Angiotensin receptor blockers Antagonism of receptors in angiotensin II. Wholesome education and receptor

In 1998, 100 years of age were accepted by the Swedish physiologist R. Tigerstedt. Mayzhe, 50 years later, in 1934, Goldblatt and the author on the model of renal hypertension first brought the key role of this hormone in the regulation of arterial grip. The synthesis of angiotensin II by Brown-Menendez (1939) and Page (1940) was one of the best ways to assess the physiological role of the renin-angiotensin-new system. The development of the first ingibitoriv of the renin-angiotensin system in the 70s (teprotid, saralazin, and later - captopril, enalapril, etc.) An offensive approach was the z'єdnan stem, selectively blocking the angiotensin II receptor. Їх vibration blockade є a fundamentally new approach to the weakening of negative effects of activation of the renin-angiotensin system. The development of these drugs has shown new perspectives in the treatment of hypertension, heart failure, diabetic nephropathy.

Apparently, the main effector hormone of the reninangiotensin system and angiotensin II is established in systemic blood flow as a result of a cascade of biochemical reactions. In 1954 L. Skeggs and the group of fahivts from Cleveland were established, that angiotensin representations in circulating blood are of two forms: in the viglyad, the decapeptide and octapeptide, which were later called angiotensin II, and angiotensin II.

Angiotensin I is established as a result of the third generation of angiotensinogen, so that it becomes viral by liver cells. The reaction is good for the day. The inactive decapitation should be given to the ACE injection and, in the process of chemical transformation, will be converted into the active octapeptide angiotensin II, which is a straining vasoconstrictive factor.

In addition to angiotensin II, physiological effects of reninangiotensin systems and healthy development are more biologically active. The most important of them is angiotensin (1-7), which is important for angiotensin I, and also (in the smaller world) - for angiotensin II. Heptapeptide (1-7) has a vasodilating and antiproliferative effect. On the secretion of aldosterone win, on the form of angiotensin II, not injected.

Before the infusion of proteinases with angiotensin II, there are more active metabolites - angiotensin III, or angiotensin (2-8) and angiotensin IV, or angiotensin (3-8). The processes associated with angiotensin III are related to the induction of the arterial vise - stimulation of receptors in angiotensin and the establishment of aldosterone.

Before the last two ten years, it was shown that angiotensin II does not occur only in systemic blood flow, but in young tissues, in fact, all components of the renin-angiotensin system (angiotensinogen, reninorin, APF, angiotensin) angiotensin II. The significance of the tissue system is summed up by the leading role in the pathogenetic mechanisms of the formation of ailments heart-vascular system on organ pivni.

Aside from the concept of the two-component reninangiotensin system and the systemic lance, to introduce a specific role in the physiological effects... The tissue lanka of the reninangiotensin system will not provide for a precondition for the function and structure of organs. Vasoconstriction and development of aldosterone in response to stimulation with angiotensin due to inert reactions, which occur in a matter of seconds, probably to the other physiological roll, as a polyagus in the blood degradation Іnshі efekti - hypertrophy of the myocardium, heart failure - develops by stretching trivial period. For the pathogenesis of chronic ailments of the heart-vascular system and general indications, it is more important, less important, it is realized by the systemic lance of the reninangiotensin system.

The size of the ACE-fallow conversion of angiotensin I into angiotensin II was established by an alternative way of education. Bulo vyavleno, which accumulated angiotensin II is trivial, unaffected by mayzhe I will blockade APF for the help of the yogi ingibitor enalaprilu. In a given bulo, it was installed, on the basis of the tissue lanka of the reninangiotensin system, and the approval of angiotensin II was introduced without the participation of ACE. Conversion of angiotensin I into angiotensin II is helpful for the participation of the other enzymes - tonin, chemistry and cathepsin. These specific proteases are not only converting angiotensin I into angiotensin II, but to split off angiotensin II without the participation of renin. In the organs and tissues of the conductor, they occupy the independent form of the APF, the way of approving angiotensin II. So, in the myocardium of people, close to 80% of them get accepted without the participation of ACE.

Angiotensin II Recipe

The main effect of angiotensin II is through its interaction with specific cell receptors. In the given hour, a few types of angiotensin receptors have been seen: AT 1, AT 2, AT3 and AT4. In humans, only AT 1, - and AT2-receptor is revealed. The first type of receptor is divided into two subtypes - AT1A and AT1B. Earlier, they respected that AT1A- and AT2B-type are only from the creatures, albeit, in the Danish hour, the stench is identified and from the people. The functions of the isoforms are still not clear. AT1A receptors prevail in cells of smooth oysters of sudins, heart, lungs, ovaries and in hypothalamus. The overhaul of AT1A receptors in the smooth meat of the Sudin indicates their role in the processes of vasoconstriction. In connection with this, the AT1B receptor prevails in the supra-nirkoval lobes, the mother, the anterior lobe of the hypophysis, it is possible to take into account that the stench is obtained in the process of hormonal regulation. The manifestation of AT1C is transmitted to the type of receptors in grisunas, however, the exact localization has not been established.

As a matter of fact, all of the heart-suckers, as well as extracardiac effects of angiotensin II, are mediated importantly through the AT1 receptor.

Smells appear in the tissues of the heart, liver, brain, nirok, nadirniki, uterus, endothelial and smooth cells, fibroblasts, macrophages, peripheral sympathetic nerves, in the conductive systems of the heart.

About the AT2 receptor is less significant, less about the AT1 type receptors. The AT2 receptor was first cloned in 1993, and its localization was established on the X chromosome. In mature organisms, the AT2 receptor is present in high concentrations in the cerebral ball of the supra-nirkoval corpuscles, in the mothers and in the cells, and the stench appears in the forehead, heart and other areas of the brain. In the membranous tissues, the AT2 receptor is represented significantly wider, lower in older adults and in them more transferable. The AT2 receptor is not in a bad state of health and becomes active in case of singular pathological conditions, such as myocardial ischemia, heart failure, and abnormalities. Those with the AT2 receptor are the most widely represented in the tissues of the fetus and their concentration decrease sharply in the first period of life, to indicate their role in the processes associated with cell growth, differentiation and development.

Vvazayut, that AT2-receptor will mediate apoptosis - the bend of the cell is programmed, as it is a natural inheritance of the processes of differentiation and development. The establishment of a wide stimulation of AT2 receptors produces antiproliferative effects.

AT2 receptors are used as physiological counterparts to AT1 receptors. Obviously, the stench controls the overwhelming growth, the mediations through the AT1 receptor, or is the factor of growth, as well as the vasoconstrictive effect of stimulating the AT1 receptors.

Vvazayut, the main mechanism of vasodilatation during stimulation of AT2 receptors is the approval of nitrogen oxide (NO) endothelium sudin.

Efekti angiotensin II

heart

The infusion of angiotensin II on the heart will start directly, and so it will be mediated - through the promotion of the sympathetic activity and concentration of aldosterone in the blood, the improvement of post-vasoconstriction. Direct action of angiotensin II on the heart of the pole in effect, as well as in the growth of cardiomyocytes and fibroblasts, as well as myocardial hypertrophy.

Angiotensin II takes part in the processes of progression of heart failure, viciousness of such unpleasant effects, such as admission to the myocardium as a result of venoconstriction and soreness of blood vessels in the onset of heart disease aldosterone-dependent reception of birth in the body, which leads to an increase in the amount of circulating blood; activation of sympathoadrenal system and stimulation of proliferation and fibroelastosis processes in myocardium.

Sudini

Together with AT, receptors for sudin, angiotensin II, a vasoconstrictor action is necessary, which leads to an arterial clutch.

The increase in OPSS in the course is also augmented by angiotensin II hypertrophy and hyperplasia of smooth blood cells, hyperproduction of colagen by stinky bladder, stimulation of endothelium synthesis, as well as the reduction of NO-relaxation.

Vasoconstrictor efficacy of angiotensin II in different parts of the vessel channel is not the same. Vasoconstriction is often infused into AT, the receptor is stimulated in the vessels of the neoplasm, nirok and shkiri. A lesser significant vasoconstrictor effect is manifested in the brain, legends, heart and skeletal muscles.

nirki

Nirkovi efekti angiotensin II play a very important role in the regulation of arterial grip. Activation of AT 1 receptors in nirok spriaє in the presence of sodium and, even more, in the organism. The whole process is realized for an additional increase in the synthesis of aldosterone and direct action of angiotensin II to the proximal viddil of the deciduous canaliculus of the nephron.

Sudini nirok, especially eferent arterioles, are highly sensitive to angiotensin II. Increasing the definitions of afferent nirkovy vessels, angiotensin II reduction of the nirk plasma flow and decreasing the fluidity of the glomerular filtration, and the reduction of the eventual arterioles with the decrease in the protein of the glomerular pressure appears.

The locally approved angiotensin II is an initial infusion on the regulation of the function of the nirok. Wine directly for nirkovy tubules, Advancing reabsorption of Na +, spraying fast mesangial cells, which changes the area of ​​the glomeruli surface.

Nervous system

Efekti, injected with angiotensin II on the central nervous system, manifests itself as central and peripheral reactions. Infusion of angiotensin on the central structure of the reaction to the arterial vise stimulation, stimulating the vasopressin and adrenocorticotropic hormone. Activation of angiotensin receptors peripheral species nervous system to produce up to the strength of sympathetic neurotransmission and the induction of noradrenal norepinephrine in the nerve endings.

The most important effect of angiotensin II is the stimulation of the synthesis and development of aldosterone in the glomerular zone of the upper body, participation in the processes of ignition, atherogenesis, regeneration. All the reactions play an important role in the pathogenesis of the disease of the heart-vascular system.

Drugs that block the angiotensin II receptor

Try to reach the blockade of the renin-angiotensin system on equal receptors for a long time. In 1972, the peptide antagonist of angiotensin II saralazin was synthesized; the protein did not know about therapeutic intake after a short period of time, partial agonistic activity and the need for internal administration. The basis for the stemming of the first non-peptide blocker of angiotensin receptors appeared to be a prelude to Japanese scientists, since in 1982 they disclaimed data on the evidence of the presence of an anti-inflammatory blockage of AT 1 receptor in older people. In 1988, a group of preliminaries on a group of R. Timmermans had synthesized a non-peptide antagonist to angiotensin II losartan, which became the prototype of a new group of antihypertensive diseases. Stagnate in the classroom since 1994

A number of AT 1-receptor blockers have been synthesized, and they have been used for the last hour. Smells are different in terms of bioavailability, level of absorption, growth in tissues, efficiency of elimination, in appearance or in the presence of active metabolites.

The main effects of AT 1-receptor blockers

Effectiveness of antagonists to angiotensin II is reinforced with specific receptors of the rest. With a high specificity and ability to use angiotensin II on equal tissues, the drugs will prevent more blockade of the renin-angiotensin system in some cases with ACE angiotensin. The prevalence of AT 1 receptor blockers in front of ACE inhibitors is also the prevalence of antibiotics in case of stagnation. Tse allow to uniquely such non-profit side reactions The accumulated bradikin, like cough and angioedema.

Blockade of AT1 receptors with antagonists of angiotensin II can lead to the suppression of the main physiological effects:

• vasoconstriction
• synthesis of aldosterone
• the development of catecholamines from the supra-nirkoval zalosis and presynaptic membranes
• seeing vasopressin
• support for the process of hypertrophy and proliferation in the syndrome of sudinus and myocardium

hemodynamic efficiency

The main hemodynamic effect of AT 1-receptor blockers is vasodilatation and, hence, a decrease in arterial pressure.

The antihypertensive efficacy of the drug is due to the specific activity of the renin-angiotensin system: in ailments with a high activity, the renin of the stench is greater.

Mechanisms, through the antagonism of angiotensin II, to lower the verdict, as follows:

• suppression of vasoconstriction and hypertrophy of the vascular disease, supplemented with angiotensin II
• decrease in reabsorption of Na + due to direct action of angiotensin II on the nirkovy tubules and through a decrease in aldosterone
• Usuniya sympathetic stimulation, enriched with angiotensin II
• regulation of baroreceptor reflexes for the formation of the structure of the reninangiotensin system in the tissue of the brain
• improvement instead of angiotensin, which stimulates the synthesis of vasodilator prostaglandins
• reduction of vivilnennya to vazopresin
• modulating diyu on endotheliy sudin
• Strengthening the approval of nitrogen oxide endothelium for the activation of AT2 receptors and bradykinin receptors we will advise circulating angiotensin II

All AT1 receptor blockers have been producing a trivial antihypertensive effect, which lasts 24 years. It will manifest itself after 2-4 working therapy and reaching a maximum of 6-8 working hours. The greater the number of drugs is applied to the dose of the arterial vise. The stench won't ruin your normal good rhythm. It’s obvious that there’s a great deal of caution, but when there is a trivial intake of angiotensin receptor blockers (lasting 2 rockets and more), it’s not possible to develop until the next day. Do not ricochet to "ricochet" the blood pressure. AT1 receptor blockers do not lower the level of AT, even though they are in the boundaries of normal values.

When using antihypertensive drugs of the other classes, it is meant that AT1 receptor blockers, producing an analogous antihypertensive effect, are less likely to suffer from side effects and are more painfully tolerated by ailments.

Diya on myocardium

A decrease in the level of arterial grip in the presence of AT 1 receptor blockers is not supervised to increase the frequency of the heart rate. It can be explained both by changes in peripheral sympathetic activity, as well as by the central drug in the way of adjusting the activity of the tissue lanka of the reninangiotensin system to the structures of the brain.

especially more important low blockade of the activity of the systemic system without mediocrecy in the myocardium and the spine, as well as the regression of the hypertrophy of the myocardium and the spine. Blockers of AT1 receptors do not only induce growth factors, which take place through the activation of AT 1 receptors, but inject onto AT 2 receptors. Suffocation of AT 1 receptors with increased stimulation of AT 2 receptors in response to an increase in the amount of angiotensin II in blood plasma. Stimulation of AT 2 -receptors in the process of growth and hyperplasia of smooth mucous membranes of sudin and endothelial clitins, and also induces the synthesis of collagen by fibroblasts.

Infusion of AT 1-receptor blockers on the processes of hypertrophy and remodeling of the myocardium is therapeutically significant for traction of ischemic and hypertensive cardiomyopathy, as well as cardiosclerosis in patients with ІHS. Experimental robots have shown how the preparation of a class can increase the coronary reserve. It is associated with this, that the amount of coronary blood flow is due to the tone of the coronary vasculature, the diastolic perfusion vise, the endometrial vise in the LSh-factors, modulated by angiotensin II antagonists. AT1-receptor blockers also neutralize the fate of angiotensin II in the processes of atherogenesis, reducing atherosclerotic lesions of the heart.

Diya for nirki

Nirki is a target organ in hypertension, it is infused into the function of AT1 receptor blocker. Blockade of AT1-receptors in nirkas with a decrease in the tone of the efferent arterioles and a decrease in nirk plasma flow. At the same time, the glomerular filtration does not change, but rather grows.

AT1-receptor blockers, allowing for the dilation of eventual nerve arteries, reducing the intra-glomerular pressure, as well as reducing the effect of angiotensin II (promoting the reabsorption of the function, breaking down nirkova lack... Prescriptions of a vibrational decrease in the tone of the eferent arterioles і, also, a decrease in the intra-glomerular vise, drugs to change proteinuria in ailments with hypertensive and diabetic nephropathy.

However, it is necessary to remember that in patients with unilateral stenosis of the nyrkovo artery, AT1 receptor blockers can suffer from an increase in creatine levels in the blood plasma and a deficiency.

The blockade of AT, receptors in the presence of natriyureticheskogo for the help of direct suppression of sodium reabsorption in the proximal tubule, as well as the induction of synthesis and vivification of aldosterone. A decrease in the amount of sodium reabsorption in the distal tubule with aldosterone to a certain diuretic effect.

Losartan, a single drug with AT 1-receptor blockers, to repair a dose-dependent uricosuric drug. The whole effect does not lie in the activity of the renin-angiotensin system and implantation kitchen salt... The mechanism of this is still not clear enough.

Nervous system

AT blockers, receptors control neurotransmis, induce peripheral sympathetic activity behind the additional blockade of presynaptic adrenergic receptors. With experimental intracerebral administration of the drug, the suppression of the central sympathetic views on the equal paraventricular nuclei is observed. As a result of the activity on the central nervous system, the increase in vasopressin decreases, and the response to sprague decreases.

Shown before consumption of AT 1-receptor blockers and side effects

In a given hour, one is shown to the intake of AT 1 receptor blockers є AG. Associativity in patients with HLS, chronic heart failure, diabetic nephropathy will be clarified in the process of clinical viprobuvan.

Due to the peculiarity of the new class of antihypertensive drugs, it is good, appropriate for placebo, tolerance. Vicious Effects with їkh stasosuvannі, it is a sign that it is higher, lower with vikoristannі. As a matter of fact, the accumulation of antagonists to angiotensin II does not lead to accumulated bradykinin and the appearance of a zoomed cough. Significantly, it is much faster to promote anxiety and neuroticism.

similar іngіbіtorіv APF, Tsi kosty can viklicati to achieve a decrease in AT in reninzolezhnaya forms of hypertension. In ailments with two-sided ringing of nirk arteries, the function of nyrok is more powerful. In patients with chronic nircovy deficiency, the development of hyperkalinemia is associated with the associated vivification of aldosterone in the process of treatment.

Stagnation of AT 1-receptor blockers in the period of vaginosity has been suggested, in connection with the possibility of the development of the fetus and its bend.

Unaffected by the guesses nezazani efekti AT1-receptor blockers are best tolerated by a sick group of antihypertensive drugs with the lowest frequency of development of side reactions.

Antagonism of AT1-receptors is good to be used practically with groups of antihypertensive agents. Especially effective їх day with.

losartan

It is the first non-peptide blocker of AT1 receptors, which has become the prototype of a class of antihypertensive drugs. In the absence of benzyl imidazole, it has no low agonistic activity to AT 1 receptors, which is 30,000 times more active than AT2 receptors. The period for which losartan is consumed is short - 1.5 2.5 hours The main biological effects of losartan are supplemented with a cyme metabolite. Yak and losartan, vin is characterized by a high selectivity to AT 1 receptors and a high agonistic activity.

The bioavailability of losartan in the middle becomes only 33%. Yogo vivedennya zhivchuyu (65%) and slice (35%). The impairment of the function of nirok is a slight infusion on the pharmacokinetics of the drug, so that in case of liver dysfunction, the clearing of both active agents changes, and the concentration of them in the blood moves.

Those who authorize it, so that the dosage of the drug more than 50 mg has been adjusted for an additional antihypertensive effect, so that they have spared more and more than a decrease in the arterial tension when the dosage is added 100 mg / day. Further, do not adjust the dose until the effectiveness of the drug is adjusted.

Great hopes were tied to the losartan stagnation in the sick with chronic heart failure. For example, data from ELITE (1997), in which losartan therapy (50 mg / dose) for 48 months, reduced the risk of death by 46% in patients with chronic heart deficiency, received an additional 50 mg, 3 times. The tests were carried out on a small contingent (722) ailments, and on a larger scale ELITE II (1992), which included 3152 patients. Met with bulo vivchennya injected losartan on the prognosis of ailments with chronic heart failure. However, the results of the last few days did not confirm the optimistic prognosis - the mortality rate of ailments on the basis of captopril and losartan was practically the same.

irbesartan

Irbesartan is a high-specific AT1 receptor blocker. The chemistry structure of the wines should be followed up to the old ones. Volodya has a high spore rate to AT 1 receptors, 10 times more for the selectivity of losartan.

In case of an antihypertensive effect of irbesartan at a dose of 150-300 mg / day and losartan at a dose of 50-100 mg / day, it is prescribed, after 24 years, when irbesartan is taken to be taken, it is lower in DAT, less losartan. After 4 long-term therapies, adjust the dose to reach the whole level of DAT (<90 мм рт. ст.) потребовалось у 53% больных, получавших ирбесартан, и у 61% пациентов, получавших лосартан. Дополнительное назначение гидрохлоротиазида более значительно усилило антигипертензивный эффект ирбесартана, чем лосартана.

In the number of pre-adolescents, it was established that the blockade of the activity of the renin-angiotensin system would cause the disease in patients with hypertension, diabetic nephropathy and proteinuria. The basis of the effect is to use an active drug for all the mediated nirkovy and systemic angiotensin II. The order of the systemic reduction of the arterial grip, which is itself, by its own means, can be used, the neutralization of the effects of angiotensin II on the organic level of pressure, the lowering of the support of the relevant arterioles. Tse to reduce the intraglomerular vise with further changes in protein. It can be found that the renoprotective effect of AT 1-receptor blockers can be more significant, but not the effect of ACE inhibitors. AT1-receptor blockers selectively act on equal to AT1 receptor, more often block the renin-angiotensin system in the tissue nirok, so as to switch the effects of angiotensin II in any way.

Renoprotective irbesartan was injected in some pre-older children with hypertension and type II diabetes with proteineuria. The drug changes the proteinuria and promotes the processes of glomerulosclerosis.

In a given hour, clinical follow-up is carried out with the introduction of a renoprotective drug to irbesartan in patients with diabetic nephropathy and hypertension. In one of them, IDNT, there is an increase in the efficiency of irbesartan and amlodipine in patients with arterial hypertension on the basis of diabetic nephropathy.

telmisartan

Telmisartan ingibu AT 1 receptor, 6 times more than losartan. It is a lipophilic drug that penetrates into the tissue.

The test of the antihypertensive efficacy of telmisartan with some other means of showing that it is not a fault of theirs.

The effect of the telmisartan is to be deposited in the first dose. Adjustment of additional dosage from 20 mg to 80 mg of supernatant can be used for two doses for GARDEN, as well as for more than a hundred changes in DAP. An adjustment dose of more than 80 mg per dose does not give an additional reduction in the arterial grip.

valsartan

The rate of decrease in SAT and DAT is infused after 2-4 regular doses, both of which are blockers of AT 1 receptors. Strengthening the effectiveness of spostering in 8 times. If you need to monitor AT to reduce, valsartan will not disrupt the normal circadian rhythm, but the T / P index, according to the annual data, is 60-68%. Efficiency is not stale in all stati, vіku and raci. Valsartan does not act on the antihypertensive efficacy of amlodipin, hydrochlorothiazide and lisinopril, which overturned the tolerance.

In the pre-season VALUE, which was published in 1999 and including 14,400 ailments from the AG from 31 regions, an analytical assessment of the effectiveness of the infusion of valsartan and amlodipin on the dots to allow the nutritional intake of the drug acceleration in patients with hypertension due to diuretics i.

Tse drugs, such as acting on the renin-angiotensin-aldosterone system. Smell block type 1 angiotensin receptors and assimilate such effects of angiotensin II, such as vasoconstriction, aldosterone secretion, vasopressin, noradrenaline, sodium and urinary tract remodeling As a result, it realizes hypotensive, antiproliferative, sodium ureteral antagonism of angiotensin II receptors.

In Danish hour, the Sartan group is represented by a choirma by food groups, which follow a chemical structure:

biphenylated tetrazole (losartan, irbesartan, candesartan);

non-phenylal tetrazole (telmisartan);

non-phenylate nettetrazoli (epprosartan);

non-heterocyclic z'єdnannya (valsartan).

Losartan and candesartan є by means of and through their active metabolism, which are set up for conversion into the liver, the solution of the preparation є without a mediocre active forms.

ARBs are also developed due to the nature of the binding to the receptors. Losartan, valsartan, irbesartan, candesartan, telmisartan dyut at the AT receptor as a non-competitive antagonist of AT II, ​​and prosartan, navpaki, as a competitive antagonist of AT II. All ARBs are characterized by a temporal affinity to the AT receptor, which transmutes AT II in a thousand times. The blockade of the RAAS, which can be reached beyond the help of the sartans, is as much as possible, the fragments of the injection on the specific receptor of AT II, ​​which can be seen not only behind the main, but also along the additional lines. Selective action on the AT II type 1 receptor will follow the sparing metabolism of enkephalin, bradikin and other biologically active peptides. It also means that the adjustments to the activity of the kininovy ​​system and the tying are not necessary for the IAPF, like dry cough and angioedema. Deyak representatives of the class may have additional power: agonism to PPARγ receptors, which is indicative of the sensitivity of peripheral tissues to insulin, uricosuric effect, and a healthy sensation of a sympathetic nervous system. It is possible, especially for metabolism and pharmacology, to clarify the specificity of the drug on the organism, to summarize those that the effect of any specific drug cannot be transferred to the group as a whole. However, already at present, at the presentations of the results of the great classics, it is possible to show the manifestation of all sartans of the home, class, defects, the head of which is stable and trivial control of the arterial grip. In addition, in a whole series of recent boules eliminated additional blood pressure-independent organoprotective effects: cardioprotection, Zakhist nirok, neuroprotection and polyglycemic control.

show:

the period of myocardial infarction;

microalbuminuria / proteinuria;

nephropathy in diabetes mellitus II;

hypertrophy of the lilac duck;

fibrillation of the anterior;

metabolic syndrome;

intolerance to IAPF.

With the efforts of the ARRA group, we are most likely to vivify in the experiment and clinical study of losartan. For new indications, the whole spectrum of positive effects in children with pathological conditions and itself is an exemplary drug, if we speak about the group as a whole.

Vicious Effects

Angiotensin II receptor blockers are very rare in adverse effects. All the changes are lower in some cases.

On the side of the heart-vascular system - orthostatic reactions, heart disease.

On the side of the intestinal tract - diarrhea, dyspepsia, nudota.

On the side of the central nervous system - headache, zapamorochennya, asthenia, depression, sudom.

On the side of the blood - neutropenia, a decrease instead of hemoglobin.

On the side of the organs, there is pharyngitis, bronchitis.

Allergic reactions.

On the side of the cystkovo-muscular system - mialgia, pain in the back, arthralgia.

Hypercalcium, adduction of alaninaminotransferase (ALT).

Prototype indications:

availability,

hyperkalієmiya,

Individual intolerance.

telmisartan also contraindications we are ill with the obstruction of zhovchividnyh shlakhiv.

lykarska vzaєmodiya

There is no need for a single preparation of drugs in the whole group with preparations of calories and calcium-free diuretics.

you can combine

The whole group of drugs can be combined practically with any other antihypertensive drugs, however, with a two-component scheme of treatment, a combination of diuretics or calcium antagonists is used. Moreover, for all presentations on the market of sartans, there are ready-made lykarsky forms with the diuretic hydrochlorothiazide.

As a prophylaxis, as well as the treatment of heart-vascular disease in the course of a general and serious approach. This kind of problem is more and more frequent for people. To that, it’s very easy to put a lot of schilia before them. Such people often call out to ignore the need to pass and take drugs, or to take drugs without a sign of a drug (for the joy of those who know). However, it is important to remember: those who, as a Likarskiy, helped him, are absolutely not a guarantor, who will help you. For the formulation of the scheme, it is necessary to have enough knowledge, a little bit of knowledge, which can be used only. It is also possible to indicate whether a preparation is possible, only if it is an individual specific to the patient's organism, the degree of severity of illness, the particularity of the disease and anamnesis. Until then, there are many year-round, ineffective politicians, children, and signs that there can be only fakhivtsi. For example, it should be referred to as sartans - a special group of lykarsky speeches (they are also called angiotensin 2 receptor blockers). What are the drugs? What are the blockers of angiotensin 2 receptors? Is the prototype shown before the registration of words to be referred to any groups of patients? In what kind of vipadki bulo used to be pre-echno zastosovuvati? What preparations are included in the given group of words? The information on all nutritional actions will be detailed in the given statistics.

Sartana

Already, the group of speeches is also called the offensive rank: blockers of receptors for angiotensin 2. Drugs that are introduced to the whole group of lykarsky zasoby, bully zrobleny zavdyaky in the development of reasons for the diagnosis of heart disease systems - trial. The current status in cardiology will continue to grow.

Angiotensin 2 receptor blockers: mechanism of action

First of all, you need to register the liquor, it is important to return, as the stink of the day itself. Yakim rank injecting angiotensin 2 receptor blockers on human organisms? The drugs of this group are linked to receptors, blocking in such a rank the meaning of the arterial grip. Tse additional help effectively to prevent hypertension. Angiotensin receptor blockers 2 are the most common ones. Fakhivtsi come to me with great respect.

Angiotensin 2 receptor blockers: classification

There is a small collection of types of sartans, who are developing for their chemistry budova. There is a good chance of vibrating the patient's receptor blockers for angiotensin 2. Preparations, the list of which will be given below, it is important to inform and discuss the correctness of the receptor in your preferred drug.

Otzhe, see the chotiri group of sartans:

• Biphenylated tetrazole.
• Non-phenolics of tetrazole.
• Nebiphenyl nettetrazole.
• Non-cyclic spoluks.

In such a rank, the number of types of rechovins, on which blockers of receptors in angiotensin 2 are added. The drugs (list of the main ones) are presented below:

• "Losartan".
• "Eprosartan".
• "Irbesartan".
• Telmisartan.
• "Valsartan".
• "Candesartan".

Shown to sucking

Accept the speech of this group is possible only for the signs of the lykar. There is a small number of vipads, in some buckets it is reasonable to use angiotensin receptor blockers.

• Hypertension. Itself is given to become ill-fated to vvazhayut the head shows to the zasosuvannya sartans. This is due to the fact that blockers of angiotensin receptors 2 of the statistic do not cause negative influences on the exchange of words, do not provoke reactive dysfunction, and do not destroy bronchial passages. The drug will be repaired in two-time intervals after a cob of treatment.
• Sertseva's lack. Angiotensin 2 receptor blockers induce diu-angiotensin-aldosterone system, which activity and provoke development of sickness.
• Nephropathy. As a result of diabetes mellitus and arterial hypertension, serious damage occurs in the function of nirok. Angiotensin 2 receptor blockers seize internal organisms and do not allow vivodity back to back.

"Losartan"

It is not effective to talk about entering a group of sartans. "Lozartan" is a blocker-antagonist of receptors in angiotensin 2. The number of other drugs in question is increased to a physical extent in people who are suffering from heart deficiency. The speech flow becomes maximum even after six years from the moment of reception. Bazhaniy effect is reached through the three-set of prescriptions for the preparation.

The main ones are shown to the victorian of the given lykarskiy zasobu є nasty:

• heart failure;
• arterial hypertension;
• Change in risk of development of insult among quiet patients, for those who change their minds before tsyogo.

It was buried vikoristovuvati "Lozartan" during the period of the child's marriage and before the hour of breastfeeding, as well as in the case of individual sensitivity to certain components in the preparation.

Receptor blockers in angiotensin 2, before which are recognized by dana lykarskiy zasib, may be viciously potent, such as zamorochennya, sleeplessness, sleep deprivation, relish, zoru, tremor, depression, discouragement, bronchitis, farytitis, gastritis, dental bile, diarrhea, anorexia, bloating, sudomy, arthritis, bile near the shoulders, in the back, legs, heart disease, anemia, impaired function of nirok, impotency, weakening of libido, erythema, alopecia, fever, , hyperkalієmiya.

Take the drug once per day, as usual, in doses determined by the drug.

"Valsartan"

Daniy Likarskiy is effective in reducing myocardial hypertrophy, as a result of the development of arterial hypertension. The syndrome of susceptibility to drug intake does not appear, if one wants to fail and blockers of angiotensin 2 receptor blockers (describe a group of sartans to help them recover, until they have the power to eat).

The main indications before the given speech are: myocardial infarction, primary or secondary hypertension, congestive heart failure.

The tablets are taken orally. Oh slid kovtati, not rozzhoyuchi. The dose of the drug is indicated by the drug. Ale, the maximum number of words, as you can accept with a stretch of dob, become six hundred and forty milligrams.

An hour you can put pressure on the organism and negative infusion of receptor blockers in angiotensin 2. Minor efficacy, such as Valsartan: decrease in libido, sverbіzh, loss of weight, neutropenia, loss of loss of quality, loss of sleep, sinusitis , b_l at the back, vertigo, nudota, vasculitis, nabryaki, rhinitis. In the event of a disagreement, whether or not they are overwhelmed by the reactions, they will inaccurately turn up to the point of failure.

"Candesartan"

The drug is taken from viglyadі tablets for oral administration. You need to take one or two times a day at the same hour, right from the reception. It is necessary to readily follow the recommendations of the fahivts. It is important not to take the drug, if you are becoming more beautiful. At the same time, the efficiency of the school's work can be reduced.

When you are victorious, take care of your children, who are suffering for a child's diabetes, or a lack of a child. About all the countries it is necessary to find out about them.

"Telmisartan"

Razglyanutiy drug soak from the shlunkovo-intestinal tract in a short term. Yogo can be accepted right from the reception. The head is shown to the arterial hypertension before the stasis. The period for which Likarskiy was born will be about twenty years. The drug is vivodil through the intestines in a practical way.

It is forbidden to take a look at the doctor during the period of vaginosity or breast cancer.

The drug may suffer from such side effects: sleeplessness, spoilage, nudity, diarrhea, depression, abdominal pain, pharyngitis, visipus, cough, malgia, infection of other malignant habits, anxiety of breast pains

"Eprosartan"

Look at the lykarskiy slid once a day. It is recommended that the amount of the drug for a one-time consumption is to become sixty milligrams. The maximum effect is reached through two or three tizhni vicistories. "Eprosartan" can be a part of complex therapy, as well as a head component of monotherapy.

In any case, it is impossible to look at the likars' time of lactation or vaginosity.

What kind of side reactions can you win with the vicorianna of "Eprosartan"? Among them, I see the following: weakness, diarrhea, zapamorochennya, headache, rhinitis, cough, bad hair, nagging, chest pain.

"Irbesartan"

Take the drug orally. Wine in a short hour gets wet from the intestinal tract. The maximum concentration of speech in the blood is infused even after two or three years. The trick does not add to the efficiency of the leads.

Hemodialysis is assigned to the patient, but it does not flow into the mechanism of the "Irbesartan" production. The word is given not to be involved in the body of people for additional hemodialysis. Let's take the rank of the drug, without beating the patient, who suffer from liver cirrhosis of the lung or the middle degree of severity.

Lykarskiy zasib slid kovtati, who do not worry. Yogo stasis is not required for yogic reception. Optimum cobbing costs one hundred and fifty milligrams for doba. Lіtnіm patients recommend repairing a trip in seventy milligrams. In the process of treatment, your doctor can take a decision about the change of dosage (for example, about її improvement for thinking about the lack of therapeutic injected into the body). In general, the patient can indicate by taking three hundred milligrams of a drug, or in principle, replace the basic drug. For example, for the treatment of ailments to another type of diabetes and arterial hypertension, the dosage of the next step changes from one hundred to fifty youngsters to add up to three hundred youngsters for the most effective medications

See the singularity of the singing out of the lykarsky zasobu. So, for patients who suffer from water-electrolyte balance breakdowns, it is necessary to have a deyaky manifestation (hyponatremia) until the ear of a drink.

If people are more likely to have a deteriorating function, then this scheme of treatment can be the same, as there were no other problems. Those are afraid of hepatic dysfunction of the lung and middle stage. At the same hour, with a one-hour hemodialysis of the pochatkova, the amount of the drug was to be blamed for but changed in proportion to the occasional one and to store seventy and five milligrams per day.

"Irbesartan" is strictly a contraindication for vicarious women, who blame the child, as it is infused directly into the process of development of the fetus. As soon as the stay came at the time of the therapy, I will remain innocently skasuvati. It is recommended that you switch to alternative medications prior to your pregnancy planning. The drug is taken out during the period of breastfeeding, since there is no information about the fact that the speech is given into breast milk.

Baby bags

Pidtrimuvati your health is a special dressing of skin people. Those who are older than vik, those who are more likely to get a report. However, the pharmaceutical industry needs a whole lot of unappreciated additional help, gradually working over the roots of more thorough and more effective drugs. In addition, they are actively involved in the fight against heart-and-heart disease and are seen in the statistics of angiotensin 2 receptor blockers. the health of the patient, and only under continuous control. Among such likarsky zasobіv see "Lozartan", "Eprosartan", "Irbesartan", "Telmisartan", "Valsartan" and "Kandesartan". It means to look at the preparations only in the onset of symptoms: with the manifestation of hypertension, nephropathy and heart failure.

At the time of self-indulgence, it is important to remember about the security, which is tied to the tsim. In the first place, with the victorious outliers of the lykarskis, it is important to accurately see the dosage and hour from the hour of the coriguvati in the fallowness from the flow camp of the patient. Carry out all the procedures in the correct order only by a professional. So, as only an eligible drug, you can, on the basis of the situation and the results of the analysis, indicate the pre-English dosage and formulate the scheme of the remedy. And the therapy will be effective only in the same way, if the patient will receive the recommendations of the doctor.

From the side, it is important with all the strength of the power to take the polish of the strong physical camp by the gentry to take the rules of a healthy way of life. Such patients need the correct order to speed up their sleep and sleep regimes, and also get enough food in the morning.

Select the tags. Take care of yourself and your loved ones. Good luck!

Tobto stink:

lower opir arteriol,

increase the venous blood pool,

increase the heart wikid, heart index,

reduce Renovascular opir,

to produce up to an increase in natiyureza (excreting sodium from a cross-section).

The concentration of the renin in the blood grows for the negative vocal link between the re-incarnations of AI in the AII. The level of angiotensin I also grows for a similar reason. The number of AII and aldosterone - to change, todi like bradykinin - to grow up for the reduction of its activation, as it is good for the participation of the ACE.

In the wicked minds, angiotensin II can be infused into the body:

1. Dіє yak vasoconstrictor (sound of blood-bearing judgment).

As a result of such an inflow, there is an increase in the arterial grip and arterial hypertension appears. In addition, the ringing of the eferent arteriol nirok should be produced until the perfusion vise in the glomeruli of the organisms is increased;

2. Make up to remodeling (change of size) and hypertrophy of the heart;

3. Lead to the activation of the processes of communication The bark of the supernatant is aldosterone, a hormone, which is in the nirkovy tubules and to produce sodium and chloride in the organisms and to produce excreted calories. I will squeeze the water, so that it can be brought up to an increase in blood volume, and, apparently, before the arterial grip.

4. Stimulate the back part of the hypophysis It leads to vasopressin (which is also called antidiuretic hormone (ADH)) and to produce water through the inflow to the nirki.

5. Znizhu rіven nirkovo ї proteinіnkіnazi.

Stagnation of angiotensin ACE decreases in angiotensin II, in the event of a decrease in blood pressure.

Mechanism of the renin-angiotensin-aldosterone system on organism and infusion on it ingibitoriv ACE.

Epidemiological and clinical studies have shown that the Angibitorium of ACE is associated with the development of diabetic nephropathy. The whole mechanism of development of the ACE Ingibitoriv, ​​vikoristovuyutsya for the prevention of diabetic nirkovo disability.

You can also say that the ACE is not effective only for the treatment of hypertension, but for the improvement of symptoms in people with a normal arterial grip.

Victory of the maximum dose of ACE for such ailments (including for the prevention of diabetes, congestive heart failure, prevention of heart disease).

Take a likuvannya call me vimag direct and incremental titration of the dose the drug, in order to keep the inheritance of a sharp decrease in the arterial grip (zapamorochennya, vrata svidomostі and іn).

Angibitorium ACE also affects the adjustment of the activity of the central parasympathetic system in healthy people and people with heart failure, with which the variability of the heart rhythm increases. There can be a change in the broadening of evil destructions to the rhythm of the heart and speed of the rapid death of people.

One of the ingibitoriv APF - enalapril also fast heart cachexia in ailments with chronic heart failure.

cachexia- tse duzhe pogoschny prognostic signs in children with chronic heart failure. Angibitories of the ACE in the Danish hour are also victorious in order to show weaknesses and atrophies in young patients without heart failure.

Vicious Effects.

Typical side reactions that occur when an IAPF is implanted include:

hypotension

• hyperkalemia

  head b_l

  dirty

  vtoma

• nirkovu lack.

Dany of the people who have passed the time will also apply to those who are able to use the ACE in the form of an ignition process.

A persistent dry cough is an alarmingly frequent side effect of the IAPF, which, as a result of getting involved, of dressings for children in the education of bradikin, would like the role of the role of speech in the process of surviving children. Patients who have coughs, often repair angiotensin II receptor antagonisms.

The loss and destruction of savory appearances, which are rarely seen when there are large ACE ingibitors, is often seen when captopril is implanted and explained by sulfhydryl particles. The same reason for the change in the frequency of captopril in the clinics, I want the drug to become more and more vicious in the scintigraphy of nirok.

One of the best side effects dії vsіh іngіbіtorіv ACE Je nirkova nedostatnіst reason viniknennya yakoї sogodnі to kіntsya not vіdoma. Deyak pre-glazed vvazhayut, well, tied with them injected on indirect homeostatic functions of angiotensin II, such as nirkovy blood circulation.

Nirkovy blood circulation can be damaged through the action of angiotensin II, an enzyme that sounds efferent arterioles of glomeruli nirok, increased by ourselves the speed of glomerular filtration (GFR). In such a rank, the very reduction of the level of angiotensin II, angiotensin II, angiotensin ACE can change the GFR, as it is a good indicator of the functionality of nirok.

If you say more accurately, the ACE ingibitories can be vicious or irritated by the nirkov deficiency in patients due to stenosis of the nirk arteries. Especially the problem of getting involved is, if the patient immediately takes NPZP (Not steroidal antiapaline drugs) and sechogy. At the same time, the implantation of three medications is also parallel to the development of nirk deficiencies.

Besides, it is obvious that the Angibitorium of the ACE can lead to hypercalculation. Stifling angiotensin II to reduce the level of aldosterone, which in its own mind thinks for the adjustment of extra calories, and, in fact, the angiotensin of the APF in the end organ can shut up the calories.

As well as the effect of turns around the world, then it can be important for the body, the protection of hypercalculation can reduce the rhythm and conductivity of the heart, as well as the importance of slowing down.

An important allergic reaction to drugs, which can be even worse, is infused on the intestinal lining and, apparently, can be in the stomach.

Likewise, at the children’s children, through the admission of the rivnya bradikininu, the nabryak Kvinke. However, it turns out that such a negative reaction of the viclikan to the genetic schism of the patient, and the bradykinin itself is split more often, is not guilty.

If vagіtnі women accept the ingіbіtori APF stretching out the first trimester of vagіnosti, then this may be the reason for the appearance of serious incidents of development, the people of dead children and the death of new women.

Expanded anomalies in the development of the fetus include:

hypotense,

Nirkov dysplasia,

Anuryi (oliguria),

low water,

Covering the intrauterine development of the fetus,

Legenev's hypoplasia,

Introduce the arterial duct,

I am not sure about the description of the skull.

Prototype

Angibitorium ACE contraindicated to patients with:

vinnennyam in the last embryo Kvinke, which is a dressing for the implantation of ingibitoriv APF;

stenosis of the nirkovo artery (bilateral or unilateral);

p_dvischenyu sensitive to the ingibitor_v ACE;

Іngіbіtori APF slіd zastosovuvati protects the patients from:

ruined functions of nirok;

stenosis of the aortic valve or damage to the heart;

hypovolemia or dehydration;

hemodialysis behind the membrane support high flow from polyacrylonitrile.

Angibitories of ACE should be applied to drugs in category D, Tobto їkh victoriannya to unicati women, who plan to be the closest hour of arrival.

In addition, in the instruction to the number of drugs, it is meant that the stench is very likely to cause the risk of birth defects, if they are taken in another, or the third trimester of vaginosity.

In the first trimester, it is also tied to the development of serious diseases, especially damage to the heart-and-heart and central nervous systems.

Prepare the calories slowly and even more carefully and for the sake of visualization of the drug, through the development of hypercalculations in the possession of the ingestion of the APF.

Classification.

Ingibitories ACE can be divided into three groups in the deposits of the molecular budovi:

captopril (Brand Capoten), the first ingibitor of the ACE;

zofenopril.

enalapril (Vasoket / Renitek);

ramipril (Altace / Tritace / Ramace / Ramiwin);

Quinapril (Accupril);

perindopril (PRESTARIUM / Coversyl / Aceon);

lizinopril (Listril / Lopril / Novatek / Prinivil / Zestril);

benazepril (Lotensin);

imidapril (Tanatril);

zofenopril (Zofecard);

One representative of the group є fosinopril (Monopril).

nature walk

Casokinins and lactokinins є products to reduce casein and milk syrovat. In natural minds (in the body of people), the stench is set in the implantation of dairy products, syrovatka, so that it is in the nature of the implantation of dairy products, especially fermented milk. Їх pouring into the arterial vise for the whole season until the end is not assigned.

Lactotropypeptides Val-Pro-Pro and Ile-Pro-Pro, which pretend to be the probiotic Lactobacillus helveticus, but are also treated with casein, can also be used to induce ACE and may cause antihypertensive functions.

Equivalency IAPF.

Angіbіtori ACE may increase the strength of the injection and, apparently, the start dose. The dosage of the drug is guilty, but it is scored in the presence of the reaction of the body to the drug, which manifests itself in the first five to ten days from the ear of the drug.

Doses of ingibitoriv ACE for arterial hypertension.

Angiotensin is a hormone that, behind the help of decile mechanisms, leads to the development of an arterial grip. Enter the warehouse so called RAAS (renin - angiotensin - aldosterone system).

In people with an increase in arterial grip, it is possible to mean so called during the period of renin activity of plasmas, which is manifested at the equal concentration of angiotensin I.

The role of angiotensin in the body

Name RAAS resemble the first letters of the warehouse yo spoluk: renin, angiotensin and aldosterone. They are irregularly tied between themselves and injecting one thing into the concentration: renin stimulating the production of angiotensin, angiotesin replenishing aldosterone, aldosterone and angiotensin hypotension. Renin is an enzyme that we vibrate in nirkas, within the so-called glomerular chambers.

Virobration of renin stimulates, for example, hypovolemia (decrease in the volume of circulating blood) and decrease in the concentration of sodium ions in plasma. Vivification in the blood is renin for angiotensinogen, so that one of the blood plasmas, which is violated, in the main, in the liver.

Renin degrades angiotensinogen to angiotensin I, which is an intermediate for angiotensin II. In the legacy of blood, before the enzyme is called angiotensin-converting enzyme, angiotensin I is converted to biologically active form, to angiotensin II.

Angiotensin II vikonuє in organism of many roles, zokrem:

• stimulates the vivification of aldosterone from measles supra-nirkovykh zalosis (a hormone, in its own heart, infuses into the water-electrolyte balance, so that it gets into the body of ions of sodium and water, more , but, also, і growth of the arterial vise).
• for the receptor, rostasovaniye in stintsi sudin, Scho to produce up to speedy sudin and p_vishennya arterial vise.
• also infused into the central nervous system, Zbіlshyuchi viroblenya vasopressin or antidiuretic hormone.

Zm_st in the blood of angiotensin I and angiotensin II

The value of the activity of renin plasmas is the result of the dosage, which is carried out in patients with arterial hypertension. After 6-8 years of no sleep when a child has been sleeping 100-120 mmol of salt per day (this is how it is called without activating the secretion of renin).

Pre-treatment with the activation of the secretion of renin in the analysis of the blood of patients from the tridenous age with the interdependent living of up to 20 mmol of salt for dobu.

Assessment of the level of angiotensin II in blood samples is carried out using additional methods of radioimmune analysis.

The standard of admission without the activation of the secretion of the renin in healthy people is close 1.5 ng / ml / year, When the last signal is activated, the level increases by 3-7 times.

The growth of angiotensin is promoted to:

• in individuals with primary arterial hypertension(That is, hypertension, as it develops independently and does not stand up to the cause), in these patients we can help you with the selection of antihypertensive drugs;
• with malignant hypertension;
• ischemia nirok, for example, the hour of the ringing of the nirkov artery;
• women who use oral contraceptives;
• renin-producing puffs.

Scho feel norms instead of angiotensin I and angiotensin II in the blood, it becomes obvious, 11-88 pg / ml and 12-36 pg / ml.