EA034975B1 - Method of treating labile and paroxysmal hypertension - Google Patents

Abstract

The present invention relates to the field of medicine, particularly to a method of drug treatment of labile and paroxysmal forms of hypertension. The method includes administering to a subject in need thereof a therapeutically effective amount of sartan and -blocker. The present invention allows to reduce lability of arterial tension and to reverse accompanying symptoms.

Description

The present invention relates to a medicament method for treating patients having labile or paroxysmal forms of hypertension.

According to statistics in Russia, more than 500,000 people die from cardiovascular diseases every year, which is 55% of the total number of deaths. At the same time, hypertension is the main cause of acquired disability and death, making the main contribution to the structure of general mortality both in Russia and in the world [1, 2].

According to the ESIA epidemiological study, in 2016 blood pressure (ABP) above threshold values of 140/90 mmHg is observed in 45 ± 3% of the Russian population, which is 8% more compared to 1994 [2, 3]. Moreover, in the UK, Canada, USA and France, hypertension is observed stably at the level of 22-31% of the population. Recently, there has been a strong rejuvenation of the disease; Blood pressure above thresholds is already observed in 14% of adolescents. It has been proven that the origins of hypertension lie in childhood and adolescence, when neurohumoral mechanisms of regulation of the activity of the cardiovascular system are formed [4].

Most of the current recommendations [4-6] for the treatment of hypertension are mainly focused on the average daily blood pressure and do not affect the phenomenon of blood pressure lability, that is, a change over time. Of course, blood pressure in both a healthy person and a patient with hypertension changes, but these changes are usually smooth. Such fluctuation is associated with many factors, such as physical activity, emotions, body position in space, respiratory cycle and so on. Another thing is when, for no apparent reason, the blood pressure value changes by several tens of mmHg over a limited period of time. In this case, it is customary to distinguish between labile and paroxysmal (pseudo-chromocytoma) hypertension. These two terms mean a significant change in blood pressure over a short period of time (paroxysm) in the presence (labile) and absence (paroxysmal) of obvious emotional stress. Unfortunately, at present, there are no quantitative criteria for making these diagnoses, nor is there an evidence base on the consequences of this pathology on the cardiovascular system. However, it is known that a decrease in systolic blood pressure (SBP) just below 140 mmHg (compared with 145 mmHg) leads to a significant decrease in the number of cardiovascular diseases [6]. In addition, taking into account the modeling data of the cardiovascular system, it can be concluded that a rapid increase and decrease in blood pressure contributes to the wear of the cardiovascular system and, therefore, leads to such severe pathologies as heart attack and stroke. It is worth noting that blood pressure lability increases with age in the presence of hypertension and a decrease in the sensitivity of baroreceptors [8].

SUMMARY OF THE INVENTION

According to the World Health Organization (WHO), the World Hypertensive League (WHL) and the International Society for the Study of Hypertension (ISH), hypertension is now recognized as the number one cause of disability and death in the world. The current Recommendations [3] indicate that hypertension is one of the most widespread diseases of civilization throughout the world, almost the most dangerous in its consequences. Being a silent killer, it takes millions of lives, leading to heart attacks, strokes, heart failure.

Moreover, in the present invention, the following terms are used, disclosed in the prior art at the time of filing of this application.

The term hypertension (either according to G.F. Lang hypertension, or sometimes arterial hypertension) is understood as a persistent increase in blood pressure above a threshold value determined from 140/90 mmHg or higher in one of the parameters (SBP and / or DBP). At the same time, according to ACC18, a threshold is understood as a blood pressure level above 130/85 mmHg.

The term labile hypertension is understood as a significant abrupt change in blood pressure in a short period of time in the presence of obvious emotional stress.

The term paroxysmal hypertension is understood as a significant abrupt change in blood pressure in a short period of time in the absence of obvious emotional stress.

The term blood pressure lability is understood as a significant abrupt change in blood pressure in a short period of time.

By the term “subject” is meant a patient of any gender and nationality, since the method of the present invention does not have gender or racial restrictions. The testing of the present invention was carried out on adult subjects, so the question of the use of the method for the treatment of children should be decided individually for a specific case by the doctor and the parents / official guardians of the patient.

The terms subject and patient are used interchangeably.

The term therapeutically effective amount is understood to be such an amount that leads to a significant decrease in lability (efficiency of at least 40%), that is, to achieve the claimed technical result.

In the presence of labile hypertension, patients report a significant increase in blood pressure during stressful situations and normal blood pressure (or blood pressure <145 mmHg) during emotional stress. Moreover, according to the Spielberg – Khanin test [9], moderate values of situational and personal anxiety are detected. Moreover, according to a study [8], blood pressure lability can be associated with pathologies such as white coat hypertension, cerebral aneurysm, chronic aortic dissection, and Marfan syndrome. Regarding white coat hypertension, it should be understood that this condition, characterized by a significant increase in blood pressure in the doctor’s office due to stress due to visiting the doctor or the measurement procedure itself, according to studies [10] does not lead to abnormal blood pressure lability outside the doctor’s office.

In the presence of paroxysmal hypertension, patients most often deny the presence of significant emotional stress, however, they associate this condition with physical symptoms such as headache, palpitations, redness, weakness, shortness of breath. Paroxysms according to [11] begin suddenly and can last from several minutes to several hours. However, some patients claim that they anticipate paroxysm. However, according to the Spielberg – Khanin test [9], unlike patients with labile hypertension, with paroxysmal low values of situational and personal anxiety are found.

For such patients, biochemical screening for pheochromocytoma is mandatory, although it occurs in 2% of patients [12]. Cachetolamines are usually normal; a slight increase during or less frequently between paroxysms is possible, which is explained by activation of the sympathetic nervous system [12]. During paroxysms, an increase in epinephrine and heart rate (HR) or an increase in norepinephrine without an increase in heart rate is possible. According to [13], this indicates the dominance of the sympathoadrenal system.

It is believed that the increased activity of the sympathetic nervous system plays a role in the development and progression of cardiovascular disease. It was shown in [14] that the lack of physical activity leads to changes in the structure of neurons in the rostral ventrolateral region of the medulla oblongata (RVLM), an area associated with the regulation of respiration and blood pressure, due to which the animal and man can abruptly disengage when a life threat occurs. A sedentary lifestyle leads to the appearance of additional branches in RVLM neurons, which makes them more sensitive to excitation. This leads to the fact that the centers of regulation in the medulla oblongata are overstimulated, which leads to a hypertrophied response to excitation and, as a result, an uncontrolled sharp increase in blood pressure. It is worth noting that an active lifestyle does not lead to changes in RVLM neurons. Thus, we can conclude that the etiology of labile and paroxysmal hypertension is also associated with a sedentary lifestyle, that is, the lifestyle that prevails in the world.

Therapy

Under health according to the Preamble to the Charter of the World Health Organization (adopted by the International Health Conference, New York, June 19-22, 1946; signed on July 22, 1946 by representatives of 61 countries, Official Documents of the World Health Organization, No. 2, p. 100, entered into force on April 7, 1948; since 1948 there is no evidence of a change in this definition; Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity (Preamble to the Constitution of WHO as adopted by the International Health Conference, New York, June 19 - July 22, 1946; signed on July 22, 1946 by the representatives of 61 States (Official Records of WHO, no. 2, p. 100) and entered into force on April 7, 1948) the state of complete physical, mental and social well-being is understood, and not only the absence of diseases and physical defects, therefore, the approach to the treatment of labile and paroxysmal hypertension should include at least the maximum possible elimination of paroxysms and ensuring both psychological and mental comfort of the patient, since according to the Geneva Declaration (adopted by the 2nd General Assembly of the World Medical Association, Geneva, Switzerland, in September 1948, supplemented by the 22nd World Medical Assembly, Sydney, Australia , in August 1968 and the 35th World Medical Assembly, Venice, Italy, in October 1983) the patient’s health is the doctor’s first reward. In the clinic, especially in human therapy, it should be considered from the point of view of personalized medicine, not as a set of pathologies having a certain race, gender and age, but on the part of its anatomical, physiological, psychological, social, cultural and spiritual components, that is, a person with all his experiences and needs, which together with organic pathology led to the disease that is currently available. Therefore, each specialist is called upon to one degree or another to provide comprehensive and complete treatment, treating not a specific disease, but the pathology or their combination that underlies the disease. However, the realities of modern life greatly limit the time that a specialist can devote to a particular patient. And although the gold standard (Golden Standart in Healthcare) has not yet been established, attention should be paid not only to the treatment of a particular pathology, especially in the light of the pathologies under consideration.

Drug therapy

To date, no clinical recommendations contain information about the diagnosis and treatment of labile or paroxysmal hypertension. The few articles that are available to clinicians focus on measuring resting BP [8]. Special attention

- 2,034,975 is given to variability and reactivity. Moreover, according to [15], antihypertensive therapy does not reduce the variability of blood pressure. Monotherapy with diuretics, calcium channel blockers or ACE inhibitors does not reduce the reactivity of blood pressure to stress. Therapy with β-blockers does not reduce the reactivity and reactivity of blood pressure to stress. Monotherapy with α-blockers blocks an increase in peripheral resistance, but the reactivity of blood pressure does not change due to an increase in cardiac output [16-21]. In contrast, studies [22–27] show that combination therapy with α- and β-blockers reduces blood pressure reactivity by inhibiting an increase in cardiac output and peripheral resistance.

According to the current Recommendations, the following classes of drugs can be used as antihypertensive therapy:

angiotensin converting enzyme inhibitors (ACE inhibitors);

α-blockers; β-blockers;

agonists of I ₁ -imidazoline receptors;

calcium antagonists (AK);

diuretics;

angiotensin II receptor blockers (ARBs or sartans).

Agonists of β-imidazoline receptors, in particular moxonidine, are sometimes used in clinical practice, most often in patients with a labile or paroxysmal form of hypertension complicated by type 2 diabetes mellitus and / or overweight. It should be noted that this drug should be prescribed to patients with grade III-IV heart failure with caution, since the study of the clinical efficacy of 3 mg moxonidine in patients with NYHA grade III-IV heart failure was interrupted due to an almost twofold excess of mortality in the control group over placebo group [28]. In this case, the use of moxonidine at a dose of 0.2 mg per day did not give a significant decrease in blood pressure and inhibition of paroxysms.

Thus, therapy with α- and β-blockers is leading today, although, as noted [8], the complete elimination of blood pressure lability is impossible.

Clonidine can be prescribed in a dose of 0.1 mg or 0.2 mg every 90 minutes. Perhaps the appointment of labetalol (100-300 mg) every 6-8 hours; in this case, a response decrease in blood pressure is achieved after 1.5-2.5 hours. It is possible to prescribe metoprolol (25-50 mg orally every 6 hours) in combination with prazosin (1 mg per os every 8-12 hours).

In addition to chronic therapy with α- and β-blockers, during severe paroxysms (SBP> 220 mm Hg or DBP> 130 mm Hg), intravenous administration of labetalol (10-20 mg) every 10-15 minutes is suggested the beginning of a response decrease in blood pressure. In the event that the answer is not achieved, nitroprusside may be administered [29].

However, the given treatment path does not lead to a significant improvement in the condition of patients.

Psychiatric therapy

With repeated severe paroxysms, it is possible to use an antidepressant (SSRIs, tricyclic antidepressant, etc.).

Psychological therapy

At the first stage, you should find out what exactly is the cause of paroxysms and, if possible, eliminate them. This may be a job associated with high responsibility, or difficulties in family life. In this case, you should consider the possibility of a job change, consultations with a family psychologist, etc.

In addition, chronic paroxysms can cause anxiety and terror in patients, and fear of death during paroxysm can become dominant in their lives. In this regard, it is recommended that the patient assure that this pathology can be treated, and death during paroxysm is unlikely [11]. In some cases [30], awareness of the etiology of paroxysm can reduce the recurrence of paroxysms. However, most patients who have experienced severe psychological trauma will continue to defend themselves against awareness of potential suppression of emotions. Most likely they will not be interested in psychotherapy and should not be forced to it. Among patients who do not have a history of psychological trauma, but who have a lifelong tendency to suppress emotions, psychotherapy can help in the treatment, although the repressive style of overcoming difficulties is very difficult to change.

Pastoral Psychological Therapy

Since a patient with labile or paroxysmal hypertension may practice a religion, the doctor must make sure that he considers pathology and / or paroxysm as part of the teachings of this religion, for example, as a result of divine conduct. Acting individually in each case, the doctor should consider involving a specialist in the field of pastoral psychology or a representative of the clergy of this religion in the treatment process

- 3,034,975 pour pastoral and psychological management of this patient.

Hypothesis

The use of both monotherapy and combination therapy did not lead to a significant decrease in blood pressure and paroxysms. In FIG. 1-3 shows the fluctuation in blood pressure in various types of therapy. They are united by the absence of inhibition of paroxysms, which account for almost 40% of the total number of measurements. However, they are distinguished by the amplitude (AD ^ - ^) of paroxysms and the average daily blood pressure. Thus, we can conditionally assume that blood pressure has both a common and a paroxysmal profile. In this case, the concept of a general blood pressure profile means the average value of blood pressure (outside of paroxysms), against which paroxysms occur, and the concept of a paroxysmal blood pressure profile means the maximum value of blood pressure that will be recorded at the time of paroxysm. That is, in this case, blood pressure in case of labile and paroxysmal hypertension is the sum of these profiles and is similar to the highway along which a drunk driver rides. At the same time, the route itself will be a common profile, and the territory outside the route, which the driver sometimes calls in, will have a paroxysmal profile.

This approach allows you to choose a combination in which one drug will reduce the value of the overall profile, and the other - paroxysmal. In this description, on individual clinical cases, the use of a combination of sartan + a-blocker will be considered.

Efficiency mark

Since, as mentioned above, blood pressure for labile and paroxysmal hypertension is significantly different from blood pressure for any other type of hypertension, the assessment of the effectiveness of therapy in terms of the average daily SBP (in this case, only the SBP is used, since the contribution of DBP is quite small) is uninformative. So, in relation to the situations of FIG. 1-3, the average daily SBP is 138 mmHg, 136 mmHg and 137 mmHg, respectively. It is important to note here that according to the European recommendations [6], the threshold value is the SBP equal to 140 mmHg, while according to the latest American (ACC18) [31] - 130 mmHg.

In order to solve this problem, a formula was derived that takes into account the number of all SBPs> 140 (for the measured period) and the value of the SBP _max exceeded the border of 140 mmHg:

I / number of GARDEN> 140 max. GARDEN [140; D - 140 \

E = 1 - ------------------- + --------------- 100% injection - in the measurement of 140

The formula shows the effectiveness of therapy in percent.

With SBP <140, the efficiency will be 100%. With reference to the situations of FIG. 1-3 efficiency was 22%, 54% and 27%, respectively.

Figures

In FIG. Figure 1 shows the change in blood pressure with amlodipine (a selective calcium channel blocker). The number of paroxysms is 34% for the measurement period.

In FIG. 2 shows the change in blood pressure while taking telmisartan. The number of paroxysms is 37% for the measurement period.

In FIG. Figure 3 shows the change in blood pressure while taking moxonidine (an agonist of C-imidazoline receptors). The number of paroxysms is 38% for the measurement period.

In FIG. Figure 4 shows the change in blood pressure with telmisartan and a combination of telmisartan + doxazosin. The number of paroxysms is 34.7% for the measurement period.

In FIG. Figure 5 shows the change in blood pressure against a combination of telmisartan + doxazosin (80 + 2). The number of paroxysms is 20% for the measurement period.

In FIG. Figure 6 shows blood pressure in combination with telmisartan + doxazosin (40 + 0.5). The number of paroxysms is 31% for the measurement period.

DETAILED DESCRIPTION OF THE INVENTION

As noted earlier in the section Medical treatment, the use of various groups of drugs, both in monotherapy and in combination therapy, did not lead to a significant decrease in blood pressure lability.

The present invention contemplates the use of per os sartan and an α-blocker for the treatment of labile and paroxysmal forms of hypertension. In its present form, sartan can reduce the overall blood pressure profile, and the a-blocker - the paroxysmal blood pressure profile.

In a preferred embodiment, sartan is used in the morning, and the α-blocker is used in the evening, however, this condition is not limiting, and the daily intake of drugs is determined by the individual characteristics of the patient's body.

In another aspect of the present invention, sartan is used in the morning, and the prescribed therapeutically effective dose of a-blocker, if in the evening the SBP is less than 135 mmHg and the DBP is optionally less than 87 mmHg, is divided into two parts, the first dose being taken in the evening and the second in the afternoon the next day, if the SBP in the afternoon is above 135 mmHg, and the DBP is not necessarily higher than 87 mmHg.

In another aspect of the present invention, sartan and optionally an α-blocker are taken together, including in the form of a combination preparation. However, the first dose of the α-blocker is preferably, but not necessarily, taken overnight.

- 4,034,975

In another aspect of the present invention, any representative of these pharmacological groups is selected as a sartan and an α-blocker, preferably, but not necessarily, the sartan is telmisartan and the α-blocker is doxazosin.

In another aspect of the present invention, sartan and an α-blocker are administered as a single tablet or drug composition (the blister contains different tablets for administration in the morning, afternoon and evening).

In another aspect of the present invention, the drugs are administered in any effective manner available at the filing date in any acceptable and effective form.

In another aspect of the present invention, psychological and / or psychiatric counseling is further provided.

In another aspect of the present invention, a therapeutically effective dose of any psychoactive drug, in particular, but not limited to, an antidepressant, anxiolytic and / or antipsychotic, is additionally taken.

In another aspect of the present invention, a therapeutically effective dose of etifoxin is additionally taken.

In another aspect of the present invention, a therapeutically effective dose of etifoxin is additionally administered for 2 weeks.

In another aspect of the present invention, a therapeutically effective dose of melatonin is additionally taken, preferably, but not limited to, 3 mg in the morning or at night.

In another aspect of the present invention, the patient has an additional pathology, for example, type 2 diabetes mellitus, gout, chronic heart failure, diseases of the gastrointestinal tract and others, limiting pathologies that are the etiology of secondary hypertension.

In another aspect of the present invention, the claimed therapy is used in combination with existing non-antihypertensive therapy.

In another aspect of the present invention, said therapy is used to treat labile or paroxysmal hypertension complicated by diabetes mellitus, provided that the dose of telmisartan reduces the blood glucose level to normal.

In another aspect of the present invention, said therapy is used along with diabetic therapy in a patient suffering from a labile or paroxysmal form of hypertension complicated by type 1 or type 2 diabetes.

In another aspect of the present invention, said therapy may be used along with or as part of another therapy, specifically, but not limited to, cell therapy.

In another aspect of the present invention, said therapy is used along with or as part of any other therapy, specifically, but not limited to manual therapy, massage, acupuncture, oriental medicine, specifically, but not limited to, Chinese or Tibetan medicine.

In all aspects of the present invention, said therapy is not used as part of an unconventional form of treatment classified as unscientific in the scientific and technical literature.

In all aspects of the present invention, said therapy is used to treat a patient having labile or paroxysmal hypertension of any nationality, any age, and any gender, preferably, but not limited to, Caucasians, elderly and senile women.

In all aspects of the present invention, said therapy may not necessarily be limited to pregnant women, since the applicant does not have sufficient information about the effectiveness of said therapy during pregnancy and the absence of teratogenic risk. However, this application does not mean a limitation of the present invention.

In all aspects of the present invention, this therapy may cause difficulty in planning a pregnancy, but cannot serve as a contraceptive.

In all aspects of the present invention, the present therapy is contraindicated in patients for whom it is contraindicated to take sartan or an α-blocker. However, in case of clinical necessity, it can be applied.

In all aspects of the present invention, said therapy may contribute to the occurrence of side symptoms characteristic of sartans and α-blockers, specifically, but not necessarily, diarrhea may develop that disappears within a few days, which cannot cause a cessation of therapy, but only a decrease in the dose of α -blocker.

In all aspects of the present invention, said therapy cannot be used by patients as self-medication without the recommendation of a specialist.

In all aspects of the present invention, said therapy may not necessarily be limited to childhood and adolescence.

In this case, the technical result of the present invention is to reduce the lability of blood pressure, as well as the relief of concomitant symptoms, such as dizziness, chills and / or an attack of fear (with a paroxysmal form).

This technical result is achieved by the introduction of per os these drugs. And although in

- 5,034,975 in the prior art, in particular in the current Recommendations, it is known to use various groups of antihypertensive (antihypertensive) drugs, both in monotherapy and as part of various combinations, combinations known from the prior art [8.16-29] did not lead to a decrease in lability HELL, as can be seen from the prior art, and FIG. 1 and FIG. 3 (E = 22% and 27%, respectively). In addition, the use of sartan itself as monotherapy also did not lead to a decrease in blood pressure lability, see FIG. 2 (E = 54%). Thus, the use of the present method, leading to the achievement of the claimed technical result, is not known from the prior art in one form or another.

The present invention relates to a method for the treatment of two forms of hypertension - labile or paroxysmal, that is, to reduce the lability of blood pressure, depending on the presence or absence of obvious emotional stress, that is, it has one purpose.

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Clin Pharmacol Ther Toxicol. 1986; 24: 249-253.

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K., Straub M., Wiltse C., Wright T. Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON), Eur J Heart Fail. 2003; 5 (5): 659-667

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31. 2017 ACC / AHA / AAPA / ABC / ACPM / AGS / PPhA / ASH / ASPC / NHA / PCNA

Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension 20017; HYP.0000000000000065

Examples.

The present invention is illustrated, but not limited to, by the following examples.

All of the examples below are specific clinical examples that were conducted on patients who signed informed consent using the Management of Hypertension research program at the Hypertension Research Foundation, the Pontifical Georgian College (registered office in Raleigh, Northern California, USA) and American Institute of Clinical Psychotherapists (registered office in Louisville, Kentucky, USA).

The names of participants are not given in accordance with the provisions of the Helsinki Declaration (1964) and the Geneva Declaration (1948) of the World Medical Association.

Example 1

Woman 69 years old, Caucasian. Notes a significant increase in blood pressure (see Fig. 1) both in the presence of stress and in its absence. In this case, it is the presence of stress at work that associates with an increase in blood pressure, because after stress it feels an increase (which is checked with a tonometer), although it is recognized that it can feel good with high blood pressure, that is, well-being is not associated with an increase in blood pressure. Meteo dependent. The experiences associated with spiritual practices are denied. Against the background of existing therapy (amlodipine three times a day, 5 mg each), as before, it has complaints of seizures (paroxysms), accompanied by a sharp and significant increase in blood pressure (up to 200/110 mmHg), a strong heartbeat and trembling throughout the body. According to the patient, she wrapped herself in a blanket and waited for the attack to pass.

History: thyroid disease (not detected at the time of inclusion in the study). Family history is aggravated by essential hypertension of the I-II degree.

A biochemical blood test (including hormones TSH, T4 free, AT-TPO and aldosterone), OAK and urine analysis at the time of participation in the study are normal. ECG and Echo-KG correspond to the age norm. Ultrasonic signs of pathological changes in the kidneys were also not detected. Blood pressure at the time of inclusion in the program ranges from 125-153 / 70-86 mmHg (several measurements). HELL _cf = 137/79 mmHg. The Osler test is negative. Thus, we can conclude the presence of paroxysmal hypertension, which is of an essential nature.

Belov’s temperament formula:

T = 15.38% X + 46.15% C + 15.38% F + 23, 09% M, where X is choleric, C is sanguine, F is phlegmatic and M is melancholic.

According to the Spielberg-Khanin test, low values of situational (25 points) and personal (27 points) anxiety are found. These data indicate the inadequate functioning of the nervous system responsible for the response to stress (most likely, RVLM neurons, see above), since these anxiety indicators indicate a patient’s low ability to perceive a threat in a wide range of situations, that is, for the most part, the situation will not have a stressful effect and cause anxiety. In addition, the MMPI test also did not reveal the presence of anxiety, as well as other deviations from the norm, with a fairly high reliability. Thus, we can conclude that the patient does not have mental disorders, and the reaction of her nervous system may be associated with the pathology of RVLM neurons.

According to the Leonhard test, an exalted personality type is significantly expressed.

The value of the effectiveness of existing therapy was 22.6%.

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As the first-choice therapy, telmisartan was proposed at a dosage of 40 mg (in the morning). Efficiency was 54%. Then, on day 5, doxazosin was added at a dosage of 1 mg (in the evening).

Efficiency was 62% (Fig. 4). Although the number of paroxysms increased, their amplitude decreased significantly, which led to a sharp increase in efficiency.

Further, the total amount of telmisartan used was increased to 80 mg (in the morning), and doxazosin to 2 mg (in the evening). Moreover, if blood pressure in the evening is lower than 135/87 mmHg (SBP values are preferred), then doxazosin was 1 mg; if the next day, blood pressure in the afternoon was above 135/87 mmHg, then 1 mg of doxazosin was additionally taken. The effectiveness of this therapy was 80%, the number of paroxysms - 20% for the measurement period (Fig. 5).

The patient notes an improvement in well-being, the absence of attacks.

Example 2

Woman 69 years old, Caucasian. Notes a significant increase in blood pressure (see Fig. 3) only in the presence of stress. At the same time, the possibility of a significant increase in blood pressure leads to fears, which, on the one hand, impede the maintenance of a normal lifestyle (the patient is afraid to leave home), and on the other hand, lead to a new increase in blood pressure. Meteo dependent. The experiences associated with spiritual practices are denied, although religious. Against the background of existing therapy (moxonidine 0.2 μg / day), as before, it has complaints of significant increases in blood pressure (up to 220/110 mmHg). In addition, the patient is fond of taking various dietary supplements.

A biochemical blood test (including hormones TSH, T4 free, AT-TPO and aldosterone), OAK and urine analysis at the time of participation in the study are normal. ECG and Echo-KG correspond to the age norm. Ultrasonic signs of pathological changes in the kidneys were also not detected. Blood pressure at the time of inclusion in the program ranges from 96-178 / 59-118 mmHg (several measurements). HELL _cf = 138/77 mmHg. The Osler test is negative. Thus, we can conclude the presence of labile hypertension, which is of an essential nature.

Belov’s temperament formula:

T = 10.52% X + 33.38% C + 14.01% F + 42.09% M, where X is choleric. C - sanguine, F - phlegmatic and M - melancholic.

According to the Spielberg-Khanin test, moderate values of situational (41 points) and personal (77 points) anxiety are detected. These data indicate a possible inadequacy in the functioning of the nervous system responsible for the response to stress (most likely, RVLM neurons, see above), since these anxiety indicators indicate the patient’s moderate ability to perceive a threat in a wide range of situations, that is, it gives increased importance only to individual elements of the situation or finds the strength and ability to control his emotional experiences.

The value of the effectiveness of the existing therapy was 28%, the number of paroxysms - 38.4% for the measurement period. As therapy, telmisartan 40 mg (in the morning) and doxazosin 0.5 mg (in the evening) were proposed. Efficiency was 47%, the number of paroxysms was 31% for the measurement period (Fig. 6). As can be seen from FIG. 6, the use of this therapy helps to reduce lability. Increased doses of telmisartan and doxazosin led to dizziness. In addition to therapy, a consultation with a psychologist was shown, and the question was raised about the additional intake of etifoxin (50 mg for 2 weeks) to reduce anxiety.

The patient notes an improvement in well-being.

Claims (5)

CLAIM 1. A method for medically treating labile or paroxysmal hypertension, comprising administering to a subject in need thereof a therapeutically effective amount of sartan and an alpha blocker. 2. The method according to claim 1, in which sartan is administered in the morning, and the α-blocker is administered in the evening. 3. The method according to claims 1 and 2, in which half the therapeutically effective amount of the α-blocker is administered in the evening, if the systolic blood pressure in the evening is less than 135 mmHg. 4. The method according to claim 3, in which half the therapeutically effective amount of the α-blocker is additionally administered on the day of the next day if the systolic blood pressure in the afternoon is higher than 135 mmHg. 5. The method according to any one of claims 1 to 4, in which the sartan is telmisartan, and the α-blocker is doxazosin.