Treatment of hypertension. Effective drugs for high blood pressure List of the most effective drugs for high blood pressure

Article publication date: 11/10/2016

Date of article update: 06.12.2018

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, cerebrovascular accident, etc.

The table shows a general list of drugs from different pharmaceutical groups 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 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.

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.

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.

Rating of high blood pressure pills with their description

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. Designed for emergency care in order to stop a 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 together 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. It:

• 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:

Summary

A large number of tablets for high blood pressure. 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.

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High blood pressure pills () in the modern classification are represented by 4 main groups: diuretics (diuretic), antiadrenergic (alpha- and beta-blockers, means that are called "drugs of central action"), peripheral vasodilators, calcium antagonists and ACE inhibitors(angiotensin converting enzyme).

This list does not include antispasmodics, such as papaverine, since they give a weak hypotensive effect, slightly reducing due to relaxation of smooth muscles, and their purpose is somewhat different.

Many people also refer to folk remedies for pressure medicines, but this, in general, is everyone’s business, however, we will consider them, since in many cases they are really effective as an auxiliary treatment, and in some (at the initial stage) they completely replace the main .

Diuretics lower blood pressure

Such a statement is absolutely correct. A set of pressure pills prescribed in the clinic, as a rule, also includes diuretics:

Diuretics are not prescribed for arterial hypertension (AH) accompanying severe renal failure. The only exception in this case is furosemide. Meanwhile, for hypertensive patients with symptoms of hypovolemia or signs of severe anemia, diuretics such as furosemide and ethacrynic acid (uregit) are strictly contraindicated.

• Captopril (Capoten) - can block ACE in a targeted manner. Beginning hypertensive patients and people with experience in this field know captopril as first aid for increasing blood pressure: a tablet under the tongue - after 20 minutes, the pressure decreases;
• Enalapril (Renitek) is very similar to captopril, but it cannot change blood pressure so quickly, although it manifests itself an hour after administration. Its action is longer (up to a day), while captopril after 4 hours and there is no trace;
• Benazepril;
• Ramipril;
• Quinapril (accupro);
• Lisinopril - acts quickly (in an hour) and for a long time (days);
• Lozap (losartan) - is considered a specific angiotensin II receptor antagonist, reduces systolic and diastolic blood pressure, is used for a long time, since the maximum therapeutic effect is achieved after 3-4 weeks.

The mechanism of action of ACE in CHF

Contraindications to the appointment of angiotensin II receptor antagonists

ACE inhibitors are not prescribed in cases of:

1. Angioedema in history (a kind of intolerance to these drugs, which is manifested by a violation of the act of swallowing, difficulty breathing, swelling of the face, upper limbs, hoarseness of voice). If such a condition occurs for the first time (at the initial dose), the drug is canceled immediately;
2. Pregnancy (ACE inhibitors negatively affect the development of the fetus, leading to various anomalies or death, therefore, they are canceled immediately after this fact is established).

In addition, for ACE inhibitors there is list of special instructions warning against undesirable consequences:

• In SLE and scleroderma, the expediency of using this group of drugs is very doubtful, since there is a considerable risk of changes in the blood (neutropenia, agranulocytosis);
• Stenosis of the kidney or both, as well as a transplanted kidney, can threaten the formation of renal failure;
• CRF requires a reduction in the dose of the drug;
• In severe heart failure, impairment of the functional abilities of the kidneys, up to death, is possible.
• Liver damage with impaired function due to a decrease in the metabolism of certain ACE inhibitors (captopril, enalapril, quinapril, ramipril), which can lead to the development of cholestasis and hepatonecrosis, needs to reduce the dose of these drugs.

There are also side effects that everyone knows about but can't do anything about.. For example, in people with functional impairment of the kidneys (especially, but sometimes without them), when using ACE inhibitors, blood biochemical parameters may change (the content increases, and potassium, but the level drops). Often, patients complain about the appearance of a cough, which is especially activated at night. Some go to the clinic to pick up another medicine for hypertension, while others try to endure ... True, they transfer the intake of ACE inhibitors to the morning hours and this somewhat helps themselves.

When is a doctor indispensable?

In the treatment of arterial hypertension, other drugs are traditionally used, which, in general, do not have pronounced features inherent in any particular group of antihypertensives. For example, the same dibazol or, say, magnesium sulfate(magnesia), which is successfully used by emergency doctors to relieve hypertensive crisis. Magnesium sulphate injected into a vein has an antispasmodic, sedative, anticonvulsant and slightly hypnotic effect. A very good drug, however, it is not easy to administer it: it must be done very slowly, so the work is stretched for 10 minutes (the patient becomes unbearably hot - the doctor stops and waits).

For the treatment of hypertension, in particular, in severe hypertensive crises sometimes pentamine-N is prescribed (an anticholinergic agent of sympathetic and parasympathetic ganglia, which reduces the tone of arterial and venous vessels), benzohexonium similar to pentamine arfonade(ganglioblokator), chlorpromazine(phenothiazine derivatives). These drugs are intended for emergency assistance or intensive care, so they can only be used by a doctor who knows their characteristics well!

The latest blood pressure medications

Meanwhile, patients try to keep abreast of the latest advances in pharmacology and are often looking for the latest drugs for pressure, but new does not mean better, and it is not known how the body will react to this. You can't prescribe these drugs for sure. Nevertheless, I would like to introduce the reader to some of these modern developments, on which great hopes are placed.

Angiotensin II receptor antagonists (ACE inhibitors) have probably been the most successful in adding to the list of innovations. This list includes drugs such as cardosal(olmesartan), thermisartan, which, they say, is now not inferior to the most popular ramipril.

If you carefully read about antihypertensive drugs, you will notice that blood pressure increases a certain mysterious substance - renin, which none of the listed drugs can cope with. However, to the delight of patients suffering from high blood pressure, a cure has recently appeared - rasilez (aliskiren), which is a renin inhibitor and may be able to solve many problems.

Newer blood pressure drugs include recently developed endothelial receptor antagonists: bosentan, enrasentan, darusentan, which block the production of a vasoconstrictor peptide - endothelin.

Folk remedies for pressure

Considering all kinds of means that can cope with high blood pressure, it is hardly possible to ignore the recipes for tinctures, decoctions, drops that have come out of the people. Some of them have been adopted by official medicine and are successfully used to treat initial (borderline and “mild”) arterial hypertension. Patients have great confidence in medicines, the manufacture of which is used for herbs growing in Russian meadows or the organs of trees that make up the flora of our vast Motherland:

Monastic tea for hypertension

The application should be said separately, too many questions are raised by this “latest folk remedy”, which, as an auxiliary or preventive measure, has really proven itself well. No wonder - the monastic collection for hypertension contains a list of medicinal herbs that improve cardiac activity, brain function, positively affect the functional abilities of the vascular wall and help well at the initial stage of hypertension.

Unfortunately, this medicine will not be able to completely replace high blood pressure pills taken for years in advanced cases of arterial hypertension, although it is quite possible to reduce their number and dose. If tea is taken constantly ...

So that the patient himself can understand the benefits of the drink, we consider it right to recall the composition of monastic tea:

• Rose hip;
• St. John's wort;
• Elecampane;
• Oregano;
• Motherwort;
• Aronia;
• Hawthorn;
• Black tea.

In principle, there may be some variations of the recipe, which should not alarm the patient, because there are so many medicinal plants in nature.

Video: folk remedies for pressure

Treatment of patients with arterial hypertension requires a lot of time. Using the method of "trial and error", the doctor looks for his own medicine for each patient, taking into account the state of the whole organism, age, gender and even profession, since some drugs have side effects that impede professional activity. Of course, it will be difficult for the patient himself to solve such a problem, unless, of course, he is a doctor.

April 27, 2012

In the treatment of hypertension, there are two approaches: drug therapy and the use of non-drug methods to reduce pressure.

Non-drug therapy of hypertension

If you carefully study the table "Risk stratification in patients with arterial hypertension", you can see that the risk of serious complications, such as heart attacks, strokes, is affected not only by the degree of increase in blood pressure, but also by many other factors, for example, smoking, obesity, sedentary lifestyle life.

Therefore, it is very important for patients suffering from essential hypertension to change their lifestyle: quit smoking. start to follow a diet, as well as choose physical activity that is optimal for the patient.

It must be understood that lifestyle changes improve the prognosis of arterial hypertension and other cardiovascular diseases to no lesser extent than perfectly controlled blood pressure with medication.

To give up smoking

Thus, the life expectancy of a smoker is on average 10-13 years less than that of non-smokers, with cardiovascular diseases and oncology becoming the main causes of death.

When quitting smoking, the risk of developing or exacerbating heart and vascular disease is reduced within two years to the level of non-smokers.

Dieting

Compliance with a low-calorie diet with the use of a large amount of plant foods (vegetables, fruits, herbs) will reduce the weight of patients. It is known that every 10 kilograms of excess weight increases blood pressure by 10 mm Hg.

In addition, the exclusion of cholesterol-containing foods from food will reduce the level of blood cholesterol, the high level of which, as can be seen from the table, is also one of the risk factors.

Limiting salt to 4-5 grams per day has been proven to lower blood pressure, since with a decrease in salt content, the amount of fluid in the vascular bed will also decrease.

In addition, reducing weight (and especially waist circumference) and limiting sweets will reduce the risk of developing diabetes, which significantly worsens the prognosis of patients with arterial hypertension. But even in patients with diabetes, weight loss can lead to normalization of blood glucose.

Physical exercise

Physical activity is also very important for hypertensive patients. During physical activity, the tone of the sympathetic nervous system decreases: the concentration of adrenaline and norepinephrine decreases, which have a vasoconstrictive effect and increase heart contractions. And as you know, it is the imbalance in the regulation of cardiac output and vascular resistance to blood flow that causes an increase in blood pressure. In addition, with moderate exercise performed 3-4 times a week, the cardiovascular and respiratory systems are trained: blood supply and oxygen delivery to the heart and target organs are improved. In addition, physical activity coupled with diet lead to weight loss.

It should be noted that in patients with low and moderate risk of cardiovascular complications, the treatment of hypertension begins with the appointment of several weeks or even months (at low risk) of non-drug therapy, the purpose of which is to reduce the volume of the abdomen (in men less than 102, in women less than 88 cm), as well as the elimination of risk factors. If there are no dynamics against the background of such treatment, tablet preparations are added.

In patients with high and very high risk according to the risk stratification table, drug therapy should be prescribed already at the moment when hypertension is first diagnosed.

Drug therapy for hypertension.

The scheme for selecting treatment for patients with hypertension can be formulated in several theses:

• For low- and moderate-risk patients, therapy begins with a single blood pressure-lowering drug.
• For patients with high and very high risk of cardiovascular complications, it is advisable to prescribe two drugs in a small dosage.
• If the target blood pressure (at least less than 140/90 mm Hg, ideally 120/80 or less) is not achieved in low- and moderate-risk patients, either increase the dosage of the drug they receive or start giving the drug from another groups at low doses. In case of repeated failure, it is advisable to treat with two drugs of different groups in small dosages.
• If BP targets are not achieved in high-risk and very-high-risk patients, one can either increase the dosage of the patient's drugs or add a third drug from another group to the treatment.
• If the patient's health worsens with a decrease in blood pressure to 140/90 or lower, it is necessary to leave the drugs at this dosage until the body gets used to the new blood pressure numbers, and then continue to lower blood pressure to the target values ​​- 110/70-120 /80 mmHg

Groups of drugs for the treatment of arterial hypertension:

The choice of drugs, their combinations and dosages should be made by a doctor, while it is necessary to take into account the presence of concomitant diseases in the patient, risk factors.

The main six groups of drugs for the treatment of hypertension are listed below, as well as absolute contraindications for drugs in each group.

• Angiotensin-converting enzyme inhibitors - ACE inhibitors: enalapril (Enap, Enam, Renitek, Berlipril), lisinopril (Diroton), ramipril (Tritace®, Amprilan®), fosinopril (Fozikard, Monopril) and others. Preparations of this group are contraindicated in high blood potassium, pregnancy, bilateral stenosis (narrowing) of the kidney vessels, angioedema.
• Angiotensin-1 receptor blockers - ARBs: valsartan (Diovan, Valsakor®, Valz), losartan (Cozaar, Lozap, Lorista), irbesartan (Aprovel®), candesartan (Atakand, Kandecor). Contraindications are the same as for ACE inhibitors.
• β-blockers - β-AB: nebivolol (Nebilet), bisoprolol (Concor), metoprolol (Egiloc®, Betaloc®) . The drugs of this group should not be used in patients with atrioventricular blockade of the 2nd and 3rd degree, bronchial asthma.
• Calcium antagonists - AK. Dihydropyridine: nifedipine (Cordaflex®, Corinfar®, Cordipin®, Nifecard®), amlodipine (Norvask®, Tenox®, Normodipin®, Amlotop). Non-dihydropyridine: Verapamil, Diltiazem.

ATTENTION! Non-hydropyridine calcium channel antagonists are contraindicated in chronic heart failure and atrioventricular blockade of 2-3 degrees.

• Diuretics (diuretics). Thiazide: hydrochlorothiazide (Hypothiazide), indapamide (Arifon, Indap). Loop: spironolactone (Veroshpiron).

ATTENTION! Diuretics from the group of aldosterone antagonists (Veroshpiron) are contraindicated in chronic renal failure and high blood potassium.

• renin inhibitors. This is a new group of drugs that have shown themselves well in clinical trials. The only renin inhibitor currently registered in Russia is Aliskiren (Rasilez).

Effective combinations of drugs that reduce blood pressure

Since patients often have to prescribe two, and sometimes more drugs that have an antihypertensive (lowering pressure) effect, the most effective and safe group combinations are given below.

• ACE inhibitor + diuretic;
• ACE inhibitor + AK;
• ARB + ​​diuretic;
• BRA+AK;
• AK + diuretic;
• AK dihydropyridine (nifedipine, amlodipine, etc.) + β-AB;
• β-AB + diuretic:;
• β-AB+α-AB: Carvedilol (Dilatrend®, Acridilol®)

Irrational combinations of antihypertensive drugs

The use of two drugs of the same group, as well as combinations of drugs listed below, is unacceptable, since drugs in such combinations increase side effects, but do not potentiate the positive effects of each other.

• ACE inhibitor + potassium-sparing diuretic (Veroshpiron);
• β-AB + non-dihydropyridine AA (Verapamil, Diltiazem);
• β-AB+ drug of central action.

Combinations of drugs that are not found in any of the lists belong to the intermediate group: their use is possible, but it must be remembered that there are more effective combinations of antihypertensive drugs.

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No. 7. Centrally acting drugs for the treatment of arterial hypertension

You are reading a series of articles on antihypertensive (antihypertensive) drugs. If you want to get a more holistic view of the topic, please start at the beginning: an overview of antihypertensives acting on the nervous system.

The medulla oblongata (the lowest part of the brain) contains vasomotor (vasomotor) center. It has two departments - pressor and depressor. which increase and decrease blood pressure, respectively, acting through the nerve centers of the sympathetic nervous system in the spinal cord. The physiology of the vasomotor center and the regulation of vascular tone are described in more detail here: http://www.bibliotekar.ru/447/117.htm(text from a textbook on normal physiology for medical schools).

The vasomotor center is important for us because there is a group of drugs that act on its receptors and thus reduce blood pressure.

Sections of the brain.

Classification of centrally acting drugs

For drugs that act primarily on sympathetic activity in the brain. relate:

• clonidine (clophelin) ,
• moxonidine (physiotens) ,
• methyldopa(may be used in pregnant women)
• guanfacine ,
• guanabenz .

In the search for pharmacies in Moscow and Belarus there is no methyldopa, guanfacine and guanabenz. but sold clonidine(strictly according to the recipe) and moxonidine .

The central component of action is also present in blockers of serotonin receptors. about them in the next section.

Clonidine (clophelin)

Clonidine (clophelin) inhibits the secretion of catecholamines by the adrenal glands and stimulates alpha 2 -adrenergic receptors and I 1 -imidazoline receptors of the vasomotor center. It reduces blood pressure (by relaxing blood vessels) and heart rate (heart rate). Clonidine also has hypnotic and analgesic effect .

Scheme of regulation of cardiac activity and blood pressure.

In cardiology, clonidine is mainly used for treatment of hypertensive crises. This drug is adored by criminals and. retired grandmothers. Attackers like to mix clonidine into alcohol and, when the victim “passes out” and falls asleep, they rob fellow travelers ( never drink alcohol on the road with strangers!). This is one of the reasons why clonidine (clonidine) has been sold in pharmacies for a long time. only by prescription .

The popularity of clonidine as a remedy for arterial hypertension in "clofelina" grandmothers (who cannot live without taking clonidine, like smokers without a cigarette) is due to several reasons:

1. high efficiency drug. Local doctors prescribe it for the treatment of hypertensive crises, as well as from despair, when other drugs are not effective enough or the patient cannot afford, but something needs to be treated. Clonidine reduces pressure even if other means are ineffective. Gradually, older people develop mental and even physical dependence on this drug.

Clonidine is recommended to use only for the treatment of hypertensive crises. for regular intake 2-3 times a day, it is undesirable, since rapid significant fluctuations in blood pressure levels during the day are possible, which can be dangerous for blood vessels. Main side effects. dry mouth, dizziness and lethargy(not allowed for drivers), development is possible depression(then clonidine should be canceled).

Orthostatic hypotension (decreased blood pressure in an upright position) clonidine does not cause .

Most dangerous side effect of clonidine - withdrawal syndrome. Grandmothers - "clofelins" take a lot of pills per day, bringing the average daily intake to high daily doses. But since the drug is purely prescription, it will not be possible to create a six-month supply of clonidine at home. If for some reason local pharmacies experience interruptions in the supply of clonidine. these patients develop a severe withdrawal syndrome. Like drinking. Absent in the blood, clonidine no longer inhibits the release of catecholamines into the blood and does not lower blood pressure. Patients are worried agitation, insomnia, headache, palpitations, and very high blood pressure. Treatment consists of the introduction of clonidine, alpha-blockers and beta-blockers.

Remember! Regular clonidine should not be stopped abruptly. It is necessary to cancel the drug gradually. replacing α- and β-blockers.

Moxonidine (Physiotens)

Moxonidine is a modern promising drug, which can be briefly called " improved clonidine". Moxonidine belongs to the second generation of agents acting on the central nervous system. The drug acts on the same receptors as clonidine (clophelin), but the effect on I 1 is imidazoline receptors expressed much stronger than the effect on alpha2-adrenergic receptors. Due to the stimulation of I 1 receptors, the release of catecholamines (adrenaline, norepinephrine, dopamine) is inhibited, which reduces blood pressure (blood pressure). Moxonidine maintains a reduced level of adrenaline in the blood for a long time. In some cases, as with clonidine, in the first hour after ingestion, before a decrease in blood pressure, its increase by 10% may be observed, which is due to stimulation of alpha1- and alpha2-adrenergic receptors.

In clinical studies Moxonidine lowered systolic (upper) pressure by 25-30 mm Hg. Art. and diastolic (lower) pressure of 15-20 mm without development of resistance to the drug during 2 years of treatment. The effectiveness of the treatment was comparable to that of a beta-blocker. atenolol and ACE inhibitors captopril and enalapril .

Antihypertensive effect Moxonidine lasts 24 hours, the drug is taken 1 time per day. Moxonidine does not increase the level of sugar and lipids in the blood, its effect does not depend on body weight, sex and age. Moxonidine reduced LVH ( left ventricular hypertrophy), which allows the heart to live longer.

The high antihypertensive activity of moxonidine made it possible to use it for the complex treatment of patients with CHF (chronic heart failure) with functional class II-IV, but the results in the MOXCON study (1999) were disappointing. After 4 months of treatment, the clinical study had to be terminated early due to the high mortality in the experimental group compared to the control group (5.3% vs. 3.1%). Overall mortality increased due to an increase in the frequency of sudden death, heart failure and acute myocardial infarction.

moxonidine causes fewer side effects compared to clonidine. although they are very similar. In comparative cross 6-week trial of moxonidine with clonidine ( each patient received both compared drugs in a random sequence) side effects led to treatment discontinuation in 10% of patients treated with clonidine, and only in 1.6% of patients. taking moxonidine. More likely to bother dry mouth, headache, dizziness, tiredness or drowsiness .

withdrawal syndrome was observed on the first day after discontinuation of the drug in 14% of those who received clonidine, and only in 6% of patients who received moxonidine.

Thus, it turns out:

• clonidine it is cheap but has many side effects,
• moxonidine costs much more, but is taken once a day and is better tolerated. It can be prescribed if drugs of other groups are not effective enough or are contraindicated.

Conclusion. if financial situation permits, clonidine and moxonidine for permanent use, it is better to choose the latter (1 time per day). Clonidine is taken only in case of hypertensive crises, this is not a drug for every day.

Treatment of arterial hypertension

What methods are used to treat arterial hypertension? When does hypertension require hospitalization?

Non-pharmacological methods of treatment of arterial hypertension

• Low-calorie diet (especially if you are overweight). With a decrease in excess body weight, a decrease in blood pressure is noted.
• Restriction of salt intake to 4 - 6 g per day. This increases the sensitivity to antihypertensive therapy. There are "substitutes" for salt (potassium salt preparations - sanasol).
• Inclusion in the diet of foods rich in magnesium (legumes, millet, oatmeal).
• Increased motor activity (gymnastics, dosed walking).
• Relaxation therapy, autogenic training, acupuncture, electrosleep.
• Elimination of hazards (smoking, drinking alcohol, taking hormonal contraceptives).
• Employment of patients taking into account their illness (exclusion of night work, etc.).

Non-drug treatment carried out with a mild form of arterial hypertension. If after 4 weeks of such treatment the diastolic pressure remains 100 mm Hg. Art. and above, then switch to drug therapy. If diastolic pressure is less than 100 mm Hg. Art. then non-drug treatment is continued up to 2 months.

In persons with a burdened history, with left ventricular hypertrophy, drug therapy is started earlier or combined with non-drug therapy.

Medical methods of treatment of arterial hypertension

There are many antihypertensive drugs. When choosing a drug, many factors are taken into account (gender of the patient, possible complications).

• For example, drugs of central action that block sympathetic influences (clophelin, dopegyt, alpha-methyl-DOPA).
• In women in the menopause, when there is low renin activity, relative hyperaldosteronism, a decrease in progesterone levels, hypervolumic states are often noted, and “edematous” hypertensive crises develop. In such a situation, the drug of choice is a diuretic (saluretic).
• There are powerful drugs - ganglion blockers, which are used in the relief of a hypertensive crisis or, together with other antihypertensive drugs, in the treatment of malignant hypertension. Ganglion blockers should not be used in older people who are prone to orthostatic hypotension. With the introduction of these drugs, the patient should be in a horizontal position for some time.
• Beta-blockers provide a hypotensive effect by reducing cardiac output and plasma renin activity. In young people, they are the drugs of choice.
• Calcium antagonists are prescribed in the combination of hypertension with coronary heart disease.
• Alpha-adrenergic blockers.
• Vasodilators (eg minoxidil). They are used in addition to the main therapy.
• Angiotensin-converting enzyme inhibitors (ACE inhibitors). These drugs are used in all forms of hypertension.

When prescribing drugs, the state of the target organs (heart, kidneys, brain) is taken into account.

For example, the use of beta-blockers in patients with renal insufficiency is not indicated, because they impair renal blood flow.

It is not necessary to strive for a rapid decrease in blood pressure, since this can lead to a deterioration in the patient's well-being. Therefore, the drug is prescribed, starting with small doses.

Scheme of treatment of arterial hypertension

There is a treatment regimen for arterial hypertension: at the first stage, beta-blockers or diuretics are used; at the second stage "beta-blockers + diuretics", it is possible to add ACE inhibitors; in severe hypertension, complex therapy is performed (possibly surgery).

A hypertensive crisis often develops when medical recommendations are not followed. In crises, drugs are most often prescribed: clonidine, nifedipine, captopril.

Indications for hospitalization

• Clarification of the nature of arterial hypertension (if it is impossible to perform studies on an outpatient basis).
• Complication of the course of arterial hypertension (crisis, stroke, etc.).
• Refractory arterial hypertension, not amenable to antihypertensive therapy.

(otherwise called hypertension) is a stable increase in blood pressure numbers above 140/90, for no apparent reason. It is one of the most common diseases in the world, especially among our compatriots. We can safely say that after fifty years, almost every citizen of the post-Soviet space suffers from high blood pressure. This is explained by overweight, smoking, alcohol abuse, constant stress and other adverse factors. What is most unpleasant in this situation is that hypertension begins to "get younger" - every year more and more cases of high blood pressure are recorded in people of working age, and the number of cardiovascular accidents (myocardial infarctions, strokes) is also growing, which leads to chronic disability with subsequent disability . Thus, arterial hypertension becomes a problem not only medical, but also social.

No, there are, of course, cases when a stable increase in blood pressure numbers is the result of some primary disease (for example, due to pheochromocytoma, a neoplasm that affects the adrenal glands and is accompanied by a high release of hormones into the blood that activate the sympathoadrenal system). However, there are very few such cases (no more than 5% of the registered clinical conditions characterized by a stable increase in blood pressure) and it should be noted that the approaches to the treatment of hypertension, both primary and, are approximately the same. The only difference is that in the second case it is necessary to eliminate the root cause of this disease. But the normalization of blood pressure numbers is just the same carried out according to the same principles, the same drugs.

Today, hypertension is treated with drugs of different groups.

Medicines

Which are used in the treatment of arterial hypertension, as well as their classification.

Of greater importance for practitioners is the conditional division of antihypertensive drugs into drugs for planned use and drugs, the action of which allows them to be used as emergency care for hypertensive crises.

Angiotensin-converting enzyme inhibitors (ACE inhibitors)

Medicines belonging to this group are the number one drugs of choice in the treatment of both primary and secondary arterial hypertension. This is mainly due to their protective effect on the vessels of the kidneys. This phenomenon is explained by the mechanism of their biochemical effects - under the action of ACE inhibitors, the action of the enzyme that converts angiotensin 1 into its active form angiotensin 2 (a substance that leads to a narrowing of the lumen of the vessels, thus increasing blood pressure) slows down. Naturally, if this metabolic process is inhibited by medication, then the increase in blood pressure also does not occur.

Representatives of drugs in this group are:

1. Enalapril (trade name - Berlipril);
2. Lisinopril (trade name - Linotor, Diroton);
3. Ramipril (trade name - Ramizes, Cardipril);
4. Fosinopril;

These drugs are representatives of this pharmacological group, which have found the widest application in practical medicine.

In addition to them, there are still a lot of medicines of a similar effect that have not found such widespread use due to various reasons.

It is important to note one more thing - all drugs from the ACE inhibitor group are prodrugs (with the exception of Captopril and Lisinopril). That is, this means that a person uses an inactive form of a pharmacological agent (the so-called prodrug), and already under the influence of metabolites, the drug passes into an active form (becomes a drug), which realizes its therapeutic effect. Captopril and Lisinopril, on the contrary, falling into the body immediately have their therapeutic effect, in view of the fact that they are already metabolically active forms. Naturally, prodrugs begin to act more slowly, but their clinical effect lasts longer. While Captopril has a faster and at the same time short-term effect.

Thus, it becomes clear that prodrugs (for example, Enalapril or Cardipril) are prescribed for the planned treatment of arterial hypertension, while Captopril is recommended for the relief of hypertensive crises.

The use of ACE inhibitors in pregnant women and while breastfeeding is contraindicated.

Beta-adrenergic blockers

The second most frequently used group of pharmacological drugs. The principle of their action is that they block adrenergic receptors, which are responsible for the implementation of the effect of the sympathoadrenal system. Thus, under the influence of drugs of this pharmacological group, not only a decrease in blood pressure figures is observed, but also a decrease in heart rate. It is customary to divide beta-adrenergic blockers into selective and non-selective. The difference between these two groups is that the former act only on beta1 adrenoreceptors, while the latter block both beta1 and beta2 adrenoceptors. This explains the phenomenon that when using highly selective beta-blockers, asthma attacks do not occur (this is especially important to consider when treating hypertension in patients suffering from bronchial asthma). It is important to note that when selective beta-blockers are used at high doses, their selectivity is partially lost.

Propranolol is a non-selective beta blocker.

To selective - Metoprolol, Nebivolol, Carvedilol.

By the way, these drugs are best used if the patient has a combination of hypertension along with coronary heart disease - both effects of beta-blockers will be in demand.

Blockers of slow calcium channels

Another pharmacological group of drugs used to treat arterial hypertension (the most interesting thing is that in Western countries these drugs are used only to treat angina pectoris). Similar to beta-blockers, they reduce the pulse and blood pressure figures, however, the mechanism for implementing the therapeutic effect is somewhat different - it is realized by preventing the penetration of Calcium ions to the smooth myocytes of the vascular wall. Typical representatives of this pharmacological group are amlodipine (used for planned treatment) and (emergency drug).

Diuretics

Diuretics. There are several groups:

1. Loop diuretics - Furosemide, Torasemide (Trifas - trade name);
2. Thiazide diuretics - Hydrochlorothiazide;
3. Thiazide-like diuretics - Indapamide;
4. Potassium-sparing diuretics (spironolactone).

To date, in hypertension, Trifas (from diuretics) is most often used - in view of the fact that it is highly effective and after its use there are no such number of side effects as when using Furosemide.

The remaining groups of diuretic drugs are used, as a rule, as auxiliary ones due to their unexpressed action, or in general, so that potassium is not washed out of the body (in this case, Veroshpiron is ideal).

Sartans

Drugs that are similar in their action to angiotensin-converting enzyme inhibitors, with the only difference being that they do not affect the enzyme itself, but the receptors for it. They are used if, after using an ACE inhibitor, a cough is observed in a patient.

Examples of drugs for the treatment of GB from this group are Losartan, Valsartan.

We should not forget about the old proven remedy - magnesium sulfate 25% solution (Magnesia) - an emergency drug for hypertensive crisis, administered intramuscularly. They should not always treat GB, but for a single decrease in blood pressure, it is an ideal remedy.

conclusions

There are many drugs for the treatment of hypertension and, as a rule, they are used in combination (in the event that resistant hypertension occurs, then a combination with second-line drugs is often used).

Suitable groups of drugs are selected by the attending physician based on the patient's condition, medical history, the presence of comorbidity and many other factors.

Video

Hypertension (AH) is an increase in blood pressure (BP) above 140/80 miHg.

There are essential and symptomatic hypertension. Essential hypertension, often referred to as essential hypertension (AH), accounts for about 90% of all cases of hypertension. In essential hypertension, the specific cause of the increase in blood pressure, as a rule, cannot be identified. In the development of this form of the disease, an important role belongs to the activation of the sympathetic-adrenal, renin-angiotensin, calecrine-kinin systems. The reasons for such activation can be hereditary predisposition, psycho-emotional overstrain, overweight, physical inactivity, etc. Hypertension is called symptomatic or secondary if the cause of the increase in pressure is diseases or damage to organs (kidneys, endocrine disorders, congenital and acquired malformations of the heart and blood vessels). Treatment of this form of GB begins with the elimination of the cause that caused the increase in blood pressure. Hypertension is not dangerous in itself - complications of hypertension pose a threat - hemorrhagic stroke, heart failure, nephrosclerosis, coronary heart disease.

Therapy of patients with hypertension has two tasks:

1. lower blood pressure below 140/90 mm Hg. Art.

2. prevent or slow down the development of complications;

Currently, a large number of groups of drugs are used to treat GB:

1. β-blockers;

2. ACE inhibitors;

5. diuretics,

4. blockers of slow calcium channels;

5. α-blockers;

6. blockers of AT1-angiotensin receptors;

7. I 1 -imidazodine receptor agonists;

8. central α 2 -adrenergic receptor agonists

9. vasodilators

10. other groups of drugs that reduce blood pressure.

However, despite the many pharmacological groups, the first four play the main role in the treatment of hypertension.

β-ADRENOBLOCKERS.

(for a detailed description of the group, see the lecture β-blockers)

β-adrenergic blockers are first-line antihypertensive drugs, their use in patients with increased activity of the sympathoadrenal system is especially important, β-blockers have several mechanisms leading to a persistent decrease in blood pressure:

Decrease in cardiac output by 15-20% due to weakening of myocardial contractility and slowing of heart rate,

Decreased activity of the vasomotor center,

Decreased secretion of renin

Decreased total peripheral vascular resistance (this effect is pronounced in drugs with vasodilating activity)

In the treatment of hypertension, preference should be given to β-blockers with vasodilating properties (carvedilol and nebivolol) and cardioselective drugs (atenolol, betaxolop, bisoprolol). The former are recommended because of increased peripheral vascular resistance in most patients. The latter, to a lesser extent than non-selective drugs, negatively affect vascular tone. In addition, cardioselective blockers are safer when prescribed to patients with bronchial asthma. In hypertension, it is advisable to use long-acting drugs (betaxolol, talinolol-retard, nadolol, atenolol). Firstly, it is more convenient for patients to take drugs once a day. Secondly, the use of short-acting drugs has disadvantages: fluctuations in the activity of the sympathoadrenal system in accordance with changes in the concentration of the drug in the body during the day, and with a sudden withdrawal of the drug, it is possible to develop the “recoil” syndrome - a sharp increase in blood pressure. A stable hypotensive effect of β-blockers develops 3-4 weeks after the start of the drug. It is stable and does not depend on the physical activity and psycho-emotional state of the patient. β-blockers reduce left ventricular hypertrophy and improve myocardial contractility.

The hypotensive effect of β-blockers is enhanced when combined with diuretics, calcium antagonists, α-blockers, ACE inhibitors.

α - ADRENO BLOCKERS.

The classification of α-adrenergic receptor blockers is based on their selectivity for various α-adrenergic receptors:

1. Non-selective α-adrenoblotators: dihydrated ergot alkaloids, tropafen, phentolamine;

2. Selective α-blockers: prozosin, doxazosin, terazosin.

Currently, selective α-blockers are used for hypertension. Drugs blocking α-adrenergic receptors reduce systemic vascular resistance, cause reverse development of left ventricular hypertrophy, improve the lipid composition of blood. The presence of a large number of α-adrenergic receptors in the smooth muscles of the prostate and bladder neck allows the use of drugs in patients with prostate adenoma to improve urination.

Prazosin is a selective α 1 -blocker of short action. When taken orally, it is rapidly absorbed from the gastrointestinal tract. The bioavailability of prazosin is 60%. More than 90% of prazosin binds to plasma proteins. The maximum concentration in the blood is determined after 2-3 hours. The half-life of prazosin is 3-4 hours. The latent period of the drug is 30-60 minutes, the duration of action is 4-6 hours. It is metabolized in the liver. 90% of prazosin and its metabolites are excreted through the intestines, the rest through the kidneys. The drug is taken 2-3 times a day, the daily dose is 3-20 mg. Prazosin is characterized by the effect of the "first dose" - a sharp decrease in blood pressure after taking the first dose of the drug, so treatment begins with small doses of the drug (0.5-1 mg). The drug causes postural hypotension, weakness, drowsiness, dizziness, headache.

Doxazosin is a long-acting α-blocker. The drug has a beneficial effect on the lipid profile of the blood, does not cause the effect of the "first dose". Doxazosin is almost completely absorbed from the gastrointestinal tract. Food slows down the absorption of the drug by about 1 hour. The bioavailability of doxazozia is 65-70%. The maximum concentration in the blood is determined 2-3.5 hours after taking the drug. The half-life is 16-22 hours. Duration of action - 18-36 hours. Doxazosin is prescribed once a day.

Phentolamine is a non-selective α-blocker. It is mainly used in the treatment of hypertensive crises associated with hypercatecholemia, for example, in patients with pheochromocytoma. In addition, phentolamine is used for diagnostic purposes in cases of suspected pheochromocytoma.

BLOCKERSα- and β-ADRENORECEPTORS.

Labetalol (trandat) is a β-adrenergic blocker, which simultaneously has an α 1 -adrenergic blocking effect. Labetalol as an α-blocker is 2-7 times less active than phentolamine, and as a β-adrenologator it is 5-18 times less active than anaprilin. the drug has a hypotensive effect, mainly due to a decrease in peripheral vascular resistance. Labetalol has little effect on cardiac output and heart rate. The main indication for the use of the drug is a hypertensive crisis.

DIURETICS

Diuretics have been used for hypertension for a long time, but at the beginning they were used as auxiliary. Now many drugs can be used for long-term monotherapy of hypertension.

Considering the negative significance of increasing the concentration of sodium ions in plasma and the vascular wall in the pathogenesis of hypertension, the main role in the treatment belongs to saluretic agents - drugs whose mechanism is associated with inhibition of sodium and chlorine reabsorption. These include benzothiadiazine derivatives and heterocyclic compounds. The latter are often called thiazide-like diuretics.

In emergency situations, for example, in a hypertensive crisis, stronger drugs are used - "loop" diuretics: furosemide and ethacrynic acid. Potassium-sparing diuretics play a supportive role and are usually given with thiazide and loop diuretics to reduce potassium loss.

The initial decrease in blood pressure with the use of saluretic diuretics is associated with an increase in sodium excretion, a decrease in plasma volume, and a decrease in cardiac output. After two months, the diuretic effect decreases, cardiac output normalizes. This is due to a compensatory increase in the concentration of renin and aldosterone, which prevent fluid loss. The hypotensive effect of diuretics at this stage is explained by a decrease in peripheral vascular resistance, most likely due to a decrease in the concentration of sodium ions in vascular smooth muscle cells. Diuretics reduce both systolic and diastolic blood pressure and have little effect on cardiac output.

Hydrochlorothiazide (hypothiazide, ezidrex)- a diuretic of medium strength and duration, a typical representative of thiazide diuretics. The drug primarily increases the excretion of sodium, chlorine and secondarily water mainly in the initial part of the distal tubules of the nephron. Hydrochlorothiazide is well absorbed from the gastrointestinal tract. The latent period of the drug is 1-2 hours, the maximum effect develops after 4 hours, the duration of action is 6-12 hours. 95% of hydrochlorothiazide is excreted unchanged in the urine.

The drug is prescribed during or after meals, 25-100 mg / day in 1-2 doses in the first half of the day. With prolonged use of the drug, the development of hypokalemia, hyponatremia, hypomagnesemia, hypochloremic alkalosis, hyperuricemia is possible. Hydrochlorothiazide can cause weakness, leukocytopenia and skin rash.

Indapamide (arifon) has not only a diuretic effect, but also a direct vasodilating effect on the systemic and renal arteries. The decrease in blood pressure during the use of the drug is explained not only by a decrease in the concentration of sodium, but also by a decrease in the total peripheral resistance due to a decrease in the sensitivity of the vascular wall to norepinephrine and angiotensin II, an increase in the synthesis of prostaglandins (E 2), and a weak anticalcium effect of the drug. With prolonged use in patients with moderate hypertension and impaired renal function, indapamide increases the glomerular filtration rate. The drug is well absorbed in the gastrointestinal tract, the maximum concentration in the blood is determined after 2 hours. In the blood, the drug is 75% protein-bound and can reversibly bind to red blood cells. The half-life of indapamide is about 14 hours. 70% of it is excreted through the kidneys, the rest through the intestines. Indapamide at a dose of 2.5 mg once a day has a prolonged hypotensive effect. Side effects when using indapamide are observed in 5-10% of patients. Nausea, diarrhea, skin rash, weakness may occur.

Furosemide (Lasix)- a strong, short-acting diuretic. Furosemide disrupts the reabsorption of sodium and chloride ions in the ascending loop of Henle. The latent period of furosemide with enteral use is 30 minutes, with intravenous administration - 5 minutes. The action of the drug when taken orally lasts 4 hours, with intravenous administration 1-2 hours. Intravenous administration of the drug at a dose of up to 240 mg / day is used to stop a hypertensive crisis. Side effects: hypokalemia, hyponatremia, hypochloremic alkalosis, dizziness, muscle weakness, convulsions.

Ethacrynic acid is close to furosemide in terms of pharmacodynamic and pharmacokinetic parameters.

Spironolactone is a potassium-sparing steroidal diuretic. The drug is an aldosterone antagonist, acts at the level of the distal convoluted tubules and collecting ducts. It has a weak and inconsistent hypotensive effect, which manifests itself 2-3 weeks after the appointment of the drug. The indication for the use of the drug is hypertension with adrenal aldosteroma. Side effects: nausea, vomiting, dizziness, gynecomastia, in women - menstrual irregularities.

ANGIOTENSIN CONVERTING FACTOR INHIBITORS (ACE inhibitors).

The renin-angiotensin system is of particular importance in the development and progression of arterial hypertension and heart failure. The function of the renin-angiotensin-aldosterone system (RAAS) is the regulation of fluid and electrolyte balance, blood pressure and blood volume. The main components of the RAAS are angiotensinogen, angiotensin I, and angiotensin II. Renin, an angiotensin-converting enzyme, and angiotensinase, an enzyme that destroys angiotensin II, take part in the activation and inactivation of these components.

The main role in renin secretion is played by cells of the juxtaglomerular (JG) apparatus in the wall of afferent arterioles of the glomeruli of the kidneys. Renin secretion occurs in response to a drop in blood pressure in the renal vessels below 85 mm or to an increase in β 1 -sympathetic activity. Renin secretion is inhibited by angiotensin II, vasopressin. Renin converts α-globulin - angiotesinogen (synthesized in the liver) into angiotensin I. Another enzyme - angiotensin-converting enzyme (ACE) transforms angiotensin I into angiotensin II. The effects of angiotensin II on target cells are mediated through angiotheisin receptors (AT). Information is transmitted intracellularly by regulatory G-proteins. They implement the inhibition of adenylate cyclase or the activation of phospholipase C or open the calcium channels of the cell membrane. These processes are the cause of various cellular effects of target organs. First of all, this concerns changes in the tone of smooth muscle cells of the vascular walls. Activation of the RAAS leads to vasoconstriction as a result of the direct action of AP on vascular smooth muscle cells and secondarily as a result of aldosterone-dependent sodium retention. The resulting increase in blood volume increases preload and cardiac output.

The study of the RAAS has led to the creation of ACE inhibitors, which have a therapeutic effect in a variety of pathologies, primarily in hypertension and heart failure.

Mechanism of hypotensive action of ACE inhibitors:

1. Due to the inhibition of ACE activity, drugs reduce the formation or release of such vasoconstrictor and sodium retention substances as angiotensin II, aldosterone, norepinephrine, vasopressin.

2. The drugs increase the content in tissues and blood of such vasorelaxants as bradykinin, prostaglandins E 2 and I 1 , endothelial relaxation factor, atrial natriuretic hormone.

3. Reducing sodium retention as a result of a decrease in aldosterone secretion and an increase in renal blood flow.

ACE inhibitors are relatively rare side effects. In addition to allergic reactions, the most famous is the appearance of a dry cough. There is an assumption that the cause of this may be excessive release of bradykinin in the bronchial mucosa. Cough is noted in 8% of patients taking ACE inhibitors for a long time.

From the group of angiotensin-converting enzyme inhibitors, captopril, enalapril maleate, lisinopril, which is a metabolite of enaprilin, ramipril, are used in clinical practice.

There are short-acting (captopril) and long-acting (more than 24 hours) drugs (enalapril, linsinopril, ramipril).

Captopril (Capoten) reduces blood pressure at any initial level of renin, but to a greater extent at elevated levels. Captopril increases the level of potassium in the blood serum. Captopril is rapidly absorbed from the gastrointestinal tract. Food intake reduces its bioavailability by 35-40%. Only 25-30% of the drug binds to plasma proteins. Its maximum concentration in the blood is reached within 1 hour. The half-life of free captopril is 1 hour, and in combination with the metabolite it is 4 hours. The drug is administered orally, starting with a dose of 25 mg 2-3 times a day. The most common side effects are cough, skin rash and taste disturbance. After stopping treatment, these symptoms disappear.

Enaladril maleate (Renitec) is hydrolyzed when taken orally and converted to its active form, enalaprilat. Its bioavailability is about 40%. After ingestion in healthy and patients with arterial hypertension, the drug is detected in the blood after 1 hour and its concentration reaches a maximum after 6 hours. T 1/2 is 4 hours. The drug is prescribed for arterial hypertension and heart failure at a dose of 5-10 mg 2 times a day. Side effects occur very rarely.

BLOCKERS OF 1-ANGIOTENSIN RECEPTORS (AT1)

For the treatment of GB, blockers of 1-angiotensin receptors (AT1) are used. The main cardiovascular and neuroendocrine effects of AT1 receptor blockers:

Systemic arterial vasodilation (decrease in blood pressure, decrease in total peripheral vascular resistance and afterload on the left ventricle);

Coronary vasodilation (increase in coronary blood flow), improvement of regional blood circulation in the kidneys, brain, skeletal muscles and other organs;

Reverse development of left ventricular hypertrophy (cardioprotection);

Increased natriuresis and diuresis, potassium retention in the body (potassium-sparing action);

Decreased secretion of aldosterone

Decreased functional activity of the symlatico-adrenal system.

In terms of the mechanism of action, AT1 receptor blockers are in many ways similar to ACE inhibitors. Therefore, the pharmacological effects of AT1 blockers and ACE inhibitors are generally similar, but the former, being more selective inhibitors of the RAAS, rarely give side effects.

Losartan is the first non-peptide AT1 receptor blocker. After oral administration, losartan is absorbed in the gastrointestinal tract, the concentration of the drug in the blood plasma reaches a maximum within 30-60 minutes. The antihypertensive effect of the drug persists for 24 hours, which is explained by the presence of an active metabolite in it, which blocks AT1 receptors 10–40 times more than losartan. In addition, the metabolite has a longer half-life in blood plasma - from 4 to 9 hours. The recommended dose of losartan in the treatment of arterial hypertension is 50-100 mg / day in one dose. Contraindications to the appointment of AT1 receptor blockers are: individual intolerance to the drug, pregnancy, breastfeeding.

Blockers of slow calcium channels

The hypotensive effect of calcium antagonists is associated with a decrease in the content of free calcium in the cytoplasm of cells due to impaired calcium entry into the cell through voltage-dependent slow calcium channels. This leads to relaxation of vascular smooth muscle cells (decrease in total peripheral resistance) and a decrease in the contractile activity of cardiomyocytes. In the treatment of hypertension, long-acting drugs are used, because. they do not cause reflex stimulation of the sympathetic nervous system. Such drugs include amlodipine, mibefradil and retard forms of verapamil, diltiazem, nifedipine.

Calcium channel blockers are relatively well tolerated by patients. The minimum number of side effects in amlodipine, diltiazem and mibefradil. The side effect of drugs is determined by the chemical structure. So, when using verapamil, constipation is often noted, the development of a sharp bradycardia, conduction disturbances, and heart failure is possible. Reception of dihydropyridines is often accompanied by reddening of the skin, a feeling of heat, the occurrence of edema, usually localized on the feet and legs.

Drugs with a central mechanism of action.

Drugs of central action reduce the activity of the vasomotor center of the medulla oblongata.

Clonidine, an imidazoline derivative, is a central mimetic of α 2 -adreno- and I 1 -imidazoline receptors. The drug stimulates the receptors of the nuclei of the solitary tract of the medulla oblongata, which leads to inhibition of the neurons of the vasomotor center and a decrease in sympathetic innervation. The hypotensive effect of the drug is a consequence of a decrease in cardiac activity and total peripheral vascular resistance. Clonidine is well absorbed from the gastrointestinal tract. When taken orally, the latent period of the drug is 30-60 minutes, with intravenous administration - 3-6 minutes. The duration of action varies from 2 to 24 hours. Clonidine is excreted from the body by the kidneys mainly in the form of metabolites. With the sudden withdrawal of the drug, a syndrome of "recoil" occurs - a sharp increase in blood pressure. Clonidine has a sedative and hypnogenic effect, potentiates the central effects of alcohol, sedatives, and depressants. Clofeliv reduces appetite, secretion of salivary glands, retains sodium and water.

Moxonidine (cint)- selective agonist of I 1 -imidazoline receptors. Activation of imidazoline receptors in the CNS leads to a decrease in the activity of the vasomotor center and a decrease in peripheral vascular resistance. In addition, the drug inhibits the renin-angiotensin-aldosterone system. The drug is well absorbed from the gastrointestinal tract and has a high bioavailability (88%). The maximum concentration in the blood is recorded after 0.5-3 hours. 90% of the drug is excreted by the kidneys, mostly (70%) unchanged. Despite a short half-life (about 3 hours), moxodonin controls blood pressure throughout the day. The drug is prescribed at 0.2-0.4 mg once a day in the morning. Moxonidine can cause fatigue, headaches, dizziness, sleep disturbance.

Vasodilators.

Vasodilators for the treatment of arterial hypertension are represented by two groups of drugs; arteriolar (hydrolasin, disacoid and minocoid) and mixed (sodium nitroprusside and isosorbide dinitrate). Arteriolar vasodilators dilate resistive vessels (arterioles into small arteries) and reduce total peripheral resistance. In this case, there is a reflex increase in cardiac activity and an increase in cardiac output. The activity of the sympathetic-adrenal system increases, followed by the secretion of renin. The drugs cause sodium and water retention. Mixed-action drugs also cause expansion of capacitive vessels (venules, small veins) with a decrease in venous return of blood to the heart.

Hydralazine (apressin)- due to the large number of side effects (tachycardia, pain in the heart, redness of the face, headache, lupus erythematosus syndrome), it is rarely used and only in the form of ready-made combinations (adelfan). Hydralazine is contraindicated in gastric ulcer, autoimmune processes.

Diazoxide (hyperstat)- arteriolar vasodilator - potassium channel activator. The effect on potassium channels leads to hyperpolarization of the muscle cell membrane, which reduces the intake of calcium ions into the cells, which are necessary to maintain vascular tone. The drug is used intravenously for hypertensive crisis. The duration of action is about 3 hours.

Minoxidil is an arteriolar vasodilator and potassium channel activator. The drug is well absorbed in the gastrointestinal tract. The half-life is 4 hours. Mnnoxidil is used orally 2 times a day.

Sodium nitroprusside (nipride)- mixed vasodilator. The hypotensive effect of the drug is associated with the release of nitric oxide from the drug molecule, which acts similarly to the endogenous endothelial-relaxing factor. Thus, its mechanism of action is similar to that of nitroglycerin. Sodium nitroprusside is prescribed intravenously for hypertensive crises, acute left ventricular failure. Side effects: headache, anxiety, tachycardia.

Sympatholytics

(See the lecture "Adrenolytics") Sympatholytics include reserpine, octadine.

Reserpine is a rauwolfia alkaloid. The drug disrupts the deposition of noradrenaline in vesicles, which leads to its destruction by cytoplasmic monoamine oxidase and a decrease in its concentration in varicose thickenings. Reserpine reduces the content of norepinephrine in the heart, blood vessels, central nervous system and other organs. The hypotensive effect of reserpine when used orally develops gradually over several days, after intravenous administration of the drug - within 2-4 hours. Side effects of reserpine: drowsiness, depression, stomach pain, diarrhea, bradycardia, bronchosiasm. The drug causes sodium and water retention in the body.

Ectadin disrupts the release of norepinephrine and prevents the reuptake of the neurotransmitter by sympathetic endings. The decrease in blood pressure is due to a decrease in cardiac output and a decrease in total peripheral vascular resistance. The bioavailability of the drug is 50%. The half-life is about 5 days. The drug causes postural hypotension, retention of sodium and water in the body, dizziness, weakness, swelling of the nasal mucosa, diarrhea. Rarely used.