How to use medicine for duodenal ulcer?

The purpose of treating duodenal ulcer is to relieve symptoms; Promote ulcer healing; Prevention of complications; Prevent recurrence. All patients with duodenal ulcer without complications should be treated by internal medicine first, and only patients with intractable ulcer or complications such as perforation and obstruction should be considered for surgical treatment. The following is my knowledge about how to use medicine for duodenal ulcer. Welcome to reading.

How to use medicine for duodenal ulcer?

Drug therapy includes: drug therapy, including the use of drugs to reduce gastric acid, drugs to enhance mucosal resistance and drugs to eradicate Hp (Helicobacter pylori); Eliminate harmful environmental factors, especially avoid using salicylate and quit smoking; Relieve mental stress; Rest.

Today we will talk about how to use medicine for duodenal ulcer.

(1) Drugs for reducing gastric acid:

Include antacids and anti-secretory drugs. Antisecretory drugs include histamine H2 receptor antagonists, gastrins, antimuscarins and proton pump inhibitors. The action sites of various anti-secretory drugs are different.

① antacid:

It can lower stomach acid, and there are many kinds of drugs. According to its systematic or non-systematic function, it can be divided into systematic antacids and non-systematic antacids.

Systemic antacids cause metabolic alkalosis (such as sodium bicarbonate) because the cationic part of them does not form insoluble alkaline compounds in the intestine; Nonsystematic antacids are relatively insoluble and difficult to absorb, because the cationic part of them forms insoluble alkaline compounds in the intestine, so they will not cause alkalization of body fluids.

Non-systematic antacids can be divided into neutralizers (such as calcium carbonate and magnesium oxide) and physical adsorbents (such as aluminum hydroxide and magnesium trisilicate) according to different properties.

Sodium bicarbonate (baking soda) is the only meaningful drug in systemic antacids. It has rapid action and can quickly neutralize gastric acid after oral administration.

The usual dosage for one treatment is 0.5 ~1.0g. It has side effects on human body, severe renal load, abdominal distension and belching, and there is a risk of ulcer perforation. For the above reasons, sodium bicarbonate should not be used as a long-term drug to treat ulcers, unless other measures cannot alleviate it.

At present, many of its compound preparations are used, such as vitale tablets (Suweile), Leweide, vibizhi, VIV and so on.

Calcium carbonate: Many people think it is the most effective antacid. The usual dose of a treatment is 2.0 ~ 4.0 grams ... It is the cheapest and effective non-systematic antacid. It has little infiltration in the intestine, so it will not cause diarrhea, on the contrary, it will cause constipation in the elderly.

A large number of applications can produce hypercalcemia, accompanied by the increase of serum phosphate, creatine and bicarbonate. Calcium carbonate should be banned in patients with kidney disease. Calcium carbonate can also lead to excessive gastric acid secretion, which may be partly the result of increased serum gastrin.

Magnesium oxide: There are two kinds: heavy and light. The difference between light magnesium oxide and heavy magnesium oxide lies in their physical properties. The former is lighter and 3 ~ 5 times larger than the latter. Generally speaking, magnesium oxide refers to heavy magnesium oxide.

The action speed of magnesium oxide is not as fast as that of sodium bicarbonate, but the action lasts for a long time. Magnesium carbonate is not easily absorbed, so it can retain a large amount of water in the intestine through osmosis, leading to diarrhea. In patients with renal damage, a small amount of absorbed magnesium ions can remain in the body, which is toxic to the central nervous system and heart.

Usually, the primary therapeutic dose of magnesium oxide is 0.6g, and generally no more than 4 doses a day will not cause obvious diarrhea. It is often mixed or used alternately with other antacids to maintain normal feces.

Aluminum hydroxide: In addition to its powerful ability to neutralize gastric acid, it can also increase the secretion of gastric mucus, thus protecting the gastric mucosa from further damage.

Long-term use of aluminum hydroxide can reduce serum phosphate and total phosphate in the body. Therefore, it is suitable for patients with chronic renal insufficiency and hyperphosphatemia. Another disadvantage of aluminum hydroxide is its constipation, so it is not suitable for patients with partial intestinal obstruction in the past. Aluminum hydroxide also has adsorption properties, which can affect the absorption of some substances and drugs. All aluminum preparations contain a considerable amount of sodium, so they are not suitable for patients with strict sodium restriction in diet.

Aluminum hydroxide tablets are not as effective as gels. Aluminum hydroxide gel contains about 4% aluminum hydroxide, and the usual dosage is 10ml. Weishuping is a Chinese patent medicine with aluminum hydroxide as the main component. Each tablet contains 0.245g of dry aluminum hydroxide gel, 0./kloc-0.05g of magnesium trisilicate and 0.0026g of belladonna extract. The usual dosage is 2 ~ 4 tablets at a time.

Aluminum phosphate: It is a neutral substance with real buffering effect. Unlike other alkaline antacids, it only has short-term acid-base neutralization. Its gel preparation is often used in clinic. Usually a single dose is 20g.

Aluminum phosphate has a strong mucosal coating effect, protecting the stomach wall from gastric acid and pepsin. It can also promote mucus secretion and directly antagonize pepsin. It also promotes blood coagulation, so it is especially suitable for peptic ulcer bleeding.

Aluminum magnesium carbonate: the usual dosage is 500 ~ 1000mg (1 tablet or 5ml suspension containing 500mg aluminum magnesium carbonate).

In addition to strong buffering capacity and acid-resistant activity, magnesium aluminum carbonate also has the following characteristics: directly inhibiting pepsin activity, protecting gastric mucosa and its barrier, and stimulating the synthesis of endogenous prostaglandin E2, thus having mucosal protection. Therefore, aluminum magnesium carbonate can not only weaken the attack factor, but also strengthen the defense factor, which is beneficial to ulcer healing.

Magnesium trisilicate: It is both a neutralizer and an effective adsorbent. It is generally believed that it takes longer to neutralize gastric acid than most antacids. Magnesium trisilicate, like other magnesium salts, has a slight purgative effect.

The commonly used single dose is1.0g. Many pharmaceutical companies often mix aluminum hydroxide with magnesium trisilicate or magnesium hydroxide to make commercially available drugs for sale. Weishuping belongs to this kind of medicine.

Clinical application of antacids;

Since the emergence of powerful anti-secretory drugs such as histamine H2 receptor antagonists and proton pump inhibitors, antacids have a tendency to be replaced. However, recent studies have proved that some antacids, especially those containing aluminum, can stimulate the synthesis of endogenous prostaglandin E2, indicating that these antacids can not only neutralize gastric acid, but also enhance and maintain the mucosal barrier. This gave birth to an ancient method of treating peptic ulcer with antacids, and provided a basis for antacids to play an important role in treating ulcers caused by non-steroidal anti-inflammatory drugs, because this ulcer is the result of inhibition of prostaglandin synthesis. In addition, because antacids can quickly relieve ulcer pain, antacids are sometimes supplemented when treated with antihistamine H2 receptor antagonists.

An ideal antacid should have the following characteristics:

A. The effect of neutralizing gastric acid is strong and lasting, keeping the pH value of gastric contents above 3.5. At this time, the digestion of pepsin mostly stops.

B.it will not produce carbon dioxide when it reacts with gastric acid.

C.it won't cause constipation and diarrhea.

D. there is no systemic impact. Although there are many kinds of antacids, none of them are ideal if measured by this standard.

This requires us to consider not only its price and palatability, but also its side effects when choosing antacids. For example, calcium carbonate and aluminum hydroxide can cause constipation, especially in the elderly. It is often necessary to add magnesium-containing compounds to overcome their constipation-causing effects.

Long-term use of antacids containing magnesium trisilicate will lead to silica urolithiasis. Various aluminum-containing compounds can adsorb organic and inorganic substances, such as tetracycline antibiotics.

The application of aluminum hydroxide can significantly reduce the level of tetracycline antibiotics in blood. It can also adsorb some anticholinergic drugs, including atropine. Aluminum hydroxide combines with inorganic phosphate in intestinal cavity, which leads to the increase of phosphate in feces and the decrease of serum phosphate concentration.

This characteristic of aluminum hydroxide can be used to treat uremia. Magnesium-containing antacids should be banned in uremia patients to avoid hypermagnesemia. Because aluminum hydroxide combines with phosphate in the intestine, long-term use will lead to abnormal bone metabolism and osteomalacia. Aluminum hydroxide gel still contains a certain amount of sodium, which is also an important factor to be considered when applying antacids to edema patients. Although calcium carbonate is the cheapest and most effective antacid, its application is limited by occasional hypercalcemia. The application of radioactive tracer shows that the absorption of calcium carbonate to calcium is the same as that of calcium gluconate to soluble salt-calcium, which is 9% ~ 37%, so it should be avoided in patients with nephropathy.

Formula: Generally speaking, liquid or powder antacids are more effective than tablets, which may be the result of faster dispersion. In vitro experiments show that the neutralization efficiency of tablets with the same antacid is lower than that of liquid preparations. If pills are used, they should be chewed before swallowing.

Duration of acid-fast treatment: The purpose of acid-fast treatment is to completely heal the ulcer. Ulcers usually take 8 weeks to heal completely. If there is obvious fibrosis, it will take longer. Symptoms often disappear long before the ulcer completely heals. Therefore, the disappearance of symptoms must not be used as the standard for stopping acid-fast treatment.

If the drug is stopped prematurely before the ulcer is completely healed, the symptoms will reappear, which is actually the deterioration of the original ulcer rather than the recurrence of the disease. Experiments show that fully healed duodenal ulcer is less likely to form ulcer than undamaged mucosa around it. In order to make the ulcer heal completely and reduce recurrence, the time of acid-fast treatment should not be less than 3 months. If conditions permit, it is best to have an endoscopic examination before stopping treatment to evaluate whether the ulcer has healed.

② Histamine H2 receptor antagonist:

The effect of histamine is mediated by H 1 and H2 receptor. H 1 receptor is located in bronchial and small intestinal smooth muscle, which is related to histamine-induced bronchospasm and small intestinal smooth muscle contraction. H2 receptor is located in parietal cells and uterus, which is related to gastric acid secretion and histamine-induced uterine contraction. Traditional antihistamines such as diphenhydramine can block H 1 receptor, while H2 receptor can only be blocked by specific H2 receptor blockers.

Cimetidine is the first histamine H2 receptor antagonist used on a large scale, which can reduce gastric acid, but its duration is short (6min). Therefore, the initial standard treatment plan is to take it four times a day, that is, 200mg per meal, 400mg before going to bed, and the total amount per day 1 1,000 mg. It turned out that two doses a day (400mg, once in the morning and once in the evening) were exactly the same as four doses a day. About 80% duodenal ulcer can be cured after four weeks of medication.

Long-term use of cimetidine will cause side effects, such as male mammary gland development and impotence, and there are also reports of slight decrease in sperm count and pituitary-testicular dysfunction. Cimetidine often leads to a slight increase in blood creatine. Some patients may have a transient increase in serum transaminase levels, but drug-induced hepatitis is rare. There are reports of thrombocytopenic purpura, agranulocytosis and even fatal bone marrow hypoplasia.

Kidney is an important part of cimetidine metabolism. The metabolic clearance rate of cimetidine decreases with age, so does the clearance rate of patients with renal failure. Therefore, the dosage of these patients should be reduced to prevent the occurrence of toxic insanity.

Ranitidine or ranitidine hydrochloride is the second widely used histamine H2 receptor antagonist. Its anti-secretory effect is 5 ~ 10 times stronger than that of cimetidine, and its action time is long. So the dosage and frequency are less than those of cimetidine. There are also few side effects. It has no antiandrogenic effect and does not affect renal function. It passes through the blood-brain barrier in a small amount, so it will not cause insanity. Although it has little effect on cytochrome P-450 system, it can also affect drug metabolism. The curative effect of ranitidine on duodenal ulcer is similar to that of cimetidine.

Famotidine, the third histamine H2 receptor antagonist that should be used in clinic, is more than 7 times stronger than ranitidine and 30 times stronger than cimetidine in inhibiting gastric acid secretion. Therefore, its dosage is small. Side effects are mild, including headache, dizziness, constipation, diarrhea, dry mouth, nausea, vomiting, abdominal distension and abdominal discomfort.

Nizatidine is a new histamine H2 receptor antagonist. Pharmacokinetic data showed that the plasma half-life was 1.4 ~ 1.5h, and the bioavailability after oral administration was >: 90%, far exceeding ranitidine and famotidine, the former was about 50%, while the latter was only 40% ~ 45%. Most of them are excreted through the kidneys in the original form of drugs. No serious side effects, no interaction with endocrine system and no change in sexual function.

Roxatidine is another new histamine H2 receptor antagonist. The inhibitory effect of the drug on gastric acid secretion induced by histamine is greater than that of cimetidine, but almost the same as that of ranitidine. Almost completely absorbed from gastrointestinal tract after oral administration (>: 95%). Its bioavailability is not affected by eating, so it is not necessary to take medicine on an empty stomach. Its bioavailability is not affected by acid agents, so in order to relieve pain as soon as possible, there is no concern about using acid agents at the same time.

The side effects of long-term maintenance treatment are mild, including constipation and diarrhea, and the laboratory parameters have not changed significantly.

As for the usage, traditionally, according to the plasma half-life of histamine H2 receptor antagonist, multiple doses are administered once a day, for example, cimetidine 200mg, 4 times a day or 400mg, twice a day; Ranitidine 150mg twice a day; Famotidine 20mg twice a day; Nizatidine 150mg twice a day; Roxatidine 75mg twice a day.

1988, GlaxoSmithKline, UK, synthesized a new ranitidine compound, namely ranitidine bismuth citrate (RBC). Red blood cells (800 mg) contain the same amount of ranitidine as ranitidine hydrochloride (300 mg) and a similar amount of bismuth as bismuth tribasic citrate (TDB)(240 mg).

In vitro studies have shown that red blood cells have dual antibacterial and bactericidal activities against Helicobacter pylori. The antibacterial activity of red blood cells against Helicobacter pylori is similar to TDB. The results of clinical research show that simple red blood cells can not eradicate Helicobacter pylori in patients with duodenal ulcer. But combined with some antibiotics (such as clarithromycin and amoxicillin), it can not only heal the ulcer, but also eradicate Hp. The usual dose is 400 mg twice a day.

(3) proton pump inhibitor:

Substituted benzimidazole compounds are the strongest inhibitors of gastric acid secretion. These drugs can inhibit the proton pump on parietal cells, also known as acid pump, that is, H K ATPase. This enzyme is located on the secretory surface of parietal cells and mediates hydrogen ions to finally enter the gastric cavity (by exchanging with potassium).

Omeprazole (omeprazole). Is the representative of this kind of drugs. It is an alkaline compound with a pH of 3.97. Gastric acid can inactivate it, so you must take enteric-coated tablets. It can stay in parietal cells for 24 hours. Therefore, its effect is lasting. It has been found in recent years that omeprazole can also inhibit Hp. Its curative effect on duodenal ulcer is better than histamine H2 receptor antagonist.

Omeprazole can also cure ulcers that cannot be cured by other methods. It is a relatively safe drug and can be well tolerated by patients. However, long-term use of omeprazole treatment still needs to be vigilant. It has been proved that omeprazole can prolong the efficacy of some drugs metabolized by cytochrome P-450 enzyme system, such as diazepam and phenytoin sodium, but the interaction between omeprazole and theophylline has not been found.

Lansoprazole is another proton pump inhibitor developed after omeprazole. Its mechanism of action and clinical efficacy are the same as those of omeprazole. A multi-center, double-blind, double-simulation study in China compared with omeprazole showed that the four-week cure rates of lansoprazole (30mg daily) and omeprazole (20mg daily) were 90.7% and 100% respectively, and the two-week cure rates of duodenal ulcer were 9 1.2% and 84.3% respectively.

Whether it is gastric ulcer or duodenal ulcer, there is no statistical difference in ulcer healing rate between lansoprazole and omeprazole. There were no serious side effects. Another study showed that the ulcer healing rate of lansoprazole 15mg/d and 30mg/d was the same. This shows that. People in China can achieve the therapeutic purpose by taking 15mg orally every day, which is different from that of foreign countries which need 30mg each time.

Pantoprazole is a recently developed proton pump inhibitor. The most suitable therapeutic dose is 40 mg per day, taken in the morning.

(2) Drugs for enhancing mucosal resistance:

Drugs that enhance mucosal resistance may mainly affect gastric mucus secretion, bicarbonate secretion and mucosal blood flow.

① sucralfate: It can stimulate local prostaglandin synthesis. Sucralfate should not be taken with food, antacids or other drugs. Can be used with food or antacids, thus affecting its therapeutic effect, and can affect the absorption of these drugs when used with other drugs. The usual dosage is 1.0g three times a day. Sucralfate is not absorbed from gastrointestinal tract, so it does not produce systemic side effects, but it can cause constipation.

② Colloidal bismuth: colloidal bismuth subcitrate or bismuth trinitrate, foreign trade name De-No 1, which is a compound bismuth salt. It has been proved that it can promote the healing of duodenal ulcer and gastric ulcer, reduce the secretion and activity of pepsin, and promote the synthesis of prostaglandin. In recent years, it has been found to have anti-Hp effect. The side effects are black tongue and black stool.

There are two dosage forms: liquid and tablet. The liquid dosage form contains 120mg of bismuth tripotassium bicitrate (calculated as Bi2O3) in 5ml. One tablet contains the same content of potassium bismuthate as 5ml liquid dosage form. The usual dosage is 480mg per day, taken twice, that is, 2 tablets or 10ml half an hour before breakfast and half an hour before dinner every day. A course of treatment is 4 weeks, and a second course can be conducted if necessary.

③ Prostaglandin: The protective mechanism of prostaglandin on gastric cells is unknown, which may be related to stimulating mucus secretion (like sucralfate, forming a mucosal protective film), stimulating gastric bicarbonate secretion (a secretion of non-wall cells, which can play an endogenous antacid role) or directly protecting the integrity of gastric epithelial cells. Low dose prostaglandin has slight side effects (mild diarrhea). Misoprostol is a common prostaglandin preparation, which can effectively treat and prevent stomach diseases caused by non-steroidal anti-inflammatory drugs.

④ Glycyrrhiza extract: Gambogic acid is obtained by hydrolyzing glycyrrhizic acid extracted from Glycyrrhiza uralensis Fisch. Gastrin has significant therapeutic value for gastric ulcer disease, and it is also used to treat duodenal ulcer disease, but its healing effect is not as good as that of gastric ulcer. This is mainly because gastrin ketone is mainly absorbed in the stomach and only a very small amount reaches the duodenum.

The possible mechanism of gastrin ketone promoting ulcer healing is:

A. increase the production, secretion and viscosity of gastric mucus.

B. inhibiting the activity of pepsin.

C. prolong the life of gastric mucosal cells.

D, protecting the gastric mucosa from bile reflux, thereby preventing the reverse diffusion of hydrogen ions.

The dosage and usage of gastrin ketone are l00mg, three times a day, then reduced to 50mg, four times a day after 2-3 weeks, then changed to 50mg after 4-8 weeks, and maintained for 2-3 times a day. Take the medicine half an hour before meals. Thiazines and potassium chloride can be used to combat their side effects. Antimuscarinic drugs and aldosterone blockers with similar structures (such as spironolactone) can reduce the efficacy of promoting gastrin production, so they should not be combined.

The main side effects of gastrin ketone are mineralocorticoid effect, aldosterone enhancement and antidiuretic effect. About 5% ~ 20% patients have headache, hypertension, edema, sodium retention and hypokalemia. These effects will last for several weeks after the treatment is stopped. Therefore, patients with hypertension, nephropathy, liver disease and heart disease should use gastrin ketone with caution. It is precisely because of these important side effects that gastrin ketone is not an ideal drug to treat peptic ulcer.

In order to avoid sodium and water retention caused by licorice extract and gastrin ketone, licorice preparation with glycyrrhizic acid removal was prepared. The preparation contains less than 3% glycyrrhizic acid, retains the curative effect and has no side effects. It is reported that it can promote the healing of duodenal ulcer, and it is also reported that its value cannot be confirmed. Some scholars believe that glycyrrhizic acid and licorice preparation is not superior to placebo in the treatment of duodenal ulcer.

⑤ Zinc acexamate: It is an organic zinc anti-ulcer drug, belonging to the drug that stimulates the protection mechanism of gastroduodenal mucosa.

Mechanism of action:

A. significantly stimulate the synthesis of mucus components (polysaccharides and glycoproteins).

B. prevent aspirin from damaging the mucosal barrier.

C. improve the microcirculation of the stomach wall.

D. As a powerful cytoprotective agent, it can resist ulcers caused by various necrotic substances. It can also reduce the secretion of acid and pepsin, thus weakening the role of attack factors at the same time.

Zinc acexamate has no serious side effects, only a few patients have dizziness, headache, nausea and vomiting. Common dosage: 300mg orally, three times a day.

⑥ Teprenone: It is a derivative of terpene. It can promote the secretion of gastric mucus and the regeneration of epithelial cells on the mucosal surface, thus reducing the damage of gastric mucosa and repairing damaged gastric mucosa and even ulcers. Mainly suitable for gastritis and gastric ulcer. Usage and dosage: Take orally, 50mg once, three times a day, within 30min after meals.

⑦ Maizilin -S granules: it is a compound preparation. It belongs to a gastric mucosal protective drug, which is suitable for treating gastritis and can be used as an auxiliary treatment of traditional therapy for peptic ulcer. Usage and dosage: Take orally, 65438+ 0.5 ~ 2.0g daily, divided into 3 ~ 4 times, after meals.

8 anti-gastrin: proglumide is a derivative of isoglutamic acid, which can reduce gastric acid secretion. The usual dose is 400 mg three times a day. Side effects include mild insomnia, fatigue, dry mouth and dizziness.

(3) Drugs to eradicate Hp: mainly antibacterial drugs, bismuth salts and proton pump inhibitors.

At present, most people are in favor of eradicating Hp for all patients with peptic ulcer infection. Eradication of Hp can reduce ulcer recurrence and prevent ulcer aggravation.