Antisecretory drugs in the treatment of peptic ulcer. Forms of release and method of application

The use of anticholinergics as antiulcer drugs explained by a decrease in the production of hydrochloric acid and pepsin, prolongation of the effect of antacids, and a decrease in the motor activity of the stomach and duodenum. At the same time, the use of drugs such as atropine, platiphylline and metacin in the treatment of peptic ulcer is inappropriate due to the systemic anticholinergic effect and, as a consequence, the high frequency of adverse reactions (dry mouth, impaired accommodation, tachycardia, constipation, urinary retention , dizziness, headache, insomnia).

Atropine and atropine similar drugs contraindicated for glaucoma, adenoma prostate gland, heart failure. Their use is undesirable in case of cardia insufficiency and gastroesophageal reflux, which often accompany peptic ulcer disease, since in such cases the backflow of acidic gastric contents from the stomach into the esophagus may increase. In addition, it has been established that the antiulcer activity of traditional (non-selective) anticholinergic drugs is insufficient. So, antisecretory effect

platyphyllinum turned out to be weak, and atropine - short-lived. Therefore, atropine, platyphylline and metacin in last years in the treatment of peptic ulcers they were rarely used, giving way to the selective drug pirenzepine.

PIRENZEPINE(Gastrocepin, Gastrozem)

Pharmacodynamics

The mechanism of action differs from atropine and other anticholinergics. Selectively blocks predominantly the cholinergic receptors of the fundic glands of the gastric mucosa, without affecting the cholinergic receptors of the salivary and bronchial glands in therapeutic doses, of cardio-vascular system, eye tissues, smooth muscles.

The leading mechanism of the antiulcer effect of pirenzepine is the suppression of hydrochloric acid secretion. When taken orally, the maximum antisecretory effect is observed after 2 hours and continues, depending on the dose taken- from 5 to 12 hours. It should be emphasized that in terms of the level of antisecretory activity, pirenzepine is inferior to both PPIs and H2 blockers.

Pirenzepine somewhat slows down gastric emptying, but, unlike non-selective anticholinergic drugs, when taken orally in average therapeutic doses does not reduce the tone of the lower esophageal sphincter. With intravenous administration of the drug, sphincter tone and esophageal peristalsis decrease.

Pharmacokinetics

Bioavailability when taken orally on an empty stomach averages 25%. Food reduces it to 10-20%. The maximum concentration of the drug in the blood serum develops 2-3 hours after oral administration and 20-30 minutes after intramuscular injection. Despite some structural similarities with tricyclic antidepressants, it does not penetrate the blood-brain barrier. Only about 10% of the drug is metabolized in the liver. Excretion occurs primarily through the intestines and V to a lesser extent - through the kidneys.

Half-life -11 hours.

ClinicalefficiencyAndreadingsToapplication

Over the years, many works have been published indicating sufficient high efficiency pirenzepine in the treatment of exacerbations of gastric and duodenal ulcers. It was noted, in particular, that the drug was able to quickly relieve pain and dyspeptic disorders. Pirenzepine did not have hepatotoxic or nephrotoxic effects and was effective in patients with so-called “hepatogenic” ulcers, usually resistant to treatment, in patients with chronic renal failure, in elderly people.

Since pirenzepine is not included in HP eradication regimens, its use is currently limited. Used to prevent the occurrence of “stress” ulcers, with chronic gastritis with increased secretory function, erosive esophagitis, reflux esophagitis, less often with US\ drome-£ fire— Elg#sst".

Unwantedmedicinalreactions

Sometimes dry mouth, accommodation disorders are observed, and less commonly, constipation, tachycardia, and headaches. Moreover, the frequency of their occurrence clearly correlates with the dose. In most cases, ADRs are mild and do not require discontinuation of the drug.

Pirenzepine usually does not cause an increase in intraocular pressure, urinary disturbances or adverse reactions from the cardiovascular system. However, in case of glaucoma, prostate adenoma and a tendency to tachycardia, the drug should be prescribed with caution.

Medicinalinteraction

Pirenzepine reduces the stimulating effect of alcohol and caffeine on gastric secretion. The simultaneous administration of pirenzepine and H 2 blockers leads to potentiation of the antisecretory effect, which can be used in patients with Zollinger-Ellison syndrome.

DosageAndwaysapplications

Orally 50 mg 2 times a day (morning and evening) half an hour before meals. The duration of the course is usually 4-6 weeks. For maintenance therapy - 50 mg per day.

Intravenously or intramuscularly - for very persistent pain syndrome (for example, with Zollinger-Ellison syndrome) - 10 mg 2-3 times a day. IN/ V the introduction is carried out slowly in a stream or (better) drip.

Formsrelease

Tablets of 25 and 50 mg; ampoules 10 mg/2 ml.

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Selective anticholinergics (M - anticholinergics)

Anticholinergics reduce acid production, inhibit the release of gastrin, reduce the production of pepsin, prolong the effect of antacids, enhance the buffering properties of food, reduce motor activity stomach and 12th intestine.

At the same time, the use of drugs such as atropine, platifillin and metacin in the treatment of peptic ulcer is limited due to the systemic nature of their anticholinergic action and, as a consequence, the high frequency adverse reactions. The latter include dry mouth, impaired accommodation, tachycardia, constipation, urinary retention, dizziness, headache, insomnia.

Atropine and atropine-like drugs are contraindicated in glaucoma, prostate adenoma, and heart failure. Their use is undesirable in case of cardia insufficiency and gastroesophageal reflux, which often accompany peptic ulcer disease, since in such cases the backflow of acidic gastric contents from the stomach into the esophagus may increase. Wide Application in clinical practice, I found the drug pirenzepine (gastrocepin), which also blocks cholinergic receptors, but in its mechanisms of action is significantly different from atropine and other anticholinergics.

Pirenzepine is a selective anticholinergic drug that selectively blocks predominantly M?-cholinergic receptors of the fundic glands of the gastric mucosa and does not affect the cholinergic receptors of the salivary and bronchial glands, the cardiovascular system, eye tissue, and smooth muscles in therapeutic doses. Despite its structural similarity to tricyclic antidepressants, pirenzepine does not cause adverse reactions from the central nervous system, since, having predominantly hydrophilic properties, it does not penetrate the blood-brain barrier.

-- Pharmacodynamics

The leading mechanism of pirenzepine in peptic ulcer disease is the suppression of hydrochloric acid secretion. When taken orally, the maximum antisecretory effect is observed after 2 hours and lasts, depending on the dose taken, from 5 to 12 hours. Night secretion of hydrochloric acid is inhibited by 30-50%, basal secretion by 40-60%, and secretion stimulated by pentagastrin by 30-40%. Pirenzepine suppresses basal and stimulated production of pepsin, but does not affect the secretion of gastrin and a number of other gastrointestinal peptides (somatostatin, neurotensin, secretin).

Pirenzepine somewhat slows down gastric emptying, but unlike non-selective anticholinergic drugs, when taken orally in average therapeutic doses does not reduce the tone of the lower esophageal sphincter. With intravenous administration of the drug, sphincter tone and esophageal peristalsis decrease.

The effectiveness of pirenzepine in the treatment of peptic ulcers was initially explained by its antisecretory activity. However, subsequent work showed that the drug has a cytoprotective effect, that is, the ability to increase the protective properties of the gastric mucosa. This effect is to some extent related to the ability to expand blood vessels stomach and increase mucus formation.

-- Pharmacokinetics

Bioavailability when taken orally on an empty stomach averages 25%, food reduces it to 10-20%. The maximum concentration of the drug in the blood serum develops 2-3 hours after oral administration and 20-30 minutes after intramuscular administration. Only about 10% of the drug is metabolized in the liver. Excretion occurs primarily through the intestines and, to a lesser extent, through the kidneys. The half-life is 11 hours.

--Clinical efficacy and indications for use

Over the past years, many studies have been published indicating the fairly high effectiveness of pirenzepine in the treatment of exacerbations of peptic ulcer and colon 12. In particular, the drug’s ability to quickly relieve pain and dyspeptic disorders was noted. Pirenzepine did not have hepatotoxic or nephrotoxic effects and was effective in patients with so-called “hepatogenic” ulcers, usually resistant to treatment, in patients with chronic renal failure, and in the elderly. There are reports of successful use of the drug in the treatment erosive and ulcerative lesions gastric mucosa caused by taking non-steroidal anti-inflammatory drugs.

In general, the use of pirenzepine at a dose of 100-150 mg per day allows achieving healing of ulcers of the 12th intestine within 4 weeks in 70-78% of patients. The drug can be used to prevent the occurrence of “stress” ulcers, as well as for preventive therapy.

-- Adverse reactions

Pirenzepine is generally well tolerated. Sometimes there is dry mouth, accommodation disorders, less often - constipation, tachycardia, headaches. Moreover, the frequency of their occurrence clearly correlates with the dose. Thus, when prescribing average therapeutic doses (100 mg per day), dry mouth occurs in 7-13% of patients, and impaired accommodation occurs in 1-4% of patients. At higher doses (150 mg per day), the frequency of these adverse reactions increases to 13-16% and 5-6%, respectively. In most cases, adverse reactions are mild and do not require discontinuation of the drug.

Pirenzepine usually does not cause increased intraocular pressure, urination problems, or adverse reactions from the cardiovascular system. However, in case of glaucoma, prostate adenoma and a tendency to tachycardia, the drug should be prescribed with caution.

-- Drug interactions

Pirenzepine - stimulating effect of alcohol and caffeine on gastric secretion. The simultaneous administration of pirenzepine and H?-blockers leads to potentiation of the antisecretory effect, which can be used in patients with Zollinger-Ellison syndrome.

-- Dosage and methods of application

In case of exacerbation of peptic ulcer - 50 mg 2 times a day (morning and evening) half an hour before meals. The duration of the course is usually 4-6 weeks. For maintenance therapy - 50 mg per day.

Intravenously or intramuscularly - for very persistent pain syndrome (for example, in patients with Zollinger-Ellison syndrome) - 10 mg 2-3 times a day. Intravenous administration produced slowly in a stream or (better) drip.

-- Release form

Tablets of 25 and 50 mg; ampoules 10 mg/2 ml

Contents of the article:

Gastroenterologists always prescribe treatment for stomach ulcers and duodenum medications, since such serious diseases can only be dealt with through diet and folk remedies it can be difficult. The treatment regimen is always selected individually for each patient, although there are standard regimens that can also be used by the doctor.

Drugs that reduce the aggressiveness of gastric juice

Drug treatment of stomach and duodenal ulcers is not possible without drugs that act on gastric juice, reducing its aggressiveness. There are several groups like this medicines.

Peripheral M-anticholinergics and calcium channel blockers

Peripheral M-anticholinergics block all subtypes of M-cholinergic receptors. Previously, these medications were often used to treat ulcers (Atropine sulfate, Pirenzepine), but in recent years they have been used less frequently. Although they have antisecretory properties, the effect is much lower, but there are many side effects.
Blockers calcium channels are also rarely used. These are drugs such as Verapamil, Nifedipine. But if the patient has not only an ulcer, but also heart disease, the doctor may prescribe these medications.

H2-histamine receptor blockers

For stomach and duodenal ulcers, doctors often prescribe H2 receptor blockers, which have been used in medicine for more than 20 years. During this time, these drugs were well studied, doctors could not help but notice that it had become easier to treat ulcers. Thanks to the fact that these drugs began to be used, the percentage of scarring of ulcers became greater, the number of operations that had to be performed due to complications of the disease was reduced, and the treatment time was significantly reduced.

Another advantage of these drugs is that they increase the formation of mucus and improve microcirculation of the mucous membrane. However, these drugs cannot be abruptly discontinued, otherwise the patient may experience withdrawal syndrome, which will lead to increased acid secretion and relapse of the disease.

Generations of H2-histamine receptor blockers

There are several generations of H2-histamine receptor blockers.

1. First generation. Cimetidine. It only lasts 4-5 hours, so you need to take this medicine at least 4 times a day. It has many side effects, for example, it affects the liver and kidneys. Therefore, now these tablets are practically not used.
2. Second generation. Ranitidine. They last longer, 8-10 hours, and have fewer side effects.
3. Third generation. Famotidine. One of the best drugs, it is 20-60 times more effective than cimetidine and 3-20 times more active than rantidine. Must be taken every 12 hours.
4. Fourth generation. Nizatidine. Not much different from Famotidine, there are no special advantages over other drugs.
5. Fifth generation. Roxatidine. It is slightly inferior to Famotidine; it has less acid-suppressing activity.

Proton pump inhibitors

These medications block the production of hydrochloric acid. They are much more effective than H2 receptor blockers, which is why these medications are often prescribed for peptic ulcers.

1. Omeprazole. This medicine helps the ulcer heal faster. After 2 weeks of treatment, duodenal ulcers are scarred in 60% of patients, and after 4 weeks – in 93%. If you treat a stomach ulcer with Omeprazole, then after 4 weeks it will scar in 73% of patients, and after 8 weeks – in 91%.
2. Lanzoprazole. The patient should take 1 capsule for two or four weeks for duodenal ulcers and up to 8 weeks for gastric ulcers. This medicine should not be taken by pregnant women, nursing mothers or cancerous tumor in the gastrointestinal tract.
3. Pantoprazole. You should not take this drug if you have hepatitis or cirrhosis of the liver. The recommended dose is from 40 to 80 mg per day, the course of treatment lasts 2 weeks for exacerbation of duodenal ulcer and 4-8 weeks for exacerbation of gastric ulcer.
4. Esomeprazole. It is used to treat duodenal ulcers (20 mg 1 week, taken with antibiotics to get rid of Helicobacter pylori) and as a prophylactic for stomach disease (also 20 mg 1 time per day for 1-2 months with long-term use NSAIDs).
5. Paries. This is a modern medicine that rarely causes side effects, moreover, it has a more persistent antisecretory effect, so already on the first day treatment will be lost heartburn and pain.

Antacids

Antacids neutralize hydrochloric acid, which is part of gastric juice. They are often prescribed for ulcers, as additional remedy. They help relieve pain and also reduce the intensity of heartburn. These drugs act quickly, much faster than other drugs, but they have a shorter therapeutic effect.

1. Almagel. Contains magnesium hydroxide and aluminum hydroxide. The medicine envelops the stomach and protects its walls; it is also an adsorbent. Cannot be used for Alzheimer's disease and liver diseases. If the patient has a duodenal ulcer or stomach ulcer, you need to drink this remedy between meals, 1 spoon up to 4 times a day. The course of treatment is from 2 to 3 months.
2. Phosphalugel. Contains aluminum phosphate. Removes gases in the intestines and collects toxins, harmful microelements, envelops the mucous membrane. For ulcers, take this medicine a couple of hours after eating or when pain occurs, dissolving the contents of the sachet in half a glass of water.
3. Maalox. When treating ulcers, drink 1 sachet dissolved in water half an hour before meals. It is an analogue of Almagel, but its effect is 2 times longer, and it does not provoke constipation, like Almagel.

Antibacterial drugs

Often peptic ulcers are caused by Helicobacter bacteria pylori To cure this disease, it is necessary to carry out antibacterial therapy. The doctor may prescribe 1 or 2 courses of antibiotics, as well as bismuth-based drugs.

Antibiotics

The following antibiotics may be prescribed:

1. Amoxicillin. This is a bactericidal drug that is used for gastritis, if it is necessary to treat duodenal ulcers or stomach ulcers caused by Helicobacter pylori bacteria. 250-500 mg of medication is prescribed every 8 hours.
2. Clarithromycin. This medicine is also used in the treatment of peptic ulcers, but only in combination with other drugs. Contraindicated in the first trimester of pregnancy and while breastfeeding.
3. Tetracycline. There are several types of this medicine, but tablets are used to treat ulcers. They are not prescribed to children under 8 years of age, pregnant women and nursing mothers, and people with kidney or liver dysfunction. Do not drink at the same time as antacids.

Preparations based on bismuth

These bismuth-based medications also help destroy bacteria:

1. De-nol. This drug is taken for stomach or duodenal ulcers, as it has bactericidal activity. It is also an anti-inflammatory agent. It protects the mucous membrane by increasing mucus production and also by creating a protective film on the surface of the ulcer or erosion. The course of treatment lasts from 4 to 8 weeks; for the next 8 weeks you should not take medications with bismuth.
2. Tribimol. These are tablets that take 120 mg up to 4 times a day, half an hour before meals or 2 hours after meals, with water. The course of treatment is 28-56 days, after which a break of 8 weeks is required.
3. Vikalin. Combination drug, which contains not only bismuth subnitrate, but also buckthorn bark, calamus root and other components. It also has an antacid effect, relieves pain, and helps get rid of constipation. The course of treatment is 1-3 months, treatment can be repeated after a month.

Treatment with medications of this group not only helps to cope with Helicobacter pylori, but also promotes rapid healing of the ulcer.

Medicines that increase the protective properties of the mucous membrane

There are drugs that increase the protective properties of the mucous membrane. All of them can be divided into two groups.

Medicines that improve the protective properties of mucus

The first is medications that increase the production of mucus and its protective properties. The attending physician may prescribe them for stomach ulcers, since for duodenal ulcers these drugs are less effective. These include the well-known De-nol, as well as the following medications:

1. Sodium carbenoxolone, which is synthesized from the acid contained in licorice root. Side effects include increased blood pressure, the appearance of edema. This medicine is not prescribed to pregnant women and children, people with arterial hypertension, heart failure, and with caution to the elderly.
2. Sucralfate. This drug also applies to absorbents and antacids. Used for stomach and duodenal ulcers. Not prescribed for kidney disease, bleeding in the gastrointestinal tract, or for young children (under 4 years old).
3. Enprostil. It also has antisecretory properties, increases the stability of the mucous membrane, and promotes the healing of ulcers.

Drugs that restore mucous membranes

For duodenal ulcers, treatment includes medications that accelerate the healing of the mucosa. They also help with stomach ulcers and other diseases. gastrointestinal tract.

1. Liquiriton. Active ingredient is an extract of the root of naked licorice and Ural licorice, this is a drug plant origin. It has an anti-inflammatory effect, relieves pain, and is also an antacid.
2. Solcoseryl. Activates metabolic processes in tissues, promotes their regeneration, rapid recovery and healing. Made from the blood fraction of calves. It is available in the form of gels, ointments, and so on, but dragees are used to treat ulcers.
3. Methyluracil. This is an anti-inflammatory drug that stimulates the human immune system and accelerates tissue growth. For diseases of the digestive system, tablets are used, which the patient can take for about 30-40 days, 4 times a day.

We talked about the main medications that are often prescribed for ulcers. But the choice of drugs is the prerogative of the doctor; it is the gastroenterologist who must decide which pills the patient should take, and which in this case it is better to refuse. Therefore, self-medication is not allowed; all drugs must be prescribed after thorough examination. The doctor not only prescribes treatment, but also monitors its effectiveness and may change the treatment regimen if the previous one did not help the patient.

He or she may prescribe other medications, such as pain management medications or probiotics after antibiotic treatment. You should trust the doctor’s opinion and follow his instructions. If you have doubts about his competence, you do not need to change the treatment regimen yourself; it is better to find another doctor whom you can completely trust.

Anticholinergics are substances that block or weaken the effects of acetylcholine, which is responsible for the presence of excitation of the nervous system. Depending on which structure of the body the anticholinergic compounds act on, there are ganglion-blocking, curare-like, central and atropine-like drugs.

Due to the ability to influence the neuro-reflex regulation of the body, they have important practical significance.

The most common natural anticholinergics are:

• • • alkaloids (atropine, scopolamine, platyphylline);
    • preparations that include belladonna, datura, henbane (used independently and in combination).

Widespread use today is also found in synthetic drugs. They contain compounds that have a more diverse effect, making them very convenient for use in practice, and the occurrence of adverse reactions is significantly reduced. In addition, most anticholinergics have analgesic and antispasmodic effects. Some other antihistamine and local anesthetic anticholinergics also have the features that characterize a group of similar medications. Among them are diprazine and diphenhydramine.

Anticholinergics: classification, list of drugs

In my own way chemical structure All anticholinergics are quite diverse. In addition, depending on the ability to block different kinds The effects of acetylcholine are distinguished:

• • m-anticholinergics;
  • n-anticholinergics.

m-Anticholinergics

Alkaloids:

• • • atropine;
    • platiphylline;
    • scopolamine

Anticholinergics of plant origin:

• • • belladonna leaves,
    • henbane,
    • Datura,
    • godson.

Semi-synthetic:

• • • homatropine

Synthetic:

• • • arpenal
    • aprofen,
    • ipratropium bromide,
    • pirenzepine,
    • metacin,
    • propenteline,
    • antispasmodic,
    • chlorosyl, etc.

Scope of use:

• • • bronchospasm;
    • preoperative premedication (prevention of hypersalivation, broncho- and laryngospasm);
    • disorders of atrioventricular and intraatrial conduction;
    • vagotonic bradycardia;
    • peptic ulcer of the duodenum and stomach;
    • spasms of smooth muscle organs (intestinal and hepatic colic, pylorospasm, etc.);
    • iritis, iridocyclitis and eye injuries (to relax the eye muscles);
    • parkinsonism and some other diseases of the central nervous system.
    • acute poisoning with anticholinesterase and cholinomimetic poisons.

M-anticholinergics are also used in diagnostic purposes, for example, when examining the gastrointestinal tract with an X-ray or when examining the fundus (to dilate the pupil).

Contraindications:

• • • glaucoma,
    • status asthmaticus,
    • atonic constipation;
    • prostatic hypertrophy and bladder atony.

Central anticholinergics (arpenal, aprofen, antispasmodic, scopolamine) should not be used by persons before or during administration vehicles or engaged in processes that require quick reactions and concentration.

n-Anticholinergics

They are divided into 2 groups:

Ganglioblocking anticholinergics

Block n-cholinergic receptors of ganglia.

• • • Benzohexonium
    • Hygronia
    • Dimecoline
    • Imekhin
    • Kamphonium
    • Quateron
    • Pahikarpin
    • Pentamin
    • Pyrylene
    • Temekhin
    • Fubromegan

Scope of use

Ganglion blocking anticholinergics are mainly used as vasodilators and antihypertensive drugs. For example:

• • • for spasms peripheral vessels(Raynaud's disease, obliterating endarteritis);
    • to relieve hypertensive crises;
    • for controlled hypotension;
    • for the treatment of duodenal and gastric ulcers (sometimes)
    • for systematic treatment arterial hypertension(rarely).

Side effects

The use of ganglion-blocking cholinergic drugs is limited due to severe side effects:

• • • dilated pupils;
    • dry mouth,
    • violation of accommodation;
    • decrease in venous pressure
    • orthostatic hypotension, etc.

Contraindications

• • • angle-closure glaucoma,
    • arterial hypotension,
    • acute myocardial infarction,
    • liver and kidney damage,
    • thrombosis.

Curare-like anticholinergics

They block n-cholinergic receptors at the neuromuscular synapses of skeletal muscles.

• • • Dioxonium
    • Ditilin
    • Melliktin
    • Pancuronium
    • Pipecuronium
    • Tubocurarine chloride

Areas of use

Curare-like anticholinergics are used mainly in anesthesiology to relax skeletal muscles:

• • • during surgical interventions,
    • endoscopic manipulations
    • when reducing dislocations, repositioning bone fragments.

Besides, curare-like agents used in complex therapy tetanus. The drug Mellictin is often used to reduce muscle tone with neurological diseases which are accompanied by disorders motor functions and increased skeletal muscle tone.

Side effects

• • • Tubocurarine chloride reduces blood pressure, which can cause laryngospasm and bronchospasm, dioxonium, diplacin tachycardia, pancuronium.
    • ditilin increases blood pressure and intraocular pressure, which can provoke cardiac arrhythmias.
    • When using depolarizing curare-like anticholinergics, pain in the skeletal muscles is observed.

Contraindications

• • • myasthenia gravis.
    • dysfunction of the liver and kidneys.
    • glaucoma
    • infants.

Carefully:

• • • elderly age;
    • pregnancy;
    • anemia;
    • cachexia.

Anticholinergics: indications for use

Today, anticholinergics are widely used in various areas medicine. The classification of their application is as follows:

• • 1. Use in a therapeutic clinic when treatment of diseases characterized by spasms is necessary smooth muscle. Here, drugs that combine neurotropic and myotropic effects and also have a selective antispasmodic effect are relevant.
    2. For diseases of the duodenum and stomach ulcers, anticholinergic drugs are used, which have antispasmodic activity and the ability to reduce the secretion of gastric juice.
    3. Use in the presence of disorders of the functionality of the nervous system. Widespread use is observed in the treatment of parkinsonism and Parkinson's disease.
    4. Sometimes drugs with similar effects are used in psychiatry, as tranquilizers.
    5. In anesthesiological practice, the effect of narcotic and sleeping pills is enhanced with the help of anticholinergic drugs.
    6. Use in the prevention and treatment of air and sea diseases.
    7. Often, such drugs are used as antidotes for intoxication of the body with toxic substances.

Overdose

When observed long-term use anticholinergics, their effect may decrease. Because of this, in the process of treating chronic diseases, doctors recommend sometimes changing medications.

In some cases, toxic side effects may occur. This usually occurs with overdose and increased sensitivity. The most common side effect are the following symptoms:

• • • development of tachycardia,
    • dry mouth,
    • the appearance of improper accommodation.

If central anticholinergics are taken, this can provoke the following dysfunctions of the nervous system:

• • • headaches and dizziness,
    • feeling of a dope in the head,
    • the appearance of hallucinations.

During use, you must be careful in doses and do not forget about individual characteristics. Even an overdose of small doses can cause tachycardia and dry mouth. If poisoning occurs, it is necessary to inject proserin intravenously. The most serious contraindication to the use of anticholinergics is the presence of glaucoma.

I created this project to in simple language tell you about anesthesia and anesthesia. If you received an answer to your question and the site was useful to you, I will be glad to receive support; it will help further develop the project and compensate for the costs of its maintenance.

For quotation: Sheptulin A.A. BASIC DRUG THERAPY OF Peptic Ulcer // Breast Cancer. 1998. No. 7. S. 1

The concepts of “anti-ulcer treatment” and “anti-Helicobacter therapy” are not synonymous. Treatment of stomach and duodenal ulcers should be comprehensive; its goal is to relieve symptoms of exacerbation of peptic ulcer disease, to achieve (as possible short time) scarring of the ulcerative defect and prevention of relapse of the disease. The right combination Basic antiulcer drugs with eradication anti-Helicobacter therapy can successfully solve these problems.

The terms "antiulcerative treatment" and "antihelicobacter therapy" are not synonyms. The treatment of ulcerative lesions of the stomach and duodenum remains complex, its goal is to alleviate the symptoms of an exacerbation of peptic ulcer, to ensure ulcerative defect healing (in the shortest time) and to prevent recurrences. A correct combination of basic antiulcertaive agents and eradicative antihelicobacter therapy may solve these problems successfully.

A.A. Sheptulin, prof. Department of Propaedeutics of Internal Diseases of the Moscow Medical Academy named after. THEM. Sechenov
A.A. Sheptulin, prof. Department of Internal Propedeutics, I.M.Sechenov Moscow Medical Academy

D Advances in the study of the pathogenesis of peptic ulcer disease in recent years, associated primarily with the identification of Helicobacter pylori (HP), have forced a radical reconsideration of previously existing approaches to pharmacotherapy of this disease. Thus, now no antiulcer treatment regimen can be considered scientifically grounded if it does not involve mandatory eradication of HP in the gastric mucosa. The vast majority of works devoted to the problems of pharmacotherapy of peptic ulcer disease touch upon certain aspects of eradication therapy. In this regard, some practitioners sometimes ask the question whether the concept of “anti-ulcer treatment” should be replaced by another - “anti-Helicobacter therapy”.
When answering this question, we always emphasize that the concepts of “anti-ulcer treatment” and “anti-Helicobacter therapy” are far from the same thing. Among the many tasks that have to be solved during anti-ulcer treatment, the most important are the following: relief of symptoms of exacerbation of peptic ulcer disease (pain and dyspeptic disorders), achievement (as soon as possible) of scarring of the ulcer defect and prevention of subsequent relapses of the disease. Anti-Helicobacter therapy, despite its exceptional importance, solves only the third problem, contributing to a significant reduction in the frequency of relapses of peptic ulcer disease during the year from 70 to 4 - 5%. When conducting anti-Helicobacter therapy, we do not set the goal of relieving pain and dyspeptic disorders (moreover, the latter may arise during its implementation). We are not We strive to achieve healing of the ulcerative defect through HP eradication, and to achieve this in 7 days (and this is the current duration of many eradication treatment regimens is impossible even theoretically. The mentioned problems are solved with the help of basic therapy, carried out not with anti-Helicobacter drugs, but with antiulcer drugs.
The variety of various pathogenetic factors of peptic ulcer disease led to the emergence of large number various drugs that, as originally assumed, acted on certain links in the pathogenesis of the disease. However, the effectiveness of many of them (for example, sodium oxyferriscarbon) has not been confirmed in clinical practice. Instead of drugs with wide range pharmacological action on various organs and body systems, drugs appeared that selectively affect only certain parts of the process of hydrochloric acid secretion. As a result, the extensive, if not exorbitantly expanded, arsenal of antiulcer drugs has undergone significant revision and radical reduction.
In 1990, W. Burget et al. published the results of a meta-analysis of 300 studies, which made it possible to establish a clear connection between the effectiveness of a particular antiulcer drug and the duration of the increase in pH in the gastric lumen during its use. The authors concluded that gastric ulcers heal in 100% of cases if intragastric pH can be maintained above 3.0 for about 18 hours per day. This fundamental conclusion, which is now referred to by the authors of almost all serious works on the pharmacotherapy of peptic ulcer disease, has made it possible to reduce the list of main antiulcer drugs. medicines, used during exacerbation of peptic ulcer for relief clinical manifestations diseases and achieving healing of the ulcer, to several main groups of drugs. These included antacids, selective anticholinergics, H blockers 2 -receptors and inhibitors proton pump.
Even in this much abbreviated form, the pharmacopoeia of antiulcer drugs confronts the practitioner with the need to decide which drug to choose. There is still no clear answer to this question in the literature, and the specific recommendations proposed in the works often differ significantly from each other.

The severity of peptic ulcer disease also varies among different patients, and therefore they may require medications that differ in the severity of the antisecretory effect. At favorable course peptic ulcer disease, rare and short-lived exacerbations, small ulcer sizes, moderate increase in acid production, absence of complications, drugs that do not have pronounced antisecretory activity can be used as basic therapy drugs and when prescribed in average therapeutic doses, capable of maintaining the level of intragastric pH above 3.0 only comparatively a short time(up to 8 - 10 hours per day), - antacids and selective M-anticholinergics.
In case of frequent and prolonged exacerbations of peptic ulcer disease, large (more than 2 cm in diameter) size of the ulcerative defect, severe hypersecretion of hydrochloric acid, the presence of complications (including a history), concomitant erosive esophagitis, N should be used as basic therapy. 2 - blockers and proton pump inhibitors that maintain the required intragastric pH levels for a much longer time (up to 12 - 18 hours per day).
Antacids. Traditionally, this group of drugs includes absorbable (sodium bicarbonate, calcium carbonate, magnesium oxide) and non-absorbable (aluminum hydroxide and aluminum phosphate, magnesium hydroxide and magnesium trisilicate) antacids. Drugs of the first subgroup cause serious adverse reactions(emphasis carbon dioxide, the “rebound” phenomenon, the development of alkalosis and “milk-alkali syndrome”), and therefore are not currently used in clinical practice.
The acid neutralizing activity of antacids (ANA) is determined by their ability to neutralize H+ ions and is expressed in milliequivalents of neutralized hydrochloric acid. In addition, antacids reduce the proteolytic activity of gastric juice (both through the adsorption of pepsin and by increasing the pH of the environment, as a result of which pepsin becomes inactive), have good enveloping properties, and bind lysolecithin and bile acids.
In recent years, data have been published on the cytoprotective effect of antacids containing aluminum hydroxide, their ability to prevent in experiment and in clinical settings the occurrence of damage to the gastric mucosa caused by ethanol and non-steroidal anti-inflammatory drugs. It was found that this cytoprotective effect is associated with an increase in the content of prostaglandins in the gastric wall when taking antacids. In addition, antacid preparations containing aluminum hydroxide stimulate the secretion of bicarbonates and increase the production of gastric mucus, have the ability to bind epithelial growth factor and fix it in the area of ​​the ulcer, thereby stimulating cell proliferation, development vascular network and tissue regeneration.
In the treatment of peptic ulcers, antacids are usually recommended as adjuvant drugs in addition to other antisecretory drugs, the main ones being way as a symptomatic remedy (for the relief of pain and dyspeptic disorders). The attitude of many gastroenterologists to the possibility of using antacids in the treatment of peptic ulcers as the main drugs remains skeptical to this day: it is believed that these drugs are significantly inferior in their effectiveness to other antiulcer drugs. In addition, the opinion was expressed that for a course of treatment of exacerbation of peptic ulcer disease, very high doses antacids and their frequent use.
Works published in recent years have allowed us to reconsider this point of view. Representative symposia on clinical aspects antacid therapy, carried out in Bermuda (1991) and Budapest (1994), showed the inconsistency of the expressed concerns. The healing rate of duodenal ulcers after 4 weeks of treatment with antacid drugs averaged 73%, which significantly exceeded the effectiveness of placebo.
In addition, it was found that the doses of antacids required for healing of ulcers were not as high as previously thought, and that during a course of therapy, the daily ANA of antacids may not exceed 200 - 400 mEq. The results obtained make it possible to use antacids for basic treatment exacerbations of peptic ulcer disease as monotherapy, but only with mild flow diseases. An important advantage of antacids here is that after taking a single dose they relieve pain and dyspeptic disorders much faster than antisecretory drugs (including N 2-blockers and omeprazole). In more severe cases, antacids can be used as symptomatic agents against the background of basic therapy carried out by other, more powerful antisecretory drugs.
Pirenzepine. It is a selective anticholinergic drug. It selectively blocks predominantly M-cholinergic receptors of the fundic glands of the gastric mucosa and does not affect the cholinergic receptors of the cardiovascular system. Unlike anticholinergics with a systemic mechanism of action, it does not cause side effects (tachycardia, accommodation disturbances, urinary retention, etc.).
The leading mechanism of the antiulcer effect of pirenzepine is associated with the suppression of hydrochloric acid secretion. When taken orally, the maximum antisecretory effect of the drug is observed after 2 hours and persists (depending on the dose taken) from 5 to 12 hours. Last works showed that this drug also has a cytoprotective effect, which is believed to be associated with the ability of pirenzepine to dilate the blood vessels of the stomach.
The use of pirenzepine in a dose of 100 - 150 mg allows achieving healing of duodenal ulcers within 4 weeks in 70 - 75% of patients, which can be considered a fairly good result.Not having such high antisecretory activity as omeprazole and H blockers 2 -receptors, it still gives a lower frequency of relapses compared to the above-mentioned drugs. This fact is due, in particular, to the fact that when using pirenzepine there is no increase in the level of gastrin in the blood, as is the case, for example, when using proton pump blockers. There have already been recommendations to prescribe pirenzepine after treatment with omeprazole in order to reduce the concentration of serum gastrin.
N 2 -blockers. H blockers 2 -receptors are among the most common antiulcer drugs currently used. Several generations of these drugs have now been used in clinical practice. After cimetidine, which for a number of years was the only representative of H 2 -blockers, ranitidine, famotidine, and a little later - nizatidine and roxatidine were sequentially synthesized.
High antiulcer activity H 2 -blockers is primarily due to their powerful inhibitory effect on the secretion of hydrochloric acid. In this case, the antisecretory effect after taking cimetidine lasts for 4 - 5 hours, after taking ranitidine - 8 - 9 hours, after taking famotidine, nizatidine and roxatidine - 10 - 12 hours.
H blockers 2 -receptors not only have an antisecretory effect, but also suppress basal and stimulated pepsin production, increase gastric mucus production, bicarbonate secretion, improve microcirculation in the mucous membrane of the stomach and duodenum, normalize gastroduodenal motility.
When using N 2 -blockers for 2 weeks, pain in the epigastric region and dyspeptic disorders disappear in 56 - 58% of patients with exacerbation of gastric and duodenal ulcers. After 4 weeks of treatment, scarring of duodenal ulcers is achieved in 75 - 83%, after 6 weeks - in 90 - 95% of patients. Frequency of scarring of gastric ulcers after 6 weeks of treatment N 2 -blockers is 60 - 65%, after 8 weeks of treatment - 85 - 70%. At the same time, a single dose of all daily dose N 2-blockers at bedtime (ie, for example, 300 mg ranitidine or 40 mg famotidine) are as effective as taking half doses twice (morning and evening).
The accumulated experience with the use of cimetidine has shown that this drug causes a variety of side effects. These include an antiandrogenic effect, hepatotoxic effect, various cerebral disorders, increased creatinine levels in the blood, changes in hematological parameters, etc. Ranitidine and famotidine, significantly superior to cimetidine in antisecretory activity, give less pronounced side effects. As for H 2 -blockers of subsequent generations (nizatidine and roxatidine), then they, while also noticeably superior to cimetidine, do not have any special advantages over ranitidine and famotidine and therefore widespread have not received.
Proton pump inhibitors. Proton pump inhibitors (H inhibitors)+ , K + -ATPases of the parietal cell) currently occupy, perhaps, a central place in the range of antiulcer drugs. This is explained by the fact that their antisecretory activity (and, accordingly, clinical effectiveness) significantly exceeds that of other antiulcer drugs. In addition, proton pump inhibitors create favorable conditions for anti-Helicobacter therapy, and therefore they are now included as a mandatory component in most eradication regimens. Of the drugs in this group, omeprazole, pantoprazole and lansoprazole are currently used in clinical practice.
Being benzimidazole derivatives, proton pump inhibitors, accumulating in the secretory tubules of the parietal cell, are converted into sulfenamide derivatives, which form covalent bonds with cysteine ​​H molecules+ , K + -ATPases and thereby inhibit the activity of this enzyme.
When taking an average therapeutic dose of these drugs once a day, gastric acid secretion throughout the day is suppressed by 80 - 98%. Essentially, proton pump blockers are currently the only drugs that can maintain intragastric pH levels above 3.0 for more than 18 hours a day and thus satisfy the requirements formulated by D. Burget et al. for ideal antiulcer agents.
Multicenter and meta-analytic studies have shown that proton pump inhibitors are by far the most effective antiulcer drugs. In 69% of patients with duodenal ulcers, scarring of the ulcer occurs within 2 weeks of therapy. After 4 weeks of treatment with proton pump inhibitors, the rate of scarring of duodenal ulcers is 93 - 100%. These drugs give good effect and in patients with peptic ulcers resistant to therapy with H 2 blockers.
Omeprazole, pantoprazole and lansoprazole differ in their chemical structure, bioavailability, half-life, etc., however, their results clinical application turn out to be almost identical.
The safety of proton pump inhibitors during short (up to 3 months) courses of therapy is very high. With long-term (especially for several years) continuous use of these drugs, hypergastrinemia occurs in patients, and the symptoms progress atrophic gastritis, and some patients may develop nodular hyperplasia endocrine cells(ECL cells) of the gastric mucosa that produce histamine.
For an objective analysis of the results of antiulcer treatment great importance has strict adherence to the protocol for the treatment of exacerbation of peptic ulcer disease, which includes the prescription of the selected drug in the appropriate dose, a certain duration of treatment, certain terms of endoscopic monitoring, and standard criteria for assessing the effectiveness of treatment.
For example, during exacerbation of a peptic ulcer, ranitidine is prescribed at a dose of 300 mg/day, famotidine at a dose of 40 mg/day, omeprazole at a dose of 20 mg/day, etc. The duration of treatment is determined by the results of endoscopic monitoring, which is carried out at two-week intervals . To assess the effectiveness of a particular antiulcer drug, they calculate not the average time (as is practiced in many domestic works), but the frequency of scarring of ulcers over 4, 6, 8 weeks, etc. Compliance with the protocol makes possible to carry out multicenter and meta-analytic studies combining dozens and hundreds of studies performed in different countries, which makes it possible to assess with a high degree of reliability (since the number of patients reaches tens and hundreds of thousands of people) the effectiveness of the drug and the influence of certain factors on it.
Important feature Modern pharmacotherapy for peptic ulcer disease is the absence of fundamental differences in approaches to the treatment of gastric and duodenal ulcers. Previously, it was believed that duodenal ulcers required the use of antisecretory drugs, and stomach ulcers required drugs that stimulate regeneration processes. It is now generally accepted that after confirmation of the benign nature of gastric ulcers, the treatment of these patients is carried out in exactly the same way as the treatment of patients with duodenal ulcers. The only difference is the duration of the course of pharmacotherapy. Considering that gastric ulcers scar more slowly than duodenal ulcers, the results of scarring of gastric ulcers are monitored not after 4 and 6 weeks of treatment, as with duodenal ulcers, but after 6 and 8 weeks.
An important issue is the tactics of pharmacotherapy for patients with hard-to-heal ulcers of the stomach and duodenum. Gastroduodenal ulcers that do not scar within 12 weeks are usually called hard-to-heal (or long-term non-healing). Their frequency, which previously reached 10 - 15%, after introduction into clinical practice proton pump inhibitors decreased to 1 - 5%.
In cases of insufficient effectiveness H 2 -blockers (ranitidine, famotidine), it is currently considered most appropriate to increase their dose by 2 times or transfer the patient to take proton pump inhibitors. If the patient initially received usual doses proton pump inhibitors (for example, 20 mg omeprazole), then they are increased by 2- 3 times (i.e., adjusted to 40 - 60 mg/day). This scheme makes it possible to achieve healing of the ulcer in approximately half of the patients with difficult-to-scar ulcers.
The high frequency of relapses of gastroduodenal ulcers after cessation of course treatment served as the basis for the development of maintenance regimens of antiulcer drugs.
Maintenance therapy H2 remains the most common currently. - blockers, including daily intake 150 mg ranitidine or 20 mg famotidine at bedtime. This makes it possible to reduce the frequency of relapses of peptic ulcer disease within a year after the main course to 6 - 18%, and within 5 years - to 20 - 28%.
Later, continuous maintenance administration of antisecretory drugs was replaced by intermittent maintenance therapy regimens. These include “yourself treatment” or “on demand” therapy, when patients themselves determine the need to take medications based on their well-being, and the so-called “weekend treatment”, when the patient remains without treatment from Monday to Thursday and takes antisecretory drugs from Friday to Sunday. Intermittent maintenance therapy is less effective than daily medication, however, this method of maintenance treatment is better tolerated by patients.
Currently, when anti-Helicobacter therapy is recognized as the basis for anti-relapse treatment of peptic ulcers, the indications for maintenance therapy with basic antisecretory drugs have narrowed significantly. It is considered necessary for patients whose peptic ulcer is not accompanied by contamination of the gastric mucosa with HP (i.e. for 15 - 20% of patients with gastric ulcers and about 5% of patients with duodenal ulcers), for patients who have at least two attempts at anti-Helicobacter therapy were unsuccessful, also for patients with a complicated course of peptic ulcer disease (in particular, with a history of perforation of ulcers).
Thus, modern pharmacotherapy for peptic ulcer disease still remains complex. The correct combination of basic antiulcer drugs with eradication anti-Helicobacter therapy allows one to successfully solve the main tasks facing a doctor when treating a patient with an exacerbation of a peptic ulcer: relief of clinical symptoms, achieving scarring of the ulcer, preventing relapses after a course of treatment.

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