Properties and the possibility of prolonged use. General characteristics of prolonged dosage forms

Prolonged dosage forms - dosage forms with modified release, providing an increase in the duration of action of the drug by slowing down its release.

Requirements for prolonged LF:

1 - the concentration of the drug substance as it is released from the drug should not undergo significant changes and should be optimal in the body for a certain period of time;

2 - Excipients, introduced into the dosage form, must be completely excreted from the body or inactivated without adversely affecting it;

3 - ways to prolong the action should be simple and affordable in execution and should not have a negative effect on the body.

The problem of prolongation of oral preparations is more complicated than that of injectables, since the process of absorption of drugs through the cell membranes of the gastrointestinal tract is unique and has its own patterns.

According to the mechanism of action, long-acting drugs for oral administration are divided into two subgroups:

1. Repeated-acting drugs with periodic release of drugs (tablets Merkenzim, Wobe-Mugos E, Uniendzyme) these drugs release drugs after two or more specific periods of time;

2. Maintenance drugs with a constant uniform release of drugs (Naproxen bilayer tablets, Nitrong, Sustak retard tablets; buccal-Trinitrolong) drugs of maintenance action provide a constant concentration of drugs without pronounced extremes, do not overload the body with excessively high concentrations of drugs. One dose of drug is separated from another by a barrier layer, which can be film, pressed, coated. Depending on the composition of the shell, drugs can be released in the required section of the gastrointestinal tract, localization of their action is observed.

The range of coated tablets is quite wide. Repeated-acting drugs are given first high concentration The drug in the body, which falls rapidly, is followed by the release of another drug and its high concentration is observed. Consequently, repeated-acting drugs, in addition to the convenience of taking for the patient, do not have therapeutic advantages over the regular intake of single doses. As an example, let us consider the mechanism of drug release from tablets of repeated action containing enzymes of plant and animal origin and coated with shells (Merkenzim, wobe-mugos E).

Merkenzym contains bromelain 750 IU, pancreatin 400 mg, bovine bile 30 mg, a combined preparation containing enzymes of plant and animal origin. Used for digestive disorders of various genesis, pancreatitis. The outer shell contains bromelain, obtained from the fruit of pineapple.

The enzyme merkenzyme breaks down proteins at pH 3-8, both in the stomach and intestines. Pancreatin and bovine bile, which are under the acid-resistant membrane, are released in the small intestine. Pancreatin digests proteins, carbohydrates, fats. Bile breaks down animal fats and vegetable oils. In the presence of bile, the digestive capacity of pancreatic lipase increases.

Vobe-mugos E tablets contain papain 100 mg, trypsin and chymotrypsin 40 mg each. Papain is an enzyme derived from the dried milky juice of unripe fruits of the melon tree (papaya) that breaks down proteins like pepsin. Trypsin and chymotrypsin are pancreatic enzymes that are under an acid-resistant shell, which protects them from decomposition by gastric acid. Tablets activate antitumor immunity, normalize the concentration of cytokines, increase the effectiveness of radiation therapy and chemotherapy.

Supportive tablets include matrix tablets. In matrix tablets, excipients form a continuous mesh structure (matrix), in which the drug is evenly distributed. The matrix can slowly dissolve in the gastrointestinal tract or be excreted from the body as a porous mass, the vapors of which are filled with liquid. In the latter case, the tablets are called frame or skeletal. The matrix serves as a barrier that limits the contact of the drug with biological fluids and controls drug release.

Enteral prolonged forms are divided, depending on the type, into:

3-frame;

4-layered (repetabs);

5-multiphase;

6 tablets with ion exchangers;

7-"drilled" tablets;

8-tablets built on the principle of hydrodynamic balance;

9-tablets, sustained release, coated

Depot Forms- these are sterile trituration tablets with prolonged release of highly purified medicinal substances for injection under the skin. It is shaped like a very small disc or cylinder. These tablets are made without fillers. This dosage form is very common for the administration of steroid hormones. In foreign literature, the term "pellets" is also used.

Retard forms- enteral prolonged dosage forms that ensure the creation of a stock of the drug in the body and its subsequent slow release. Usually they are microgranules of a medicinal substance surrounded by a biopolymer matrix (base). They dissolve in layers, releasing another portion of the drug. They are obtained by pressing hard-core microcapsules on tablet machines.

Repetabs- These are tablets with a multilayer coating that provide repeated action of the drug substance. They consist of an outer layer with a drug that is designed to be released quickly, an inner shell with limited permeability, and a core that contains another dose of the drug.

Multilayer (layered) tablets make it possible to combine medicinal substances that are incompatible in terms of physicochemical properties, prolong the action of medicinal substances, regulate the sequence of absorption of medicinal substances at certain intervals.

For the production of multilayer tablets, cyclic tablet machines with multiple filling are used. The machines can carry out triple spreading, performed with different granules. Medicinal substances intended for different layers are fed into the feeder of the machine from a separate hopper. A new medicinal substance is poured into the matrix in turn, and the lower punch goes lower and lower. Each medicinal substance has its own shade or color, and their action is manifested in the order of dissolution of the layers. In these tablets, the layers of the drug substance alternate with layers of the excipient, which prevent the release of the active substance before being destroyed by various factors. gastrointestinal tract.

Frame tablets- This is a kind of tablets with a continuous, evenly extended release and supportive action of medicinal substances. A classic example of matrix technology.

To obtain them, excipients are used that form a matrix or a network structure in which the medicinal substance is included. Such a tablet resembles a sponge, the pores of which are filled with a soluble substance (a mixture of a medicinal substance with a soluble filler - sugar, lactose, etc.)

These tablets do not disintegrate in the gastrointestinal tract. Depending on the nature of the matrices, they can swell and dissolve slowly or retain their geometric shape during the entire period of stay in the body and be excreted as a porous mass, the pores of which are filled with liquid. Thus, the drug substance is released by washing out.

Auxiliary substances for the formation of matrices are divided into hydrophilic, hydrophobic, inert and inorganic.

Hydrophilic matrices - from swelling polymers (hydrocolloids): hydroxypropyl-, hydroxypropylmethyl-, hydroxyethylmethylcellulose, methyl methacrylate, etc.

Hydrophobic matrices - (lipid) - from natural waxes or from synthetic mono, di - and triglycerides, hydrogenated vegetable oils, higher fatty alcohols, etc.

Inert matrices are made from insoluble polymers: ethylC, polyethylene, polymethyl methacrylate, etc. To create channels in the water-insoluble polymer layer, water-soluble substances (PEG, PVP, lactose, pectin, etc.) are added. Washing out of the tablet frame, they create conditions for the gradual release of drug molecules.

To obtain inorganic matrices, non-toxic insoluble substances are used: Ca2HPO4, CaSO4, BaSO4, Aerosil

Tablets with ion exchangers- prolongation of the action of a medicinal substance is possible by increasing its molecule due to precipitation, on an ion-exchange resin. Substances bound to the ion exchange resin become insoluble, and the release of the drug into digestive tract based on ion exchange only.

For the production of tablets and granules with ion exchangers, various fillers are used, which release the medicinal substance as they break down. Thus, a mixture of a substrate with an enzyme is proposed as a filler. The core contains the active substance, which is covered by a shell. The drug shell contains a pharmacologically acceptable, water-insoluble, film-forming micromolecular component and a water-soluble blowing agent (cellulose ethers, acrylic resins and other materials). The creation of tablets of this type makes it possible to release macromolecules of active substances from them within a week.

"Perforated" tablets. The "drilling" of planes in tablets creates an additional phase interface between the tablet and the medium. This, in turn, causes a certain constant release rate of the drug, since as the active substance dissolves, the release rate decreases in proportion to the decrease in the surface area of ​​the tablet.

Hydrodynamically balanced tablets. These tablets are given such a balance of hydrodynamic properties that they are buoyant in gastric juice and retain this ability until the drug is completely released from them. Basically, this type of tablet is used to treat stomach diseases associated with hypersecretion of hydrochloric acid. Mostly antacids.

In injectable dosage forms, a slowdown in absorption can be achieved by the formation of labor-soluble compounds: salts, esters, and various complexes. An example is the various salts of penicillin and other antibiotics. Absorption delay possibly due to the formation of ethers active ingredients with fatty acids. Suction rate drug from an injection solution also depends on the viscosity of this solution: the use of numerous non-aqueous solvents is based on this principle, as well as the addition of special excipients - prolongators, such as polyvinylpyrrolidone, methylcellulose, dextrin, etc. to aqueous solutions. Of interest is the "transformation" injectables into microcrystalline suspensions. A microcrystalline suspension of insulin is widely known, which made it possible to reduce the number of frequent and painful injections in diabetes mellitus.

The problem of prolongation of oral dosage forms is more complex than injectable ones, since the process of absorption of medicinal substances through the cell membranes of the digestive tract is unique and is determined by more complex patterns. In this regard, according to the mechanism of action, prolonged-release oral dosage forms can be divided into dosage forms with periodic release of certain doses of the drug substance, those. repeated action; dosage forms with a constant uniform release of the drug substance, those. supportive drugs.

Repeated action drugs called preparations in which two or more doses of the active substance are released after several defined periods of time. They are usually produced in the form of tablets and dragees. In these dosage forms, one dose of the drug substance is separated from another by a barrier layer, which can be film, pressed or coated. Depending on its composition, a dose of a medicinal substance can be released after a given time, regardless of the localization of the drug in the gastrointestinal tract, or at a certain time in a certain department. So, when using acid-resistant coatings, one part of the drug is released in the stomach, and the other - in the intestines. Period general action At the same time, the drug is prolonged depending on the number of doses of the medicinal substance contained in it (i.e., on the number of layers of the tablet or dragee).

The simplest solution to the issue of creating a repeated action drug is tablets consisting of a core tablet, an acid-resistant barrier layer and an outer layer. The outer layer includes the first (initial) dose of the drug, which is released in the stomach immediately after taking the tablet. The acid-resistant barrier layer covering the core tablet prevents it from disintegrating in the stomach. When moving to the intestine, this layer is rapidly destroyed, after which it becomes possible to disintegrate the core tablet and release the second dose of the drug contained in it. The duration of action of the tablets reaches 8-12 hours.

Repeated action preparations can also be presented in the form of pills, designed similarly to tablets: they consist of two layers of the drug separated by an enteric layer.

Maintenance drugs more effective than periodic action, as they provide a fairly constant concentration of the drug at its therapeutic level without pronounced extremes, do not overload the body with extremely high concentrations. It has great importance in the treatment of diseases caused by pathogenic microorganisms, since a drug of this type has a powerful and constant effect on microorganisms, in contrast to frequent doses of the usual dosage form or repeated action drugs. The danger of intermittent exposure lies, first of all, in the fact that it does not always lead to the death of microorganisms, and sometimes even contributes to an increase in their resistance to this drug component.

One of the most effective and convenient dosage forms of supporting action are spansules. These are small, coated granules - micro-pellets, placed in hard gelatin capsules with caps.

Tablets also occupy a certain place among the dosage forms of supporting action. To obtain one of the types of such tablets, called retard, micropellets are compressed, like a tablet granulate, using soft fat auxiliary components that protect the micropellets from destruction during the tableting process.

An interesting example of getting maintenance tablets are pills with so called the insoluble framework. The medicinal substance is released from them by leaching. Such a tablet can be compared with a sponge, the pores of which are filled with a mixture of a medicinal substance with indifferent, easily soluble excipients - lactose, mannitol, etc. These tablets with an insoluble framework are produced either on conventional tablet machines or on tablet machines designed for pressing multilayer tablets. They are multilayer tablets coated with protective layers from two end layers. In this case, the drug is released first from the side surface of the middle layer, and as the protective layers dissolve, from the end surface as well.

prolongation can also be carried out by chemical means: by increasing the size of the drug molecule, achieved by attaching it to ion-exchange resins. Medicinal substances of the main nature are attached (bind) to cation exchangers with sulfo groups -0-OS 2 (created upon contact with a liquid pH 2.0) or carboxyl groups (pH 5.0-6.0). The latter give off cations in the gastric juice very quickly, while the sulfocationites are much slower. The process of ion exchange in the gastrointestinal tract continues for a considerable time, and the rate of release of the drug throughout the gastrointestinal tract remains approximately the same, and in the case of the addition of the drug to strong ion exchangers (for example, sulfonates), it depends on the ionic strength of the digestive juices and almost does not depends on pH. The release of the drug substance is slowed down as a result of the free diffusion of the molecules of this substance through the network of polymer chains that form the ion exchanger. In this case, the release rate varies depending on the particle size of the ionite, as well as on the number of branches of the polymer chains. Substances of an acidic nature, for example derivatives of barbituric acid, are attached to anion exchangers for the purpose of prolongation. However, in the gastrointestinal tract, such substances are released by no more than 80%. Ion exchangers with medicinal substances adsorbed on them are produced in the form of hard gelatin capsules with caps or tablets.

A medicine for hypertension is prescribed if the patient is at risk. It includes people who blood pressure constantly exceeds 160/100 mm Hg. Art. Individuals who are in the low-risk category are primarily advised by experts to correct their lifestyle and moderate physical activity.

If these measures do not help, doctors prescribe special preparations. What are the most effective medicines for hypertension?

1. Vascular tone. The more vasospasm, the higher the pressure. This indicator depends on the state of small arteries - arterioles.
2. Volume of circulating blood. The higher this value, the higher the pressure.
3. Functioning of the heart. The harder it beats, the more blood is pumped. This also causes an increase in pressure.

To choose the best medicine for hypertension, you need to consult a doctor. Similar drugs appointed in the following situations:

• With an increase in pressure to 160-90 mm Hg. Art.;
• With an increase in the indicator to 130/85 mm Hg. Art. - this is important for people with heart or kidney failure, as well as diabetes.

It is recommended to give preference to drugs that need to be drunk once a day, or drugs that have an effect of 12 hours. However, in most cases, doctors prescribe combination therapy, which includes two drugs at once. This allows you to reduce the dosage and minimize the risk side effects.

The main groups of drugs for hypertension

There are a number of remedies to help reduce blood pressure. To get the desired result and choose the most effective medicine hypertension, you should consult a doctor.

Beta blockers

These drugs can be used as monotherapy or complex therapy. They give a result in the development of a resistant form of the disease. They are allowed to be used in the presence of a heart attack in history and angina pectoris. Also, these funds are allowed in chronic heart failure and atrial fibrillation.

The mechanism of action of these drugs is based on stopping the production of renin and angiotensin, which lead to vasoconstriction. These drugs block beta receptors. Isolated therapy with beta-blockers lasts 2-4 weeks. The doctor may then prescribe a combination with a diuretic or calcium channel blocker.

Non-selective means include the following:

• Carvedilol;
• propranolol;
• Sotalol;
• Oxprenolol.

• Atenolol;
• bisoprolol;
• Nebivolol;
• Betaxolol.

Alpha blockers

These drugs block alpha-adrenergic receptors, which provides an irritating effect of norepinephrine. This leads to a decrease in blood pressure.

Effective remedy from this category is doxazosin. It is used to eliminate attacks of high blood pressure or long-term therapy. However, many other products from this group are now out of production.

calcium antagonists

These drugs are usually divided into several categories:

• Dihydropyridines - this group includes amlodipine, nifedipine;
• Benzodiazepines - these include diltiazem;
• Phenylalkylamines - verapamil belongs to this category.

These tools increase load tolerance. They can be used in combination with ACE inhibitors. Thanks to this, it is possible to avoid the use of diuretics.

Calcium antagonists are often prescribed for elderly people with cerebral atherosclerosis. They are used in the combination of hypertension with angina pectoris or arrhythmia.

Angiotensin 2 antagonists

These are relatively new drugs for hypertension, which successfully reduce pressure throughout the day. They can be used once a day - in the morning or before bedtime.

The maximum duration of action of candesartan is up to 2 days. Also in this group are drugs for hypertension, which lower blood pressure for 24 hours.

These drugs rarely provoke a dry cough. They do not cause a rapid drop in pressure and do not lead to the development of a withdrawal syndrome. A stable effect can be achieved 4-6 weeks after the start of therapy.

These modern drugs for hypertension can be used in the renal form of the disease, as they can eliminate the spasm of the vessel wall. Also, these drugs can be part of combination therapy for a stable form of the disease.

Diuretics

Thiazide diuretics and sulfonamides, which are included in the category of saluretics, help to improve the synthesis and excretion of urine. This provides a decrease in edema of the vessel wall, which leads to an increase in their lumen. Thanks to this, it is possible to reduce the pressure.

This category includes hydrochlorothiazide, hypothiazide. These substances prevent the reverse absorption of chloride and sodium ions by the tubules of the kidneys, which provokes their excretion. Medicines from this group have no effect on normal pressure.

Sulfonamides include indapamide, arifon, indal. These funds are used for complex forms hypertension. They may also be part of combination therapy for the development of resistant hypertension.

Indapamide is included in approved hypertension medications for type 2 diabetes because it does not affect blood glucose levels.

Angiotensin-converting enzyme inhibitors

These drugs block the enzyme that converts angiotensin to renin. Thanks to their use, it is possible to reduce blood flow to the heart muscle. Drugs from this group become a reliable prevention of cardiac muscle hypertrophy and restore it in the presence of this problem.

ACE inhibitors with a sulfhydryl category are used to eliminate hypertensive crises. These include captopril, benazepril.

ACE inhibitors with a carboxyl group include

enalapril

lisinopril,

perindopril

So, enalapril has a positive effect on the life expectancy of patients. However, it provokes an undesirable side effect in the form of a dry cough.

How to choose a cure for hypertension

To choose the most safe medicine hypertension, you need to see a doctor. When prescribing medications, a specialist takes into account a number of criteria. These include the following:

• Patient's age;
• Pathologies of the heart vascular system;
• Complications that are present in other organs.

The doctor will select a combination treatment that includes a number of drugs. This will provide a complex effect on the mechanism of the appearance of hypertension. The use of several drugs at once reduces the volume of each of them. This will reduce the risk of side effects.

List of the best drugs for hypertension of the new generation

Each new generation of hypertension medicine has many advantages. These include excellent effectiveness of therapy and a minimum of side effects. Today there are two categories of such drugs. These include:

• ACE inhibitors - from this group, you can choose such a new medicine for hypertension as lisinopril, monopril or prestarium;
• Calcium channel blockers - this category includes lacidipine, nimodipine, felodipine.

Effective drugs for hypertension have a gentle effect on the body. They do not lead to violations of potency or mental disorders. Thanks to their use, it is possible to improve the quality of life. However, these drugs should not be used without a doctor's prescription.

Fast acting high blood pressure pills

Such drugs are required to eliminate the symptoms of a hypertensive crisis. They should be present in the medicine cabinet of every person with arterial hypertension. First aid supplies include the following:

• Captopril;
• Nifedipine;
• Clonidine.

Side effects and contraindications

Contraindications directly depend on the category of the drug. However, many drugs are forbidden to use in such situations:

• Pregnancy;
• Lactation;
• Obstruction of the bile ducts;
• Complicated diseases of the kidneys and liver;
• Bronchial asthma;
• Hypersensitivity to the components of the remedy;
• Decompensated heart failure;
• Age less than 18 years.

Finding a cure for hypertension without side effects is quite problematic. Each drug can lead to undesirable health effects. The most common side effects include the following:

• allergic reactions;
• Pain in the digestive organs;
• Nausea and vomiting;
• stool disorders;
• A sharp drop in pressure;
• Depressive states;
• Feeling of dryness in the mouth;
• Sleep disorders.

If such symptoms appear, the drug should be immediately discontinued and consult a doctor. The specialist will be able to choose a more suitable analogue. Sometimes symptomatic therapy is required.

The safest medicine for hypertension

So far, there are no drugs for hypertension without side effects. Scientists have not been able to develop a substance that will bring the desired result without harm to health.

However, if we consider new drugs, they have many advantages over drugs of previous generations. These include the following:

• High efficiency;
• Prolonged action - this makes it possible to minimize the dosage of the drug and minimize the risk of side effects;
• Complex action - this list of drugs for hypertension includes drugs that perform several functions at once.

Physiotens is included in the category of third-generation drugs. It almost does not provoke side effects in the form of dry mouth or increased sleepiness. This drug is allowed to be used in patients with bronchial asthma and diabetes mellitus.

New agents that have been successfully used to treat hypertension include selective imidazoline receptor agonists. They reduce pressure, have a minimum of contraindications and very rarely provoke side effects. This group includes rilmenidine and monoxidine.

Beta-blockers of the new generation, which are actively used to combat hypertension, include nebivolol, labetalol. They rarely provoke side effects and almost do not harm human health. With the help of such funds, it is possible to prevent the occurrence of complications of hypertension.

Reviews

Reviews of the best drugs for hypertension confirm the high effectiveness of these drugs:

Marina: For the treatment of hypertension, I use a new generation drug - lisinopril. An effective tool that helps reduce pressure. During the use, there were never any side effects, so I am very pleased with the result.

Anna: With pressure drops, I went to the doctor, who diagnosed me with arterial hypertension. As a result, he prescribed a whole complex of beta-blockers and other drugs. Since then, my condition has improved significantly. Therefore, I advise everyone not to delay, but to consult a doctor in a timely manner.

Now you know how to choose a cure for hypertension. To minimize the risk of side effects and not harm your health, it is very important to see a doctor in time. Thanks to adequate and complex therapy, it will be possible to improve your condition.

Popular drugs

Among the most commonly used antihypertensive drugs in medical practice in recent years:

CAPTOPRIL (capoten, tensiomine) - suppresses the formation of angiotensin-2 described in the section on the mechanism of development of hypertension and eliminates its vasoconstrictive effect on arterioles; lowers the formation of aldosterone in the adrenal glands. Indications: arterial hypertension, chronic heart failure. It has side effects and contraindications. With simultaneous use with potassium-sparing diuretics, hyperkalemia is possible.

CAPOZID contains captopril and a diuretic - hydrochlorothiazide (hypothiazid). Antihypertensive drug of prolonged action. It has a number of side effects and has contraindications.

ENALAPRIL (enam, enap, reniten) belongs, along with capoten, to drugs that suppress the formation of angiotensin II and eliminate the vasoconstrictor effect of the latter. Reduces total peripheral vascular resistance, lowers blood pressure. Indications - as for the capoten. It is used, like all other antihypertensive drugs, strictly according to the doctor's prescription.

ENAP-N (contains enapril and hydrochlorothiazide (hypothiazid) - a diuretic, which leads to a decrease in the sodium content in the vascular wall and helps to lower blood pressure.

PRESTARIUM (perindopril) reduces blood pressure by disrupting the formation of angiotensin II and eliminating its narrowing effect on blood vessels (see "secondary link in the pathogenesis of hypertension"). Indications: arterial hypertension and chronic heart failure. Reduces myocardial hypertrophy. Treatment under the supervision of a doctor.

ATENOLOL (synonyms - tenolol, tenor-min, norton, falitonsin, etc.) is a cardioselective beta-blocker. It has a hypotensive effect, which stabilizes by the end of the second week of the drug. It has significant advantages over non-selective beta-blockers, such as propranolol (obzidan, inderal). Indications: arterial hypertension, prevention of angina attacks, tachycardia. Exercise caution while taking clonidine, reserpine, alpha-methyldopa.

TENORIC (tenoretic) contains atenolol and a diuretic - chlorthalidone. Indications are the same as for atenolol - arterial hypertension.

METAPROLOL (Betaloc, Corvitol, Metolol, Specicor, etc.) is a selective beta-adrenergic blocking effect mainly on the beta-1 receptors of the heart. Indications: arterial hypertension, prevention of angina attacks, cardiac arrhythmias, secondary prevention after myocardial infarction.

KARDURA (active ingredient - dexazosin) has a vasodilating effect by selective blockade of alpha-1-adrenergic receptors of the heart. Causes a clinically significant decrease in blood pressure as a result of a decrease in total peripheral vascular resistance. Indications: arterial hypertension.

Means regulating the level of blood pressure

See also amiloride, brinaldix, veroshpiron, hypothiazide, dalargin, diltiazem, oxodoline, triamterene, furosemide, cyclomethiazide, etc.

Beta-blockers

Atenolol (Atenolol)

Synonyms: Apo-Atenol, Atenobene, Atkardil, Betacard, Dignobeta, Catenol, Tenolol, Tenormin, Falitonsin, Ormidol, Atenol, Blockium, Katenolol, Hypoten, Myocord, Normiten, Prenormin, Telvodin, Tenoblock, Tenzikor, Velorin, Vericordin, Atenil, Atenova, Atenosan, Blockotenol, Vazkoten, NovoAtenol, Pantanol, Lure, Sinar, Unilok, etc.

Pharmachologic effect. Atenolol is a selective (cardioselective) beta-blocker.

Differs in duration of action. The half-life (the time for which '/2 doses of the drug is excreted) is 6-9 hours.

Indications for use.

It can be prescribed to patients with a tendency to bronchospasm (narrowing of the lumen of the bronchi) and spasm of peripheral vessels with a lower risk than non-selective beta-blockers.

Method of application and dose. Assign inside in a single dose of 0.05-0.1 g (50-100 mg = 1/2-1 tablet). Take a long time.

Side effects and contraindications.

Release form. Tablets of 0.1 g, film-coated.

Storage conditions.

ATEGEKSAL KOMPOSITUM (Atehexal compositum)

Pharmachologic effect.

Indications for use.

Method of application and dose.

Side effect.

Contraindications.

Release form.

Storage conditions. List B.

Atehexal compositum

Pharmachologic effect. Combined antihypertensive drug. Atenolol, which is part of it, is a cardioselective beta-adrenergic blocker (selectively blocking beta-adrenergic receptors of the heart), slows down the heart rate, reduces the stroke and minute volumes of the heart, reduces the activity of renin (an enzyme involved in the regulation of blood pressure) in the blood plasma. Oxodoline is a diuretic (diuretic) and natriuretic (removing sodium ions in the urine) long-acting agent that inhibits sodium reabsorption (reabsorption) mainly into the distal

nyh (located on the periphery of the kidney) tubules of the kidneys.

Indications for use. Arterial hypertension (persistent rise in blood pressure) in the absence of a sufficient effect from the separate use of each of the active substances that make up the drug.

Method of application and dose. The dose of the drug is set individually. The drug is taken 1 time per day before breakfast, without chewing. Wash down with a sufficient amount of liquid. The daily dose is 1 tablet containing 100 mg of atenolol and 25 mg of oxodoline, or 50 mg of atenolol and 12.5 mg of oxodoline.

During treatment, periodic monitoring of liver function indicators, as well as electrolyte (ionic) blood composition (especially potassium levels), concentrations of glucose, uric acid, lipids (fats), and creatinine in blood plasma is necessary.

When taking insulin or oral antidiabetic agents at the same time, blood glucose levels should be monitored regularly.

If after long-term treatment there is a need to cancel the drug, this should be done as slowly as possible, since a sudden cancellation can lead to a decrease in the blood supply to the myocardium (heart muscle) and a rapid increase in blood pressure.

Side effect. Arterial hypotension (lowering blood pressure), bradycardia (rare pulse), syncope, atrioventricular conduction disturbances (conduction of excitation through the conduction system of the heart), heart failure. In rare cases, Raynaud's syndrome (narrowing of the lumen of the vessels of the extremities). Hypokalemia, hyponatremia, hypomagnesemia, hypochloremia (decrease in the content of potassium, sodium, magnesium, chlorine ions in the blood), rarely - hyperkalemia (increase in the content of potassium in the blood). Feeling tired, dizzy, feeling stunned, headache, nightmares, hallucinations (delusions, visions that acquire the character of reality), depression (a state of depression). Nausea, vomiting, constipation or diarrhea. Bronchospasm (sharp narrowing of the lumen of the bronchi) in predisposed patients. Rarely - anemia (decrease in hemoglobin in the blood), leukopenia (decrease in the level of leukocytes in the blood), thrombocytopenia (decrease in the number of platelets in the blood), skin

rash. In some cases, acute nephritis (inflammation of the kidney), vasculitis (inflammation of the walls blood vessels), liver dysfunction.

Contraindications. Heart failure; acute myocardial infarction; violations of atrioventricular and / or sinoatrial conduction (conduction of excitation through the conduction system of the heart); sick sinus syndrome (heart disease, accompanied by a violation of the rhythm); bradycardia (when the heart rate at rest is less than 50 beats / min); predisposition to bronchospasm; pronounced violations peripheral circulation; severe renal dysfunction (creatinine clearance / rate of blood plasma clearance from the end product of nitrogen metabolism - creatinine / less than 50 ml / min); glomerulonephritis (kidney disease); severe liver dysfunction, accompanied by impaired consciousness; hypokalemia; acidosis (acidification of the blood); gout; simultaneous reception of MAO inhibitors; pregnancy; lactation; hypersensitivity to atenolol and other beta-blockers, oxodoline and other thiazide and loop diuretics.

The drug in some cases may impair the patient's ability to drive a car or other mechanisms. This effect is enhanced by alcohol.

Release form. Tablets in a package of 30, 50 and 100 pieces. 1 tablet contains 50 mg of atenolol and 12.5 mg of oxodoline or 100 mg of atenolol and 25 mg of oxodoline.

Storage conditions. List B.

CALBETA (Calbeta)

Pharmachologic effect. Combined drug, which includes selective (selective) beta-blocker atenolol and calcium channel blocker nifedipine. It has a pronounced hypotensive (lowering blood pressure) effect. It also has antianginal (anti-ischemic) and antiarrhythmic activity. With prolonged course use, it causes regression of hypertrophy (decrease in hypertrophy / sharp increase in size /) of the left ventricle of the heart, which has developed as a result of a prolonged rise in blood pressure.

Indications for use. Arterial hypertension (persistent rise in blood pressure), angina pectoris, especially when combined with hypertension (rising blood pressure) or extrasystole (cardiac arrhythmias).

Method of application and dose. Assign 1 capsule 1 or 2 times a day.

Treatment with the drug should be carried out under the control of water-electrolyte (water-ion) balance.

Side effect. Fatigue, headache, hyperemia (redness) of the face, a feeling of heat (these side effects are usually noted at the beginning of treatment and disappear on their own after 1-2 weeks of course administration). Perhaps the development of hyponatremia, hypokalemia and hypochloremia (decrease in the content of sodium, potassium and chlorine in the blood), alkalosis (alkalinization). Rarely - dyspeptic phenomena (digestive disorders). Conduction disturbance (conduction of excitation through the heart muscle) is possible.

Contraindications. Sinus bradycardia (rare rhythmic pulse), myocardial conduction disturbances, severe heart failure, hypersensitivity to the components of the drug.

Release form. Capsules containing 0.05 g of atenolol and 0.02 g of nifedipine, in a package of 10 pieces.

Storage conditions. List B. In a dark place.

LABETALOL (Labetalol)

Synonyms: Abetol, Albetol, Amipress, Ipolab, Labetol, Labrocol, Lamitol. Operkol, Presolol, Trandat, Trandol, etc.

Pharmachologic effect. Refers to the "hybrid" adrenoblockers, blocking both beta- and alpha-adrenergic receptors.

The combination of beta-adrenergic blocking and peripheral vasodilator (vasodilating) action provides a reliable antihypertensive (lowering blood pressure) effect. The drug does not significantly affect the amount of cardiac output and heart rate.

Indications for use. Apply labetalol to reduce blood pressure in hypertension (high blood pressure) of varying degrees. Unlike conventional beta-blockers, it has a rapid antihypertensive effect.

Method of application and dose. Inside appoint in the form of tablets (during meals) 0.1 g (100 mg) 2-3 times a day. At severe forms increase the dose of hypertension. The average daily dose is 600-1000 mg in 2-4 doses. For maintenance therapy, use 1 tablet (100 mg) 2 times a day.

In hypertensive crises (rapid and sharp rise in blood pressure), labetalol is administered intravenously slowly at a dose of 20 mg (2 ml of a 1% solution). If necessary, repeat injections at intervals of 10 minutes. Preferably labetalol is administered as an infusion. For this, a 1% injection solution in ampoules is diluted with an isotonic solution of sodium chloride or glucose to a concentration of 1 mg / ml. Enter at a rate of 2 ml (2 mg) per minute. Usually the required dose is 50-200 mg.

Intravenous administration is carried out in a hospital (hospital) with the patient lying down (due to a rapid and significant decrease in blood pressure).

Side effect. When using labetalol, dizziness, headache, nausea, constipation or diarrhea, fatigue, pruritus are possible.

Contraindications. Labetalol is contraindicated in patients with severe heart failure, atrioventricular blockade (impaired conduction of excitation through the heart).

Bronchospasm (a sharp narrowing of the lumen of the bronchi), the drug usually does not cause, but in patients with bronchial asthma care should be taken.

Release form. Tablets of 0.1 and 0.2 g (100 and 200 mg) of 30 and 100 pieces per pack; 1% solution for injection in ampoules of 5 ml (50 mg per ampoule).

Storage conditions. List B. In a dark place.

METIPRANOLOL (Metipranolol)

Synonyms: trimepranol.

Pharmachologic effect. Non-selective (non-selective) beta-blocker. In its action, it resembles propranolol. By beta-adrenergic blocking action is more active than propranolol. According to the negative inotropic effect (decrease in the strength of heart contractions), it is much weaker than propranolol. The onset of hypotensive (lowering blood pressure) action 1-2 hours after taking the drug inside. The negative chronotropic effect (decrease in heart rate) of metipranolol lasts 10 hours.

Indications for use. Hypertension (persistent rise in blood pressure).

Method of application and dose. As an antihypertensive (lowering blood pressure) agent, 10 mg is prescribed 2-3 times a day. After a weekly interval, the dose can be increased. The maximum daily dose is usually 80 mg.

Side effects and contraindications. See propranolol.

Release form. Tablets of 10 and 40 mg.

Storage conditions. List B. In a dark place.

METOPROLOL (Metoprolol)

Synonyms: Betaloc, Bloxan, Specicor, Protein, Lopresor, Neoblock, Opresol, Selopral, Vasocardin, Corvitol, Methohexal, Metolol, etc.

Pharmachologic effect. It is a selective (cardioselective) beta! adrenoblocker (selectively blocking beta-adrenergic receptors of the heart).

Indications for use. Applied with hypertension (persistent increase in blood pressure).

Method of application and dose. Apply inside and intravenously. Inside appoint a dose of 100-200 mg per day - 2-3 doses. If necessary, increase the dose. Maximum daily dose -: 400 mg. Tablets of prolonged (long-term) action are prescribed 1 tablet 1 time per day. In the morning after eating.

When using a daily dose of more than 200 mg, the cardioselective effect of the drug decreases, i.e. it blocks beta- and beta2-adrenergic receptors.

If necessary, the daily dose can be administered in 1 dose in the morning. The drug is taken before or during meals with water.

In case of insufficient effectiveness, other antihypertensive (lowering blood pressure) agents are additionally prescribed.

Side effects and contraindications are the same as those of atenolol. Metoprolol should not be given intravenously if systolic ("upper") blood pressure is less than 110 mm Hg. Art. In patients with bronchospastic phenomena (narrowing of the lumen of the bronchi), the simultaneous administration of beta-adrenostimulating drugs is recommended.

Release form. Tablets of 50 and 100 mg in a package of 30; 100 and 200 pieces; retard tablets 200 mg in a package of 14 pieces; 1% solution in ampoules of 5 ml in a package of 10 pieces.

Storage conditions. List B. At a temperature not higher than +25 "C.

NADOLOL (Nadolol)

Synonyms: Korgard, Anabet, Betadol, Nadik, Solgol.

Pharmachologic effect. Beta-blocker of non-selective action (blocks beta- and beta2-adrenergic receptors). It does not have a negative inotropic effect (does not reduce the strength of heart contractions). It has a long duration of action.

Indications for use. Hypertension (persistent rise in blood pressure) in various stages.

Method of application and dose. Assign inside (in the form of tablets) regardless of the meal. Due to the long-term effect, it can be used 1 time (sometimes 2 times) per day. The dose is adjusted depending on the effect. With hypertension (raising blood pressure), 40-80 mg is prescribed 1 time per day, gradually (at weekly intervals) the dose is increased to 160 mg per day, rarely up to 240 mg (in 1-2 doses) per day. Can

simultaneously use diuretics (diuretics) or vasodilators (drugs that dilate blood vessels).

Side effect. When using nadolol, fatigue, insomnia, paresthesia (numbness in the limbs), dry mouth, bradycardia (slow pulse), and gastrointestinal disorders are possible in some cases.

Contraindications. The drug is contraindicated in bronchial asthma and a tendency to bronchospasm (narrowing of the lumen of the bronchi), sinus bradycardia (rare pulse) and heart block (impaired conduction of excitation through the conduction system of the heart) I I-III degree, cardiogenic shock, with pulmonary hypertension (increased pressure in the vessels of the lungs), "congestive" heart disease. Do not prescribe the drug to women during pregnancy and lactation. Caution is needed in renal and hepatic insufficiency, diabetes mellitus.

Release form. Tablets of 20; 40; 80; 120 and 160 mg (0.02; 0.04; 0.08; 0.12 and 0.16 g) in vials of 100 and 1000 pieces.

Storage conditions. List B. At room temperature, protected from light.

KORZID (Corzid)

Pharmachologic effect. Combined preparation containing nadolol and diuretic bendroflumethiazide.

Indications for use. Used to treat hypertension (high blood pressure).

Method of application and dose. Assign 1-2 tablets depending on the patient's condition. In the future, the dosage regimen is determined according to the instructions of the attending physician.

Side effects and contraindications are the same as for nadolol.

Release form. Combination tablets containing 40 mg of nadolol and 5 mg of bendroflumethiazide and tablets containing 80 mg of nadolol and 5 mg of bendroflumethiazide.

Storage conditions. List B. In a dry, dark place.

PENBUTOLOL (Penbutolol)

Synonyms: Betapressin.

Pharmachologic effect. A non-selective beta-blocker with a moderately pronounced intrinsic sympathomimetic activity (prevents the decrease in heart rate that develops as a result of blockade of the beta-adrenergic receptors of the heart). The hypotensive (lowering blood pressure) effect begins within 2 weeks of treatment, full effect- after 6-8 weeks.

Indications for use.

Method of application and dose. Inside, 40 mg 1 time per day in the morning. After 3-6 weeks. the dose can be increased to 80 mg 1 time per day. The maintenance dose is 20 mg per day.

The hypotensive effect can be enhanced by combination with diuretics, peripheral vasodilators, methyldopa and alpha-blockers.

Side effect.

Contraindications. Atrioventricular blockade (impaired conduction of excitation through the conduction system of the heart) I-III degree; bradycardia (rare pulse - less than 50 per 1 min); heart failure; hypotension (low blood pressure), cardiogenic shock, bronchial asthma, chronic bronchitis, emphy

earth of the lungs (increase in airiness and decrease in the tone of the lung tissue).

Release form. Tablets and dragees of 20 and 40 mg.

Storage conditions. List B. In a dark place.

Pindolol (Pindololum)

Synonyms: Visken, Blocklin, Karvisken, Durapindol, Penktoblok, Pinadol, Pinbetol, Pindomex, Pinlok, Prindolol, etc.

Pharmachologic effect. It is a non-cardioselective beta-blocker (non-selectively blocking beta-adrenergic receptors). It has a hypotensive (lowering blood pressure) effect. Indications for use. Hypertension (persistent rise in blood pressure), hypertensive crisis (rapid and sharp rise in blood pressure).

Method of application and dose. When hypertension is prescribed, starting with 5 mg (1 tablet) 2-3 times a day; if necessary, the dose is gradually increased to 45 mg per day (in 3 divided doses). The hypotensive effect is somewhat less pronounced than with the use of propranolol. You can combine the use of pindolol with saluretics (diuretics that increase the excretion of sodium and chlorine) and other antihypertensive (lowering blood pressure) drugs (in reduced doses).

Intravenously injected slowly (within 5 minutes) 0.4 mg (2 ml of 0.02% solution) under the control of blood pressure. If necessary, you can re-enter 1 ml (0.2 mg) every 15-20 minutes.

In hypertensive crises (rapid and sharp rise in blood pressure) in patients with stage I and II hypertension, 1 mg is administered in 20 ml of a 5% glucose solution.

Side effects and contraindications. Possible side effects and contraindications are the same as with other non-selective beta-blockers (see Propranolol).

Release form. Tablets of 5, 10 and 15 mg; slow-acting tablets of 20 mg; oral solution containing 5 mg in 1 ml (0.5%) - 20 drops in 1 ml; 0.004% solution for injection in ampoules of 2 ml (0.8 mg per ampoule).

Storage conditions. List B. In a dark place.

VISKALDIX (Viskaldix)

Pharmachologic effect. Combined drug containing pindolol and diuretic brinaldix, which has a prolonged (long-term) hypotensive (lowering blood pressure) effect.

Indications for use. Arterial hypertension (persistent rise in blood pressure).

Method of application and dose. Assign in the initial dose of '/2 tablet 1 time per day during breakfast. If after 2-3 weeks there is no sufficient decrease in blood pressure, the dose should be increased to 2-3 tablets per day in 2 divided doses (morning and afternoon).

Side effect. Dizziness, fatigue, dyspeptic symptoms (digestive disorders), sleep disturbances. These effects are temporary and do not require discontinuation of the drug. In rare cases, skin reactions, depression, hallucinations (delusions, visions that acquire the character of reality), thrombocytopenia (decrease in the number of platelets in the blood), leukocytopenia (decrease in the number of leukocytes in the blood).

Contraindications. Same as for propranolol.

Release form. Tablets containing 10 mg of pindolol and 5 mg of brinaldix.

Storage conditions. List B. In a dark place.

PROPRANOLOL (Propranololum)

Synonyms: Inderal, Obzidan, Stobetin, Anaprilin, Propranolol hydrochloride, Alindol, Angilol, Antarol, Avlocardil, Bedranol, Betadren, Brikoran, Cardinol, Karidorol, Dederal, Deralin, Dociton, Elanol, Elib-lock, Inderex, Naprilin, Noloten, Opranol, Propanur , Propral, Pilapron, Sloprolol, Tenomal, Tiperal, Novo Prolol, Propra ratiopharm, Proprabene, Apopranolol, etc.

Pharmachologic effect. Weakening the effect of sympathetic impulses on beta-adrenergic receptors of the heart, propranolol reduces the strength and frequency of heart contractions, blocks the positive chrono- and ino-tropic effect of catecholamines (prevents an increase in the strength and frequency of heart contractions under the action of catecholamines). It reduces the contractility of the myocardium (heart muscle) and the amount of cardiac output. Myocardial oxygen demand decreases.

Blood pressure under the influence of propranolol decreases. The tone of the bronchi due to the blockade of beta2-adrenergic receptors increases.

In hypertension (persistent increase in blood pressure), propranolol is prescribed mainly in the initial stages of the disease. The drug is most effective in young patients (up to 40 years of age) with a hyperdynamic type of blood circulation and with an increased content of renin. A decrease in blood pressure is accompanied by a decrease in cardiac output due to a slowing of the pulse and a decrease in the stroke volume of the heart. Peripheral resistance is moderately increased. The drug does not cause orthostatic hypotension (drop in blood pressure when moving from a horizontal to a vertical position). There is evidence of the effectiveness of the drug also in renal hypertension (persistent rise in blood pressure due to kidney disease).

Indications for use. Hypertonic disease.

Method of application and dose. Assign propranolol inside (regardless of the time of admission to write). Usually begin in adults with a dose of 20 mg (0.02 g) 3-4 times a day. With insufficient effect and good tolerance, gradually increase the dose by 40-80 mg per day (at intervals of 3-4 days) to a total dose of 320-480 mg per day (in some cases up to 640 mg) with the appointment of equal doses in 3-4 doses . Cancellation of the drug is carried out gradually.

Usually propranolol is used for a long time (under close medical supervision).

In patients with pheochromocytoma (a tumor of the adrenal glands), alpha-blockers should be used in advance and simultaneously with propranolol.

The hypotensive (lowering blood pressure) effect of propranolol is enhanced when it is combined with hypothiazide, reserpine, apressin and other antihypertensive drugs.

There is evidence of the use of propranolol in combination with alpha-blocker phentolamine in hypertension (moderate and severe forms)

With an overdose of propranolol (and other beta-blockers) and persistent bradycardia, it is administered intravenously

intravenously (slowly) atropine solution 1-2 mg and beta-adrenergic stimulant isadrin 25 mg or orciprenaline 0.5 mg.

Side effect. When used, side effects are possible in the form of nausea, vomiting, diarrhea (diarrhea), bradycardia (rare pulse), general weakness, dizziness; allergic reactions (skin itch), bronchospasm (narrowing of the lumen of the bronchi) are sometimes observed. Possible phenomena of depression (depression).

In connection with the blockade of beta2-adrenergic receptors of peripheral vessels, the development of Raynaud's syndrome (narrowing of the lumen of the vessels of the extremities) is possible.

Contraindications. The drug is contraindicated in patients with sinus bradycardia, incomplete or complete atrioventricular blockade (impaired conduction of excitation through the conduction system of the heart), with severe right and left ventricular heart failure

accuracy, with bronchial asthma and a tendency to bronchospasm, diabetes mellitus with ketoacidosis (acidification due to excess ketone bodies in the blood), pregnancy, disorders of peripheral arterial blood flow. It is undesirable to prescribe propranolol for spastic colitis (inflammation of the colon, characterized by its sharp contractions). Caution is needed with the simultaneous use of hypoglycemic (lowering blood sugar levels) agents (risk of hypoglycemia / lowering blood sugar levels below normal /). In patients with diabetes mellitus, treatment should be carried out under the control of blood glucose.

Release form. Tablets of 0.01 and 0.04 g (10 and 40 mg); 0.25% solution in 1 ml ampoules.

Storage conditions. List B. In a dark place

Calcium antagonists of prolonged action in the treatment of arterial hypertension

Martsevich S.Yu. Kutishenko N.P.

State Research Center for Preventive Medicine, Ministry of Health of the Russian Federation, Moscow

Introduction

Antagonists calcium- a large group of drugs, the main property of which is the ability to reversibly inhibit the current calcium through the so-called slow calcium channels. These drugs have been used in cardiology since the late 70s and by now have gained such great popularity that in most developed countries occupy one of the first places in terms of frequency of prescription among drugs used for treatment cardiovascular disease . This is due, on the one hand, to the high clinical efficacy antagonists calcium. on the other hand, a relatively small number of contraindications to their appointment and a relatively small number of side effects caused by them.

Buy sharing Antagonists calcium- a large group of drugs, the main property of which is the ability to reversibly inhibit the flow of calcium through the so-called slow calcium channels. These drugs have been used in cardiology since the late 70s and by now have gained such great popularity that in most developed countries. This is due, on the one hand, to the high clinical efficacy antagonists calcium, on the other hand, a relatively small number of contraindications to their appointment and a relatively small number of side effects caused by them.

In recent years, dosage forms have been increasingly used antagonists calcium prolonged actions. Such dosage forms have been created for almost all currently used groups. antagonists calcium.

Classification antagonists calcium

There are various classifications of calcium antagonists. By chemical structure distinguish: dihydropyridine calcium antagonists (nifedipine, nicardipine, felodipine, lacidipine, amlodipine, etc.), benzodiazepine derivatives (diltiazem) and phenylalkylamines (verapamil). Calcium antagonists also distinguish by duration actions . To calcium antagonists of short duration actions(first generation calcium antagonists) refers to conventional tablets of nifedipine, verapamil, diltiazem, to maintain permanent effect they must be administered 3 or even 4 times a day. to calcium antagonists prolonged actions(second generation calcium antagonists) include either special dosage forms of nifedipine, verapamil, diltiazem, which provide a uniform release of the drug for a long time (IIa generation drugs), or drugs of a different chemical structure that have the ability to circulate in the body for a longer time (IIb generation drugs: felodipine , amlodipine, lacidipine).

Second-generation calcium antagonists are prescribed 1 or 2 times a day. The longest lasting effect of all calcium antagonists is amlodipine . its half-life reaches 35-45 hours.

Main pharmacological properties

Despite the same mechanism actions calcium antagonists at the cellular level, the pharmacological properties of various drugs in this group are quite different. The most significant differences are observed between dihydropyridine calcium antagonists (nifedipine), on the one hand, and phenylalkylamine derivatives (verapamil) and benzodiazepine derivatives (diltiazem), on the other hand.

Dihydropyridine calcium antagonists primarily act on the smooth muscles of the peripheral arteries, i.e. are typical peripheral vasodilators. As a result, they reduce arterial pressure (BP) and reflexively can increase the heart rate (HR), for which they are also called pulse-increasing calcium antagonists. Dihydropyridine calcium antagonists in therapeutic doses do not affect the sinus node and the conduction system of the heart, so they do not have antiarrhythmic properties. They also do not affect myocardial contractility.

The selectivity of action on peripheral vessels differs among different dihydropyridine calcium antagonists. Nifedipine is the least selective in this regard, amlodipine and lacidipine have the highest selectivity. Due to gradual onset of action and long half-life amlodipine does not cause reflex tachycardia or its manifestations are insignificant.

Verapamil and diltiazem have a significantly less pronounced peripheral vasodilating effect than dihydropyridine calcium antagonists. Their action is dominated by a negative effect on the automatism of the sinus node (due to this, they are able to reduce heart rate and are called pulse-reducing calcium antagonists), the ability to slow down atrioventricular conduction, and have a negative inotropic effect due to the effect on myocardial contractility. These properties bring together verapamil and diltiazem with b-blockers.

Indications and contraindications for the appointment of calcium antagonists

All calcium antagonists have been successfully used for treatment arterial hypertension. stable exertional angina, vasospastic angina. The pulse-lowering calcium antagonists verapamil and diltiazem are widely used as antiarrhythmic drugs (for treatment supraventricular arrhythmias). These drugs, however, are contraindicated in patients suffering from sick sinus syndrome, patients with impaired atrioventricular conduction. In these last two conditions (very common in elderly patients), only dihydropyridine calcium antagonists can be used. If we recall that the use of dihydropyridine calcium antagonists is also possible in a number of situations when the use of b-blockers is contraindicated or undesirable (peripheral circulatory disorders, obstructive pulmonary diseases, bronchial asthma), it becomes clear why dihydropyridine calcium antagonists are often the drugs of choice.

The use of pulse-reducing calcium antagonists is undesirable in patients with impaired left ventricular function, as it can cause even more deterioration. The use of dihydropyridine calcium antagonists in such patients is safer, however, in such cases, preference should be given to more selective dihydropyridine calcium antagonists, primarily amlodipine. In a special study PRAISE (Prospective Randomized Amlodipine Survival Evaluation) it was demonstrated that the administration of amlodipine to patients with chronic heart failure and a significantly reduced left ventricular ejection fraction was not only completely safe, but also significantly improved prognosis in such patients.

calcium antagonists in treatment arterial hypertension

All calcium antagonists have the ability to reduce blood pressure in patients arterial hypertension and are successfully used as antihypertensive drugs. It is noteworthy that the ability to reduce blood pressure in these drugs is more pronounced when they are prescribed to patients with arterial hypertension and less pronounced when they are given to individuals with normal blood pressure. High efficacy and good tolerability of calcium antagonists in arterial hypertension made them very popular among doctors and patients. In most countries Calcium antagonists continue to occupy one of the first places in terms of frequency of prescription among drugs used for treatment arterial hypertension .

Most researchers believe that different calcium antagonists have approximately the same hypotensive effect. Nevertheless, the impression is created that the actual antihypertensive effect of dihydropyridine calcium antagonists is somewhat more pronounced than the pulse-reducing calcium antagonists. According to various researchers, the number of patients who achieve a significant hypotensive effect (decrease in diastolic blood pressure to 90 mm Hg or 10 mm Hg or more), when prescribing calcium antagonists, ranges from 55 to 80%, which is not differs from the results obtained with the use of other antihypertensive drugs.

For antihypertensive drugs prolonged actions it is very important that the effect completely overlaps the 24-hour interval and persists until the next dose of the drug. Since antihypertensive drugs are taken, as a rule, in the morning, the therapeutic effect should cover the morning hours, since this period of the day is the most vulnerable in terms of the development of serious cardiovascular complications. Modern calcium antagonists prolonged actions (amlodipine, lacidipine) when prescribed for the treatment of hypertension clearly provide the required value of the ratio final effect / peak effect >=0.5 . The calculation of this indicator allows, to a certain extent, to give a comprehensive assessment of both the magnitude and duration of the hypotensive effect of the drug. According to a number of studies, for diastolic blood pressure, the ratio of the final effect / peak effect is 0.5-1.0 for amlodipine, prescribed at a dose of 5-10 mg.

Left ventricular hypertrophy, which is a compensatory response to increased blood pressure over a long period of time, is now recognized as one of the major risk factors for cardiovascular complications. Available data suggest that treatment with calcium antagonists can lead to a decrease in the severity of myocardial hypertrophy and thereby reduce the risk of serious cardiovascular complications. Ismail F. Islim et al. in their study showed that after 20 weeks of therapy at an effective dose of 5-10 mg, amlodipine leads to a significant decrease in the mass of the myocardium of the left ventricle . a significant decrease in the thickness of the interventricular septum and rear wall left ventricle, a significant and statistically significant decrease in peripheral resistance. At the same time, there were no significant changes in the size of the cavities of the left ventricle, ejection fraction, stroke volume and cardiac output.

As you know, there is still no consensus on which drugs should be used to start therapy for arterial hypertension. Diuretics and b-blockers are often called first-line drugs. It should be noted, however, that calcium antagonists have significantly fewer contraindications to prescribing than many other antihypertensive drugs, and do not cause a number of side effects characteristic of other antihypertensive drugs.

So, calcium antagonists, unlike diuretics, do not cause adverse metabolic changes (do not affect the level of electrolytes, lipids, uric acid, blood glucose). The advantages of calcium antagonists over b-blockers in patients with obstructive pulmonary disease and peripheral arterial disease were mentioned above. Calcium antagonists never cause the common complication of angiotensin-converting enzyme (ACE) inhibitors, such as coughing.

Because calcium antagonists prolonged actions are part of the main medicines for the treatment of coronary artery disease, their appointment is especially indicated for patients with arterial hypertension and concomitant coronary heart disease, especially in cases where the appointment of b-blockers is contraindicated for any reason.

Benefits of long acting calcium antagonists

Long-acting drugs were created in order to simplify the regimen of taking the drug to once a day and thereby improve patient adherence to treatment. Adherence is known to be particularly poor in patients with hypertension, as the disease is usually asymptomatic. Given that the treatment of arterial hypertension is carried out for a long time, for many years, and that the success of this therapy, in particular, its effect on the prognosis of the disease, depends significantly on the regularity of treatment, it becomes clear that this property can be decisive.

Another advantage of long-acting calcium antagonists is that they significantly less likely than short-acting calcium antagonists to produce side effects (this pattern is characteristic primarily for dihydropyridine calcium antagonists). This is due to the fact that short-acting calcium antagonists quickly create a high concentration of the drug in the blood, which causes significant, sometimes excessive vasodilation and significantly increases the tone of the sympathetic nervous system. That is why the side effects of dihydropyridine calcium antagonists associated with peripheral vasodilation (tachycardia, redness of the skin, dizziness, feeling hot) are much more common with short-acting drugs.

In addition, long-acting calcium antagonists are drugs that are able to provide an adequate therapeutic effect in patients who do not always take therapy regularly, when the interval between doses of the drug can be 48 hours. It has been shown that a single dose of amlodipine leads to only a slight decrease in the antihypertensive effect of therapy. In a comparative study that examined the possibility of developing a withdrawal syndrome while taking amlodipine and perindopril, conducted by Zannad F. et al. it was shown that 48 hours after taking the last dose of amlodipine, only slight rise Blood pressure and systolic and diastolic blood pressure were lower in patients receiving amlodipine than in patients receiving perindopril. The absence of a sharp rise in blood pressure with an unintentional skipping of the drug indicates a low likelihood of developing a withdrawal syndrome while taking amlodipine and increases the safety of therapy with this drug.

Possibility and feasibility of combination therapy with calcium antagonists and other drugs

Combination therapy for arterial hypertension can be used both to achieve a more pronounced decrease in blood pressure, and to reduce the dose of the drug and reduce the likelihood of side effects.

The possibility and feasibility of combination therapy in relation to calcium antagonists should be considered differentially for different subgroups of these drugs. So, verapamil and diltiazem are well combined with most other groups of antihypertensive drugs, with the exception of b-blockers. In the latter case, the likelihood of side effects of each of the drugs increases significantly. Dihydropyridine calcium antagonists, on the contrary, are well combined with b-blockers. This combination not only significantly enhances the severity of the hypotensive effect, but also significantly reduces the likelihood side effects. In particular, tachycardia, which can still appear with the appointment of long-acting dihydropyridine calcium antagonists, is completely eliminated when a b-blocker is added to therapy.

Dihydropyridine calcium antagonists, in addition, are well combined with ACE inhibitors, diuretics. Such combinations have been successfully used in a number of large international studies.

Do calcium antagonists affect the life prognosis of patients

Since the mid-1990s, there has been constant discussion about whether long-term use of calcium antagonists is safe. The reason for them was the data obtained back in the 80s, demonstrating the ability of short-acting dihydropyridine calcium antagonists, prescribed without b-blockers, to adversely affect the outcome of the disease in patients with unstable angina and acute infarction myocardium. None special studies proving the possibility of a negative effect of long-acting calcium antagonists neither in patients with coronary heart disease, nor in patients with arterial hypertension does not exist. In the Lancet in 2000, data from a special analysis were published, proving that the long-term use of long-acting calcium antagonists in patients with arterial hypertension is not only safe, but also leads to a significant decrease in the likelihood of developing a cerebral stroke and the likelihood of developing coronary disease hearts and its complications. According to this analysis, the efficacy and safety of calcium antagonists were in no way inferior to those of ACE inhibitors.

The safety of long-term treatment of arterial hypertension with long-acting calcium antagonists from the dihydropyridine group is confirmed by the results of the recently completed HOT and INSIGHT studies. In the study HOT (Hypertension Optimal Treatment) it was demonstrated that a significant decrease in diastolic blood pressure (average to 82.6 mm Hg) under the influence of drug therapy with felodipine, both in the form of monotherapy and in combination with other antihypertensive drugs, leads to a significant decrease in the likelihood of heart failure. – vascular complications and increase in life expectancy of patients.

In research INSIGHT (International Nifedipine GITS Study Intervention as a Goal in Hepertension Treatment) it was demonstrated that long-term administration of a special dosage form of nifedipine - nifedipine-GITS (gastrointestinal therapeutic system) to patients with arterial hypertension - is no less effective and safe than treatment with diuretics. Additional analysis from this study showed that nifedipine has positive influence on the prognosis of the life of patients, and the severity of this action of nifedipine is not inferior to that of diuretics.

Conclusion

Thus, the data available to date strongly suggest that efficacy and safety of treatment with long-acting calcium antagonists patients with arterial hypertension. In some cases, when other antihypertensive drugs are contraindicated, these drugs may be the drugs of choice. The ability to prescribe these drugs once a day makes them very convenient for long-term regular treatment.

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10. Zannad F, Bernaud C.M. Fay R. Double-blind, randomized, multicentre comparison of the effects of amlodipine and perindopril on 24h therapeutic coverage and beyond in patients with mild to moderate hypertension. Journal of Hypertension 1999; 17:137–146

11. Zannad F. Boivin J.M. Lorraine General Physician Investigators Group. Ambulatory 24–h blood pressure assessment of the felodipine–metoprolol combination versus amlodipine in mild to moderate hypertension. J.Hypertens. 1999;17:1023–1032.

12. Hansson L. Zanchetti A. Carruthers S.G. et al. Effects of intensive blood–pressure lowering and low dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998;351:1755–1762.

13. Brown M.J. Palmer C.R. Castaigne A. et al. Morbidity and mortality in patients randomized to double–blind treatment with a long–acting calcium–channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 2000;356:366–372.

ISPOLIN - OMU of prolonged action

• The most effective drugs high blood pressure
• Fast acting pressure pills
• Long acting pressure tablets
• Rating of drugs (in tablets) with their description
• Combined drugs
• Combined administration of several drugs
• Summary

An increase in blood pressure (abbreviated as A / D) affects almost every person after 45-55 years. Unfortunately, hypertension cannot be completely cured, so hypertensive patients have to constantly take pressure pills for the rest of their lives in order to prevent hypertensive crises (attacks of increased pressure - or hypertension), which are fraught with a lot of consequences: from severe headache to heart attack or stroke.

Monotherapy (taking one drug) gives a positive result only at the initial stage of the disease. A greater effect is achieved with the combined intake of two or three drugs from various pharmacological groups, which must be taken regularly. It should be borne in mind that the body gets used to any antihypertensive pills over time and their effect weakens. Therefore, for stable stabilization of the normal level of A / D, their periodic replacement is necessary, which is carried out only by a doctor.

A hypertensive patient should know that drugs that reduce pressure are fast and prolonged (long-term) action. Drugs from different pharmaceutical groups have different mechanisms of action, i.e. to achieve an antihypertensive effect, they affect various processes in the body. Therefore, for different patients with arterial hypertension, the doctor may prescribe different means, for example, atenolol is better for one to normalize pressure, and for another it is undesirable to take it because, together with the hypotensive effect, it reduces the heart rate.

In addition to directly reducing pressure (symptomatic), it is important to influence the cause of its increase: for example, treat atherosclerosis (if there is such a disease), prevent secondary diseases - heart attack, disorders cerebral circulation and etc.

The table shows a general list of drugs from different pharmaceutical groups prescribed for hypertension:

Drugs prescribed for hypertension

These medicines are indicated for the treatment of hypertension (persistent high blood pressure) of any degree. The stage of the disease, age, the presence of concomitant diseases, individual characteristics of the organism are taken into account when choosing a remedy, selecting a dosage, frequency of administration and a combination of drugs.

Tablets from the sartans group are currently considered the most promising and effective in the treatment of hypertension. Their therapeutic effect is due to the blocking of receptors for angiotensin II, a powerful vasoconstrictor that causes a persistent and rapid increase in blood pressure in the body. Long-term use of tablets gives a good therapeutic effect without the development of any undesirable consequences and withdrawal syndrome.

Important: only a cardiologist or a local therapist should prescribe drugs for high blood pressure, as well as monitor the patient's condition during therapy. A self-made decision to start taking some kind of hypertensive drug that helps a friend, neighbor or relative can lead to disastrous consequences.

Further in the article we will talk about which drugs are most often prescribed for high blood pressure, their effectiveness, possible side effects, as well as combination regimens. You will get acquainted with the description of the most effective and popular drugs - Losartan, Lisinopril, Renipril GT, Captopril, Arifon-retard and Veroshpiron.

List of the most effective drugs for high blood pressure

Pills for hypertension with a quick effect

List of rapid-acting antihypertensive agents:

• furosemide,
• Anaprilin,
• captopril,
• Adelfan,
• Enalapril.

Fast-acting drugs for hypertension

At high pressure, it is enough to put half or a whole tablet of Captopril or Adelfan under the tongue and dissolve. The pressure will drop in 10-30 minutes. But it is worth knowing that the effect of taking such funds is short-lived. For example, the patient is forced to take Captopril up to 3 times a day, which is not always convenient.

The action of Furosemide, which is a loop diuretic, is the rapid onset of severe diuresis. Within an hour after taking 20-40 mg of the drug and in the next 3-6 hours, you will begin to urinate frequently. Blood pressure will decrease due to the removal of excess fluid, relaxation of the smooth muscles of the vessels and a decrease in the volume of circulating blood.

Pills for hypertension prolonged action

List of long-acting antihypertensive drugs:

• metoprolol,
• diroton,
• Losartan,
• Cordaflex,
• prestarium,
• bisoprolol,
• Propranolol.

long-acting antihypertensive drugs

They have a prolonged therapeutic effect, designed for the convenience of treatment. It is enough to take these medicines only 1 or 2 times a day, which is very convenient, because maintenance therapy for hypertension is indicated constantly until the end of life.

These funds are used for long-term combination therapy for hypertension of 2-3 degrees. Features of the reception are a long-term cumulative effect. To obtain a stable result, you need to take these drugs for 3 or more weeks, so you do not need to stop taking them if the pressure does not decrease immediately.

The list of antihypertensive drugs is compiled, starting from the most effective with a minimum of undesirable consequences to drugs with more frequent side effects. Although in this respect everything is individual, it is not in vain that one has to carefully select and, if necessary, adjust antihypertensive therapy.

Losartan

A drug from the sartans group. The mechanism of action is to prevent the powerful vasoconstrictor action of angiotensin II on the body. This substance, which has a high activity, is obtained by transformation from renin, produced by the kidneys. The drug blocks the AT1 subtype receptors, thereby preventing vasoconstriction.

Systolic and diastolic blood pressure decreases already after the first oral administration of Losartan, the largest after 6 hours. The effect persists for a day, after which it is required to take the next dose. Persistent stabilization of pressure should be expected after 3-6 weeks from the start of admission. The drug is suitable for the treatment of hypertension in diabetics with diabetic nephropathy - damage to blood vessels, glomeruli, kidney tubules due to metabolic disorders caused by diabetes.

What analogues does it have:

• Blocktran,
• lozap,
• Presartan,
• xartan,
• Losartan Richter,
• Cardomine-Sanovel,
• Vasotens,
• Lakea,
• Renicard.

Valsartan, Eprosartan, Telmisartan are drugs from the same group, but Losartan and its analogues are more productive. Clinical experience has shown its high efficiency in eliminating elevated A / D, even in patients with a complicated form of arterial hypertension.

Lisinopril

It belongs to the group of ACE inhibitors. The antihypertensive effect is noted already 1 hour after taking the desired dose, increases in the next 6 hours to a maximum and lasts a day. This is a drug with a long cumulative effect. Daily dosage - from 5 to 40 mg, taken 1 time per day in the morning. In the treatment of hypertension, patients note a decrease in pressure from the first days of admission.

List of analogues:

• diroton,
• Renipril,
• Lipril,
• Lizinovel,
• Dapril,
• Lizacard,
• Lisinoton,
• Sinopril,
• Lysigamma.

Renipril GT

It is an effective combination drug consisting of enalapril maleate and hydrochlorothiazide. In combination, these components have a more pronounced antihypertensive effect than either individually. The pressure is reduced gently and without loss of potassium by the body.

What are the analogues of the tool:

• Berlipril Plus,
• Enalapril N,
• Ko-renitek,
• Enalapril-Acri,
• Enalapril NL,
• Enap-N,
• Enafarm-N.

Captopril

Perhaps the most common drug from the group of ACE inhibitors. Created for emergency assistance for the relief of hypertensive crisis. For long-term treatment, it is undesirable, especially in elderly people with atherosclerosis of the cerebral vessels, since it can provoke a sharp decrease in pressure with loss of consciousness. May be administered with other hypertensive and nootropic drugs, but under strict A/D control.

List of analogues:

• Kopoten,
• Kaptopres,
• Alcadil,
• catopyl,
• Blockordil,
• Captopril AKOS,
• Angiopril,
• rilcapton,
• Capopharm.

Arifon-retard (indopamide)

Diuretic and antihypertensive agent from the group of sulfonamide derivatives. In complex therapy for the treatment of arterial hypertension, it is used in minimal doses that do not have a pronounced diuretic effect, but stabilize pressure during the day. Therefore, when taking it, you should not wait for an increase in diuresis, it is prescribed to lower pressure.

• indopamide,
• Acrypamide
• Perinide,
• Indapamid-Verte,
• indap,
• Acripamide retard.

Veroshpiron

Potassium-sparing diuretic. Take from 1 to 4 times a day courses. It has a pronounced diuretic effect, while not removing potassium from the body, which is important for the normal functioning of the heart. Used only in combination therapy for the treatment of arterial hypertension. If the dose prescribed by the doctor is observed, it does not cause side effects, with rare exceptions. Long-term treatment in high doses (more than 100 mg / day) can lead to hormonal disorders in women and impotence in men.

Combined drugs for high blood pressure

To achieve the maximum hypotensive effect and ease of administration, combined preparations have been developed, consisting of several optimally selected components at once. This is:

• Noliprel (indopamide + perindopril arginine).
• Aritel plus (bisoprolol + hydrochlorothiazide).
• Exforge (valsartan + amlodipine).
• Renipril GT (enalapril maleate + hydrochlorothiazide).
• Lorista N or Lozap plus (losartan + hydrochlorothiazide).
• Tonorma (triamterene + hydrochlorothiazide).
• Enap-N (hydrochlorothiazide + enalapril) and others.

Combined use of several drugs for high blood pressure

Combination therapy is the most effective in the treatment of arterial hypertension. To achieve stable positive results, the simultaneous intake of 2-3 drugs necessarily from different pharmacological groups helps.

How to take pills for high blood pressure in combination:

high blood pressure pills a large number of. With hypertension of the 2nd and 3rd degree, patients are forced to take medications constantly in order to keep their pressure normal. For this purpose, combination therapy is preferable, due to which a stable antihypertensive effect is achieved without hypertensive crises. Only a doctor should prescribe any drug for pressure. Before making a choice, he will take into account all the features and nuances (age, the presence of concomitant diseases, the stage of hypertension, etc.) and only then will he select a combination of drugs.

For each patient, an individual treatment regimen is drawn up, which he must adhere to and regularly monitor his A/D. If the prescribed treatment is not effective enough, you need to contact the doctor again to adjust the dosages or replace the drug with another one. Self-administration of medications, based on the reviews of neighbors or acquaintances, most often not only does not help, but also leads to the progression of hypertension and the development of complications.

Modern drugs for the treatment of hypertension should not only and not so much lower high blood pressure. Their task is to prevent irreversible damage to target organs, maintain target blood pressure numbers, and prevent hypertensive crises and complications of hypertension. When prescribing this or that medicine, the doctor takes into account possible risks, tries to minimize the list of side effects. Consider the general principles of choice, a list of the latest generation of antihypertensive drugs.

On the principles of choosing antihypertensive drugs

The initial stage of hypertension in 90% of cases is explained by psycho-emotional factors. The problem is exacerbated by poor lifestyle and nutrition. Isolated cases of increased blood pressure develop into a disease.

Based on the nature of the disease, drugs are prescribed in extreme cases. Antihypertensive drugs have an impressive list of side effects. It is recommended to influence high blood pressure figures with pills only when the patient has minimized the risk factors:

• gave up alcohol and smoking;
• lost excess weight;
• reduced the amount of salt in the diet, diversified it with fresh vegetables and fruits;
• took up sports.

If the lifestyle has changed, and hypertension does not recede, antihypertensive pills are prescribed. Principles of drug selection:

1. You need to start with half the dose. Drank - checked the pressure in half an hour. If there is no effect, increase the dosage.
2. It is impossible to exceed the recommended dose. The medicine for pressure does not help - you need to find another drug. And again start at half the dosage.
3. If the remedy does not fit due to side effects, stop taking it and consult a doctor for another appointment.
4. It is more convenient to take one medicine for pressure, rather than 2-3 tablets. New products are combined preparations, which include several active substances.
5. It is desirable to find a drug that must be used once a day. Many modern medicines have a prolonged action.
6. It is important to take medicines for high blood pressure daily, continuously. Even when the state of health is normal and the numbers on the tonometer are not increased. Unauthorized breaks are not allowed.

Hypertension can be called a purely individual disease. The same remedies work well for some patients, but are completely ineffective against high blood pressure in others.

Classes of drugs for hypertension

1. Diuretics. Diuretics, aimed at removing excess fluid from the body. They have a number of side effects: dry mouth, tachycardia / bradycardia, dizziness, nausea, leg cramps, lethargy, frequent mood swings.
2. ACE inhibitors. Reduce the secretion of a hormone that causes blood vessels to constrict. Of the undesirable effects - a rapid decrease in blood pressure, allergies, dry cough.
3. Beta blockers. Reduce the heart rate, as a result of which the pressure normalizes. Side effects - a strong reduction in heart rate, lethargy, skin rashes.
4. calcium antagonists. They affect the tone of blood vessels, relaxing their walls. As a result, the pressure is normalized. Of the negative effects, we note increased heart rate, dizziness, strong hot flashes.
5. Angiotensin-2 antagonists. They are assigned if ACE inhibitors don't help. Drugs of this class protect the vasculature from angiotensin-2. Negative reactions of the body - nausea, allergies, dizziness.

New generation drugs directly inhibit renin activity. This is a hormone produced by the kidneys in response to problems in the body (oxygen starvation of the organ). Due to increased secretion, the pressure rises. Today, new tools are available for practical use.

Researchers are constantly looking for the most effective drugs, which will not only relieve symptoms, but also reduce the risk of heart attacks, strokes, kidney failure and similar complications. The list of new generation products is constantly updated.

In multidrug-resistant hypertension, selective endothelin receptor antagonists may be effective. The most effective are new pills, which include five main classes.

General principles of appointment and combination

The list of remedies for hypertension is huge. Until now, drugs that have been tested for decades are prescribed for blood pressure (a well-known composition is a new name). There are a lot of new things in this list (modern combinations, special mechanisms of action).

As a rule, doctors are guided by the following recommendations for prescribing drugs:

Concomitant diseases / complications	Medicines for hypertension
	Diuretic	ACE inhibitors	Beta blockers	calcium antagonists	Angiotensin-2 blockers
Diabetes	+	+	+	+	+
History of myocardial infarction		+	+
Heart failure	+	+	+		+
Prevention of recurrent stroke	+	+
Chronic pathologies of the kidneys		+			+

Possible combinations of drugs of different classes:

Blood pressure drug class	Indications for use
Diuretics
Thiazides	chronic heart failure, elderly age, ischemia; african race
Loop diuretics	Chronic heart failure, kidney disease
Aldosterone receptor antagonists	Chronic heart failure, myocardial infarction in the patient's history
Beta blockers	Myocardial infarction in history, angina pectoris, tachycardia, arrhythmia; as drugs of choice for congestive heart failure
calcium antagonists
Dihydropyridines	Old age, ischemia, pathologies of the peripheral vascular system, atherosclerosis, pregnancy
Phenylalkylamines
Benzodiazepines	Old age, angina pectoris, supraventricular tachycardia, atherosclerosis
ACE inhibitors
With sulfhydryl group	Chronic heart failure, left ventricular dysfunction, relief of hypertensive crises, type 1 diabetes mellitus, the presence of protein in the urine, non-diabetic nephropathy
With carboxyl group	chronic heart failure, type 2 diabetes, metabolic disorders, prevention of recurrent stroke, stable ischemia
AT-2 receptor blockers (sartans)	Type 2 diabetes mellitus, urinary albumin protein, renal hypertension, left ventricular enlargement, failure of other high blood pressure medications

Today, sartans are the drugs of choice. Medicines have appeared in pharmacological practice relatively recently, but they effectively reduce pressure. Taken once a day and are valid for 24-48 hours.

List of drugs for hypertension

Hypertension group	Action	List of drugs
Diuretics (diuretics)	Activate the production and excretion of urine. As a result, edema is removed from the walls of blood vessels, their lumen increases - pressure decreases.
Thiazide	Do not allow chloride and sodium ions to get back into the renal tubules. Substances are excreted and pull liquid along with them.	hydrochlorothiazide, hypothiazide, Cyclomethiazide
Loop diuretics	Relax the smooth muscles of blood vessels, increase renal blood flow.	Torasemide, furosemide, bumetonide, priretanide
Aldosterone receptor antagonists	They block the action of aldosterone, are potassium-sparing diuretics.	Eplerenone, Veroshpiron
Beta blockers	They inhibit the secretion of renin, a vasoconstrictor hormone. Suitable for mono and combination therapy, treatment of resistant hypertension. Drugs of choice - after a heart attack, with chronic heart failure, angina pectoris, persistent atrial fibrillation.	Non-selective: Nebivolol, Acridilol, carvedilol, Atram, Carvidil, recardium, Celiprolol. Selective: bisoprolol, Atenolol, coronal, Niperten, metoprolol, Lokren.
ACE inhibitors	They block the enzyme that converts angiotensin to renin, prevent thickening of the heart muscle, and treat its hypertrophy. Reduce blood flow to the heart.	With a sulfhydryl group: captopril, Lotensin, Zocardis. With carboxyl group: enalapril, lisinopril, prestarium, Khortil, Quadropril, Trandolapril.
Angiotensin-2 receptor blockers	Sartans reduce blood pressure gradually, do not provoke a withdrawal effect. Effective in renal hypertension - relax the vascular walls. Provide stable action within a month or two from the start of treatment.	Candesartan (has a maximum duration of effect - up to 48 hours); Losartan, Valsartan, Eprosartan, Micardis.
calcium channel inhibitors	Increase physical endurance. They have proven themselves in the treatment of elderly patients with cerebral atherosclerosis, with arrhythmias and angina pectoris.	amlodipine, Calcigard, Verapamil, Cardil.

Drugs for centrally acting hypertension:

• Clonidine. It has not been used in standard therapy for a long time. But it still has its adherents among the elderly who do not want to change the treatment or are accustomed to the active substances of the pills.
• Moxonidine. Effective in metabolic syndrome and mild degree hypertension. Acts very gently. Analogues - Physiotens, Tenzotran, Moxonitex.
• Andipal. Light tool. More suitable for the treatment of vegetative-vascular dystonia. It is not used to treat hypertension.

A doctor should prescribe treatment and choose drugs. However, some information about medicines ah from hypertension will help the patient ask competent questions at the reception.

The drug of prolonged action (p. prolongatum; syn. P. Durant) P., which has a longer therapeutic effect than other drugs containing the same medicinal substances.

Big Medical Dictionary. 2000 .

See what a "long-acting drug" is in other dictionaries:

I Preparation in morphology (Latin praeparo, praeparatum to cook, prepare) a biological object (body part, organ or part thereof, tissue area, cell or group of cells, microorganisms, etc.), prepared for macro or microscopic ... ... Medical Encyclopedia

- (French durant lasting, persisting) see Long-acting drug ... Big Medical Dictionary

- (synonyms: bronchodilators, bronchodilators, bronchodilators) drugs of different pharmacological classes, combined into one group according to their common ability to eliminate bronchospasm, acting on the tone of bronchial muscles and ... ... Medical Encyclopedia

Active ingredient ›› Naltrexone * (Naltrexone *) Latin name Vivitrol ATX: ›› N07BB04 Naltrexone Pharmacological groups: Opioids, their analogues and antagonists ›› Means for correcting disorders in alcoholism, toxic and drug addiction ... ...

Active ingredient ›› Paracetamol* + Phenylephrine* + Chlorphenamine* (Paracetamol* + Phenylephrine* + Chlorphenamine*) Latin name Coldact Flu Plus ATX: ›› N02BE51 Paracetamol in combination with other drugs (excluding psycholeptics)… … Vocabulary medical preparations

Active ingredient ›› Benzylpenicillin* (Benzylpenicillin*) Latin name Procain Benzylpenicillin ATX: ›› J01CE01 Benzylpenicillin Pharmacological group: Penicillins Nosological classification (ICD 10) ›› A22 Anthrax ›› A46… … Medicine Dictionary

ECMONOVOCILLIN- (Ecmonovocillinum; list B), antimicrobial drug, consisting of novocaine salt of benzylpenicillin (600,000 IU) and 0.25% aqueous solution of ecmolin (5 ml). The ingredients are released in separate hermetically sealed vials. Before… … Veterinary Encyclopedic Dictionary

Active ingredient ›› Haloperidol* (Haloperidol*) Latin name Haloperidol decanoate ATX: ›› N05AD01 Haloperidol Pharmacological group: Antipsychotics Nosological classification (ICD 10) ›› F20 Schizophrenia Composition and dosage form Solution ... Medicine Dictionary

- (Glibutidum). Butyl biguanide hydrochloride. Synonyms: Adebit, Silubin, Adebit, Buformin hydrochloride, Buformini hydrochloridum, Butylbiguanid, Butylnite, Gliporal, Glybigid hydrochloride, Krebon, Silubin, etc. White crystalline powder ... ... Medicine Dictionary

GLIBUTID (Glibutidum). Butyl biguanide hydrochloride. Synonyms: Adebit, Silubin, Adebit, Buformin hydrochloride, Buformini hydrochloridum, Butylbiguanid, Butylnite, Gliporal, Glybigid hydrochloride, Krebon, Silubin, etc. White crystalline ... ... Medicine Dictionary

Prolonged solid dosage forms

We continue a series of publications of articles by young professionals studying factory technology. The future of the Russian pharmaceutical industry depends on those who will come to work for Russian pharmaceutical production tomorrow. Therefore, the training of highly qualified engineers, technologists, quality specialists should begin even at the university. We hope that the topic of the release of prolonged solid dosage forms is especially relevant for our readers-manufacturers.

E.A. Chursina, 5th year student of the Faculty of Pharmacy, Department of General Pharmaceutical and Biomedical Technology, MMA named after THEM. Sechenov

Prolonged dosage forms (from lat. Prolongare - lengthen_ - these are dosage forms with a modified release. Due to the slowdown in the release of the medicinal substance, an increase in the duration of its action is ensured.

The main advantages of these dosage forms are:

The possibility of reducing the frequency of reception,

The possibility of reducing the course dose,

The ability to eliminate the irritating effect of drugs on the gastrointestinal tract,

The ability to reduce the manifestation of major side effects.

The following requirements are imposed on prolonged dosage forms:

The concentration of the drug as it is released from the drug should not be subject to significant fluctuations and should be optimal in the body for a certain period of time.

Excipients introduced into the dosage form must be completely eliminated from the body or inactivated.

Methods of prolongation should be simple and affordable in execution and should not have a negative effect on the body. The most physiologically indifferent is method of prolongation by slowing down the absorption of drugs. Depending on the route of administration, prolonged forms are divided into dosage forms. retard shapes and medicinal depot forms. Taking into account the kinetics of the process, dosage forms are distinguished with intermittent release, continuous and delayed release. Depot dosage forms (from French depot - warehouse, set aside. Synonyms - dosage forms deposited) are prolonged dosage forms for injection and implantation, which ensure the creation of a supply of the drug in the body and its subsequent slow release. Depot dosage forms always enter the same environment in which they accumulate, in contrast to the changing environment of the gastrointestinal tract. The advantage is that they can be administered at longer intervals (sometimes up to a week). In these dosage forms, slowing down absorption is usually achieved by using poorly soluble drug compounds (salts, esters, complex compounds), chemical modification - for example, microcrystallization, placing the drug in a viscous medium (oil, wax, gelatin or synthetic medium), using systems delivery – microspheres, microcapsules, liposomes.

The modern nomenclature of depot dosage forms includes:

injection forms - oil solution, depot suspension, oil suspension, microcrystalline suspension, micronized oil suspension, insulin suspensions, injection microcapsules.

Implant Forms - depot tablets, subcutaneous tablets, subcutaneous capsules (depot capsules), intraocular films, ophthalmic and intrauterine therapeutic systems. For parenteral application and inhalation dosage forms, the term “prolonged” or more generally “modified release” is used.

Dosage forms of retard (from Latin retardo - to slow down, tardus - quiet, slow; synonyms - retards, retarded dosage forms) - these are prolonged dosage forms that provide the body with a supply of a medicinal substance and its subsequent slow release. These dosage forms are used primarily orally, but are sometimes used for rectal administration. Previously, this term also referred to prolonged injectable forms of heparin and trypsin.

To obtain dosage forms of retard, physical and chemical methods are used.

To the physical include coating methods for crystalline particles, granules, tablets, capsules; mixing medicinal substances with substances that slow down absorption, biotransformation and excretion; the use of insoluble bases (matrices), etc.

Main chemical methods are adsorption on ion exchangers and formation of complexes. Substances bound to the ion exchange resin become insoluble and their release from dosage forms in the digestive tract is based solely on ion exchange. The release rate of the medicinal substance varies depending on the degree of grinding of the ion exchanger and on the number of its branched chains.

Depending on the production technology, dosage forms are distinguished retard of two principal types - reservoir and matrix.

Tank molds They are a core containing a drug and a polymeric (membrane) shell that determines the release rate. The reservoir can be a single dosage form (tablet, capsule) or a medicinal microform, many of which form the final form (pellets, microcapsules). Matrix-type retard forms contain a polymer matrix in which the drug is distributed, and very often has the form of a simple tablet. Dosage forms of retard include enteric granules, retard dragees, enteric-coated dragees, retard and retard forte capsules, enteric-coated capsules, retard solution, rapid retard solution, retard suspension, double-layer tablets, enteric tablets, frame tablets, multilayer tablets, tablets retard, rapid retard, retard forte, retard mite and ultraretard; multiphase coated tablets, film coated tablets, etc.

Taking into account the kinetics of the process, dosage forms are distinguished with intermittent release, with continuous release and delayed release.

Dosage forms with periodic release (synonym - medicinal Intermittent-release formulations are sustained-release formulations that, when administered to the body, release the drug in portions, essentially resembling the plasma concentrations generated by conventional administration every four hours. They provide repeated action of the drug.

In these dosage forms, one dose is separated from another by a barrier layer, which can be film, pressed or coated. Depending on its composition, the dose of the drug substance can be released either after a given time, regardless of the localization of the drug in the gastrointestinal tract, or in certain time in the required part of the digestive tract.

So when using acid-resistant coatings, one part of the drug substance can be released in the stomach, and the other in the intestine. At the same time, the period of the general action of the drug can be extended depending on the number of doses of the drug in it, i.e. from the number of layers of the tablet or dragee. Dosage forms with periodic release include two-layer tablets and two-layer dragees (“duplex”), multilayer tablets.

Dosage forms with continuous release- these are prolonged dosage forms, upon introduction into the body of which the initial dose of the drug substance is released, and the remaining (maintenance) doses are released at a constant rate corresponding to the rate of elimination and ensuring the constancy of the desired therapeutic concentration. Dosage forms with a continuous, evenly extended release provide a maintenance effect of the drug. They are more effective than periodic release forms because provide a constant concentration of drugs in the body at a therapeutic level without pronounced extremes, do not overload the body with excessively high concentrations.

Dosage forms with continuous release include frame tablets, tablets and capsules with microforms, etc.

Delayed release dosage forms- these are prolonged dosage forms, with the introduction of which the release of the drug substance into the body begins later and lasts longer than from the usual dosage form. They provide a delayed onset of drug action. Suspensions of ultralong, ultralente with insulin can serve as an example of these forms.

Of particular interest among prolonged dosage forms are tablets.

Prolonged tablets (synonyms - tablets with prolonged action, tablets with prolonged release) - these are tablets, the drug substance from which is released slowly and evenly or in several portions. These tablets allow you to provide a therapeutically effective concentration of drugs in the body for a long period of time.

The nomenclature of prolonged tablets includes implantable tablets, or depot; retard tablets, frame, multilayer, multiphase. These include Depakin Chrono, Cardil, Nifecard HL, Trittiko, Sustonite).

Tablets implantable (syn. - implantablets, depot tablets, tablets for implantation) are sterile trituration tablets with prolonged release of highly purified medicinal substances for injection under the skin. It is shaped like a very small disc or cylinder. These tablets are made without fillers. This dosage form is very common for the administration of steroid hormones. In foreign literature, the term "pellets" is also used. Examples - Disulfiram, Doltard, Esperal.

Retard tablets are oral tablets with prolonged (mainly intermittent) release of drugs.

Usually they are microgranules of a medicinal substance surrounded by a biopolymer matrix (base). They dissolve in layers, releasing another portion of the drug. They are obtained by pressing hard-core microcapsules on tablet machines. As excipients, soft fats are used, which are able to prevent the destruction of the microcapsule shell during the pressing process.

There are also retard tablets with other release mechanisms - delayed, continuous and evenly extended release. Varieties of retard tablets are duplex tablets, structural tablets. These include Dalfaz SR, Diklonat pretard 100, Potassium-normin, Ketonal, Kordaflex, Tramal Pretard.

Repetabs - These are tablets with a multi-layer coating, providing repeated action of the drug. They consist of an outer layer with a drug that is designed to be released quickly, an inner shell with limited permeability, and a core that contains another dose of the drug.

For the manufacture of these tablets, cyclic tablet machines with multiple filling are used. The machines can carry out triple spreading, performed with different granules.

Frame tablets (syn. Durulas, durules tablets, matrix tablets, porous tablets, skeletal tablets, tablets with an insoluble frame) are tablets with a continuous, evenly extended release and supporting action of the drug. This dosage form is obtained by including (incorporating) the drug into a network structure (matrix) of insoluble excipients, or into a matrix of hydrophilic substances that do not form a high viscosity gel. The material for the "skeleton" are inorganic compounds - barium sulfate, gypsum, calcium phosphate, titanium dioxide and organic - polyethylene, polyvinyl chloride, aluminum soaps. Skeletal tablets can be obtained by simply compressing the drugs that form the skeleton. These tablets do not disintegrate in the gastrointestinal tract. Depending on the nature of the matrix, they can swell and dissolve slowly or retain their geometric shape throughout the entire period of stay in the body and be excreted as a porous mass, the pores of which are filled with liquid. tew. Thus, the drug is released by washing out. Dosage forms can be multi-layered. It is important that the medicinal substance is located mainly in the middle layer. Its dissolution begins from the lateral surface of the tablet, while from the upper and lower surfaces only auxiliary substances diffuse from the middle layer through the capillaries formed in the outer layers. At present, the technology for obtaining frame tablets using solid dispersed systems (Kinidin durules) is promising.

Speystabs - these are tablets with a medicinal substance included in a solid fatty matrix that does not disintegrate, but slowly disperses from the surface.

Lontabs These are extended release tablets. The core of these tablets is a mixture of drugs with high molecular weight waxes. In the gastrointestinal tract, they do not disintegrate, but slowly dissolve from the surface.

One of the modern methods of prolonging the action of tablets is coating them with shells, in particular with Aqua Polish coatings. These coatings provide prolonged release of the substance. They have alkaliphilic properties, due to which the tablet is able to pass through the acidic environment of the stomach in an unchanged state. The solubilization of the coating and the release of the active substances takes place in the intestine. The release time of the substance can be controlled by adjusting the viscosity of the coating. It is also possible to set the release time of the various substances in the combined preparations.

Examples of compositions of these coatings:

Aqua Polish,

Methacrylic acid / Ethyl acetate

Sodium carboxymethylcellulose

Talc

Titanium dioxide.

In another embodiment, the coating replaces sodium carboxymethyl cellulose with polyethylene glycol.

Often, the process of microencapsulation is used to prolong dosage forms.

Microencapsulation - the process of encasing microscopic particles of solid, liquid or gaseous medicinal substances. Most often, microcapsules with a size of 100 to 500 microns are used. Particle size< 1 мкм называют нанокапсулами. Частицы с жидким и газообразным веществом имеют шарообразную форму, с твердыми частичками – неправильной формы.

Possibilities of microencapsulation:

a) protection of unstable drugs from environmental influences (vitamins, antibiotics, enzymes, vaccines, sera, etc.);

b) masking the taste of bitter and nauseating drugs;

c) release of medicinal substances in the desired area of ​​the gastrointestinal tract (enteric-soluble microcapsules);

d) prolonged action. A mixture of microcapsules, differing in size, thickness and nature of the shell, placed in one capsule, ensures the maintenance of a certain level of the drug in the body and an effective therapeutic effect for a long time;

e) combination in one place of drugs that are incompatible with each other in pure form (use of separating coatings);

f) "transformation" of liquids and gases into a pseudo-solid state, i.e. into a bulk mass consisting of microcapsules with a hard shell filled with liquid or gaseous medicinal substances.

Application of microcapsules

A number of medicinal substances are produced in the form of microcapsules: vitamins, antibiotics, anti-inflammatory, diuretic, cardiovascular, anti-asthma, antitussive, sleeping pills, anti-tuberculosis, etc.

Microencapsulation opens up interesting possibilities with a number of drugs that cannot be realized in conventional dosage forms. An example is the use of nitroglycerin in microcapsules. Conventional nitroglycerin in sublingual tablets or drops (on a piece of sugar) has a short period of action. Microencapsulated nitroglycerin has the ability to be released in the body for a long time.

Microencapsulation Technology

Existing microencapsulation methods: physical; physical and chemical; chemical.

Physical methods. Physical methods for microencapsulation are numerous. These include drageeing, spraying, spraying in a fluidized bed, dispersion in immiscible liquids, extrusion methods, electrostatic method, etc. The essence of all these methods is the mechanical coating of solid or liquid particles of medicinal substances. The use of one or another method is carried out depending on whether the “core” (the contents of the microcapsule) is a solid or liquid substance.

spray method. For microencapsulation of solids that must first be reduced to fine suspensions. The size of the resulting microcaps sul 30 - 50 microns.

Dispersion method in immiscible liquids . For microencapsulation of liquid substances. The size of the obtained microcapsules is 100 - 150 microns. Here the drip method can be used. heated emulsion oil solution drug substance stabilized with gelatin (emulsion type O/B) is dispersed in cooled liquid paraffin using a stirrer. As a result of cooling, the smallest droplets are covered with a rapidly gelatinous shell. The frozen balls are separated from the liquid paraffin, washed with an organic solvent and dried.

The method of "spraying" in a fluidized bed. In devices like SP-30 and SG-30. The method is applicable to solid medicinal substances. Solid cores are liquefied with an air stream and a solution of a film-forming substance is “sprayed” onto them using a nozzle. Solidification of liquid shells occurs as a result of the evaporation of the solvent.

extrusion method. Under the influence of centrifugal force, the particles of medicinal substances (solid or liquid), passing through the film of the film-forming solution, are covered by it, forming a microcapsule.

Solutions of substances with significant surface tension (gelatin, sodium alginate, polyvinyl alcohol, etc.)

Physical and chemical methods. Based on phase separation, they allow encapsulating a substance in any state of aggregation and obtaining microcapsules different sizes and film properties. Physicochemical methods use the phenomenon of coacervation.

coacervation– formation of droplets enriched with a dissolved substance in a solution of macromolecular compounds.

As a result of coacervation, a two-phase system is formed due to delamination. One phase is a solution of a macromolecular compound in a solvent, the other is a solution of a solvent in a macromolecular substance.

A solution richer in a macromolecular substance is often released in the form of coacervate droplets - coacervate drops, which is associated with the transition from complete mixing to limited solubility. A decrease in solubility is facilitated by a change in such system parameters as temperature, pH, concentration, etc.

Coacervation during the interaction of a polymer solution and a low molecular weight substance is called simple. It is based on the physicochemical mechanism of sticking together, "raking into a heap" of dissolved molecules and separating water from them with the help of water-removing agents. Coacervation during the interaction of two polymers is called complex, and the formation of complex coacervates is accompanied by the interaction between (+) and (-) charges of molecules.

Method of coacervation is as follows.
First, in a dispersion medium (polymer solution), the cores of future microcapsules are obtained by dispersion. The continuous phase is, as a rule, an aqueous solution of the polymer (gelatin, carboxymethyl cellulose, polyvinyl alcohol, etc.), but sometimes it can also be a non-aqueous solution. When conditions are created under which the solubility of the polymer decreases, coacervate drops of this polymer are released from the solution, which are deposited around the nuclei, forming the initial liquid layer, the so-called embryonic membrane. Then there is a gradual hardening of the shell, achieved using various physico-chemical methods.

Hard shells make it possible to separate the microcapsules from the dispersion medium and prevent the penetration of the core substance to the outside.

Chemical methods. These methods are based on polymerization and polycondensation reactions at the interface between two immiscible liquids (water-oil). To obtain microcapsules by this method, first the drug is dissolved in oil, and then the monomer (for example, methyl methacrylate) and the corresponding catalyst for the polymerization reaction (for example, benzoyl peroxide). The resulting solution is heated for 15 - 20 minutes at t = 55 about C and poured into an aqueous solution of the emulsifier. An M/B type emulsion is formed which is held to complete the polymerization for 4 hours. The resulting polymethyl methacrylate, insoluble in oil, forms a shell around the droplets of the latter. The resulting microcapsules are separated by filtration or centrifugation, washed and dried.

Apparatus for drying tablet mixtures in a fluidized bed SP-30

Designed for drying powdery materials and tablet granules that do not contain organic solvents and pyrophoric impurities in the pharmaceutical, food, chemical industries.

When drying multicomponent mixtures, mixing is carried out directly in the apparatus. In dryers of the SP type, it is possible to carry out dusting of tablet mixtures before tableting.

Specifications

Operating principle: The air flow sucked into the dryer by the fan is heated in the calorific unit, passes through the air filter and is directed under the mesh bottom of the product tank. Passing through the holes in the bottom, the air brings the granulate into suspension. Humidified air is removed from the working area of ​​the dryer through a bag filter, the dry product remains in the tank. After drying, the product is transported in a trolley for further processing.

List of used literature

1.V.I. Chueshov, Industrial drug technology: textbook. - Kharkov, NFAU, 2002. 715 p.

2.material of lectures of the Department of General Pharmaceutical and Biomedical Technology, MMA. THEM. Sechenov

3. Brief Medical Encyclopedia

4. www.pharm.witec.com.

5.www.golkom.ru

6.www.gmpua.com

7.http:|//protabletki.ru

8.www.rosapteki.ru