Thiazide diuretics in the treatment of arterial hypertension

Short Wiklad

JG O'Brien, SA Chennubhotla, RV Chennubhotla Am Fam Physician 2005;71:2111-7, 2118

1Div. Also the article Internal and post-clinical hyperhydration and dehydration: etiology, pathophysiology, diagnosis, treatment. – Medicine for the world. – 1999. – T. VIII. – Part 3. – P. 460-469; T. VII – Part 4. – pp. 523-530.

Spots are often eliminated in clinical practice, and their more effective treatment has recently been developed. First of all, it is important to understand the etiology of the bumps: they can be caused by illnesses that are unsafe for life, such as congestive heart failure, or in some kind of good manners, in addition to troubling experiences in a sedentary position. The marks can be separated by one end or they can be generalized and massive. The stink is due to the inheritance of an imbalance in blood circulation, including impaired hemodynamics at the level of the capillaries, which is due to the loss of water and sodium, and the displacement of blood from the vascular bed into the interstitium. The most common etiology of pimples: venous insufficiency, increased penetration of the capillary wall and an increase in the volume of blood plasma due to the retention of sodium and water.

PATHOPHYSIOLOGY

Swelling occurs when the amount of filtration increases due to the influx of displacement of the hydraulic pressure in the capillaries or the interstitial oncotic pressure, increased penetration of the capillaries or a decrease in the oncotic pressure of the blood plasma i. Nitric acids play a central role in maintaining the balance of urinary fluid in the body by controlling the amount of urinary fluid in addition to changing the excretion of sodium and water. The primary regulator of blood volume in the body is the antidiuretic hormone, which appears to influence changes in blood volume, vascular tone and arterial pressure. Sodium and other anions are the main components of the post-peritoneal region, instead of which they accumulate at narrow intervals. The presence of sodium chloride in the body is equivalent to its elimination over several days; As the need progresses, through the early period, excretion increases compensatoryly. In this way, the volume of vital fluid is maintained at a constant level, regardless of the amount of fluid needed in the body.

In order to understand the role of sodium suppression in maintaining plasma volume, it is important to understand the concept of effective arterial blood volume (EABV). EOAC is responsible for the homeostatic mechanisms of supporting BCC and, in turn, regulates the reabsorption of sodium in the bloodstream. EOAC correlates with the volume of postcellular fluid. In healthy individuals, when there is sufficient sodium in the body, the volume of post-vital fluid and EOAC rises, the sodium rapidly increases and thus the normal value of the volume of fluid is restored. When the rhubarb EOAC is dehydrated and the post-vitamin level decreases, the suppression of sodium in the body is activated through the renin-angiotensin-aldosterone mechanism, which leads to the renewal of the bcc. When the function of the brain is reduced, the distribution of tissue in the body is destroyed. When swelling develops, a decrease in level of EOAC activates volume/pressure receptors, including low pressure baroreceptors in the venous system, high pressure baroreceptors in the great vessels, nitric and hepatic receptors.

In patients with primary sodium blockage, afferent stimulation is suppressed. As the volume of the posterior tissue increases, swelling appears, and the volume of the EOAC decreases. The inheritance of this stimulates the efferent reflex pathways, reducing sodium suppression, activating the sympathetic nervous system, stimulating the renin-angiotensin-aldosterone system and promoting vasopressin.

Regardless of those caused by changes in the heart rate or other reasons, it occurs through those whose compensatory mechanisms help to maintain the volume of blood plasma.

Diuretics

Maintaining water-salt balance in the body is the most important condition for maintaining stable blood pressure levels. Renal nephrons regulate fluid volume and electrolyte content in the body through secretion and reabsorption. The water-salt balance can be disturbed in a number of conditions, including hypertension, heart or kidney failure, as well as nephrotic syndrome, cirrhosis, etc.

Diuretics can normalize water-salt balance by increasing the rate of urine flow and excretion of Na+ and the accompanying anion, usually Cl-. The major determinant of extracellular fluid volume in the body is NaCl, and most diuretics reduce extracellular fluid volume by reducing total body NaCl [1].

Today, both thiazide and thiazide-like diuretics and loop diuretics are used to treat arterial hypertension.

Principles of celebration

Treatment of swellings is used in the fight against the first illnesses (if possible), surrounded by sodium with the fluid to minimize the clogging of the fluid and, as a result, stagnation of the skin. Therefore, it is important to establish a clinical diagnosis and, if possible, use non-pharmacological treatment methods, especially diuretics.

Not all patients with marks will require drug therapy; In some patients, it is enough to limit the infusion of sodium to the level, lower than the volume of sodium, and raise the lower ends above the level of the left atrium. In most patients, it is necessary to add sedatives to non-pharmacological approaches, which are especially effective in the treatment of intravenous salt. The choice of diuretic, the method of administration and dosage depend on the initial illness, the importance of overcoming and the urgency of the problem. It is important to know the pharmacokinetics and pharmacodynamics of various drugs.

Diuretics act on different structures of nitric acid (Table 1). Loop diuretics (furosemide, bumetanide and torsemide) block the transport of sodium and potassium chloride at the exit of the loop of Henle, while thiazide diuretics block the electrically neutral transport of sodium chloride in the distal loops. and winding channels. Amiloride is capable of blocking apical sodium channels in the cervical collecting ducts. These drugs closely bind to albumin. All diuretics, in addition to spironolactone, are absorbed in the lumen of the nephron, where they show their effect from the beginning.

Table 1. Physiological classification of diuretics (per DH Ellison, 1994)

After oral administration, the absorption of furosemide on average reaches 50% (varies between 10–80%). The absorption of bumetanide and torsemide is stickier and reduces to 80–100%. Thiazide diuretics, such as chlorothiazide and hydrochlorothiazide, may appear unchanged; Other drugs (bendroflumetazide and indapamine) are metabolized in the liver. The frequency of administration of sedatives depends on the hour of administration from blood plasma: thiazide diuretics with a different hour of administration can be prescribed once or twice a day.

Loop diuretics have a short duration of delivery (ranging from 1 year for bumetanide to 3-4 years for torsemida), so they must be taken more often than thiazide-based ones. The action of loop diuretics is rapidly administered, after which the drugs immediately begin to reabsorb sodium, which negates the action of ecchymoses, a process called post-diuretic suppression of sodium chloride. If the patient takes a large amount of sodium chloride from the skin, and the hour of sechogenic administration is short (there is no need for loop diuretics), then the post-diuretic addition of sodium chloride completely compensates for the initial loss of sodium. For patients taking loop diuretics, carefully monitor sodium intake.

Thiazide and thiazide-like diuretics

Mechanism of action

Thiazide and thiazide-like diuretics act mainly in the cortical segment of the nephron loop, at the site of inhibition of the reabsorption of cations (potassium, sodium, magnesium). They block the transport protein that ensures the transfer of sodium and chlorine into tubular epithelial cells, as a result of which the excretion of these electrolytes in the urine increases. The excretion of calcium ions, on the contrary, decreases [2]. This is accompanied by increased diuresis and a decrease in circulating blood volume [3].

In elderly patients, thiazide and thiazide-like drugs are more effective than β-blockers and ACE inhibitors [3].

Even in low doses, they have fairly high antihypertensive activity, which is not inferior to the effect of calcium antagonists and α1-adrenergic blockers [4].

According to research, with regular use of thiazide and thiazide-like diuretics, systolic blood pressure (BP) decreases by an average of 10–20 mmHg. Art., and diastolic - by 5–15 mm Hg. Art. In addition, drugs of this group reduce peripheral vascular tone [2].

Indications and properties

Drugs in this group are used both as monotherapy and in combination with other antihypertensive drugs for arterial hypertension. In addition, they are prescribed for chronic heart failure, renal dysfunction, premenstrual syndrome (to reduce swelling associated with PMS).

Thiazides and thiazide-like diuretics, like most other classes of modern antihypertensive drugs, exhibit a complex cardiovascular effect [3]:

• reduce blood pressure;
• prevent the development of cardiovascular complications;
• reduce cardiovascular mortality.

The effect on cardiovascular risks is due to the ability of drugs in this group to reverse the development of left ventricular hypertrophy. Another positive property is that they increase the effectiveness of antihypertensive drugs of the other four pharmacological groups.

When taking some drugs of this group, the level of uric acid increases, and slightly - glucose and atherogenic lipids [2].

Individual representatives

• Hydrochlorothiazide is one of the most studied and popular diuretics used to treat hypertension. Efficacy and a high safety profile have been proven in long-term randomized studies, so this diuretic is one of the drugs of choice for long-term treatment of hypertension [4].
• Indapamide, unlike other thiazide (and thiazide-like) diuretics, blocks calcium channels in the muscular wall of the arteries, reducing peripheral vascular resistance and exerting a direct vasodilator effect [2, 5]. Indapamide has proven significant organoprotective effects - regression of left ventricular hypertrophy, kidney protection. Hypothiazide is significantly superior in its effect on systolic blood pressure [5]. In addition, the drug does not affect glucose levels and is suitable for use in diabetes mellitus [2].

Portability

Thiazides and thiazide-like diuretics in low doses are well tolerated and do not cause significant changes in carbohydrate and lipid metabolism. Rarely, usually in men, gout may develop while taking medications [4]. In addition, thiazide diuretics have an adverse effect on erectile function.

What should I warn the client about?

• During treatment, electrolyte balance may be disturbed, therefore, if you experience dry mouth, thirst, heart rhythm disturbances, or unusual fatigue during treatment, you should contact your doctor as soon as possible [6].
• When taken together with alcohol, orthostatic hypotension may occur (a sharp decrease in pressure when changing body position from horizontal to vertical) [6].
• At the beginning of treatment with drugs of this group, it is not recommended to drive a car or perform work that requires increased attention. The duration of this period is individual [6].
• Thiazide and thiazide-like diuretics may contribute to the development of erectile dysfunction. If a client purchases drugs from this group (including as part of combination drugs) and PDE-5 inhibitors, it is appropriate to warn him about the possible negative impact of the former on sexual function.

Reasons for the ineffectiveness of treatment with diuretics

Resistance to diuretics is the inability to achieve a negative sodium balance in the body, regardless of the administration of high doses of diuretics (for example, furosemide in an additional dose of 240 mg). This should be switched off in patients with persistent swelling, which requires adequate treatment with diuretics, physical activity and sodium intake from the skin (less than 2 g/day).

To combat resistance to diuretics, it is important to know the pharmacokinetics of various diuretic drugs. Bumetanide, when used as a substitute for furosemide, is absorbed more quickly after oral administration. Adaptation of the epithelium of the distal convoluted tubules to chronic stagnation of diuretics can be eliminated by adding another sedative drug that acts on a different part of the nephron. More often than not, the use of short-acting sechoginic or long-term diuretics interferes with sodium reabsorption, which may result from the administration of sechoginic drugs. Patients will require close monitoring for immediate detection of side effects such as hypokalemia and hypovolemia. Patients who are resistant to diuretics who are receiving intensive care may not require continuous intravenous infusion of loop diuretics.

Table 2 shows other potential reasons for the ineffectiveness of diuretic treatment. The problem may lie not in proper resistance to drugs, but in an incomplete treatment regimen; This is especially important for elderly patients, who need to take off a lot of medications and apply an unstoppable treatment to the risk group. Such illnesses can be separated from the treatment of the sechogins, so as to be left dry. Resistance to sedatives may occur due to the concomitant use of NSAIDs, which may inhibit the action of diuretics. The use of NSAIDs can reduce resistance to sechoginal ones.

Table 2. Reasons for the failure of therapy with loop diuretics (after Dormans TP et al., 1998)

Another potential reason for the ineffectiveness of therapy is the development of tolerance to diuretics. Short-term tolerance should be suspected if, after the first dose is administered, a change in response to the drug begins to occur. It is important to remember that as a result of the change in the BCC, a compensatory reaction occurs in order to avoid further loss of life. Long-term tolerance is lost in patients, when it is difficult to withdraw loop diuretics, and as a result of difficult contact with disorders in the body, there is hypertrophy of the distal segments of nephrons, which reabsorb more sodium and thus change the normal diuresis. Increasing the dose of a loop diuretic with long-term tolerance is unlikely to increase diuresis, as the additional use of a thiazide-like drug, which is applied to another segment of the nephron, will lead to a synergistic and rapid increase diuresis. To avoid a decrease in the effectiveness of other diuretics, it is also necessary to add diacarb, which acts on the proximal convoluted tubule.

Loop diuretics

Mechanism of action

Diuretics acting at the level of the loop of Henle are the most potent representatives of this class of drugs, since 20-30% of all filtered sodium is reabsorbed through this segment of the nephron. By reducing the volume of circulating blood, loop diuretics reduce the load on the myocardium, reduce congestion in the lungs and relax the vascular wall. They are characterized by a rapid onset of action and a powerful short-term effect [7].

Indications and properties

The scope of use of loop diuretics is usually limited to emergency situations. They are prescribed for edema syndrome of various origins. In arterial hypertension, drugs of this series are used for hypertensive crises, resistance to thiazide diuretics, as well as for concomitant severe renal failure [7]. An exception may be the modern loop diuretic torasemide.

Individual representatives

• Furosemide is a powerful loop diuretic. Dilates blood vessels, increases renal blood flow, has antiaggregation activity. It is used for acute conditions, rarely for the treatment of hypertension [6]. The drug is “reserved” for patients resistant to traditional antihypertensive therapy.
• Torsemide is a loop diuretic, which is characterized by a less pronounced peak effect and a longer duration of action compared to furosemide. The antihypertensive effect has been proven in a number of clinical studies. They are used both for long-term treatment of hypertension and as part of combination therapy for chronic heart failure [7]. However, current guidelines for the treatment of hypertension do not mention the drug as a first-line treatment [3].

Portability

Loop diuretics can contribute to a sharp decrease in blood pressure and the development of orthostatic hypotension.

What should I warn the client about?

• Excessive loss of fluid and/or electrolytes may occur while taking loop diuretics. It is important to tell the buyer that if you experience dry mouth, increased thirst, or dizziness, you should contact your doctor as soon as possible.
• Loop diuretics are not recommended for use by vehicle drivers and people whose work requires increased concentration.
• Drugs in this group should not be taken at night due to their powerful diuretic effect.

Persistent heart failure

In patients with moderate or major congestive heart failure, activation of the renin-angiotensin system causes vasoconstriction of afferent and efferent arterioles. The neurohumoral response includes the release of aldosterone by hormones; an increase in the tone of the sympathetic nervous system, which implies an increase in sodium reabsorption in the proximal tubules; secretion of antidiuretic hormone, which leads to increased reabsorption of water in the collecting ducts and, as a result, to hyponatremia.

Regardless of widespread congestion, improvement in survival in patients with congestive heart failure has not been achieved, due to spironolactone - according to the findings of Pitt B. et al. (1999), this drug reduced sickness and mortality in patients with heart failure class III and IV (according to NYHA classification). At the All -Great Great Doslіzhennyas, Vijivannya Patziantvs of the Service (Packer M. et al., 1992) Sechogіnni was stacked in combinations with the same drugs, I forgot more burning symptoms. Before promoting diuresis, through the veins and after intravenous administration, loop diuretics change the wedging pressure in the pulmonary capillaries and increase the capacity of the venous bed. Loop diuretics are effective as monotherapy for treating moderate or major stage cardiac failure. In most patients with heart failure, until death, there is obvious nitric deficiency due to the inheritance of primary illness, prerenal azotemia, or a secular decrease in nitric function. Due to the presence of competition with endogenous organic ions for the place of binding in the tubules of the liver, in patients with heart failure, loop diuretics must be prescribed in higher doses.

Liver cirrhosis2

2Div. Also, ascites is a worsening of liver cirrhosis.

– Medicine for the world.
– 1998. – T. V. – Part 1. – P. 4-11 and Ascites: a new look at the classic problem.
– Medicine for the world. – 2004. – T. XVI. – Part 2. – P. 77–83. (Note switch)

To treat ascites with swellings associated with cirrhosis, you can apply more principles to the importance of sechoginal and the exchange of sodium in the skin. Ascites is often associated with liver cirrosis, which worsens the prognosis. The importance of treating ascites is divided into three stages: in the first stage, ascites is diagnosed only by ultrasound; in the other case, there is apparently a slightly symmetrical enlargement of the abdomen; with the third - a sign of enlargement of the abdomen. To identify the etiology, a sample of ascitic tissue can be taken. In fact, the universal recommendation in this situation is to remove sodium and water.

In case of ascites of the 2nd or 3rd stage, to combat hyperaldosteronism, it is absolutely necessary to take spironolactone at a dose of 100–200 mg per day, every hour. In addition to this, you can monitor the results of treatment. Vaginal expenditure should not exceed 0.5 kg per day in patients without peripheral swellings and 1.0 kg with obvious swellings. If there is no reaction to the addition of 100 mg spironolactone, a low dose loop diuretic can be added. In case of overly aggressive treatment with diuretics, acute hepatorenal syndrome may occur. Side effects of spironolactone administration include hyperkalemia, metabolic acidosis, and gynecomastia, which usually resolve after dose reduction or drug administration.

The treatment of choice in patients with stage III ascites is paracentesis due to the use of transection and injection of sodium. However, since the volume of the liquid exceeds 5 liters, it is recommended to remove it in one procedure. To prevent neurological complications after paracentesis, it is necessary to carry out infusion therapy with a synthetic plasma exchanger or albumin, especially after evacuation of more than 5 liters of liquid. In patients with refractory ascites, there are indications for transjugular intrahepatic portosystemic shunt (TIPS). At the end of the randomized follow-up M. Rossle et al. (2000) found that TIPS is superior to large-volume paracentesis in eliminating ascites and prolonging survival (58 vs. 32% in patients who lost 2 days of life). Many patients with ascites and cirrhosis are candidates for liver transplantation.

Thiazide diuretics in the treatment of arterial hypertension

In June 2007, at the European Congress on Hypertension in Milan (Italy), new European guidelines for the treatment of arterial hypertension (HTN) were announced. Particular attention of cardiologists was directed to the place of certain classes of drugs in treatment regimens for hypertension.

6 rational combinations of antihypertensive drugs have been proposed [1]:

• thiazide diuretic + angiotensin-converting enzyme (ACE) inhibitor;
• thiazide diuretic + angiotensin receptor blocker;
• calcium antagonist + ACE inhibitor;
• calcium antagonist + angiotensin receptor blocker;
• calcium antagonist + thiazide diuretic;
• beta blocker + dihydropyridine calcium antagonist.

Based on the above, we can conclude that calcium antagonists (4 times) and thiazide diuretics (3 times) appear most often in combinations.

Thiazide diuretics have long been used as agents for the treatment of hypertension. In the 2007 European guidelines, the target groups for whom diuretics are preferred include elderly patients with systolic hypertension as well as heart failure [1].

However, the use of medium and high doses of thiazide diuretics is currently considered undesirable: for example, hydrochlorothiazide at a dose of 100 mg/day increases the risk of sudden death, and at doses of 50–100 mg/day does not prevent the development of coronary heart disease (CHD). In this regard, the recommended doses of thiazide diuretics are currently 12.5–25 mg/day, which do not always achieve an adequate diuretic and antihypertensive effect [2]. In addition, limiting the doses of thiazide diuretics is also associated with their negative effect on carbohydrate, fat and purine metabolism [3]. Therefore, in the 2007 European recommendations, gout was included as absolute contraindications to the use of thiazide diuretics, and metabolic syndrome and impaired glucose tolerance were included as relative contraindications. In addition, special emphasis is placed on the fact that high doses of diuretics cannot be prescribed to pregnant women due to the possibility of reducing circulating blood volume (CBV) and deteriorating blood supply to the fetus. However, we should not forget that diuretics can delay the development of chronic heart failure in patients with hypertension (Davis BR, 2006).

Thus, it is obvious that the scope of application of thiazide diuretics in the treatment of hypertension is quite limited. In this regard, the thiazide-like diuretic indapamide is of particular interest.

Indapamide has a dual effect, due to which it has a short-term and long-term antihypertensive effect. The short-term effect is associated with the effect of the drug on the proximal part of the distal tubules of the nephron and represents a natriuretic effect characteristic of representatives of the diuretic class as a whole. As for the long-term antihypertensive effect, it is unique to indapamide and occurs due to a direct vasodilating effect on the smooth muscle cells of the vascular wall [4].

The antihypertensive effect of indapamide retard 1.5 mg was compared with amlodipine (5 mg/day) and hydrochlorothiazide (25 mg/day) in a study of 605 patients with hypertension treated with the above drugs for 3 months. The number of patients responding to monotherapy was slightly higher in the indapamide-retard group (75.3%) compared with the amlodipine (66.9%) and hydrochlorothiazide (67.3%) groups. In the subgroup of patients with isolated systolic hypertension, a similar trend was observed: the number of respondents in the indapamide-retard group was 84.2%, while in the amlodipine group - 80%, hydrochlorothiazide - 71.4% [5].

The multicenter LIVE (Left ventricle hypertrophy: Indapamide Versus Enalapril) study examined the effect of indapamide and enalapril therapy on regression of left ventricular myocardial mass (LVMM). 505 patients (255 - indapamide group; 250 - enalapril group) with mild and moderate hypertension were prescribed indapamide retard 1.5 mg/day or enalapril at a dose of 20 mg once a day for 1 year. Therapy with indapamide led to a significant decrease in LVMM (p < 0.001); similar results were not obtained in the enalapril group. Indapamide also reduced the severity of left ventricular hypertrophy (LVH) to a greater extent than enalapril (p < 0.049) [6, 7].

Thiazide diuretics have been prescribed in combination with ACE inhibitors for a very long time: many pharmaceutical companies have even developed fixed combinations of these components. In a large number of studies, the combination of indapamide with perindopril also showed good results. However, there are not many studies on the effectiveness of combinations of indapamide with other classes of the drug.

In this regard, we found the work of Hashimoto J. et al interesting. [8], who added indapamide at a dose of 1 mg to 76 patients receiving ACE inhibitors, angiotensin receptor blockers, and calcium antagonists as monotherapy, but failed to achieve target blood pressure (BP) values ​​with this treatment. During 4 weeks of combination therapy in these three groups, the dynamics of the level of 24-hour blood pressure monitoring, home blood pressure measurements, and random blood pressure measurements were assessed. In all groups, a significant decrease in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was noted. The decrease in SBP in the evening and pulse blood pressure was significantly more pronounced in the angiotensin receptor blocker + indapamide group compared to the calcium antagonist + indapamide group. Thus, the addition of indapamide to antihypertensive therapy led to an additional hypotensive effect that lasted 24 hours.

Until recently, only three classes of drugs were thought to have nephroprotective effects: ACE inhibitors, angiotensin receptor blockers, and calcium antagonists (mainly phenylalkylamines). The nephroprotective effect of thiazide-like diuretics was demonstrated in the NESTOR study [9]. In 570 patients with hypertension and type 2 diabetes mellitus, a comparative study of the effect of indapamide retard 1.5 mg and enalapril 10 mg on the severity of microalbuminuria (MAU) was carried out during one-year therapy. There was a decrease in MAU by 37% in the enalapril group and by 45% in the indapamide-retard group. Thus, the nephroprotective effect of indapamide retard 1.5 mg turned out to be comparable and even slightly higher than that of enalapril.

Another study examined the effect of indapamide retard at a dose of 1.5 mg prescribed for 3 months, compared with placebo, on 24-hour blood pressure monitoring, carbohydrate and lipid metabolism in patients with type 2 diabetes mellitus [10]. A significant decrease in average daily blood pressure was detected in the indapamide group compared to placebo. In addition, there was no effect of the therapy on electrolytes, creatinine, lipid spectrum, uric acid, liver transaminases, insulin levels, glycosylated hemoglobin and glucose tolerance test results.

Considering that diuretics have long established themselves as the drug of choice for the treatment of elderly patients, especially those with isolated systolic hypertension (ISAH). The multicenter X-CELLENT study included 1,758 patients with systolic-diastolic hypertension or ISAH, who were then randomized into 4 groups, which received monotherapy with indapamide retard 1.5 mg/day, amlodipine 5 mg/day, candesartan cilexetil 8 mg/day and placebo for 3 months. Compared to the placebo group, a significant decrease in blood pressure was noted in all groups. The advantage of indapamide in patients with ISAH was the virtually no effect of the drug on normal DBP values ​​while reducing SBP; the remaining drugs reduced both SBP and DBP. In addition, in this group of patients, indapamide retard reduced average daily SBP to a greater extent than amlodipine. All three types of therapy were well tolerated [11].

As we indicated above, a dose of hydrochlorothiazide of 12.5–25 mg/day is considered metabolically neutral. In the work of A. A. Semenkin et al. A comparative study of the antihypertensive effectiveness and metabolic effects of indapamide retard (1.5 mg/day) and hydrochlorothiazide (25 mg/day) was conducted. Despite the comparable antihypertensive effect, in the group of patients receiving hydrochlorothiazide, after 3 months there was a significant increase in triglyceride levels by 15.3% (p < 0.05) and glucose by 12.2% (p < 0.05), and also a significant deterioration in endothelium-dependent vasodilation by 17% (p < 0.05) [12].

Of interest is the potential expansion of indications for the use of indapamide, in particular, its use in the treatment of chronic heart failure accompanied by edema syndrome. In one recent study in patients with persistent peripheral edema, indapamide 2 mg was added to furosemide (40–120 mg/day), which resulted in a significantly greater diuretic effect without a significant effect on plasma potassium and creatinine levels [13].

Thus, the original indapamide has more than convincingly proven its antihypertensive effectiveness and organoprotective properties during research. In an attempt to combine low cost with high quality of the drug to provide the majority of patients with hypertension with drugs of adequate action, modern generics of indapamide and, in particular, the drug “Ravel SR”, produced in a dose of 1.5 mg, are of particular interest. The drug has successfully proven itself after a trial in Slovenia in 2005–2006. study [4], which examined its antihypertensive efficacy and tolerability. The drug was prescribed to 1419 patients (58.1% women, mean age 61.9 ± 11.6 years), who showed a decrease in SBP by 14.1% and DBP by 11.1%. The development of adverse events while taking Ravel SR was noted in only 2.5% of patients (the most common were dry mouth and dizziness - 0.42% each, and 1 patient required correction of potassium levels due to the development of hypokalemia without discontinuation of the drug) .

The effectiveness and tolerability of Ravel SR was also studied in domestic studies. S. V. Nedogoda et al. [14] compared therapy with Ravel SR 1.5 mg/day and hydrochlorothiazide 25 mg in patients with hypertension and obesity. Patients of the 1st group received Ravel SR for 6 months, patients of the 2nd group were prescribed hydrochlorothiazide at a dose of 25 mg/day for the first 3 months, and then they were transferred to Ravel SR (3 months). The results of the study showed that while taking Ravel SR, achieving target blood pressure values ​​occurred 15% more often than with hydrochlorothiazide. It was noted that only on therapy with Ravel SR there was an improvement in vascular elasticity (as assessed by pulse wave velocity) and a decrease in myocardial hypertrophy, as well as an improvement in carbohydrate and lipid metabolism.

Also of interest are the results of the BOLERO program (Basic treatment and antihypertensive effect: the drug “Ravel SR” in patients with arterial hypertension), aimed at studying the antihypertensive effectiveness of the slow-release form of the drug and its effect on quality of life. It was shown that the use of indapamide retard for 2 months led to a decrease in SBP and DBP in men by 18%, and in women by 15%. During treatment, cardiovascular risk decreased to the same extent in men and women, and the improvement in quality of life was more noticeable in the group of women [15].

The emergence of each new high-quality and safe generic drug is a step towards ensuring that Russian patients demonstrate higher adherence to hypertension treatment. Currently, patients with hypertension in the Russian Federation who have a target blood pressure level do not exceed 5–15% of the population, while in Western Europe there are more than 30% of such patients. The drug "Ravel SR" (indapamide retard) 1.5 mg as an antihypertensive drug with a mild diuretic effect has every opportunity to expand the boundaries of the use of diuretics outlined by modern recommendations for the treatment of hypertension.

For questions regarding literature, please contact the editor.

D. A. Napalkov , Candidate of Medical Sciences MMA named after. I. M. Sechenova , Moscow

Nephrotic syndrome3

3Div. also article Scratches of the lower ends: diagnostic orientation

. – Medicine for the world. – 1999. – T. VI. – Part 1. – pp. 27-31. (Note switch)

Nephrotic syndrome often causes swelling and is characterized by severe proteinuria, hypoalbuminemia, hyperlipidaemia and swelling. Discussion will continue as to whether the swelling is a consequence of the decrease in oncotic pressure, or the evidence of an excessive amount of sodium, which is necessary to stop the water; Most of the researchers tend to converge on another hypothesis. Treatment includes the exchange of intravenous sodium and a combination of loop diuretics, aldosterone antagonists and drugs for the treatment of primary illness.

Chronic venous insufficiency4

4The same article Varicose veins: not only a cosmetic problem

. – Medicine for the world. – 2000. – T. VIII. – Part 3. – P. 130-136; Part 4. – pp. 201-203. (Note switch)

Venous insufficiency is a common etiology of swellings of the lower ends. If swelling appears, especially one-sided, it is necessary to exclude thrombosis of the deep veins of the lower end. Until the swelling of the legs heals, persistent dermatitis, swelling and cellulite will occur. The effectiveness of diuretics is limited. Keeping the nose in an elevated position above the level of the heart and tightening the thick punches can change venous insufficiency and swelling.

Scrubs, due to the action of the lips

Foot swelling is caused by many medications, especially vasodilators, estrogens, NSAIDs and calcium channel blockers. Among calcium channel blockers, the most common compounds are dihydropyridine5. The intensity of the effect lasts for a long time and grows over time. Remnants of drug effects result from capillary hypertension; for their treatment, ACE inhibitors and angiotensin receptor blockers are effective, rather than sedative ones.

5 This group includes amlodipine, felodipine, isradipine, nifedipine, nemodipine, nitrendipine, lacidipine, rhiodipine. (Note switch)

Beta blockers

Beta-blockers (BABs) have been used for many years as first-line treatment for hypertension.

Mechanism of action

The action of drugs in this group is based on the blockade of β1- and β2-adrenergic receptors located in various organs. Depending on the selectivity of the blockade, which is determined by the β1/β2 ratio, beta blockers are divided into selective and non-selective. The latter (propranolol, pindolol, sotalol) are practically not used in cardiology today [8].

Modern cardioselective beta blockers (metoprolol, bisoprolol, betaxolol and others) exhibit a complex of cardiovascular effects [8]. They lower heart rate and reduce the activity of the renin-angiotensin-aldosterone system by blocking renin synthesis in the kidneys. Thus, they exhibit antianginal and antiarrhythmic effects, and also reduce blood pressure.

Indications and properties

Drugs in this group are indicated for long-term treatment of hypertension with concomitant angina, as well as for treatment after myocardial infarction and for certain types of arrhythmia.

However, beta blockers also have a significant drawback: they do not affect the incidence of cardiovascular events and arterial stiffness, and also do not have a beneficial effect on the condition of target organs [8].

Individual representatives

• Bisoprolol is one of the most popular selective β1-blockers. Provides controlled dose-dependent blood pressure reduction. Due to its high selectivity, it can be used in special groups of patients - patients with diabetes and patients with lipid metabolism disorders [9].
• Carvedilol is a drug that stands out from a number of selective biologically active agents. Shows an additional vasodilating effect. It blocks β1- and β2-receptors, as well as (slightly) α1-receptors of peripheral arteries, helping to reduce peripheral vascular resistance and a more pronounced decrease in blood pressure compared to other representatives of this group.
• Nebivolol is a new generation beta blocker with high selectivity for β1-adrenergic receptors. It has a direct vasoconstrictive effect by stimulating the production of nitric oxide by the vascular endothelium. It is tolerated significantly better than other beta blockers [9].

Portability

BBs can have a number of side effects that negatively affect the quality of life. Among them:

• heart rhythm disturbance;
• neurological reactions - depression, insomnia;
• dyspeptic symptoms - nausea, vomiting, constipation or diarrhea.

1 male patient out of 199 develops erectile dysfunction while taking drugs of this group [8].

What should I warn the client about?

Visitors, having studied the instructions for use and familiarized themselves with the impressive list of side effects, may doubt whether it is worth taking such a “harmful” drug. The primary goal is to explain that if there are indications (arterial hypertension due to coronary heart disease, cardiac arrhythmias, heart failure, migraine, pregnancy, glaucoma), the benefits of taking beta blockers are much higher than the potential risk of side effects. In addition, according to research, only 3–5% of patients cannot take drugs from this group due to developing adverse reactions [8].

Lymphedema6

6Div. also the article by Lymphedema

. – Medicine for the world. – 2004. – T. XVII. – Part 2. – pp. 77–86. (Note switch)

The term “lymphedema” refers to a set of conditions that are characterized by excessive regional accumulation of protein-rich substances in the interstitium. Distinguish between primary and secondary lymphedema (in the world, the lymphoma is more frequent and develops with filariasis). In the USA, lymphedema is most often treated after removal of the axillary lymph nodes (up to 80% of patients after this operation).

Differentiating lymphedema from other forms of swelling is important, especially in the early stages. The presence of lymphedema is indicated by Stemmer's sign, a bump on the dorsal surface of the foot with a “square” appearance of the toes. To confirm the diagnosis, CT or NMR can be performed (sensitivity to human NMR, lower CT). Lymphedema can be distinguished from other types of swelling due to the presence of the characteristic “honeycomb” structure of the subcutaneous fat cells.

Indications for treatment include an increase in arm circumference by 2 cm, equal to the preoperative period. It’s a very difficult time to stop wearing a tight garment, to carefully look behind the skin, to stop the weakening of arterial pressure and the squeezing of an injured end. Effective measures may include physical exercises, looking after the skin, wearing compression panties or mittens, comprehensive anti-abdominal physiotherapy, a two-phase process of special manual massage and drainage of lymph nodes. At the early stages of the disease, diuretics may be effective; Prote then the stench rarely helps. Surgical treatment is less effective, but can ensure a change in the volume of endocrine tract in patients with an important form of elephantiasis.

Prepared by Bogdan Boris