Seven drugs should not be used in combination with omeprazole.🈲🈲🈲

Omeprazole is a proton pump inhibitor. It is also the most commonly used gastric acid suppressant drug. It is a fat-soluble weakly basic drug. After oral administration by patients, it will be specifically distributed in the secretory tubules of the parietal cells of the gastric mucosa. A high acid environment will convert it into the active ingredient of sulfenamide. It inhibits the activity of hydrogen-potassium ATPase on the gastric parietal cells to block the secretion of gastric acid and increase the pH of gastric juice. Therefore, its inhibitory effect on gastric acid secretion caused by various reasons is long-lasting and potent. Omeprazole is suitable for stomach diseases such as gastric ulcer and duodenal ulcer.

What diseases can omeprazole be used to treat?

1. Gastroesophageal reflux: These patients experience symptoms such as acid reflux and heartburn. Omeprazole can inhibit the secretion of gastric acid to control the symptoms and promote the recovery of esophagitis.
2. Peptic ulcer: abnormal secretion of gastric acid and pepsin can be treated with omeprazole. It can effectively suppress stomach acid and promote the healing of peptic ulcer. At the same time, it can also relieve various related symptoms and reduce complications.
3. Upper gastrointestinal bleeding: Omeprazole can increase the pH of the stomach and reduce the redissolution of blood clots in the stomach. Therefore, upper gastrointestinal bleeding in patients caused by various diseases can be treated with omeprazole.

Which drugs should not be used in combination with omeprazole?

Acidic drugs: Omeprazole is a weakly basic drug. It decomposes rapidly in an acidic environment. Therefore, omeprazole is often made into enteric-coated tablets or capsules. When acidic drugs and omeprazole are used in combination, a neutralization reaction may occur and affect the efficacy of the drug. Acidic drugs such as ambroxol hydrochloride, ornidazole and vitamin B6 should not be used in combination with omeprazole.

Clopidogrel: It is an anti-platelet aggregation drug. Most proton pump inhibitors reduce the production of the active metabolite of clopidogrel, thereby reducing the efficacy of clopidogrel. Among the proton pump inhibitors, omeprazole has a significant effect on clopidogrel. If clopidogrel needs to be used in combination with a proton pump inhibitor, a proton pump inhibitor with less effect such as rabeprazole or pantoprazole should be used.

Digoxin: It is a commonly used cardiac glycoside drug in clinical practice. Its hydrolysis needs to be carried out in an acidic environment. Therefore, omeprazole inhibits gastric acid secretion, which will increase the pH value in the stomach and reduce the hydrolysis of digoxin. The combination of the two will reduce or eliminate the activity of digoxin.

Iron supplements: Growing children or pregnant women sometimes need to take iron supplements to supplement the iron in the body in order to avoid iron deficiency anemia. However, the stomach needs an acidic environment to absorb iron properly. Because omeprazole inhibits gastric acid secretion, the body cannot absorb iron normally.

Nifedipine: It is a commonly used antihypertensive drug in clinical practice. Omeprazole inhibits the enzymes that metabolize nifedipine, thereby increasing the body's absorption of nifedipine. There is an increased risk of hypotension and the risk of adverse effects.

Ketoconazole: It is an antifungal medicine. The release of its drug effect needs to rely on the secretion of gastric acid. The secretion of gastric acid is inhibited by omeprazole to increase the pH value of the stomach. The release of ketoconazole is thus reduced and the bioavailability is reduced, which in turn weakens the antifungal effect.

Probiotics such as Bifidobacterium and Lactobacillus: They can regulate intestinal flora and improve symptoms such as constipation and diarrhea. These probiotics require an acidic environment to remain active. Therefore, they should not be used in combination with antacids.

Precautions for Omeprazole.

When omeprazole is used for peptic ulcer, 1 to 2 times a day, 20 mg each time, the patient swallows once in the morning or once in the morning and evening. The course of gastric ulcer treatment is generally 4 to 8 weeks. The course of treatment for duodenal ulcer is generally 2 to 4 weeks. When omeprazole is used for gastrinoma, the patient should take 60 mg once a day. The total daily dose is adjusted to 20 to 120 mg according to the patient's condition. If the total daily dose exceeds 80 mg, patients should take it in two divided doses. In order to prevent omeprazole from dissolving in the acidic stomach, it is generally made into enteric-coated tablets or capsules. Enteric-coated preparations are generally recommended to be taken on an empty stomach or before meals. It will ensure that the pH value of the stomach will not be affected by food, which will cause the drug to dissolve and release in the stomach in advance, resulting in ineffectiveness.

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Treatment options for Helicobacter pylori.👀

Helicobacter pylori (Hp) is a bacterium with a high infection rate in clinical practice. It can cause stomach ulcers and chronic gastritis and other stomach diseases. The long-term effects of these stomach problems can even lead to stomach cancer. Some studies have pointed out that the incidence of stomach disease caused by Hp is about 6 times that of stomach disease caused by other reasons. About 90% of patients with chronic gastritis and gastric ulcers carry Helicobacter pylori.

Indications for Helicobacter pylori.

The infection rate of Helicobacter pylori in the world is very high. Hp infection rates in some countries exceed 50%. Gastritis caused by Hp is an infectious disease. Treatment is generally necessary for Hp-positive patients. For Hp-positive patients with the following indications, they should undergo Hp eradication therapy. 

Eradication therapy is strongly recommended for Hp-positive patients with the following indications:

1. Peptic ulcer with or without activity and with or without a history of complications.
2. Gastric mucosa-associated lymphoid tissue.

Eradication therapy is recommended for Hp-positive patients with the following indications:

1. Has a family history of gastric cancer.
2. Chronic gastritis is accompanied by symptoms of gastric mucosal atrophy, erosion or indigestion.
3. Long-term use of proton pump inhibitors (PPIs).
4. The treatment plan requires long-term use of non-steroidal anti-inflammatory drugs.
5. Early gastric tumors have undergone endoscopic resection or subtotal gastrectomy.
6. Idiopathic thrombocytopenic purpura.
7. Unexplained iron deficiency anemia.
8. Other Hp-related diseases such as hyperplastic gastric polyps, lymphocytic gastritis.
9. Hp infection has been confirmed.

Drugs that can eradicate Helicobacter pylori.

The main treatment regimen for empirical eradication of Helicobacter pylori is PPI + 2 kinds of antibacterial drugs + bismuth. It is recommended to use for 10 or 14 days. Eradication rates with these regimens can reach 85 to 94%.

1. Proton pump inhibitors.

PPIs can inhibit the secretion of gastric acid and increase the pH of the stomach. It will increase the chemical stability of antibiotics, the concentration of antibiotics in the stomach and reduce the minimum inhibitory concentration to enhance the effect of antibiotics. In order to improve the eradication rate, it should generally be used the drugs with high curative effect, stable action and less influence by CYP2C19 gene polymorphisms, such as rabeprazole. They are generally recommended to be taken twice a day, half an hour before meals. 

1. Omeprazole: It is a first-generation PPI. Its recommended dose is 20mg daily. Its onset is slower.
2. Lansoprazole: It is a first-generation PPI. Its recommended dose is 30mg daily. It onset is faster than omeprazole.
3. Pantoprazole: It is a first-generation PPI. Its recommended dose is 40mg daily. It onset is similar to that of omeprazole.
4. Rabeprazole: It is a second-generation PPI. Its recommended dose is 10mg or 20mg daily. It onset is the fastest.
5. Esomeprazole: It is a second-generation PPI. Its recommended dose is 20mg daily. It onset is similar to that of lansoprazole.

2. Antibacterial drugs.

Acidic environments reduce their efficacy. It is generally recommended to take it after meals. The following are commonly used antibacterial drug combinations:

• Amoxicillin 2 times a day, 1000mg each time + Clarithromycin 2 times a day, 500mg each time.
• Amoxicillin 2 times a day, 1000mg each time + Levofloxacin 500mg once a day or 200mg twice a day.
• Amoxicillin 2 times a day, 1000mg each time + Furazolidone 2 times a day, 100 mg each time.
• Tetracycline 3 or 4 times a day, 500mg each time + Metronidazole 3 or 4 times a day, 400 mg each time.
• Tetracycline 3 or 4 times a day, 500mg each time + Furazolidone 2 times a day, 100 mg each time.
• Amoxicillin 2 times a day, 1000mg each time + Metronidazole 3 or 4 times a day, 400 mg each time.
• Amoxicillin 2 times a day, 1000mg each time + Tetracycline 3 or 4 times a day, 500mg each time.

Gastric acid had relatively little effect on the activity of tetracycline, metronidazole, and furazolidone. The other effects of gastric acid were amoxicillin > clarithromycin > levofloxacin.

3. Bismuth.

Bismuth pectin (undetermined standard dose) and bismuth citrate (220 mg) are recommended to be taken twice a day, half to one hour before meals. Stools will turn black after taking bismuth. Short-term use of bismuth for 1 to 2 weeks has a high safety. Helicobacter pylori is not resistant to bismuth because it is directly killed by bismuth. Bismuth can additionally increase the eradication rate of resistant strains of Hp by 30 to 40%. A quadruple regimen containing bismuth should be used whenever possible in the empirical treatment of Hp, unless the patient has a contraindication to bismuth or resides in a low resistance rate.

How to choose a treatment plan?

The choice of treatment regimen is to choose a combination of antibiotics. The choice of PPI and bismuth is generally not limited unless the patient has a contraindication or intolerance. The selection of antibiotics should be based on the patient's allergy history, medication history, and local Hp antibiotic resistance. Efficacy, cost, convenience, and adverse reactions should also be considered.

1. Initial empirical treatment.

The above combinations of antibacterial drugs are not divided into first-line or second-line. The combination with high efficacy should be used in the initial treatment. However, Combinations containing levofloxacin are not intended as initial treatment regimens. The main reason for the decrease in eradication rate is the increased drug resistance of Hp. If Hp is resistant to one of the two antibacterial drugs, the eradication rate drops to 50 to 60%. If Hp is resistant to both antibiotics, the eradication rate is only about 10%. Antibiotics were selected according to the resistance of local Hp. Drug susceptibility testing can be performed if necessary. Amoxicillin generally has a strong effect on Hp and is not easy to develop drug resistance. Patients without allergies have fewer adverse reactions. It can be considered as the first choice. Furazolidone has more serious adverse reactions. It is only used for Hp infections that are difficult to eradicate.

Primary resistance rate of Hp:

	Resistance rate
Amoxicillin	0-5%
Clarithromycin	20-50%
Furazolidone	0-1%
Levofloxacin	20-50%
Metronidazole	40-70%
Tetracycline	0-5%

Eradication rates and incidence of adverse effects of treatment regimens:

	Eradication rate	The incidence of adverse reactions
Amoxicillin + Clarithromycin	85-94%	Low
Amoxicillin + Levofloxacin	85-89%	Medium
Amoxicillin + Tetracycline	85-89%	Medium
Tetracycline + Metronidazole	85-94%	Medium to high
Tetracycline + Furazolidone	85-94%	Medium to high
Amoxicillin + Metronidazole	85-94%	Medium to high
Amoxicillin + Furazolidone	85-94%	Medium to high

2. After failure of initial treatment.

Choose one of the remaining treatment options for treatment. The selection should refer to past treatment regimens. It is generally not reused. 

Metronidazole at conventional doses is fully functional when Hp is not resistant, but it is completely ineffective when resistant. Its dose can increase to 1600mg daily in 4 divided doses to overcome drug resistance. Therefore, if repeated use of metronidazole is required, its dose needs to be increased to 1600 mg per day. When this dose has been used for the initial treatment, it should not be used again. 

In addition, increasing the dose of metronidazole (1600mg/day) or furazolidone (300mg/day) can improve the efficacy, but the adverse reactions will also increase.

3. Treatment of patients with penicillin allergy.

Tetracycline can be used instead of amoxicillin. It is recommended to use tetracycline in combination with furazolidone or metronidazole. Tetracycline combined with levofloxacin is also effective.

When tetracycline cannot be used, clarithromycin can be used instead. Such as clarithromycin combined with furazolidone, metronidazole or levofloxacin.

Prevention of Hp.

The main route of Hp infection is the digestive tract. Saliva can be its carrier. Therefore, pay attention to the hygiene of tableware and disinfect regularly.

Studies have shown that Hp can survive in fresh water for at least 3 years. It also survives 4 to 10 days in tap water. Water should be cooked thoroughly before drinking.

The development of an Hp vaccine may be the best way to prevent infection in the future.

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When omeprazole is used in combination with drugs, pay attention to the interaction.👀

Omeprazole is a proton pump inhibitor (PPI) that can be converted into sulfenamide compounds by protonation in an acidic environment. This compound can specifically bind to the α subunit of H+/K+-ATPase and inhibit its acid secretion activity. It is currently one of the most commonly used drugs for the treatment of acid-related diseases in clinical practice.

Omeprazole

The sulfinyl group in the chemical structure of omeprazole can be decomposed in acidic solution to cause polymerization and discoloration. Its stability may be affected by various factors such as the pH value of the solution, light, and temperature. This leads to contraindications between omeprazole and a variety of drugs.

1. The influence of pH.

Omeprazole is a benzimidazole compound and a weakly alkaline substance. The effect of pH change on its stability is particularly obvious, which can lead to its discoloration and precipitation. The main reasons are:

• Causes chemical structure changes: Omeprazole is relatively stable when the pH is around 9.0. It is easy to decompose in acidic environment to produce sulfone compounds and sulfide compounds, which cause discoloration of the solution.
• Causes solubility changes: Omeprazole is insoluble in water. After it is made into sodium salt, the solubility is improved. The maximum concentration commonly used in clinic is 40mg omeprazole sodium dissolved in 100ml normal saline (concentration is 0.4mg/ml). When the pH value of the omeprazole sodium solution decreases, free omeprazole is formed, causing turbidity or precipitation.

Acidic drugs: 

Omeprazole sodium is weakly alkaline. It will react with acidic drugs to produce new compounds. Reactions such as precipitation and discoloration will occur, and at the same time will lead to a reduction of active ingredients. Such acidic drugs include sulfacetamide, penicillin sodium, cefotaxime, piperacillin, fructose diphosphate sodium, vitamin C, vitamin B6, aminophylline, cimetidine, gentamicin and so on.

Drugs that depend on the pH of the stomach for absorption: 

Iron agents are mainly absorbed in the form of ferrous ions, which depend on the presence of gastric acid. The non-absorbed ferric iron can be converted into the divalent iron that can be absorbed under the action of gastric acid. Omeprazole can inhibit gastric acid, affect the absorption of iron, and reduce the efficacy. When the pH in the stomach rises, the tetracycline drug easily becomes insoluble free tetracycline, the absorption is reduced, and the curative effect is reduced. The absorption of ketoconazole also depends on sufficient gastric acid secretion. The acid suppression effect of omeprazole can reduce the absorption of ketoconazole and the blood concentration. The low acid environment can also reduce the absorption of itraconazole, so if necessary, acidic beverages can be used to take its capsule preparation.

2. Drugs related to metabolic enzymes.

Omeprazole is mainly metabolized to 5-OH-omeprazole by CYP2C19, or metabolized to omeprazole sulfone by CYP3A4, the former being the main metabolic pathway. Omeprazole can delay the elimination of drugs metabolized by the liver cytochrome P450 system in the body. Therefore, when omeprazole is combined with drugs related to CYP2C19 metabolizing enzymes, interactions are likely to occur.

Clopidogrel (CYP2C19 substrate):

Clopidogrel is a prodrug. It can only exert its antiplatelet effect after it enters the body and is metabolized by CYP2C19. Omeprazole is also metabolized in the liver by CYP2C19. The simultaneous use of the two may produce competitive inhibition. Clopidogdar does not have the effect of anti-platelet aggregation, which increases the risk of patients with ischemic stroke, compound stroke and myocardial infarction.

Diazepam (CYP2C19 substrate):

Omeprazole can weaken the metabolism of diazepam and increase its efficacy by inhibiting liver cytochrome P450 enzymes. Therefore, when used in combination, it should be monitored for enhanced sedation. If necessary, reduce the dose of diazepam.

Warfarin:

Omeprazole delays the clearance of warfarin by acting on the CYP450 enzyme system. The increase in warfarin exposure increases the international normalized ratio (INR) and prolongs the prothrombin time, which may lead to abnormal bleeding and even death. INR and prothrombin time should be monitored when used in combination. If necessary, adjust the warfarin dose to ensure that the INR is within the target range.

CYP2C19 or CYP3A4 inhibitors (such as voriconazole) and inducers (such as rifampicin):

Voriconazole can increase the exposure of omeprazole, except that patients with Zollinger-Eye syndrome may need to adjust the dose of omeprazole, and other generally do not need to be adjusted. Rifampicin can reduce the blood concentration of omeprazole. The combination of the two should be avoided.

Cilostazol (CYP2C19 substrate):

Omeprazole can increase the exposure of the active metabolite of cilostazol (3,4-dihydro-cilostazol). The dosage of cilostazol should be reduced to 50 mg once, twice a day.

Citalopram (CYP2C19 substrate):

Omeprazole can increase the exposure of citalopram and increase the risk of Q-T interval prolongation. The maximum dose of citalopram when used in combination should be 20 mg per day.

3. Other.

Methotrexate:

Omeprazole can inhibit the H+/K+-ATPase of the kidney. This will inhibit the active secretion of methotrexate and increase its blood concentration and toxicity.

Bismuth agent, montmorillonite powder, hydrotalcite, etc.:

They have a certain adsorption effect on omeprazole and can reduce the efficacy of omeprazole. In addition, the bismuth agent can better form a film in an acidic environment, and play the best role in protecting the gastric mucosa. If it is in a low-acid environment, its efficacy is reduced.

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What is the difference between antacids, H2 receptor blockers and proton pump inhibitors❓❓❓

Gastrointestinal diseases are common diseases in daily life, and there are many types of treatment drugs, such as gastric acid secretion inhibitors, antacids, gastric mucosal protective drugs, and gastrointestinal motility drugs. They have their own characteristics, different mechanisms of action, indications and usage. Therefore, we must learn to choose more accurately and use drugs rationally according to the characteristics of stomach diseases. Gastric acid secretion inhibitors and antacids are two drugs that are frequently used in digestive tract diseases. Here we briefly describe the differences in their pharmacological mechanisms, indications, usage and dosage, adverse reactions and precautions.

1. Pharmacological mechanisms

Gastric acid secretion inhibitors

    H₂ antagonist:

• It can block H₂ receptors of parietal cells. It inhibits basic gastric acid and nocturnal gastric acid secretion. It also inhibits gastric acid secretion caused by gastrin and M receptor agonists. Studies have shown that H₂ antagonist has a significant inhibitory effect on gastric acid secretion at night, but it has a poor control effect on gastric acid secretion during the day.
• Commonly used drugs: cimetidine, famotidine, ranitidine.
•  Acid suppression strength: famotidine > ranitidine > cimetidine.

    Proton pump inhibitor (PPI)

• It is an H⁺/K⁺-ATPase inhibitor that can inhibit central or peripheral gastric acid secretion. It can effectively inhibit basic gastric acid secretion or various forms of stress-induced gastric acid secretion.
• Commonly used drugs: Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole.
• Acid suppression strength: esomeprazole > rabeprazole > pantoprazole > lansoprazole and omeprazole.

Antacids

• They are weakly alkaline substances, which directly neutralize gastric acid in the stomach after oral administration and increase the pH of the gastric juice to reduce the activity of pepsin (when the pH of the gastric juice is 1.5-2.5, the most active). Antacids such as aluminum hydroxide neutralize gastric acid and cover the gastric mucosa to form a gel-like protective layer to prevent gastric acid and pepsin from invading again.
• Commonly used drugs: aluminum hydroxide, aluminum phosphate, magnesium hydroxide, sodium bicarbonate.

2. Indications

Gastric acid secretion inhibitors

• Acute gastric mucosal disease, gastroesophageal reflux disease, peptic ulcer or bleeding, prevention of stress mucosal injury of upper gastrointestinal tract. PPI can be combined with antibacterial drugs to eradicate Helicobacter pylori.

Antacids

• Relieve stomachache, acid reflux and heartburn caused by hyperacidity. It can be used for functional dyspepsia, chronic gastritis, peptic ulcer or bleeding, acute gastric mucosal lesions and reflux esophagitis.

Different

• Antacids directly neutralize gastric acid and have a quick effect. However, as the stomach empties and cannot neutralize the continuously secreted gastric acid, the duration of action is very short. PPI has a strong, complete and long-lasting acid-inhibiting effect, and its acid-inhibiting ability greatly exceeds that of H₂ antagonist. Usually, the time for antacids to make the stomach pH> 4 is only 4 hours, H₂ antagonist is 8 hours and PPI can reach 18 hours.

3. Dosage

Classification	Drug name	Dosage	Taking time
H2 antagonist	Cimetidine	0.2g/time, 2 times/day, daily dose ≤0.8g	During meal and before bedtime
	Famotidine	20mg/time, 2 times/day, the daily dose is 40mg.	After breakfast, dinner or before bedtime.
	Ranitidine	0.15g/time, 2 times/day	Early morning and before bed
PPI	Esomeprazole	20-40mg/time, 1-2 times/day	1h before meal
	Ilaprazole	5-10mg/time, 1-2 times/day	Take it on an empty stomach in the morning
	Lansoprazole	30mg/time, 1-2 times/day	0.5h before meal
	Omeprazole	20mg/time, 1-2 times/day 0.5h before meal	0.5h before meal
	Pantoprazole	20-40mg/time, 1-2 times/day	1h before meal
	Rabeprazole	10-20mg/time, 1-2 times/day	0.5h before meal
Antacids	Aluminum hydroxide	0.6-0.9g/time, 3 times/day	1h before meal
	Aluminum Phosphate Gel	1-2 packs/time, 2-3 times/day	0.5h before meal
	Sodium bicarbonate	0.3-1g once, 3 times a day.	Before meal

H₂ antagonist has no obvious irritation to gastric mucosa, and its absorption and utilization are basically not affected by gastric contents. Generally, it can be taken after a meal or before going to bed.

Since PPI has an inhibitory effect on the "active pump" on the cell membrane of the gastric parietal cell, it has no effect on the "rest pump" in the cytoplasm, and the proton pump regeneration is mainly completed at night, so the best effect is to take the drug in the morning. PPI can only obtain the maximum acid suppression effect when it acts on food to stimulate the gastric parietal cells to be active. Therefore, it is recommended that PPI be taken 15 to 60 minutes before a meal in the morning.

The purpose of taking antacids is to neutralize excessive stomach acid, so it is generally best to take it half an hour before a meal or when stomach pain occurs.

4. Course of treatment

H₂ antagonist is generally taken continuously for no more than 12 weeks.

PPI is used for gastric ulcer medication for 6 to 8 weeks and duodenal ulcer is 4 weeks. The course of anti-Helicobacter pylori treatment is 10 to 14 days. The course of treatment for gastroesophageal reflux disease should be at least 8 weeks. Preventive use of PPI, elective surgery: Use one dose before surgery and use ≦ 24h after surgery. Fasting or parenteral nutrition: After establishing enteral nutrition, consider stopping PPI.

Antacids are generally taken for no more than 7 consecutive days.

5. Adverse reactions

Gastric acid secretion inhibitors

H₂ antagonist may induce rapid drug resistance during use and may cause gastric acid rebound after stopping. Others include nausea, vomiting, diarrhea, leukopenia, elevated serum transaminase, male sexual dysfunction and breast enlargement, galactorrhea and neuropsychiatric symptoms such as headache, dizziness, hallucinations, mania, etc.

Adverse reactions caused by short-term use of PPI are rare, such as headache, diarrhea, nausea, gastrointestinal flatulence, abdominal pain, constipation, dizziness, itching, and rash, etc., which are generally mild. Long-term treatment (>1 year), long-term overdose (>1.75 times the standard dose) may cause serious adverse reactions, such as osteoporosis and fractures, pneumonia, intestinal infections, iron deficiency anemia, vitamin B12 deficiency, hypomagnesemia and gastric mucosal lesions.

Antacids

Long-term use of aluminum hydroxide can cause severe constipation and even intestinal obstruction. Long-term use of aluminum hydroxide in the elderly can affect the intestinal absorption of phosphate, which can lead to osteoporosis. Large doses of aluminum phosphate can also cause mild constipation. Aluminum salt is absorbed and deposited in the brain, which can cause senile dementia.

Magnesium hydroxide can easily cause diarrhea.

Repetitive use of large doses of sodium bicarbonate can easily cause abdominal distension, sodium retention and secondary gastric acid secretion. Eating dairy products during medication may cause milk-alkali syndrome (manifested by nausea, vomiting, weakness, polyuria, and muscle pain).

6. Precautions

Gastric acid secretion inhibitors

    H₂ antagonist

• Antacids can reduce the concentration of gastric acid and form a protective film on the surface of the ulcer, thereby hindering the absorption and function of H₂ antagonist. Therefore, H₂ antagonist should not be combined with antacids.
• Avoid the combination of H₂ antagonist and PPI unless there is a nighttime acid breakthrough (taking PPI during the day and taking H₂ antagonist before going to bed can significantly reduce the incidence).
• Cimetidine can inhibit the activity of liver cytochrome P450 and can interact with warfarin, phenytoin and other drugs. The dose needs to be adjusted when combined. Ranitidine has a weak effect on liver drug enzymes and famotidine has almost no effect.
• In order to reduce the occurrence of the rebound phenomenon of H₂ antagonist withdrawal, it is generally advocated to stop the drug by the decrement method, such as changing from 2 times a day to once a day, then to once every other day after 1 week, and gradually stop the drug.

    PPI

• PPI needs to be combined with H⁺. It activated in an acidic environment and irreversibly combined with the sulfhydryl group of the proton pump through the disulfide bond. It causes the proton pump is permanently inactivated. Therefore, PPI should not be combined with antacids.
• It has liver enzyme inhibitory effect. Combining with clopidogrel can reduce the efficacy of the latter. Among them, omeprazole has the most obvious inhibitory effect, and PPI with weaker CYP inhibition (such as pantoprazole) may be a better choice.
• Mucosal protective agents such as sucralfate need to form a protective film in an acidic environment. Acid inhibitors increase the pH of the stomach and reduce the efficacy of such drugs. Since mucosal protective agents are attached to the surface of the gastric mucosa, they can affect the activation of PPI. Therefore, the two types of drugs should not be used in combination, and the two should be taken separately.

Antacids

• The main factors affecting the efficacy of antacids include drug neutralization ability, gastric acid secretion and emptying rate. Prolonging the action time of the drug in the stomach can enhance the curative effect, and the prokinetic drug will shorten the residence time of the antacid in the stomach when promoting intestinal motility. Therefore, it is not recommended to take the prokinetic drug and antacid at the same time. In addition, the effect of increasing the frequency of administration is better than increasing the single dose.
• Aluminum can affect the absorption of certain drugs, such as tetracycline, iron, digoxin, cimetidine, etc., when the two are used together, an interval of 1-2h is required.

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Inventory of various new discoveries of metformin😎😎😎

Metformin is an anti-diabetic drug and a classic oral hypoglycemic agent. Since its inception in 1957, it has been used clinically for more than 60 years. It is currently one of the most widely used oral hypoglycemic drugs in the world. Even though there are many new hypoglycemic drugs, metformin is still the primary drug for type 2 diabetes.

Metformin was born in 1929 and originated from galega officinalis. In 1957, French diabetologist professor Jean Sterne first used metformin for clinical hypoglycemic reduction. Then its application value is still being discovered. Let us take a look at what new discoveries have been made recently.

1. Cancer

Acidic phospholipids play an important role in regulating electrostatic membrane association of programmed cell death ligand 1 cytoplasmic domain (PD-L1-CD). Metformin can competitively dissociate PD-L1-CD from the membrane and affect the stability of PD-L1. This revealed that the molecular mechanism of metformin's anti-tumor effect and provided new ideas for related immunotherapy targeting PD-L1.

There are many studies that supporting metformin can decrease the risk or improve the symptoms of cancer patients. Such as esophageal squamous cell cancer, pancreatic cancer, primary bone cancer.

2. Obstetrics & Gynecology

a. Improve neonatal obesity

    Metformin has many benefits for mother's blood glucose and neonatal obesity, including improved blood glucose, reduced caesarean section, reduced mother's weight, lower insulin requirements,  lower birth weight and obesity measurements of newborns.

b. Prevent adverse pregnancy outcomes in patients with polycystic ovary syndrome

    Metformin can prevent late period abortion and premature birth in women with polycystic ovary syndrome.

3. Metabolic diseases

Metformin can improve the metabolic status of patients treated with systemic glucocorticoids. It can not only reverse the metabolic complications caused by the use of systemic glucocorticoids, but also reserve the anti-inflammatory effects of glucocorticoids. It benefits many patients taking systemic glucocorticoids.

4. Cardiovascular System

 a. Heart failure

    Non-diabetic heart failure patients with reduced ejection fraction (HFrEF) use metformin to reduce myocardial oxygen consumption and improve myocardial efficiency.

b. Left ventricular hypertrophy

    Metformin treatment significantly reduced the left ventricular mass index. Patients taking metformin reduced left ventricular thickening by two time less. In addition, metformin also reduced blood pressure, oxidative stress, and weight. Metformin has the potential to improve cardiovascular health.

c. Air-pollution-induced thrombosis

    Atmospheric particulate matter can induce alveolar macrophages to release pro-inflammatory factors including interleukin 6 (IL-6), leading to arterial thrombosis and death.

    Metformin blocks the mitochondrial electron transport and inhibits the production of reactive oxygen species, thereby blocking the release of IL-6 and inhibiting the formation of arterial thrombosis. This confirms that metformin can be used as a potential therapeutic drug to prevent cardiovascular diseases caused by air pollution.

5. Nervous system

a. Cognitive and nerve recovery after brain tumor surgery

    For children with brain tumor patients who have received craniocerebral radiotherapy, metformin can significantly improve their statement memory and working memory function, repairing white matter damage. Metformin is also safe and tolerable in this population.

b. Multiple Sclerosis

    After treatment with metformin, oligodendrocyte precursor cells can restore their response to the signal of promoting-differentiation, promote the regeneration of nerve myelin. This is useful for the treatment of central nerve demyelination such as multiple sclerosis.

c. Cognitive decline and dementia

    Patients with type 2 diabetes who take metformin have slower cognitive decline and a lower risk of dementia.

6. Locomotor system

a. Osteoarthritis

    Metformin can prevent the occurrence and development of osteoarthritis, alleviate the pain sensitivity associated with osteoarthritis in mice. Its protective effect on cartilage is mainly through the activation of AMPK signals.

b. Intervertebral disc degenerative disease

    Metformin can promote the release of small extracellular vesicles of mesenchymal stem cells, increase the level of proteins that regulate cell proliferation in the vesicles, and can optimize the application effect of extracellular vesicles in the regeneration and repair of intervertebral discs.

7. Digestive system

Metformin stimulates bile secretion in the intact liver, but this drug can also cause severe damage to bile acid secretion.

8. Infection

a. COVID-19

   Metformin inhibits the activation of NLRP3 inflammasomes and the production of IL-1β in cultured macrophages and alveolar macrophages, as well as the secretion of inflammasome-independent IL-6, thereby attenuating lipopolysaccharide and COVID-19 induced acute respiratory distress syndrome. Metformin can be a potential treatment for severely patients with COVID-19 and other induced acute respiratory distress syndrome.

b. HIV

    Metformin reacted on mitochondrial respiratory chain complex-I and inhibit the oxidative phosphorylation (OXPHOS) pathway. It inhibited the replication of human CD4⁺ T cells and HIV-1 virus in humanized mouse models. It revealed that metformin and others OXPHOS pathway inhibitors may be an adjunct to treat AIDS.

👉Metformin has also anti-aging effect. Most effects still are at the research stage and may not be used on treatment. Therefore, metformin still deserves more in depth research.

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