal ulcer and 6-8 weeks for gastric ulcer with PPI treatment.
Strength of different types of PPI
Who is the stronger PPI in terms of acid suppression strength, onset of action and duration of acid suppression? We will introduce them one by one.
1.Acid-suppressing strength: It has been confirmed that the acid-suppressing strength of esomeprazole is significantly higher than other types of PPI, followed by rabeprazole, while the acid-suppressing strength of pantoprazole, lansoprazole and omeprazole is similar.
2, onset of action: rabeprazole has the most binding sites with enzymes, so rabeprazole is the PPI with the fastest onset of action, and can play the maximum acid inhibiting effect within 5 minutes, followed by lansoprazole, omeprazole and pantoprazole again.
3. Duration of acid inhibition: The duration of acid inhibition was measured by monitoring the percentage of time PH>4 within 24 hours after taking the drug, and the results of the study showed that the duration of acid inhibition with oral esomeprazole 40 mg was longer than that with omeprazole 40 mg, lansoprazole 30 mg, and rabeprazole 20 mg.
4. Effectiveness in the treatment of different diseases: Clinical data showed that esomeprazole was superior to other PPI formulations in the treatment of gastroesophageal reflux disease and peptic ulcer caused by NSAIDs, and esomeprazole was superior to omeprazole in the eradication of Helicobacter pylori.
In conclusion, esomeprazole has the strongest acid-suppressive effect, followed by rabeprazole, and pantoprazole and lansoprazole may be superior to omeprazole. In clinical application, the application of acid-suppressive drugs should be individualized according to the patient’s condition needs.
Adverse effects of PPI and its mechanism
The short-term application of PPI is well tolerated, but long-term use may also bring many risks, so let’s talk about the adverse effects.
1. Fracture: Several studies have shown that long-term application of PPI and increasing the dose of PPI can increase the risk of fracture. Possible mechanisms are as follows.
(1) PPI inhibits the secretion of gastric acid, which increases the PH in the stomach and reduces the absorption of calcium;
(2) Some scholars found that omeprazole also inhibits vacuolar proton pump on osteoclasts and increases osteoblast activity, which interferes with the resorption-reconstruction balance of bone tissue, making bones more brittle and more prone to fracture under external force;
(3) Elevated PH in the stomach can reflexively cause increased secretion of gastrin, and gastrin and omeprazole can both cause parathyroid hyperplasia and hyperfunction, causing low calcium and high phosphorus, directly causing osteoporosis.
2, Infection: PPI can increase the risk of infection, mainly including respiratory infections, spontaneous peritonitis and Clostridium difficile infection.
(1) Respiratory infections: long courses of PPI and high doses of PPI are more likely to cause respiratory infections. Possible mechanisms are as follows: PPI inhibits gastric acid secretion and increases the PH in the stomach, resulting in bacterial overgrowth in the upper gastrointestinal tract and translocation into the respiratory system; H+-K+-ATP enzymes not only exist in the cells of the stomach wall but also in the respiratory tract, which can alter the PH value of glandular secretion in the respiratory tract and promote bacterial overgrowth in the respiratory tract in situ; PPI may weaken the activity of neutrophils and natural killer cells, resulting in decreased immunity. leading to a decrease in the immunity of the body.
(2) Spontaneous peritonitis: Previous studies have shown that the use of PPI in patients with cirrhosis may increase the risk of spontaneous peritonitis. The possible mechanism is that the intestinal wall of patients with cirrhosis is edematous and the intestinal permeability is increased, which weakens the shielding effect of bacteria and causes spontaneous peritonitis due to the invasion of bacteria from the intestine into the peritoneal cavity, while PPI weakens the barrier function of the gastrointestinal tract. However, the results of a recent multicenter prospective study with a large sample showed that the occurrence of spontaneous bacterial peritonitis in cirrhotic patients was not associated with PPI.
(3) Clostridium difficile infection (CDI): The risk of CDI is increased 0.6-2 times in patients with PPI application compared to those without PPI, and the possible mechanism is that PPI lowers the gastric mucosal barrier, leading to the multiplication, translocation, and toxin production of opportunistic pathogenic bacteria such as CD, which cause diarrhea.
3, hypomagnesemia: a study shows that the dose of PPI, regardless of high or low, can cause hypomagnesemia, the possible mechanism for the long-term application of PPI may affect the function of transient receptor potential M6 channel, leading to impaired absorption of magnesium in the small intestine and the body’s total magnesium reserves progressive reduction, and finally depletion. Long-term application of PPI patients should regularly detect the blood magnesium concentration.
4, iron deficiency anemia and vitamin B12 deficiency: It has been reported that the long-term application of PPI may lead to iron deficiency anemia and vitamin B12 deficiency, the mechanism is the acidic environment in the stomach is an important condition for the absorption of iron and vitamin B12, long-term acid suppression may lead to iron and vitamin B12 absorption disorders.
5, gastric fundic gland polyps: Some studies have shown that the risk of fundic gland polyps in patients who have applied PPI for more than 1 year is 4 times higher than that in patients who do not use PPI, and can degenerate and disappear after discontinuing PPI.
Acute interstitial nephritis: Omeprazole was first reported to cause acute interstitial nephritis in 1992, followed by other PPI-induced acute interstitial nephritis, which is a rare but serious adverse drug event. The drug and its metabolites can act as a semi-antigen, bind to the normal components of the tubular basement membrane to form a complete antigen, or be deposited in the renal interstitium as a trigger antigen, inducing an immune response by directly opposing the antigen.
7, Skeletal muscle and myocardial adverse reactions: Some studies have confirmed a clear causal relationship between PPI and various myopathies such as polymyositis. In addition, some studies have shown that pantoprazole can inhibit intracellular calcium signaling and myofilament activity in cardiac muscle, thereby inhibiting myocardial contraction.
8.Risk of cardiovascular events due to combination with clopidogrel: It has been shown that the combination of clopidogrel and PPI increases the risk of cardiovascular events and mortality by the mechanism that PPI is a CYP2C19 enzyme inhibitor and clopidogrel needs to be biotransformed by CYP2C19 in the liver. The use of PPIs may therefore reduce the active conversion and antiplatelet effect of clopidogrel, increasing the risk of cardiovascular events and the risk of rethrombosis. Among the PPIs, rabeprazole, which is 85% metabolized by a non-enzymatic pathway, has the least effect on clopidogrel, followed by pantoprazole, which has a weak binding to cytochrome P450 enzymes.
In conclusion, the long-term application of PPI has various risks and prevention is important. If possible, long-term application of PPI should be avoided, and if long-term application is necessary, the monitoring of its adverse effects should be strengthened to minimize the occurrence of adverse effects.
The application of PPI in special populations
1. Renal insufficiency: no need to adjust the dose.
2. Hepatic insufficiency: no dose adjustment is required for mild to moderate hepatic insufficiency, and dose adjustment is required for severe hepatic insufficiency, such as omeprazole and esomeprazole daily dosage should be <20 mg.
3.Elderly: no dose adjustment is required.
4.Children: omeprazole and lansoprazole can be used in children, according to body weight, the dosage of omeprazole is 20 mg and the dosage of lansoprazole is 30 mg when weight <20 10="" 15="" kg="" >20 kg, while no relevant studies have been reported for other classes of PPI.
5. Pregnant and lactating women: According to the drug instructions, the safety levels of various pregnancy drugs are omeprazole (Class C), lansoprazole (Class B), pantoprazole (Class B), rabeprazole (Class B) and esomeprazole (Class C), which should be used with caution according to the specific conditions of pregnant women.
Summary
In conclusion, different types of PPIs have different acid-suppressive strengths and pharmacokinetics, so their clinical application should be individualized; long-term application has more adverse effects, so long-term application should be avoided; if long-term application is necessary, attention should be paid to regular monitoring of adverse effects; finally, attention should be paid to the use of PPIs in special populations.
At present, there is no substitute for PPIs in gastrointestinal diseases, but care should be taken to avoid abuse and the phenomenon of “dare to use, dare not stop”.