Treatment of arterial hypertension in children

The goal of treating arterial hypertension in children is to achieve stable normalization of arterial pressure to reduce the risk of early cardiovascular diseases and mortality. Treatment objectives include the following:

• achieving target blood pressure levels, which should be less than the 90th percentile for age, gender, and height;
• improving the patient's quality of life;
• prevention of damage to target organs or reversal of existing changes;
• prevention of hypertensive crises.

General principles for the management of children and adolescents with arterial hypertension have been developed.

• If a child or adolescent is found to have blood pressure that corresponds to the concept of “high normal blood pressure”, drug therapy is not administered; non-drug treatment and observation are recommended.
• If a child or teenager is diagnosed with arterial pressure corresponding to the concept of “stage I arterial hypertension”, drug therapy is prescribed if non-drug treatment is ineffective for 6-12 months.
• If stage II arterial hypertension is detected in a child or adolescent, drug treatment is prescribed simultaneously with non-drug therapy.
• If a teenager aged 16 years or older is identified as being in a high risk group, drug therapy is prescribed simultaneously with non-drug therapy, regardless of the degree of arterial hypertension.
• Before starting drug treatment, it is advisable to conduct daily monitoring of blood pressure: if it is revealed that the time index of arterial hypertension during the day or night exceeds 50%, this serves as an indication for drug treatment; if the time index of arterial hypertension does not exceed 50%, it is advisable to continue non-drug therapy.
• The choice of drug is made taking into account the individual characteristics of the patient, age, concomitant conditions (obesity, diabetes mellitus, state of the autonomic nervous system, left ventricular myocardial hypertrophy, functional state of the kidneys, etc.).
• Treatment begins with a minimum dose of one drug to reduce adverse side effects; if an insufficient hypotensive effect is observed with good tolerability of the drug, it is advisable to increase its dose.
• If there is no hypotensive effect or the drug is poorly tolerated, it is replaced with a drug of a different class.
• It is advisable to use long-acting drugs that provide control of blood pressure for 24 hours with a single dose.
• If monotherapy is ineffective, it is possible to use combinations of several medications, preferably in small doses.
• The effectiveness of the antihypertensive drug is assessed 8-12 weeks after the start of treatment.
• The optimal duration of drug therapy is determined individually in each specific case; the minimum duration of drug treatment is 3 months, with treatment for 6-12 months being preferable.
• With adequately selected therapy, after 3 months of continuous treatment, a gradual reduction in the drug dose is possible up to its complete discontinuation with continuation of non-drug treatment with stably normal blood pressure; monitoring of the effectiveness of non-drug treatment is carried out once every 3 months.

Non-drug treatment of arterial hypertension in a child

The issue of the need for regular drug treatment for the labile course of the disease, which is most typical in childhood and adolescence, remains under discussion to this day. According to WHO experts, non-drug methods of treating the labile form of arterial hypertension in children and adolescents can be recommended as the main and even the only methods of treating arterial hypertension in children and adolescents.

Non-drug treatment should begin with normalizing the daily routine. Mandatory components of the daily routine should be morning exercises, alternating mental stress with physical exercises, walks of at least 2-3 hours a day, and night sleep of at least 8-10 hours. TV viewing and computer activities should be limited (up to 30-40 minutes a day). It is recommended to increase the child's physical activity, including swimming, skiing, skating, cycling, and active games.

Stage I arterial hypertension in the absence of organic lesions or concomitant cardiovascular diseases cannot be an obstacle to participation in sports competitions. It is necessary to measure arterial pressure every 2 months to assess the effect of physical exercise on its level.

Restrictions on sports and other activities should only apply to a small number of people with stage II hypertension. With stage II hypertension, children and adolescents are restricted from participating in sports competitions.

Treatment of autonomic dysfunction begins with herbal and physical therapy.

Phytotherapy includes sedative herbs (sage, hawthorn, motherwort, valerian, St. John's wort, wild rosemary, peony), marsh cudweed, infusion of eucomia leaves and skullcap, diuretic herbs (lingonberry leaf, bearberry, birch buds). Courses of phytotherapy are prescribed for 1 month every quarter.

Physiotherapeutic procedures with sedative, hypotensive, and antispasmodic effects are prescribed: galvanization, diathermy of the carotid sinus area, Vermel electrophoresis (with 5% sodium bromide, 4% magnesium sulfate, 2% aminophylline, 1% papaverine), electrosleep with a pulse frequency of 10 Hz. It is possible to prescribe one of the above procedures or use two in sequence. Massage and magnetotherapy of the collar area are used.

Water treatments include carbon dioxide and sulphide baths (for sympathicotonia), salt-pine baths (for vagotonia), Charcot shower, fan and circular shower (to normalise vascular tone).

If normalization of the daily routine and non-drug methods of treating arterial hypertension are ineffective, basic vegetative therapy, including vascular and nootropic drugs, is indicated.

Nootropic, or GABAergic, drugs affect the γ-aminobutyric acid system of the brain and are effective as neurotropic drugs.

Gamma-aminobutyric acid (aminalon, 1 t = 0.25 g) eliminates cerebral circulation disorders, improves the dynamics of nervous processes in the brain, improves thinking, memory, and has a mild psychostimulating effect. Prescribed 1 tablet 3 times a day.

Aminophenylbutyric acid (phenibut, 1 tablet = 0.25 g) has a tranquilizing effect, reduces tension, anxiety, and improves sleep. Prescribed 1 tablet 2-3 times a day.

Hopantenic acid (pantogam, 1 tablet - 0.25 g) improves metabolic processes, increases resistance to hypoxia, has a hypotensive effect, reduces motor excitability, activates mental activity, physical performance. Prescribed 1 tablet 3 times a day.

The drugs are prescribed in courses as monotherapy for at least 1 month, alternation of drugs for 1 month is possible, a combination with vascular agents is more effective. Courses are held 2 times a year.

Medicines that improve cerebral hemodynamics, eliminate headaches, dizziness, and memory loss. Prescribed in courses as monotherapy for at least 1 month, alternating medicines for 1 month is possible.

Methods of prescribing drugs that improve cerebral hemodynamics

Preparation	Release form	Dose	Frequency of administration per day
Oxybral	Syrup 60 or 120 ml Retard capsules 30 mg	5-10 ml syrup 1 retard capsule	3 1
Ginkgo biloba leaf extract (Bilobil)	Tablets of 40 mg	1 tablet	3
Vinpocetine (Cavinton)	Tablets of 5 mg	1 tablet	?
Cinnarizine	Tablets of 25 mg	1 tablet	2

Drug treatment of arterial hypertension in a child

Indications for drug hypotensive therapy in adolescents depend on the degree of arterial hypertension. Arterial hypertension of the II degree is an absolute indication for the appointment of hypotensive therapy.

In stage I arterial hypertension, antihypertensive therapy is prescribed in the following situations:

• there are symptoms of target organ damage;
• non-drug therapy is ineffective for more than 6 months;
• symptoms of high risk of developing cardiovascular diseases (dyslipoproteinemia, insulin resistance, obesity, hereditary predisposition to arterial hypertension, hypertensive crises) were identified.

A major but understudied problem is the possibility of using modern antihypertensive drugs used to treat adult patients with arterial hypertension in childhood. Currently, numerous clinical studies conducted in adults with arterial hypertension have shown that regular intake of antihypertensive drugs reduces mortality rates and the risk of myocardial infarction, stroke, and heart failure. Currently, there are no results of long-term observations of children with high blood pressure that could demonstrate how high blood pressure in childhood affects mortality rates in adulthood. Five main groups of antihypertensive drugs are used to treat arterial hypertension in childhood, which are used with the greatest efficiency in adult patients: diuretics, beta-blockers, ACE inhibitors, calcium channel blockers, angiotensin II receptor antagonists. Over the past five years, several clinical studies have been conducted on the possibility of using antihypertensive drugs in childhood. The safety and effectiveness of such drugs as irbesartan, enalapril, and felodipine for lowering blood pressure have been demonstrated. Multicenter trials on the safety and effectiveness of ACE inhibitors (fosinopril) and angiotensin II receptor antagonists (losartan) in adolescents have been completed.

Beta-blockers are divided into non-selective, blocking beta1- and beta2-adrenergic receptors, such as propranolol (obzidan, inderal), and selective, blocking only beta1-adrenergic receptors. Some beta-blockers are characterized by their own (internal) sympathomimetic activity, which manifests itself along with the beta-blocking action by a weak agonistic effect on the same receptors. Depending on the internal sympathicotonic activity, beta-blockers are divided into two subgroups:

• without internal sympathomimetic activity, these include metoprolol, atenolol, betaxolol (locren);
• with internal sympathomimetic activity.

Beta-blockers have negative chronotropic, dromotropic, bathmotropic and inotropic properties, increase baroreflex sensitivity, reduce total peripheral vascular resistance, inhibit the activity of the sympathetic nervous system, reduce renin secretion by the kidneys, inhibit the formation of angiotensin II in the vascular wall, increase the secretion of atrial natriuretic factor, and inhibit the secretion of T4 _and insulin.

Methods of administration of the main beta-blockers

Preparations	Dose for children	Dose for teenagers	Initial dose per day	Maximum daily dose	Frequency of administration per day
Atenolol	0.8-1.0 mg/kg	0.8 mg/kg	0.5-1.0 mg/kg	From 2.0 mg/kg to 100 mg	2
Metoprolol (betaloc')	-	50-100 mg	1.0-2.0 mg/kg	From 6.0 mg/kg to 200 mg	2
Propranolol (Inderal, Obzidan)	0.5-1.0 mg/kg	0.5-1.0 mg/kg	1.0-2.0 mg/kg	From 4.0 mg/kg to 200 mg	3
Bisoprolol (concor)	-	0.1 mg/kg	2.5 mg	10 mg	1

The main indications for the use of beta-blockers are stable arterial hypertension in combination with hyperkinetic hemodynamics, tachycardia, and excessive sympathicotonic effects.

Prescribing medications requires monitoring of blood glucose and lipid levels, ECG monitoring every 4 weeks after the start of treatment. Regular assessment of the patient's emotional state and muscle tone is necessary.

The main side effects of beta-blockers are bradycardia, AV block, depression, emotional lability, insomnia, memory impairment, fatigue, bronchospastic reactions, hyperglycemia, hyperlipidemia, muscle weakness, and erectile dysfunction in young men.

Beta-blockers are contraindicated in obstructive pulmonary diseases, conduction disorders, depression, hyperlipidemia, diabetes mellitus. In addition, their use is undesirable in arterial hypertension in athletes and physically active patients, in sexually active young men.

ACE inhibitors block the conversion of angiotensin I to angiotensin II in the blood and tissues, inhibit the breakdown of bradykinin, stimulate the synthesis of vasodilating prostaglandins, endothelial factors, reduce the activity of the sympathetic nervous system and the level of aldosterone in the blood, affect the pressor natriuretic hormone. The pharmacodynamic effects of ACE inhibitors include a hypotensive effect due to dilation of arteries and veins (without affecting heart rate and cardiac output), increased sodium excretion by the kidneys (associated with renal vasodilation), reduced pre- and afterload on the heart, improved diastolic function of the left ventricle, effects on growth factors, reduced left ventricular hypertrophy, and vascular wall hypertrophy. The drugs improve the quality of life; withdrawal syndrome is not typical for them.

Indications for the use of ACE inhibitors: hypokinetic type of hemodynamics, increased plasma renin activity, systolic-diastolic arterial hypertension, diabetes mellitus.

Methods of administration of the main angiotensin-converting enzyme inhibitors

Preparations	Dose for children	Dose for teenagers	Initial dose	Maximum daily dose	Frequency of administration per day
Captopril	0.05-0.1 mg/kg	37.5-75 mg	0.3-0.5 mg/kg per dose	6 mg/kg	3
Enalapril	0.1-0.2 mg/kg	5-40 mg	From 0.08 mg/kg to 5 mg per day	From 0.6 mg/kg to 40 mg	1-2
Fosinopril	0.05-0.1 mg/kg	5-20 mg	From 0.1 mg/kg to 10 mg per day	40 msh	1
Lisinopril (Diroton)	-		From 0.07 mg/kg to 5 mg per day	From 0.6 mg/kg to 40 mg	1-2

The main side effects of the drugs are the occurrence of "first dose hypotension", hyperkalemia, dry cough, and very rarely azotemia and Quincke's edema. Contraindications to the use of drugs are pregnancy, hyperkalemia, and renal artery stenosis.

Calcium channel blockers are a large group of drugs, very heterogeneous in chemical structure and pharmacological properties, which have a competitive effect on potential-dependent calcium channels. According to their chemical structure, they are divided into three groups: phenylalkylamine derivatives (verapamil, gallopamil), benzothiazepine derivatives (diltiazem, kleshnazem), and dihydropyridine derivatives (nifedipine, amlodipine, felodipine).

Currently, dihydropyridine drugs are used to treat arterial hypertension in children and adolescents. They are distinguished by vasoselectivity and do not have a negative inotropic and dromotropic effect. The antihypertensive effect of calcium channel blockers is based on their ability to cause vasodilation as a result of inactivation of potential-dependent calcium channels of the vascular wall and a decrease in OPSS. Among the dehydropyridine calcium channel blockers, amlodipine, isradipine, and felodipine have high vasoselectivity.

Indications for the use of calcium channel blockers are low renin activity, the need to combine antihypertensive therapy with NSAIDs, ineffectiveness of ACE inhibitors, and the presence of contraindications to the use of beta-blockers. Calcium channel blockers are the drugs of choice for patients with dyslipoproteinemia and renal dysfunction. The main side effects are dizziness, facial flushing, peripheral edema, bradycardia, atrioventricular block (non-dihydropyridine), and gastrointestinal disorders. Contraindications for the use of calcium channel blockers are conduction disorders.

Nifedipine is available in two forms: rapid release and slow release. Rapid release nifedipine (10 mg tablets) begins to act very quickly, but has a short half-life in blood plasma (2-7 hours), which makes it difficult to use for long-term therapy. It is advisable to use the drug to relieve crises (single dose of 10 mg). Slow release nifedipine (osmoadalat - 10 mg tablets) has a significantly longer half-life in plasma (12 to 24 hours), which is why it is used to treat arterial hypertension.

Methods of administration of the main calcium channel blockers

Preparation	Initial dose per day	Maximum daily dose	Frequency of administration per day
Amlodipine (Norvasc)	2.5-5 mg	5 mg	1 dose for children >6 years old
Felodipine (Plendil)	2.5 mg	10 mg	1
Isradipine	0.15-0.2 mg/kg	From 0.8 mg/kg to 20 mg	2
Nifedipine (osmo-adalate)	0.25-0.5 mg/kg	From 3 mg/kg to 120 mg	1-2

The mechanism of action of angiotensin II receptor antagonists is associated with the blockade of angiotensin regardless of the pathway of its formation, which ensures their high efficiency and good tolerability. Unlike taking ACE inhibitors, the administration of these drugs is not accompanied by such a side effect as cough. The drugs are prescribed in case of side effects when using ACE inhibitors. intolerance to drugs of other groups. Side effects: dizziness, headache, weakness, periodic edema. Contraindications: hypersensitivity, hyperkalemia, dehydration, pregnancy. Patients with liver pathology should be prescribed smaller doses. Use with caution in case of bilateral renal artery stenosis or stenosis of the renal artery of a single kidney (increased risk of renal dysfunction), moderate and severe renal dysfunction, congestive heart failure.

Routes of administration of the main angiotensin II receptor antagonists

Preparation	Initial dose per day	Maximum daily dose	Frequency of administration per day
Irbesartan (for children over 6 years old)	75-150 mg	150-300 mg (for patients over 13 years old)	1
Losartan	From 0.7 mg/kg to 50 mg	From 1.4 mg/kg to 100 mg	1

The hypotensive effect of diuretics is due to a decrease in total peripheral vascular resistance, vascular response to vasoactive substances. Thiazide and thiazide-like diuretics in low doses are used as hypotensive agents. They are effective and the most cost-effective hypotensive drugs that can be used both for monotherapy and in combination with other drugs. High doses are not used due to the possibility of complications and side effects. The main side effects of diuretics are hypokalemia, hyperuricemia, hyperlipidemia, hyperglycemia, erectile dysfunction in young men, and orthostatic hypotension. Special indications for prescribing diuretics include metabolic syndrome (MS), obesity, diabetes mellitus, increased sensitivity to table salt, left ventricular myocardial hypertrophy, and systolic arterial hypertension. The recommended drugs are listed below.

• Hydrochlorothiazide (hypothiazide) - 25 mg tablets. Children are prescribed 1-3 mg/kg per day orally in 2 doses; adolescents - 12.5-25 mg orally 1-2 times a day. It should be used with caution due to the possibility of side effects, it is necessary to monitor the level of potassium, glucose, blood lipids, and ECG every 4 weeks of treatment. Low doses of the drug (6.25 mg once a day) increase the effectiveness of other antihypertensive drugs without undesirable metabolic effects.
• Indapamide (1.5 mg tablets) with delayed release (Arifon retard). Older children and adolescents are prescribed 1.5 mg orally once a day. The dose is not increased. It is necessary to monitor the potassium level in the blood, ECG monitoring every 8 weeks of treatment.
• Loop diuretics (furosemide) are used only in the treatment of hypertensive crises and concomitant renal failure. Newborns are prescribed 1-4 mg/kg orally 1-2 times a day or 1-2 mg/kg intravenously or intramuscularly 1-2 times a day; children - 1-3 mg/kg per day (maximum up to 40 mg per day) orally in 1-2 doses or 1-2 mg/kg intravenously or intramuscularly 1-2 times a day; adolescents - 20-40 mg orally 1 time per day.

Prognosis of arterial hypertension

The stability of blood pressure values allows us to predict to what extent the values of elevated blood pressure detected in children and adolescents can be extrapolated to the blood pressure level in adults. Information on the stability of blood pressure levels is provided by long-term (prospective) studies.

When monitoring the blood pressure level in over 6,600 children for 6 years with an interval of 2 years, low stability of blood pressure indicators was established. The stability coefficient (correlation between the blood pressure value during the first and subsequent measurements) for systolic blood pressure was 0.25, for diastolic blood pressure - 0.18. In this regard, a single increase in blood pressure cannot be considered as arterial hypertension and a risk factor for coronary heart disease; dynamic observation is necessary. When comparing the blood pressure level measured at 9 and 30 years, stability of SBP was noted only in men, and stability of DBP was absent in both men and women. At the same time, during a 10-year observation of children with arterial hypertension, the stability coefficient was significantly higher: for SBP it was 0.32, for DBP - 0.53.

Blood pressure remains elevated in 33-42% of adolescents, in 17-25% arterial hypertension becomes progressive, i.e. every third child with arterial hypertension may develop hypertension in the future.

When observing the natural course of juvenile arterial hypertension for 33 years, spontaneous normalization of arterial pressure was noted in only 25% of cases. Thus, there is a dissociation between the low stability of normal arterial pressure values and the higher stability of elevated arterial pressure values. In this regard, long-term dispensary observation of children with recurring increases in arterial pressure is mandatory in order to prevent the development of arterial hypertension and its transformation into hypertension.