Ingibitories of angiotensin converting the enzyme APF preparations. Also - ingibitories of ACE, and spheres of drug administration

Hypertension - the most widened ailment of the heart-vascular system. For lіkuvannya tsyogo zhvoryuvannya vikoristovuyut preparations from different pharmacological groups. Among them one can see the ACE Ingibitories - to reach the young class of antihypertensive patients, which is becoming popular among patients and patients. It will be explained by the high efficiency of the order with a good profile of portability.

The first ingibitor of ACE, and captopril itself, was synthesized in 1975. Since then, the distribution of new drugs in the center is active pharmacological group... There are dozens of chemistry speeches from the group, but there are more than a dozen representatives in the medical field.

Classification

Single classifications of ingibitoriv APF German. Їх

One of the variants of the ACE Ingibitoriv Classification Transfers for the chemical structure in the speech, which includes the group:

• sulfhydril,
• carboxyalkyl,
• phosphinilnuyu,
• hydroxamic.

The analysis of the ACF tsikh pidgroup showed that the presence of any group in the warehouse does not have any significant indications of the authorities.

Regarding biological activity, there are 2 types of ACE:

1. Active leaks, as they themselves show biological activity. Tsya pidgrupa is represented by lizinopril, captopril, cenonapril and libenzapril.
2. Prolіkіv, is transformed into active metabolism, sent to the organism. All the representatives of the group, crim 4, described by the visce, will be protected.

Ingibitories of angiotensin converting to enzyme may be trivial lіkuvalnogo efectu... According to the following, they are added to the tags, which may be:

• long-term effect (fosinopril, lizinopril and in., when they go 1 time in 24 years);
• average triviality effect (enalapril, scho take 1-2 times for dobu);
• short effect, like vimagapiti drug 2-3 times for doba (captopril).

Pharmacological power of ACE

Attracting effects of angiotensin-converting enzymes will not take care of the power of attracting the activity of the angiotensin-converting enzyme, which will prevent the regulation of the reninangiotensin system.

Angiotensin-converting enzyme є active participant regulation of blood vice and water-electrolyte balance. From the beginning of the speech process, the conversion of angiotensin-I into angiotensin-II, which will be done by forceful vessel-sounding effect.

ACE blockers, attracting angiotensin-converting enzyme, assimilate fresh and neurohumoral injections of angiotensin-II into the heart-vascular system. Before an hour I receive a tsikh lіkіv vіdbuvayut galmuvannya affirmation:

• arginin-vasopresin;
• norepinephrine;
• іnhikh words, which exhibit antinatriuretic and vasoconstitutional power.

Krym, the representatives of the group make the difference to bradykinin and the other kinins, which they accumulate in the body. These words may cause natriuretic and vascular dilatation power.

ACE blockers show their antihypertensive speech instantly changing the confirmation of the vasodilatory speech and the accumulation of the vasodilating speech. Peripheral arterial and venous vasodilatation before the hour of treatment with the help of the group does not occur more often in the heart. The stench to reduce the blood flow in the vessels, to increase the heart wikid, to diminish the blood flow.

Pereshkodzhannya approval of angiotensin II, in addition to reducing the vice, to improve the education of the glomerular arteriole nirok, while reducing the intraglomerular hydrostatic vice. tse:

• assimilation of internal glomerular hypertension;
• more progressing urazuennya nirok, including diabetic.

Such a nephroprotective effect is to prevent the possibility of stagnation of ACE for the therapy of diabetic nephropathy, but not superimposed on the blood pressure. For the safety of the efficiency of treatment, follow the trimmings of the low-salt day.

The management of the decrease in post- and preloading on the heart muscle increases the decrease in the dilatation of the empty myocardium and increases the tolerance of physical pressure. Tse allow vikoristovuvati preparations of a group in ailments due to the heart deficiency of the stagnant type.

Class-specific powers of ACE є Cardioprotective, which are manifested by the regression of HLS (hypertrophy of the lingering slurry) and the advancement of ischemic and reperfusion lesions of the heart meat.

Change of pharmacodynamic effects in ACE:

• enlarged veins and arteries;
• reduction of front and rear protection;
• reduction of intraglomerular hypertension;
• regression GLSH;
• the improvement of myocardial changes, changes in the shape of the chambers and the dilatation of the louse;
• p_advishennya dyuresis and natriyuresis;
• Zakhist nirok;
• improvement of dryness to insulin.

The range of ACE blockers is more pronounced in individuals of the middle age, hypertension is most often due to the increase in the activity of sympathoadrenal and renin-angiotensin systems.

showing

Angibitorium ACE is mainly used for the therapy of hypertension. Protest, out of numerical manifestations of defects, the list of indications has been expanded by the next rank:

• symptomatic and sensory hypertension;
• the heart's lack of heart is clinically circulated;
• lowering of the fraction of the wikid of the livy slung;
• chronic overrun nirkova lack;
• diabetic urozhennya nirok.

ACE blockers are shown in Persha Cherga if they are present:

• heart failure;
• red diabetes;
• myocardial infarction, transferred in the past.

Prototype

I want the APF Ingibitories to lose a high profile of safety, however, I will become sick and ill, with any kind of harrowing. tse:

• ringing of nirkovy arteries;
• vagіtnіst;
• important break of nirkovo disability;
• intolerance of group speeches;
• breastfeeding;
• hypercalm;
• childish vіk.

It is not recommended to take an ACE overnight with alopurinol, rifampicin, indomethacin, lithium drugs, cytostatics, kalizbergayuchih drugs, immunosuppressants and psychotropics of the phenothiazine series.

Pobichna diya

All the secondary effects of the ACE are divided into 2 types: specific and nonspecific. Up to the first type negative injections Introduce:

• dry cough;
• hypotonia;
• dysfunction nirok;
• quay Kvinke;
• hyperkalemia.

Negative non-specific character can manifest itself:

• anemia;
• headache;
• by the ruins of the dawn and the relish;
• hanging on shkіrі;
• pickling distribution;
• leukopenia;
• spoiled;
• allergic reactions;
• asthenia;
• impotency;
• rhinitis;
• we are sick with myaz;
• broken blood;
• dry in my mouth;
• bronchospasm і ін.

perevagi iAPF

The number of carried out preliminaries brought the antihypertensive activity of the representatives of the ACE to complement a number of additional passages. tse:

• nephroprotective effect;
• lowering the frequency of development of insult and myocardial infarction;
• high profile bezpeki;
• organoprotective diu;
• metabolic neutrality (to lose fat and carbohydrate profile);
• anti-atherosclerotic diu (in case of drugs);
• Possibility of stagnation in case of diabetes mellitus;
• trust in the development of congestive heart failure.

Characteristics of okremikh representatives

Vvazhaєtsya, scho captopril, scho volodya in the shortest hour of the day, old. I’ll pick up a thought about Enalapril, drinking it will take 2 times to do it. However, the goals are so popular, like the new generation of ACE Ingibitories, which can ease the grip of blood in the norm when 1 tablet is implanted for a supplement. The price is backed by its efficiency and affordable price. Until then, there are a lot of reliable results until the last day, before we finish the new roads. new generation iAPF.

captopril

Tsey drug is short-lived, but at the same hour the most effective. Cerebrate him with an indispensable method in case of hypertensive crisis. If the language is lowered, the vice will be repaired in 10-15 minutes, and if it is in the middle - after 30-40 minutes.

Through non-trivial diya for trivial love of hypertension, victoriously. In such vipadkah it is necessary to spend 3 times. Let it go as well trade name Kapoten.

enalapril

One of the best living ACE Ingibitors. Win has the widest list of indications available at a price and to achieve an effective one. The tablets are stagnant 1-2 times per dose (in the amount of the doze), right off the shelf. In organism it transforms into an active metabolite, the title of enalaprilat.

Vyroblyayutsya liquors bagatma pharmaceutical companies under different names:

• Berlipril ®,
• Envipril,
• Yenam,
• invorio,
• renitek,
• Ednit,
• Enap.

ramipril

Another representative of the group with extensions is shown. The very same person is given a pass at the choice of symptoms for the prevention of stroke, as well as infarction.

The drug surrounds the zone of expanded necrosis in case of infarction and delayed vivacity. The development process takes 1-2 years to receive and triple.

List of drugs with ramipril at the warehouse:

• Charter,
• Piramit,
• Corporate,
• Ramikardia,
• Tritace.

perindopril

tse lykarska rechovina It is often a weak antihypertensive effect, which in most cases is stagnant in a combination of diseases. Most often it is recognized for the treatment of heart failure, lower hypertension.

For a one-time implantation, it will appear in 4-6 years. With repeated stasis, the triviality of the effect is saved for 36 years.

In pharmacies you can arrange for the names:

• Perineva,
• PRESTARIUM,
• Parnavel,
• Arentopres,
• Coverex.

lizinopril

It is also a popular drug, which is older than the representatives of the group and provokes a dry cough.

Likas fix it in a year, reaching a maximum of 6 years and saving the effect by pulling it out. To be issued by pharmaceutical virobniks under the names:

• Diroton,
• Irumed,
• Dapril,
• Lieten,
• Zoniksem,
• Lizinoton.

trandolapril

Liks show their hypotensive effect after 1 year, after receiving and taking care of 24 years. You can be overwhelmed by hypertension with a heart ischemia.

Let go of trandolapril under the name Gopten.

fosinopril

Tsі lіki dine, yake to carry to last generation iAPF. Yogo specialness - vivedennya s organism with nirkami and liver in equal proportions, dear ones nirok. Welcome every 24 years.

Let the speech go by the names:

• Fozicard,
• Fozinap,
• monopril,
• Fozinotek.

Vibir of the representative of the IAPF for the treatment of hypertension

Ingibitories of ACE are stagnant both independently and in a complex with other drugs. The decision about these signs is guilty of accepting the license of the patient for the purpose of identifying the obviousness of possible indications, as well as the cases, for which the group's likings will be ineffective.

• Vibrating a specific response, changing the response from a trivial day, vrahoyuchi with a whole individual tolerance to the drug by the patient and the reaction of the body to the patient.
• The dose of liquids is picked up empirically, on the basis of the minimum recommended and step-by-step change in every demand.
• The rate of blood pressure reduction is accelerated after 2-3 years of therapy with a randomly selected dose of the first dose.

In the case of the ineffectiveness of treatment by the ACE inhibitors, the combination of therapy with other hypotensive diseases is indicated. Naybezpechnіshim and dіevim get involved in taking ACE with a calcium antagonist or diuretic. If necessary, the signs of these combinations are allowed for a visual guide.

3
1 FGAOU VO First MGMU im. I.M. Sechenov Ministry of Health of Russia (Sechenov University), Moscow
2 FGAOU VO “First MGMU im. I.M. Sechenov "Ministry of Health of Russia, Moscow
3 KSMA - branch of FGBOU DPO RMANPO MOZ of Russia, Kazan

For a quote:Єrmolaєva A.S., Dralova O.V., Maksimov M.L. іngіbіtor APF of the third generation of fosinopril in the treatment of patients with heart-and-heart disease // RMZ. 2014. No. 12. S. 906

Heart-sudinni ailment є the main cause of death in Europe and to become more than 4.3 million deaths a lot. Arterial hypertension (AH) is considered to be the most widespread heart-and-heart disease(Nearly 40% of the mature population of RFі have adjustments AT) is the most important factor in the development of the main heart-vascular acceleration, such as myocardial infarction and acute impairment of cerebral circulation, which leads to a high mortality rate in industrialized countries.

Renіn-angіotenzin-aldosteronovoї system (RAAS) rozglyadaєtsya yak main factors regulyatsії arterіalnogo vises i homeostasis, graє central role in viniknennі AG that її naslіdkіv, vistupaє in yakostі neodmіnnogo participant Sertsevy-sudinnogo continuum pochinayuchi of Etap vplivu chinnikіv riziku, potentsііrovanіya rozvitku atherosclerosis, endothelial dysfunction, ischemic ailments heart (ІХС), hypertrophy of LSh, remodeling of the myocardium and completing the final heart failure, as well as development chronic ailments nirok (XXN).

In this hour, 5 main classes of antihypertensive drugs are recommended for the treatment of hypertension: angiotensin-converting enzyme (angiotensin converting enzyme), angiotensin II receptor blockers (ARB), blockers of adipose blood pressure On the other antihypertensive therapy, there can be a change in the activity of the RAAS. One of the ways of reducing the activity є driving the synthesis of angiotensin II.

ACE is a highly effective drug, widely used in the treatment of heart-vascular disease: AH, IXC, chronic heart failure (CHF). The relevance of this disease in the practice of treating the heart-vascular system has been supplemented by the effects of blockade of neurohumoral systems, vaso, cardio and nephroprotective powers.

Throughout the rest of the rock, the number of ACEs is growing unhealthy, so differentiation is made for pharmacokinetic powers, triviality, activity of the drug, and the level of tissue bioavailability. For a chemical budic preparation, it is developed according to the fact that it is a chemical group (sulfhydryl, carboxyalkyl, phosphinic or hydroxamic) in its molecules to contact zinc in the active centers of angiotensin converting enzyme.

At the heart of the clinically significant pharmacological effects of ACE is their ability to adjust the activity of the enzyme (ACE or kinase II), which converts angiotensin of the 1st century. angiotensin II, and in such a rank injected into the function of the RAAS. Angiotensin II is used as the main effector of the RAAS. Angiotensin II, activating AT 1 receptor, low vasoconstrictor pressure. Before the infusion of angiotensin II, the speed of smooth blood cells is seen, the speed of the myocardium, the production of aldosterone, as well as the catecholamines from the cerebral speech halls of the nerves Angiotensin II also regulates the transport of sodium behind the aid of intestinal epithelial cells and nirok. Up to physiological functions locally produce angiotensin II in response to inflammation, proliferation of cellin, mitosis, apoptosis, migration and differentiation of cells

ACE inhibitors reduce the secretion of aldosterone and vasopresin, overshoot the ruin of bradykinin. Bradykinin accumulated in the endothelium, acting through the β 2 -receptor of bradykinin, wicks relaxation of smooth mucous membranes of sudin and spirits of the fallow endothelium of the relaxing factor and vasoactive prostaglandin 2 In addition, due to the infusion of ACE, the synthesis of the second subozymatic and antinatriuretic rechovins (norepinephrine, arginine-vasopresin, endothelin-1) decreases, which also plays a role in the pathogenesis of cardiac dysfunction. The main organoprotective effects of ACE are enhanced by the blockade of ACE in small tissues (for example, sudins, nirks, hearts).

The development of the main pharmacological effects of ACE: hemodynamic, neurohumoral, antiproliferative, nirkov and etc.

The hemodynamic effect of ACE is realized through the reduction of the peripheral peripheral vascular system, viclicati natriyuresis, however, the inflow to the heart rate is small. A decrease in the tone of peripheral vasculature can also be attributed to the blockade of tissue ACE, which can lead to a decrease in angiotensin II century. organs-targets (for example, the judgment seat). In patients with a normal and moving arterial vise without a heart defect, it is practically not possible to infuse an ACE into a healthy volume of heart and shock. Reflexive tachycardia, mabut, for the rakhunok flowing into the baroreceptor, improving parasympathetic activity and, perhaps, changing the sympathetic activity, does not occur on the view of the other vasodilators of the ACE. Also, it is not possible to change the heart rate per hour physical navantazhennya... Stagnation of the ACE will reduce the health of the cardiomyocytes before relaxation. іAPF to change the hypertrophy of all іddіlіv hearts in patients with ІХС, AG, who are suffering from insulin-independent for diabet(SD) and heart failure. Also, ACE inhibitors reduce endothelial dysfunction. The power was given to bind to the weakening of vasoconstriction and to the strengthening of nitric oxide as a result of the improvement of the approval of bradykin in the blockade of ACE.

In patients with CHF, ACEF will reduce clinical symptoms, the quality of life, improve the progress of ailments and reduce the prognosis, and also predict the onset of clinically recurrent decompensations. The price is discussed in both arterial and venous vasodilation. Venous vasodilatation increases the volume of venules, changes in vantage on the right atrium, as a result of the change in the grip in the vein of the legacy, decreases in vantage due to the amount of lingering blood flow.

Arterial vasodilatation to reduce the peripheral vascular support and increase the heart vikidu. Short course priya іAPF suprovodzhuєtsya zmenshennyam vmіstu angіotenzinu II, Prote for mehanіzmom negative zvorotnogo zv'yazku zbіlshuєtsya vikid renіnu i rіven angіotenzinu I. Angіotenzin II volodіє vasoconstrictor dієyu bearing-down on the muscles gladkom'yazovih klіtin, pіdsilyuє skorotnіst mіokarda, stimulyuє produktsіyu aldosterone aktivuє ekskretsіyu kateholamіnіv from the cerebral speech of the supra-nirkoval zalosis and from the sympathetic nerve ends, stimulating the sympathetic nervous system, Pidsilyu sprague and bazhannya live to solon uzhu. Angiotensin II also regulates the transport of sodium behind the aid of intestinal epithelial cells and nirok. In addition, ACE inhibits change in plasma adrenaline, norepinephrine and vasopresin.

Besides, before the adjustment of the level of angiotensin I to produce an increase in the concentration of bradykinin, as well as the activation of alternative ways of converting to angiotensin I in the 1st century. angiotensin II. In such a rank, the antioxidant activity of ACE promotes kinins, prostacyclin, and nitrogen oxide. With trivial congestiveness of ACE, aldosterone is reduced, normally stimulated by hyperkalemia, hypermagnesemia and ACTH, so that sodium and water should be produced to the extent possible.

With a trivial congestive ACE inhibitor, the antiproliferative effect is: a decrease in the hypertrophy of the vertebral column of the vertebral column and myocardium, a decrease in the proliferation of the posterior matrix. Possible mechanisms of the ACE to change the hypertrophy of the myocardium are involved: the mechanical reason for the reduction of the anterior vantage and reduction of the stimulation, as well as the change in the sympathetic activity and decrease in the growth. In addition, the ACE can change the approval of the collagen for the reduction of angiotensin II instead of angiotensin II, which is not the case on the fibroblast, so, bit by bit, for the stimulation of the secretion of aldosterone. Galmuvannya of growth and proliferation of smooth cells and fibroblasts in the media of arteries is to be brought to an increase in education, as well as updating and improvement of elasticity of the arterial wall. In such a rank, the central hemodynamics normalize and the peripheral vascular opir decreased.

According to the explanation of the antiphibrotic action of the ACE on the myocardium in hypertension. Pre-adolescents vvazayut, as well as an effect of ACE є as a result of blocking the hydrolysis of N-acetyl-seryl-aspartame-lysyl-prolin, which leads to a decrease in the proliferation of fibroblasts, fiery clitin, and expressive growth factor. In addition, ACE inhibitors cardiomyocyte apoptosis.

іАПФ nadayut a friendly effect on nirki, t. to. widen more important arterioli and less injected into afferentnі. In such a rank, the intraglomerular grip decreases, proteinuria changes, and blood flow decreases with a slight change in glomerular filtration. Unimportant to the change of the court support in the glomeruli, the glomerular filtration rate is unimportant, or to be improved at once from the filtration fraction. As a result, the improvement of nirkova hemodynamics of growth natriyuresis, changes in the aldosterone viroblast, which leads to the hopeful progress of nephropathy.

RAAS has an important role in the pathogenesis and progressive atherosclerosis. In such a rank, when the ACE is recognized, the development of atherosclerosis is promoted as a result of the blockade of the approval of angiotensin II and an increase in the concentration of bradycin and nitrogen oxide, which reduce the endothelial function.

In the published analytical analysis of three dosages (HOPE, EUROPA, PEACE) for the infusion of ACE in 29 805 patients with apparent atherosclerosis, altogether without dysfunction of the lingual slug, deaths on indicators of extravagant reduction of postoperative (7.8 versus 8.9%, p = 0.0004) and cardiovascular (4.3 versus 5.2%, p = 0.0002) mortality, nonfatal myocardial infarction (5.3 versus 6, 4%, p = 0.0001), cerebral strokes (2.2 versus 2.8%, p = 0.0004), heart failure (2.1 versus 2.7%, p = 0.0007) shunt (6.0 versus 6.9%, p = 0.0036). The authors made a mistake, that the sign of ACE was guilty of being recognized in all patients with an intermediate risk in the presence of an atherosclerotic process.

In such a rank, ACE is indicated for the treatment of hypertension (class IA). In patients with hypertension, the primary method of treatment is the control of the arterial grip, which can be reached for additional supplementation, and to reduce the risk of heart-vascular delay during trivial therapy. The ACE can also look like if you have a first line in ailments with heart failure, systolic dysfunction of the lingual dysfunction, or SD, who have suffered an IM or an insult, as well as in patients of groups high rhiziku coronary ailments heart.

For the last ten years of up to 30 days of chemistry, you should be admitted to the class of IAPF. One of the most effective, safe and economical ACEs is fosinopril sodium (Monopril). A clinically important aspect of fosinopril is of the type of ACE inhibitors, the presence of an excess of phosphinic acid in its chemical formula. The specificity of the structure of the preparation gives a number of unique powers, which are used to recognize one of the drugs in this class, and to allow the introduction of it to the third, most successful, generation of the APF.

Fozinopril є with spills and for the release of moisture and transformation (in the liver, mucous intestinal tract, nirkah, bloodstream) into the active metabolite - fosinoprylate, which is linked to blood by 95% (95%). The period for which fosinopril is administered should be 12-15 years, when the antihypertensive effect is increased to 1 p. / Sut. The drug develops a superficially high lipophilicity - the lipophilicity index of fosinoprilat becomes 2.0 OD, while for enalaprilat it is 0.108 OD. The process of penetrating fosinoprilat through the cell membranes allows the activity of not only circulating, but also tissue RAAS in the heart, legends, marks, and the brain to be absorbed. It has been experimentally shown that phospinoprylate induces ACE in the heart muscle in the larger world, but not ramiprylate and enalaprilat, but to lie in the basis of the larger On the basis of these APFs (captopril, enalapril, lizinopril, and in.) the introduction of an active metabolite from the gum and navpaki, with the liver deficiency of the growth of the ectopia from the section. The drug is most effective in children, as well as in patients with pathological liver and niroc.

Clinically significant with fosinopril, which is a virulent type of large ACE, є good tolerance. So, in patients with CHF II-IV functional class according to the NYHA classification, the frequency of side effects in the presence of fosinopril and placebo was practically not recognized. There is a low incidence of dry cough in the region. Apparently, a dry cough, vicious coughs with ACEs, is weaker or more likely to occur when switching to fosinopril. So, in the sub-baseline, oral dosage with enalapril, it is shown that there is a significantly greater risk of coughing when fosinopril is detected. 179 ailments were included in the tse doslіdzhennya, they were also treated with an ACE inhibitor through the development of a cough. With the attempt to update the treatment of the bullet, it is more successful with the vibration of fosinopril - repeated development of the cough has become more and more severe in the case of enalapril. Likewise, when you are stagnant, there are fewer clinical and biological side effects, especially in "groups of patients" - in the case of those who suffer from hypertension or ailments on the Central House. Fozinopril as a result of a manual dosage regimen - a one-time reception without a 24-year control of an arterial vise (the rate of surplus to peak effect - 64%) and a start of the first year in the early rankings. Pochatkova dobova dose fosinopril in hypertension to become 10 mg one-time with the available additional drops to 20-40 mg. With CHF, the pochatkova dobova dose is 5-10 mg (in ailments with hypotonia - 2.5-5 mg), the average therapeutic is 10-20 mg, the maximum is 20-40 mg.

Prescribed FOPS (757 ailments over 60 years old) have a price of AT for 12 years. lіkuvannya fosіnoprіlom buv reached 80% of patients, and some of them prescribed 12.5 mg to achieve a shortened therapeutic result. For preschoolers FLIGHT (19,432 ailments from AH, 989 of them are older than 75 years) after 12 years. from a cob of lіkuvannya tsіlyove AT was reached in 79.8% of patients. Apparently, the antihypertensive activity of fosinopril is gradually growing in the first spine of the disease, AT is often within reach of the central cells without the manifestation of elements of compensatory damage heart rhythm, And the drug does not lead to a sharp arterial vise. Diya of fosinopril, as a rule, does not lie in the form of specific features and ailments.

When conducted by the Russian programs PRAPOR (Fozinopril at Lykuvanna arterial hypertension) Evaluated the amount of uptake of the whole amount of AT in the ailments with myako and small AH in the outpatient drains with monotherapy with phospinopril (10-20 mg / add) or the second supplement with hydrochloric acid. In total, 2557 patients were included in the pre-session bully, with 26.7% of individuals over 60 years old. Tsilove AT was reached in 62.1% of patients. Vicious Effects in 8.3% of the sick, and only 5.2% of patients needed a drug.

In the case of pre-admission FAGOT (Pharmacological evaluation of ACE administration of fosinopril in the outpatient treatment of patients with arterial hypertension), 2596 patients were included in the treatment of patients with serous factor The efficacy of monotherapy with phospinopril, either on the basis of hydrochlorothiazide and on oral therapy (diuretics, BAB, calcium antagonists) in patients Riznogo viku... Cylove AT in case of taking fosinopril and hydrochlorothiazide was reached in 67.8% of patients. It has been shown that the rate of adolescence of a hypotensive effect and its turnover in the presence of fosinopril does not develop in patients of the abducted young vik, Ale vishche, nіzh at the victorian traditional scheme of the lіkuvannya. Fosinopril was clearly shown to be easy to use and economical in terms of efficiency.

Fozinopril is effective in the development of hypertrophy of the lingering slurry (LSH) in hypertension, i.e. Vin does not only reduce the arterial grip, but rather regresses the structural remodeling of the chambers of the heart. Stretching 9 ms. The mass of myocardium of the LS decreases in individuals with a rotated hypertrophy by 5 g, and in the group of porosity - a growth. More importantly, even more importantly, the evidence of hypertrophy of the LSh wall is one of the key predictors of heart-and-death catastrophes. The drug is also sympathetically infused to prevent atherosclerosis of the carotid arteries. It is shown that the complex is anti-media in the center of the court channel after 36 years. the regular intake of the drug will decrease by 0.0278 ± 0.03 mm, at that hour the posture of the intake of fosinoprint will only decrease.

The results of the subordinate blind placebo-controlled dosage of PHYLLIS demonstrated a galvanic effect of therapy with fosinopril (20 mg / dob) on the progression of atherosclerosis in the carotid basin, i.e. antiatherogenic activity. 508 AH ailments with asymptomatic atherosclerotic lesions of sleepy arteries and great hylocs took part in pre-sludges. The middle term is reserved for the sklavs of 2.6 rock. Tovshchina complex іntima-medіа, as the zone of atherosclerotic lesions, in ailments, who took fosinopril, reliably and similarly changed. In such a rank, even in decilkoh doslidzhennyah, it was demonstrated that fosinopril is an anti-atherogenic effect in ailments of hypertension, taken on the edges of the vessels of the court channel.

Fozinopril can also improve the diastolic function of FS in young individuals with myakoia hypertension without hypertrophy of the FS. The presenters took the fate of 66 young people (middle age 36 years), from the average triviality of the AH, for the sake of medical documentation, 5.4 years. The dose of fosinopril was 20 mg / day. The group of control was eliminated with a combination of hydrochlorothiazide and hydralazine. Monotherapy with phospinopril has demonstrated unprecedented changes in normalization of diastolic function of LSH and prevention of hypertrophy of LSH.

PREVEND IT (Prevention of Renal Vascular End-Stage Disease Intervention Trial) was carried out to support the vascular nephroprotective effect of fosinopril, which was not tied to the reduction of the arterial vise. Pre-treatment included 854 patients with microalbuminuria, who were prescribed 2 drugs for 46 months: pravastatin and fosinopril, placebo control. main meta given doslіdzhennya There was an assessment of the infusion of fosinopril and pravastatin for cardiac abdominal acceleration and deficiency in patients with microalbuminuria, normal level of arterial grip and zagalnye cholesterol. Pershі 3 mіs. The level of albumen was often lowered among the ailments, as they removed fosinopril, which was consumed by a stretch of 4 rockets with caution. Zastosuvannya pravastatin is not supervised by the snake of microalbuminuria. In patients with a placebo, fosinopril changed the risk of insult, without infusing the risk of myocardial infarction.

The stagnation of fozinopril is a pre-urban developmental ACE, which is characterized by mutually compensated by the way of ecclesiasticalism from the section and by<30 мл/мин). Аргументом в пользу выбора именно этого препарата у больных ХСН с исходными гиперкреатининемией и/или снижением СКФ является установленный в клинических исследованиях минимальный по сравнению с другими иАПФ риск нарастания сывороточных концентраций креатинина и калия. У пожилых больных с изолированной систолической АГ (исследование FOPS), у которых вероятность провокации ухудшения функции почек иАПФ максимальна, применение фозиноприла не было сопряжено с появлением признаков почечной недостаточности. Безопасность фозиноприла с точки зрения влияния на функцию почек установлена и в крупных отечественных контролируемых исследованиях (проект «Три Ф») .

When porіvnyannі fosinopril y i nіfedipіnu viglyadі under study is dіyuchoї gastroіntestinalnoyu terapevtichnoї System (GІTS) in 241 of ailments parenhіmatoznimi zahvoryuvannyami nirok hronіchnoyu nirkovoyu nedostatnіstyu i, y yakih for poperednіy Year sposterіgalosya podvoєnnya rіvnya kreatinіnu plasma krovі, wires lіkuvannya fozіnoprіlom 10-20 mg / day porіvnyannі with nifedipin supplementation 30-60 mg / day. Kintsev points in the preliminaries were the submission of the level of creatine and the need for hemodialysis. After 3 fatalities, 36% of illnesses in the group were cautioned by nifedipin, and 21% of patients (p<0,05) в группе, получавшей фозиноприл, достигли конечной точки. При этом уровень протеинурии на фоне лечения фозиноприлом уменьшился на 57% от исходного, в группе терапии нифедипином — возрос на 7% .

Visnovok. ACE fosinopril (Monopril) is an effective drug that allows not only to reach the whole level of arterial pressure in patients with hypertension, but also can bring cardio-, vaso- and nephroprotective effect of hypertension. Fozinopril (Monopril) can serve as a Vibor preparation in the form of hypertensive therapy for hypertension in certain groups of patients. For optimal organoprotective effect, fosinopril can be successfully used in monotherapy and in combination, including with tiazidnimidiuretics or calcium antagonists. At the same time in its own practical efficiency, good tolerance and simplicity of testing, fosinopril can be recommended for the therapy of patients with hypertension, including Ch.

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Orlov V.A., Gilyarevsky S.R., Urusbieva D.M., Daurbekova L.V.
Russian Medical Academy of Education of the Ministry of Health and the Russian Federation, Department of Clinical Pharmacology and Therapy

Ingibitories of angiotensin converting enzyme (IAPF) will become an external stone in most widespread heart-vascular diseases. In the last few years, the indications for the recognition of the IAPF have become quite widespread, the plans to prove the effectiveness of the IAPF, for the prevention of uncomfortable heart-vindicators in high-risk patients. At the same time, the problem of portability of the IAPF continues to be relevant.

Infusion of the pharmacological authorities of the IAPF on their clinical efficiency and development of secondary effects

There is a large part of the secondary effects of the IAPF, as can be seen from the table. 1, in order to be established by authorities that are far-reaching for the whole group, because the pharmacological evidence of drugs is not to blame for the great pressure on the frequency of development of side effects for the blame of quiet, as it appears to be evident in the storage of molecules of the drug.

The reason for the APF may be that the chemical structure of the active part of the molecule is susceptible to the release of the ACE, bioavailability, the hour of the release in the plasma, the elimination of tissue proliferation, growth, before the dispute. Ingibitories of ACE can be divided into three groups in the presence of the chemical structure of the active part of the molecule.

Captopril є with a prototype of the IAPF, for revealing sulfhydryl groups; The leading representatives of the group are fentiapril, pivalopril, zofenopril and alacepril. Previous in vitro studies have shown that the presence of sulfhydryl groups can increase the potency of the drug, as long as it does not lie in the form of ACE reactions (involving free radicals, injected into the synthesis of prostaglandins). However, the data have not been approved in the clinical reports.

Sered ACE fosinopril is a single drug in which a part of the molecule is active to avenge the phosphonil group. Most of the ACE to replace the carboxyl group in the active part of the molecule. The main pharmacological authorities of the ACE inhibitors are presented in table. 2. Captopril appears from other drugs in a short period of time to fall in plasma. Behind the blame of fosinopril, trandolapril and spirapril, IAPF are mainly used in nirkami, which is why it is necessary to change the dose for ailments with impaired function of nirok. It is a great part of the IAPF to fit into the body of the eyes of the pricks, as it becomes active in the course of the esterifikatsii in the heart. As a rule, prodrugs may be more readily available with active drugs.

Hypotonia for the reception of the first dose

All ІАПФ zdatnі viklicati arterialny hіpotonіyu. A decrease in AT, which is promoted for a long period of time after taking the first dose of the IAPF, is seen as a result of the development of the renin-angiotensin system (RAS). A decrease in AT is more pronounced in ailments, but a high level of renin and angiotensin II plasmas are on the cob, for example, in ailments who receive high doses of diuretics.

If you want to develop hypotonia in case of IAPF treatment, start tying it up with the first dose, you can use it for more stages of therapy. The decrease in the arterial grip of the intake of the first dose is small and asymptomatic, but it does not lead to the destruction of the perfusion of vital organs. However, in a small part of the sick, hypotonia may be evident, which is supervised by symptoms of hypoperfusion of the heart, brain and niroc.

If you want to see that illnesses from CHF may be advised against the first dose, the development of a clinically significant hypotonia, as a result of the improvement of IAPF therapy, it is less than 10% of patients. In ailments with persistent hypertension, if they do not take out the other antihypertensive drugs, an ear of ACPF therapy is often used to develop clinically significant hypotonia.

Prior to the factors, the development of circulating hypotonia, the diagnosis of hyponatremia and hypovolemia, blooming, on the basis of diuretics, bloating or diarrhea. Pohiliy vіk, the manifestation of rotated and / or accelerated arterial hypertension (including malignant or renin-depleted Renovascular hypertension) are involved in factors of the rhizic of significant hypotonia. The cob deterioration of the function of nirk and stenosis of the nirk arteries can also promote the development of hypotension when receiving the first dose of IAPF. We are sick, if there is one or more of these factors in the risk, on the cob stage of the IAPF therapy, control in the minds of the stationary can be known.

Rizik the development of hypotonia by taking the first dose and the ear of IAPF therapy can be brought to a minimum, as well as taking into account singing tactics.

It is especially important to seek the euvolemic camp until the moment of cob therapy, if necessary, correct dehydration. You may also be familiar with the time spent in the kitchen salt, for the lesser degree of living in the early period of life.

In the case of a high risk, the development of hypotonia after taking the first dose, or on the cob of therapy, does not give a small dose of a short-term preparation (for example, captopril at a dose of 6.25 mg), and it is also recommended to take a dose of short-term preparation (for example, captopril at a dose of 6.25 mg). In general, I switched to a trivial drug.

There are two characteristics of perindopril that make it safe for you to get sick in these situations: (1) the behavior of the ear; (2) the incidence of significant hypotensive activity in normotensive patients when prescribed in small doses.

Navookarasu N.T. et al. in 80 ailments with CHF in a sub-baseline, randomized, placebo-controlled, pre-existing condition, the reduction of the arterial pressure was reduced for the first intake of 2 mg perindopril, 6.25 mg captopril, 2.5 mg enalapril and 2.5 mg l. Vimіryuvannya arterial vise was carried out dermal 30 min, stretching for the first 2 hours, and then dermal period. The maximum decrease in mean AT was 5.3 ± 2.5 mm Hg. Art. for perindopril, 13.3 ± 3.3 mm Hg. Art. - for enalapril, 15.0 ± 5.7 mm Hg. Art. - for lizinopril, 16.8 ± 5.7 mm Hg. Art. - for captopril і 5.9 ± 2.7 mm Hg. Art. - for a placebo. The indications when tested against placebo were found to be reliable for all drugs (p<0,05), кроме периндоприла.

The development of hypotonia is often interconnected with an ACPF in the early term and myocardial infarction. Vvazhaєtsya, scho the lower boundary of the systolic arterial vise, in which case it is possible to sign an IAPF in the early term of myocardial infarction, є 100 mm Hg. Art. ... Coughing ІАПФ in ailments on myocardial infarction, pummeled with hypotonia, mostly in quiet ailments, in those with a low arterial vise on the cob (<100 мм рт. ст.); но даже у этих больных развитие гипотонии не ухудшало ближайший прогноз.

In ISIS-4 (Fourth International Study of Infarct Survival) and GISSI-3 (Gruppo Italiano per lo

Studio della Sopravvivenza nell'Infarto miocardico) arterial hypotonia, amalgamated by the therapy of IAPF, supervised by a more friendly prognosis, due to hypotonia, which has developed on the smallest patients.

In addition, the descriptions of the development of refractory to the introduction of catecholamines of cardiogenic shock in a patient of 42 years with an infarction of myocardial infarction of the anterior localization, which debuted in a lot of legends, after 2 years. Pislya the first reception in the middle of lisinopril. Intra-intravenous injection of plasma-assisted changes and norepinephrine will not reduce the hemodynamic status. Only when the intravenous injection of angiotensin II was indicated, there was no more increase in the systemic judicial support, which was superseded by the regression of clinical manifestations of shock.

The presence of hemodynamically significant aortic stenosis interferes with the contraindications for the sign of IAPF through the development of non-rooted hypotonia. Unimportant on the price, in the literature, there are some reports about the presence of ACE in patients with critical aortic stenosis, like supravodzhuvalaya positive influx on hemodynamics, especially with the manifestation of heart failure. Unimportant on the basis of experimental and clinical data about the positive injection of ACE into the function and processes of remodeling of the heart in aortic stenosis, nutrition about the possibility of practical stagnation with the given pathology, until there is too much

Damaged function of nirok

The importance of the correct assessment of the negative inflow of the IAPF on the function of nirok viz. On one side, the IAPF is widely used for the treatment of arterial hypertension, CHF, diabetic and non-diabetic nephropathy. On the other hand, they are unaffected by those with the IAPF who develop a lack of blood circulation, increase the speed of ecclesiastical natrium and hope for the progression of chronic cases of depression, inherently suffering from supine syndrome

The whole form of hostile disability (GNN) is inviting to develop unobtrusively for a cob of IAPF therapy, or else it is possible to win it and in the future it looks like an ear of illness, especially in those with CHF.

Gostru nirkov lack of most often begins as a decrease in the function of nirok, it is necessary to manifest itself as an increase in the concentration of creatine plasma. If you want a creatine level, if you diagnose acute renal failure, definitely not of a value, if you increase it by 0.5 mg / dL (44 μmol / L) in patients with cob-like creatine<2,0 мг/дл и более чем на 1,0 мг/дл при исходном его уровне >2.0 mg / dl The spectrum of clinical manifestations of acute renal failure can vary from early oliguria and asymptomatic increase in plasma creatine levels before anuria.

The imperfection of the appearance of a low level of deficiency is to move in quiet drops, if the low perfusion grip cannot be adjusted to an adequate level of performance in the case of a decrease in the middle AT, if the amount of glomerularity is very strong. Vigorous hypotonia and a low grip of the heart can lead to the development of negative hemodynamic inheritance of IAPF therapy. The prevalence of GFR due to the level of angiotensin II is especially strong with a change in the volume of postcardiac birth, circulating bilateral stenosis of the nirk arteries, as well as stenosis of the normal arteries, as well as the functional and dominal Nareshty, IAPF can increase the risk of development of a serious nirkovy deficiency in ailments, such as taking medications for a sufferer, for example, non-steroidal anti-pyretic drugs (NPZP) or cyclosporine A.

Rizik the development of hospitality nirkova deficiency at the same therapy of the IAPF of advertizing also in individuals with chronic nirkovy deficiency (CHNN), whether of any ethology. The change in the number of nephrons in ailments with chronic nircum deficiency is superimposed on compensatory functional changes, which are directed to the GFR response, and in zokrem - by hyperfiltration. An important component of the positive action of the IAPF in such ailments, as it can be seen, is the reduction of glomerular hyperfiltration for rakhunok and important vasodilatation and reduction of the glomerular capillary vise. Already, the assertion of hyperfiltration in children with chronic nircum deficiency at the first stage will inevitably lead to a decrease in the GFR and increase in the blood of the family and creatine. For the sake of it, it will simply be a manifestation of the fact that the preparations were beginning to be pushed by the bazhans in this vypadku diya, straightforward to the preservation of the function of nirok. A practical indication of the cich is the warning є those who do not have an indicator of the level of creatine, for which only the value of this value will become indications for the sign of IAPF. In case of impaired functions, nirok pidvischennya

Plasma creatinine level by 10-20% as a result of normal є therapy, and by itself it cannot be a drive for the correction of a drug. For the blame of inadequate lowering of the mean AT lower than the level necessary for adequate perfusion in all situations with chronic incapacitations of chronic abnormalities, the reduction of the average APF is superimposed by a 20% decrease in SKF; In the course of the process, there is a stabilization or a decrease in creatine level for the development of a trivial renoprotective action of the IAPF.

With a decrease in perfusion, the activation of the renin-angiotensin system (RAS) is seen. On the basis of a large number of vessels, such as infusing nirok, angiotensin II, vasoconstriction, as well as acute vasoconstriction, leading to a deep increase in intracranial pressure. In case of renovascular hypertension and congestive CHF, glomerular filtration begins to grow for the reduction of the filtration vise on the smallest glomerular arterioles. Constriction of arteriol to try to sell angiotensin II. On the way to the ІАПФ, the developers of the suppression of the approval of angiotensin II, and it is possible, the accumulated bradikinin, to reduce the support of the current arterioles, as it is pulling for itself to change the glomerular filtration rate.

On the other side, not only the therapy of IAPF, the reduction of nirkoval vasoconstriction in order to decrease the level of postglomerular vasoconstriction to increase nircovascular blood flow. In order to increase the level of blood circulation in a larger world, the level of GFR decreases in the smaller world. The whole mechanism of chastkovo compensates for the reduction of the glomerular filtration vice.

All ІАПФ, which induce the synthesis of angiotensin II in nirkas, build up the reduction of the nirok function. However, in most cases, they are asymptomatic and werewolves. The deterioration of the function of nirok, wiclicans of the IAPF, in the bagatokh vipadkah does not progress, unimpressed on the advanced therapy of the IAPF.

Trivially, there is a serious lack of heart, by itself, it often leads to significant deterioration of the function of nirok, so it is not easy to see the negative inflow of IAPF on the function of nirok dysfunction, vicious dysfunction, basic dysfunction. But nevertheless, in some cases of the inheritance of the deterioration of the function of the nirok, the vicious therapy of the IAPF, it can be serious and it can clutter up the life.

With CHF, impaired function of nirok, it is possible to assess for additional GFR, є an independent predictor of an uncomfortable prognosis. In ailments with an amicable heart deficiency, plasma creatinine levels in the course of APF therapy either do not change, or move insignificantly. It has been established that in about 30% of patients with a heart deficiency of ACE inhibitors, there can be achieved a significant increase in creatine plasma levels. However, in a given function, you should be able to stabilize and not to increase the amount of creatine added. Acceptable on the basis of the IAPF therapy to increase the level of creatine plasma<30% от исходного.

In preligens Studies of Left Ventricular Dysfunction (SOLVD) 3379 ailments with systolic dysfunction LS (FM LS<35%) в течение 2,5 лет получали эналаприл или плацебо. Ухудшение функции почек (повышение уровня креатинина плазмы более чем на 0,5 мг/дл) произошло у 16% больных в группе эналаприла и у 12% пациентов группы плацебо, то есть, больные, получавшие эналаприл, имели на 4% большую вероятность развития нарушения функции почек. При мультивариационном анализе более пожилой возраст, терапия диуретиками и сахарный диабет оказались факторами, способствующими снижению функции почек на фоне лечения ИАПФ, в то время как терапия β-блокаторами и более высокая ФИ ЛЖ выступали как ренопротективные факторы .

Meta-analіz troh great randomіzovanih klіnіchnih doslіdzhen efektivnostі ІAPF at sistolіchnoї disfunktsії LS i / abo sertsevoї nedostatnostі vnaslіdok іnfarktu mіokarda SAVE (Survival and Ventricular Enlargement), AIRE (Acute Infarction Ramipril Efficacy) i TRACE (Trandolapril Cardiac Evaluation) viyaviv scho Sered 5387 patsієntіv when ACEI was eliminated, the frequency of impaired function was 5.2%, and on placebo - 3.6% (p<0,0001) .

With the manifestation of a nirkovy lack of therapy with captopril, it is necessary to fix the changes in doses (from 1 to 6.25 mg per day) and titrate the dose even more frequently, increasing by 1 mg per day, or two. If the level of creatine in the plasma is 142 μmol / l, it is recommended to start therapy with enalapril at a dose of 2.5 mg per day, increase the amount of skin by 2.5 mg for 4 or more days to the whole or the maximum tolerable dose.

Looking around Mason N.A. Assigned to the injection of ACE therapy on the function of nirok, two robots are guided, in which captopril and preparative preparations are used. For the given tsikh doslidzhen, the therapy of short-term IAPF supravodzhuvalasya by a lesser frequency of degradation of the function of nirok. The whole fact can be explained by a greater or more severe blockade of ACE against the background of therapy with active IAPF drugs. However, when the therapy of low doses of enalapril was victorious on the cob, there was a significant reduction in the function of nirok.

Podvіynyi shlyakh vivedennya fosinoprila to rob him with a preparation Vibor in case of vicoristanna in patients with impaired function of nirok. It is reported that the ailments have a decrease in the SCF<30 мл/мин индекс кумуляции фозиноприла достоверно ниже, чем лизиноприла и эналаприла. По сравнению с фозиноприлом, лизиноприл увеличивает риск лекарственой кумуляции в 2,23 раза, а эналаприл – в 1,44 раза .

Try to change the steps of the deterioration of the function, but instead of replacing ACE inhibitors with angiotensin II receptor blockers, they did not work. In the recent Evaluation of Losartan in the Elderly Study (ELITE), there were no indications for the treatment of captopril and losartan in a number of ailments, in some cases the increase in the size of the mortar , 5%.

The suppression of IAPF therapy with diuretics, or NPZP, is also a factor that screwed up to the development of the deterioration of the function of nirok. With a one-hour intake of aspirin and ІAPF dilatation of afferent arterioles for the development of vasodilating prostaglandins, it can be suffocated, which can lead to an increase in blood flow and a large decrease in blood flow. If you want the oil refinery, zokrema sulindak, you can push a smaller turn of the nirkovy effect, all the preparations of the whole group are guilty of vikoristovuvatsya with great protection when recognized at once from the IAPF. Preparations from a group of selective blockers of cyclooxygenase-2 so itself, as nonselective NPZP, can reduce the function of nirok. In patients with CHF, there is a unique one-hour therapy of IAPF and NPZP, and if such a combination is necessary, retreat monitoring of the function of nirok is carried out.

In a retrospectively conducted retrospective dosage, which included 576 ailments with CHF, it was shown that one-hour reception of the IAPF and aspirin was supervised to recover from the state of health for 30 days. In order to make more recommendations, it is not necessary to receive an IAPF and aspirin at the same time, it is necessary to confirm these donations in a prospective consultation. At the same hour, a systematic analysis of the dosage of IAPF and aspirin in the early term for a state of myocardial infarction, which included the data of 96,712 patients, showing the high efficiency of the IAPF, however

For ailments due to the congestive heart deficiency and the development of the deterioration of the function, until the residual solution of the IAPF can be taken into account, it is necessary to pick up a few steps. In quiet people, if the nobility of severe malnutrition in the implantation of kitchen salt or the change in diuretic therapy does not lead to the improvement of the function of nirok, it is possible to try to change the dose of IAPF.

As soon as the therapy of the IAPF is brought to the fore, then, for the stabilization of the function, it is possible to preserve the information on the smallest monitoring of the function.

To reduce the risk of a hostile deficiency, ample therapy with an IAPF, it is necessary for additional support, including laboratory, to reveal the ailments with a high risk of development. In principle, tactics, the development of nirkov deficiency in ailments with a high rhizic was taken away, similar to that in ailments with a high risik the development of a hypotonia after receiving the first dose.

If I want the IAPF, as it has already started, it’s stagnant with the method of reducing the proteinuria in the ailments because of the infirmities of the disease, the IAPF therapy can lead to the development of the proteinuria. In the early pre-juvenile captopril, the intake of high doses (> 450 mg / dose) in the ailments with the acute fever of the juveniles, the appearance of proteine ​​in 3.5% of the vapors, at that time, during the period of protest, there were more low doses of the supplement in the second half. captopril, 1.4% in case of enalapril treatment and 0.72% in case of lizinopril treatment. Proteinuria, viklikana ІАПФ, invite to pass independently, unaffected by the continued therapy, that with the real monitoring of ailments can prodovzhuvati priyom ІАПФ, with the blame for the development of nephrotic syndrome. As soon as azotemia develops from the protein, and especially, as the protein reaches a great variety (> 3 g / dobu), the IAPF is necessary to skasuvati.

There are described 3 vypekty of development of nirkovo glucosuria, amalgamated therapy of IAPF. In one type of glucose level, glucosuria developed in an aortic 42 years with arterial hypertension on the same type of enalapril; Glucosuria was developed in terms of 2 to 16 years. from the cob of therapy. The mechanism for the development of glucose in the form of ACE therapy has not been precisely established, but rather to be transferred to the ACE injection on the transport systems in the proximal tubules.

hyperkalієmіya

As a result of a decrease in the secretion of aldosterone, all of the ACE inhibitors are transferred to an increase in sodium and water consumption and to reduce the loss of calories. The development of hypercalculus on the same therapy of the IAPF can be tied to the lowering of the functions of the children. Concentration of calories in plasma produces a healthy correlation with GFR. In ailments, the amount of cleanscreatin is lower than 40 ml / hv, the amount of calories in the plasma will develop 5.5 mmol / l.

If all Іngіbіtorі ІАПФ can be reduced to a small (clinically insignificant) increase in the concentration of calories in plasma for a decrease in the level of aldosterone, a seryogyperkalієmiya is developed quickly. Hypercalculation can be seen in quiet drops, if there is an increase in the necessary caliber or a change in its ecclesiasticality. The most risky development of hyperkaliєmії є in ailments with a cob deteriorated function of nirok. Hypoaldosteronism is also a factor in the development of hypercalcium associated with ACE therapy. One-hour therapy with drugs kaliyu, kalіy-zberіgayuchih diuretics or combinations of diuretics, before the warehouse of which include kalіy-sberіgayuchі drugs, also in some types of vyadki can take the development of hypercalculation.

To reduce risk, the development of hypercalculus to the ear of IAPF therapy has a function of low and low electrolytes in plasma.

If necessary, the patient is guilty of hypovolemia. Whenever possible, on the cob of ACE therapy, preparations of calcium and calcium F-sparing diuretics are more beautiful than timchasovo skasuvati. During the first hour of testing the IAPF it is recommended to repeat the duration of the electrolytes in the plasma, more often when the dose of the IAPF is increased, and the function of developing the hyperplasia is increased.

cough

A frequent dry cough is the most frequent side effect of the IAPF, which is very common. For the first time, the development of a cough on aphids of IAPF was described in 1985 with captopril liquefaction. The frequency of the development of cough, swollen with ACE therapy, after the literature, rises from 0.7% to 44%.

In the first early childhood coughs, coughing did not develop as a side effect of the IAPF, and in early robots the frequency of coughing on the background of IAPF therapy was only 1-2%.

A cough can develop on aphids, whether it be a drug from the IAPF group. Dani about those who do the drugs before they viklikayut cough, superintelligible. Nowadays, in Denmark, a thought about a higher frequency of coughing on the background of therapy with captopril and enalapril can be explained only by those who first appeared on the market and were recognized as the most frequent. One authorized the same frequency of coughing when using captopril or enalapril, at that time they stopped coughing, but the frequency of coughing on aphids of enalapril was 2 times higher than in the case of captopril.

If you have a cough on aphid IAPF, it’s not possible to develop a cough or hyperreactivity of bronchial tubes, but it’s 2 times more likely to develop in women, but not in choloviks. The data of the retrospective analysis indicate a significant indication of cough frequency in the development of cough on aphids, such as winery, in the middle, in 14.6% of females and 6.0% of choloviks. To be impressed, such indications can be explained by a higher low cough threshold in women in some cases.

The severity of pre-singing races (negro and zhovtoy) is a factor in the development of cough in the background of IAPF therapy. So, before a session, held in Hong Kong in Chinese ailments due to heart failure, it became possible for a persistent cough to develop in 44% of them had IAPF removed (in 46% of the ailments who had taken captopril, and in 41.8% had the ailment). At the same time, there was no connection between the dose of IAPF and the development of a cough.

The reason for racial inclinations in the frequency of having a cough in the background of IAPF therapy has not been precisely established. Negotiate racial awareness of the pharmacokinetics and pharmacodynamics of the ACE, as well as the sensitivity of the cough reflex.

In patients with CHF, cough develops significantly more often, not in patients with arterial hypertension, in 26% and 15% of cases, apparently. Cough, obumovation ІАПФ, with CHF, start to appear earlier, lower with hypertension.

To get involved, one of the hypotheses about the cause of the development of cough in the background of IAPF therapy cannot adequately explain the nature of this side effect.

Naybіlsh frequent mechanism vvazhayut pіdvishennya on tlі drive APF rіvnya bradikіnіnu.

Ingibuvannya ACE in the legends can lead to accumulation of bradykinin in the upper dichny paths, causing the development of a cough. Bradykinin stimulates nonelinating afferent sensitive 3 fibers by pouring into the J type receptor, which take part in the cough reflex.

Degradation of substance P - a neurotransmiter for afferent sensitive nerves, and especially of C fibers - also helps to get rid of ACE. Otzhe Ingibuvannya APF can be supravodzhuvatisya as much as possible in the infusion of the whole substance. The synthesis of prostaglandin E, which is vicious with bradykinin and substance P, can cause bronchoconstriction.

Transmission of the manifestation of genetic schism to the development of cough on the background of IAPF therapy. The polymorphism of the ACE gene has been inoculated, about 16% of people are homozygous for the same allele of the gene. So the incidence of coughing in the middle of patients, when they get an ACE, is approximately equal to the frequency of homozygosity for the new allele of the ACE gene. Patients who are homozygous for this allele may have a higher concentration of ACE. Less concentration of ACE can be used to increase the amount of bradikin, substances R and prostaglandins, and induce coughing.

Cough, coughing ІАПФ, squeaky is characterized by a feeling of rash in the back stints of the pharynx.

The cough is dry, urivial, trivial and paroxysmal. You can be strong in a horizontal position and on the floor, but you can get hoarse, vomit, and no coughing at the time of coughing. The cough does not lead to significant changes in the function of the legends, signs of bronchial obstruction or hypersensitivity. When a cough appears, it is impossible to lie down in the dose of ACE, and it can be wininicated at low doses. In fact, in one dose it is indicated that a decrease in the dose of IAPF should be reduced to a decrease in the frequency of coughing. The cough is swirling on the floor, which is poured into the year of the sick prodovzhuvati lykuvannya ІАПФ.

An hour from the ear of IAPF until the development of a cough can become 24 years. Up to 1 rock. A retrospective analysis of the development of a cough on aphids of the IAPF has emerged, from the ear of therapy until the first time about the appearance of a cough to take place in the middle 14.5 hours.

Unimportant for those who are not safe for coughing as a side effect of the IAPF, as well as for delivering patients to the patient, but not for those who are not safe, up to 50% of the ailments are self-conscious about lukuvannya when sick. It was reported that in the middle of the sick, for those on the background of the IAPF, a cough developed, the quality of life was worse, and the level of depressiveness in the case of patients, for those of whom had no cough.

Proof of interconnection between the drug and the development of the cough becomes a foldable problem. Call in medical documentation a cough, an IAPF speculation, to see how it manifests itself as a pathology (infections, allergies, obstructive lesions, gastroesophageal reflux). In addition, in a number of cases of cough, there can be many reasons why, not related to the IAPF (bronchial asthma, pneumonia, chronic bronchitis, laryngitis, infections of the upper dysfunctional pulmonary diseases, arteries, kurinnya).

Diagnostics of the difficult in identifying a cough, swollen with IAPF, is also tied to it, but it is often necessary to come at night and sometimes try to do it in a horizontal position. In ailments due to the congestive heart deficiency of the disease, it is important to recognize the signs of paroxysmal problems.

So, as a cough can be winicatized when taking all ІАПФ, replacing one ІАПФ for іnshiy, it’s unlikely that you can give it to me. However, in some cases, the fact of coughing is indicated by replacing one IAPF with one: quinapril for fosinopril, as well as captopril for enalapril.

In order to make sure that you have a cough and cough with ACEI, it is recommended to take the drug for 4 days. If you want to cough up the cough, it will take 1-7 days to pass, sometimes it will take up to 2 days. When the therapy is being updated, the same cough may occur again.

There is no unequivocal opinion on nutrition about those in which there are problems with the development of a cough, followed by a skasovuvati IAPF. Ailments, which stagnate the IAPF with the drive of arterial hypertension, can be transferred to the intake of drugs in the first class. Patients with heart failure and ailments, who have suffered myocardial infarction, IAPF are overloaded with Vibor drugs. Angiotensin II receptor blockers, I want them to be a viable alternative to ACE in the whole situation, or before the ACE in the whole category of ailments. In such a rank, it is necessary to make the nobles' poses relevant until they change their coughs, pummeled by the IAPF.

In decilkoh small pre-sluggish children were given pharmacological coughs until the cough was reduced, but they were diagnosed with ACPF therapy. Deyak with pre-juvenile drugs in a dyut on the backward mechanics of developing a cough, at that time they pour on those pathophysiological mechanisms, which are specific for the development of a cough, a vicious ІАП.

Preparations for coughs, which are recognized for terms of 1-4 months. gave leash a team hour effect. In principle, the preparations are vvazhayutsya non-effective for stifling a cough, puffed up with ACE.

Chromoglikat sodium nibilsh vivcheniy is a drug for cough suppression, poured with ACE. Wine is a stabilizer of ogryadnykh cells, the power of attracting such mediators to heat, such as histamine, bradykinin and prostaglandin, is great. To get involved in the chromoglikat decrease in the stimulation of bronchial 3 nerve fibers and for the reduction of cough, coughing of IAPF.

In 2 patients with placebo-controlled intercourse dosage, in 10 ailments with CHF and cough, developed on aphids of ACE, the efficacy of chromoglycate was administered at a dose of 2 inhalation 4 times a day. With the provocation of coughing and the establishment of a vicious cough sensitiveness, vikorisovyvuyuvuyutsya capsaicin. In 9 out of 10 patients who had chromoglycate in the case of a placebo, they had significant changes in cough (p<0,01), однако ни у одного пациента кашель не исчез полностью.

baclofen- an agonist of γ-aminobutyric acid, it is recognized in case of meat spasticity. Baclofen is used to drive substance R in legends. Before the additional transmission of baclofen by the authorities, it can be seen that the central cough reflex is suppressed, which can also be effective when coughs are not on the go.

The efficacy of Baclofen for coughing, as well as for aphid therapy with captopril, enalapril or fozinopril was given in a 4-year prospective patient with a pre-existing diagnosis. Seven patients were treated with baclofen at a dose of 5 mg 3 times a day from the 1st to the 7th day until the end of the day and at a dose of 10 mg 3 times a day - from the 8th to the 28th day. The change in cough was indicated on the 4th day, and the maximum effect - on the middle, on the 11th day. In 6 ailments, there was an external cough. In all the patients, the decrease in cough took place after 28-74 days after drinking baclofen, and in one patient, the cough started to cough up. It is necessary to confirm these results in placebo-controlled dosage.

theophilin For obvious data, except for bronchodilating diy, volodya with protivapalny power, which can obumovlyuvaty change cough, vicious ІАПФ. The energetic mechanism of the theophiline will tie with the suffocation of substance P in the sensitive nerve fibers of the spirited nobles.

In a subordinate blind, randomized, placebo-controlled, intercourse, 10 patients received an injection of theophilin at a dose of 8.5 mg / kg once a day for 2 weeks. on cough sensitivity to capsaicin. During the period of treatment with theophilin, cough suppression was indicated in 8 patients. It is also described that therapy with theophilin in a dose of 200 mg 2 times a day when taking coughs in the middle of 4 females, who took captopril to drive arterial hypertension.

sulindak- ingibitor of cyclooxygenase, which can play a potential role in a cough caused by IAPF, for reducing the synthesis of prostaglandins and reducing the level of bradykinin. Zdatnist sulindak drive cough, obumovaniya ІАПФ, the bullet was detected when cautioned for five patients, in those who cough changed to aphids, received sulindak in a dose of 100 mg 2 times a day. For those who are ill, the cough will go up, and for the fifth, the cough has been renewed only in 2 years. Until you take Chergovo dose sulindak.

The efficacy of sulindak bull was diagnosed in a small sublinear blind, randomized, placebo-controlled, intermittent disease, which included 6 ailments with arterial hypertension and a cough, rosy for aphilous ailoma therapy. Therapy with sulindak in a dose of 200 mg / day was carried out for 1 duration. Acceptance of sulindak supplementation with statistically significant changes in the sensitivity of the cough reflex to capsicin and changes in cough (p<0,05 для обоих показателей).

I will look at the lack of efficiency of the refractory index in patients with CHF, or diabetic nephropathy through negative influx into the function of nirok, until the change in cough, mabut, cannot be taken away.

preparations zaliza... Not long ago, a randomized placebo-controlled trial was carried out, and it was shown that in ailments with coughing, induction of ACE inhibitors, taking 256 mg of sulfate of saline for a stretch of 4 types. allows you to reliably change the frequency of cough. The mean value of the cough scale was significantly reduced in the group of oral cavity (s 3.07 ± 0.70 to 1.69 ± 1.10; p<0,05) и не изменялось в группе плацебо (с 2,57±0,80 до 2,35±1,22; p>0.05). Three ailments in the group have a cough. In both groups, there was no significant change in laboratory parameters, including indicators of peripheral blood, level of blood plasma and feritin plasma. We can use the mechanism of action to reduce the synthesis of NO for the reduction of the activity of the NO-synthase enzyme in the epithelial cells of the bronchi.

Thus, all the preliminaries of the effectiveness of drug therapy, which are directly related to the reduction of cough, accumulated by the IAPF, are not enough in order to present a reconfirmation of proof of the healthiness of medicinal preparations in order to increase the development of a wide range of drugs.

angioedema

Angioneurotic swelling in the presence of IAPF occurs at a frequency of 0.1-0.3% and will potentially threaten life with a side effect.

Dane slowed down to manifest itself by a local swelling of the lips, tongue, mucous membrane of the mouth emptying, larynx, nose and other parts of the face.

Mechanism of development of a secondary effect of IAPF is linked to a single bradykin or one of its metabolites. Angioneurotic development can be used to increase the amount of prostaglandin products, as a result of which they are victorious in the production of prostaglandins.

Such a rank is given by the side effect of the manifestation of the pharmacological action of the IAPF, which, perhaps, becomes overworldly in particular with genetically adjusted sensitivity.

All IAPF can be accelerated. Most often it develops on the cob of IAPF therapy, but it can also appear in case of trivial abuse. In the analysis of 163, there was evidence of the development of an anioneurotic swelling on the same therapy of the IAPF in 21% of patients with a history of developing for 24 years. From a cob of a drink, and in 20% - after 6 m / s. and more. In the middle, the development of an anioneurotic nabryk began after 3 days. from the cob of therapy.

Angioneurotic embryo of the same values ​​is also on the basis of the IAPF with the most reliable profile - perindopril. If the frequency of their occurrence during the analysis of data of 47 351 patients with arterial hypertension, they took part in the post-marketing preliminaries, became low and became only 0.006%, with the use of 320 patients, they achieved Find out the data about the greater strength of individuals of the negro race to the development of an anioneurotic person, so that you can use the data about the information about racial insights and in the frequency of the debate of some of the minor events.

Zvvychay dan of accelerated manifestation of symptoms, like passing through a stretch of decilkoh days during the treatment of IAPF therapy.

However, in some cases, angioedema can be manifested by such abnormal symptoms as respiratory distress, laryngospasm, laryngospasm, swelling of the larynx and obstruction of recurrent paths and leads to a lethal result. Moreover, when navіt rozvitku virazhenogo angіonevrotichnogonabryaku, obumovlenogo terapієyu ІAPF, scho minds in vimagaє lіkuvannya vіddіlennya іntensivnoї terapії in bіlshostі vipadkіv vzaєmozv'yazok nabryaku of terapієyu ІAPF not rozpіznaє, Especially, if angіonevrotichniynabryak rozvivaєtsya in vіddaleny perіod od cob terapії ІAPF. Deyakі authorize to those, that the reference frequency of an anioneurotic trick, pummeled by therapy ІАПФ, іs, nіzh tse is accepted in respect. So, when analyzing 4970 cases of malignancy before an allergologist, anxiety diagnoses were diagnosed in 122 cases, and in 10 of them there were diagnoses of IAPF therapy, tobto, in 8.2% of therapies there were diagnoses of angioedema.

The small intestine should be taken into the small intestine until the localization of an aneurotic form is small. Angio-neurotic intestinal obstruction can develop in the presence of a large mouth and mouth emptying, as well as in an isolated visceral angioedema.

Chase M.P. et al. describe two episodes of acceleration in a 72-year-old woman, which manifested themselves with scargia on abdominal pain, bloating and diarrhea.

A computer tomography for an hour on both epizodia showed a swelling of the wall of the small intestine. Analysis of anamnestic tributes showing that in 1 ms. Before the first episode of the disease, she was treated with lizinopril, the dose of which was reduced in 24 years. Up to the cutaneous epizode of an angioneurotic form. The writing of the ІАПФ ІАПФ epizodi of the angioeurotic dumbbell did not repeat itself for the first time with caution.

Ailments, in those on the background of ACEF therapy, it was indicated that they had an angioedemic malformation (including mild symptoms), were not guilty of taking ACEI therapy.

Ailments due to idiopathic angioedema in anamnesis may be due to the development of rapid development of rapid development in patients with IAPF.

shkirni visipi

The visoka frequency of development of the shkіrny visipu of the bullet is revealed in the cob doslіdzhennya captopril. At the same time, it was tied to the presence of sulfhydryl groups in the warehouse of the captopril molecule. However, it appeared that the temporal frequency of the visipu in the cich doslіdzhennyah bula, shvidshe for everything, was pummeled with a large dose of captopril (600-1200 mg / dobu). Podalshі doslіdzhennya, in which the menshі dosi (<150 мг/сут), выявляли меньшую частоту сыпи.

Visip is found in 1-5% of ailments, as they recognize IAPF in the drive of arterial hypertension. Shkirny visip, amazed by the therapy of IAPF, in a large number of cases, maculopapullous visipus, which is localized on the hands and upper part of the tulub. Visip zzvychay to develop with a stretch of the first 4 types. from the cob of therapy (most often - stretching out the first few days). Visip more often than not, so you can only have a decal for years or days, so you don’t expect to see the IAPF.

Tie the viscous line with an ACE injection into kinase II (an enzyme, an identical ACE). The determination of the activity of kinase II is to lead to the potentiality of the activity of kinases in the school and the development of ignition reactions preceded by histamine. The development of visipiv, in the basis of which lies the whole mechanism, can be cleaned up with the use of IAPF. However, with regard to the appearance of cross-reactivity between captopril and enalapril, which can be used as a basis, it can be used to show a number of mechanisms in the process of bitwise action. Such a rank, if the visip is on the smallest reception of any IAPF, then, imovirno, docilely tried to test vicoristovuvati the first preparation of the whole group.

Dysgeusia and "burned movi syndrome"

Іngіbіtori APF іnіdі viclіkіut ruin svakoї sensitiveness (dysgeusіya). Tsei effectively describe the ailments in a simple way, yak vratta gusto, savoring a metal gingerbread, lingering liquorice grimminess, or twisting gusto. The frequency of development of the loss of relish sensitivity when taking captopril at doses less than 150 mg / day becomes 0.1% to 3%, and at doses over 150 mg / day it increases to 7.3%. Earlier, dysgeusia was more often described when using captopril in small amounts of ACE inhibitors. If I want the destruction of the relish sensitivity, I will link up with the manifestation of sulfhydril groups, to find place in the molecules of captopril, and the destruction of the device will take place on the basis of the therapy with enalapril and lisinopril, which does not disturb the group.

It is not allowed to let it go, but this is a bit of a game that can be used for all the IAPF.

Destruction of relish is often є werewolves і know independently (in the case of bagates, in the case of a stench, they only smell 2-3 months long, unimportant for further therapy). Protest, dysgeusia negatively infuses on the quality of the life of the ailments, changes the sickliness to the liking and can help reduce the weight of the sick.

The factor of zinc deficiency to the destruction of relish sensitiveness is a zinc deficiency; Descriptions of vypadok usunennya of an unsuitable malt ginger in the mouth, poured with captopril therapy, meaning that in the middle of the selenium methionin.

"Syndrome of burned movi" is manifested by the symptoms of burning in the mov, throat, lips and / or heaven, which are similar to such when drinking hot drinks or hospitable strains. "Syndrome of scalded movi" In the case of rapid accelerated therapy of IAPF and in the development of aphthous stomatitis and inflamed diseases, which can also describe how the accelerated therapy of IAPF is described. The development of "burned movi syndrome" is indicated in patients with captopril, enalapril and lizinopril, ala, imovirno, and may be on the other side of therapy for IAPF. This acceleration is not connected with the deterioration of relish sensitivity, zooming of the IAPF, and the mechanism of its development has not been established.

hematological efficacy

Angibitories of ACE induce a slight decrease in the level of hemoglobin and hematocrit, as for most ailments it is not less important. Describes the development of aplastic anemia during the therapy with captopril. There was also about the development of aplastic anemia in two ailments with the use of lisinopril at a dose of 5 mg per dose; Moreover, in both cases of illnesses, the bully of the kidnapped and old man (64 and 79 years). The growth of aplastic anemia in one fall is determined in 6 ms. from the cob of lіkuvannya lizinopril, and in іnshomu - after 15 days. With transplantation, niro anemia, poured over with IAPF, hiymovirnishe, develops in as much as a decrease in the level of eritropoietin.

Neutropenia and agranulocytosis are obviously common side effects of ACEI therapy. In case of high doses of captopril (150 mg per day or more) and in important ailments, the rate of growth is increased. Thus, in ailments with a normal level of creatine plasma and in the daytime of diffuse tissue diseases, the frequency of development of neutropenia in the course of therapy with captopril became 0.02%, and in patients with systemic heartworms more than 2%. Інші autoimmune illnesses also increase the risk of development of neutropenia, accumulation of IAPF. Ymovіrno, the price is tied to the power of the IAPF to induce antinuclear antibodies. Neutropenia, a minor autoimmune genesis, develops in about 7% of ailments on autoimmune disease, when captopril is removed. In addition, a rise in neutropenia is observed with one-hour signs of cytostatics and captopril. It is also indicated that the development of granulocytopenia in the presence of an interferon and an ACE inhibitor is more important for the development of granulocytopenia.

Hepatotoxicity

Hepatotoxicity is rarely, but not seriously, secondary to the action of the IAPF therapy. Hepatotoxicity is indicated when using captopril, enalapril and lisinopril. The overdrive of ACE inhibitors for hepatotoxicity means the ability to develop on the basis of therapy with ACE inhibitors.

Of 17 ailments, in some of whom the development of hepatotoxicity was described, 14 were eliminated with IAPF for the drive of arterial hypertension and 3 for the drive for congestive heart failure. Nirkov's lack was indicated in 5 of the cich ailments, 4 of them required hemodialysis. Zhovtyanitsya Bula is the most frequent clinical manifestation of hepatotoxicity, ample therapy for ACE. In some cases, the zhovtyanitsa developed in a dozen hour after the appearance of an asymptomatic increase in the amount of lusen phosphatase or transaminases. When analyzing laboratory indicators, in 13 cases there were signs of cholestatic lesions, and in one case it was not a purely hepatocellular lesion. In all patients, the morphological dosage of the liver is violated.

With a total of 8 drops, there are signs of cholestatic lesions, in 2 - of a low lesion, in 2 - signs of necrosis of hepatocytes, and in 1 drop - signs of hepatocellular disease. In a large number of vypadkiv during the development of the APF, the normalization of the liver enzymes is normalized in the term of 2 types. up to 9 ms. for the correction of therapy.

The mechanism of development of hepatotoxicity on the basis of ACEI therapy is not clear. Transmission of mechanisms of hepatotoxicity: injection of sulfhydryl group and captopril and hypersensitivity reactions. Krym, strangled for the rakhunok ІАПФ activity of kininazi II to produce to the brink of bradykinin. The transformation of arachidonic acid into prostaglandin can be improved instead of bradycin. Prostaglandins and leukotroins, which are products of the metabolism of arachidonic acid, play an important role in the functional hepatobiliary system. I, if the prostaglandins get hooked on the hepatobiliary system, they can stimulate the synthesis of prostaglandins that can be mediated through ACE cholestasis. Zokrema, it is established, that prostaglandin A1 reduces the fluidity of the flow of zhovchi in dogs, and 16,16-dimethyl-prostaglandin E2 - in humans. Leukotrieni volodyut is more significant for hepatotoxic effect. About hypersensitivity as the mechanism of development of hepatotoxicity on the basis of IAPF therapy, refer to the biopsy of the liver, which appears in a large number of cases of cholestatic shock, which is typical for reactions of this type.

Negative inflow on the plate

Negative inflow for the period of time is contraindicated before the value of the IAPF for the hour of vaginosity. Captopril and enalapril can easily penetrate the placenta and produce an accelerated pregnancy in a newborn fetus. Victory efficiencies are recognized when all IAPFs are received. We can use the mechanism of negative infusion on the fetus є lowering the placental blood flow for rakhunok vasoconstrictor bradykinin on the placenta.

Previously, it was shown on the animals that ACPF is not a teratogenic effect at the early stages of vaginosity before the hour of the phase of organ formation, but it is not safe at the later stages of vaginosity (before the hour of the period). The effect can be increased by the swirling arterial hypotonia in the fetus before another hour or the third trimester of vaginosity. Therapy ІАПФ for every hour of vaginosti led to an unstable ossification of amniotic rіdina (oligogіdramnіon), nircum deficiency of a fetus and a neonatal, fetal death and neonatal, to neonatal anemia, hypotension. In the course of the therapy of the IAPF before the hour of vaginosity, defects were tied in the development of the cranial part of the skull, and on the other hand, there was no unequivocal thought.

Women of reproductive health, who accept ACE therapy, are guilty of effective contraceptive use. If women of early childhood with arterial hypertension take ACE, then the memory of the need for different vaginosity to transfer ailments to the intake of an antihypertensive drug from the group.

When an unscheduled vaginosity is established for women who are able to accept the IAPF, the tactic is to lay it down as a term of vaginosity. So, there are data about those, that the exposure of the IAPF in the early term of vaginosity supervises with a small risk of negative influx on the fetus, and in all kinds of changes in vaginosity it is not necessary. However, it is not guaranteed that the fetus will be safe in the first trimester of vaginosis during the first trimester of pregnancy. All vipadkas need medical attention.

visnovok

Thus, the range of side-by-side diy ІАПФ reaches a wide range. I’ll look at, in most important situations, alternatives to the IAPF in Danish hour, it’s necessary to go to the analysis of the side effects of these drugs, in order to avoid taking care of the therapy and avoiding the risk of survival. Greater real-time monitoring of the IAPF therapy, in a sense, will allow the polypsy to be clinically effective in the treatment of ailments to heart-damn deaths in the minds of practical protection of health.

literature
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Chemistry for the therapy and prevention of heart ailments ingibitors of angiotensin converting enzyme(APF). Modern emotions allow you to effectively eliminate the problem of illness by fixing due to hypertension, ending the heart's lack.

The principle of the development of the drug is that the drug is blocking angiotensin, which is indicative of the sounding of sudin. Angiotensin zmushuє viroblyaty aldosterone, which in most cases, is the cause of overwhelming disease.

Classification of ingibitoriv APF

All lines of the group can be divided into several types. All the stench comes from one kind of one and the designation for the treatment of a particular ailment. Similarly, there is a sense of the generation and the more recent version may be more effective.

All of them are close to chotiroh vidіv іngіbіtorіv, the stench viglyadayut the offensive rank:

1. Ingibitori sulfhydryl group;
2. carboxyl group;
3. phosphinyl group;
4. іngіbіtori naturnі.

• Pererakhovanі vische see and become active, so as the stench may cause biological activity, skin from the same types of viconuє one function of attracting angiotensin, alerobit in a simple way, penetrating and vivedennya to the organism.
• The stench can also be accumulated in a smart way in the clitines... The skin preparation has a positive effect on the myocardium and the whole body.
• Also there are some ACE drugs, such as inactive speeches and are called spikes. It will become more active if you lose moisture from the intestinal tract as a result of hydrolysis, as well as a viable option, if the metabolism occurs in the liver.
• All licars' forms are introduced to them. unavoidable description of active groups. The decals of the classes are formed from the beginning, which are designed in a way that is highly motivated and fast-paced.

drug change

Find medications for mittovoy, which can help with an attack of hypertension, as well as medications that can be used for trivial therapy without showing negative effects. Also, it is possible to reach through the ryznoї shvidkostі vmoktuvannya, for example, the expansion of the drug kapoten soak from the shlunkovo-intestinal tract for a period of years, dalі, vivoditsya nirkami.

Report list of medications in residential buildings with hypertension:

The Danish list is incomplete, every day more and more effective drugs of the new generation are released. If you need to change it, you will need a consultation with a Fakhiv citizen before your appointment.

There is also a stench that can be shown as the following: the destruction of robots, rotations of atherosclerosis of the swelling, їkh from the protection of stagnation in case of diabetes mellitus.

You will know even more in the analogue statistics

Pharmacological authorities

• Be-ingibitor APFє in a unique lykarsky way, as it helps to normalize the concentration of ions in calories and magnesium, and in its own turn to improve the transport systems of membrane cells.
• With a tsyom heart m'yaz repairs more actively work (even earlier than you won a bully in a driven mill), thus allowing you to more beautifully endure physical installation.
• Head authorities є Sudinosilicate... In case of a trivial interruption of arterial hypertension, if there are trochi of hypertrophy of the myocardium of the slunk, an ACE inhibitor can be helped, regression of the hypertrophic part will be seen.
• Blood circulation of all organs Significantly pollipshuєtsya, if the brain is trivial hour seeing sisneve hunger through the sound of sudin tied with angiotensin, then the problem will be violated.
• Even more importantly, Zdatne vzamodiyati with інshim preparations for complex treatment of serous ailments.

As a result of the re-insurance, the ingibitories can be infused into approximately 4 areas in the body:

1. The inflow to the heart-vessel system at the viglyadі polіplshennja function and zagalniy camp.
2. After pouring on the nirki, here the ACE will shrink the dyuresis, change the migration of macrophages and monocytes.
3. Neurohumoral effects in viglyadi suppression of angiotensin, decrease in the activity of the sympathoadrenal system.
4. The infusion on cells appears in the polyphenyl metabolism of glucose and anti-combustion.

Shown to sucking

In the first place, if the ailment is diagnosed, the zvuzhennya of the sudin is diagnosed, the yak is tied with angiotensin of the first or another type є is shown to the zasosuvannya.

More reportable list of ailments, for which denominations are recognized as a type of ailments:

In case of ailments, lyki vistupaє is a component of complex therapy, for example, a drug for nobility of attacks. In case of a simple interruption of the disease, you can be victorious in the quality of monotherapy.

It is even more important for people with periodic attacks of hypertension, given the drug, so that it is possible to significantly reduce the attack.

List of drugs in the last generation, which can help with an attack:

• zofenopril;
• fosinopril;
• lazinopril.

They are overwhelmed by the fact that the part of the drug in a given place is given a stove, which allows them to be victorious for those people, who have a lack of nirkov.

Prototype

In general, the drug is well tolerated, albeit, as if it were the only drug, there is no evidence.

A general list of counter-indications:

• stay and breastfeeding year;
• stenosis of the girl's aorta;
• strong dyuresis (wine can lead to a strong drop in the arterial vise);
• nirkova lack (at the same time with her a powerful reception of new generation ingibitors);
• stenosis of the artery of a single nirka;

It is possible to show the proof, as it can be revealed only as a likarem.

Likewise є ailments, for which there are signs of stagnation with great protection, they include such ailments:

1. autoimmune ailments;
2. deterioration of the function of nirok and stove;
3. abducted vіk.

It is not a matter of self-reliance to recognize an ACE drug, since a prescription is required for its purchase. Likar carried out an external history and anamnesis for the first time.

If there will be a contraindication, even if there will be more cinnamon, it will not be possible for a Skoda, then it may be considered stagnant under strict control.

Pobichna diya

In case of dosing, it was specified in the instructions or individually taken with a viable drug, the frequency of side effects is still low. For tabletting forms, the reaction is characteristic of organism in viglyadas of boredom and intolerance.

In the medical practice, the following secondary effects are fixed for the given drug:

• hypotonia can develop on the smallest reception (the camp is opposed to the sliding vice);
• the normal robot may be destroyed;
• to show headache and spoiled;
• tediousness and decreased appetite;
• development of allergic reactions;
• with implantation of advanced doses, arterial hypotension is possible.

In general, I will be destroyed It can be strongly reversed, if a person has a serious pathology, for example, in a large number of cases, robotic damage has been fixed in people with ailments, as if he had a problem before taking a likarsky zasob.

Іngіbіtori ACE with diabetic diabetics vіdmіnno to cope with the charges laid on them by the employees, ala, serioznі uzhenіya nirok that іnh organs through the primary illness, then at all times it is possible to wipe out serioznі inheritance. Likewise, doykikh people have a cough for an hour.

Mechanism of Diya

Mechanism for a drug of goodness, that is, the ability to understand the details of that, as the drug is pratsyu.

Іngіbіtori dіyut in such a way:

Speaking in a simple way, it is just that the hormone angiotensin doesn’t produce a sound effect.

Also, injecting into bradikinin is allowed to significantly expand the sudini, thereby increasing the effectiveness of the drug.

Bradykinin is a peptide, which in a great number reduces the arterial grip.

Also, they are combined in a unique way, therefore, ACE blockers are widely appreciated in the treatment and suppression of attacks against diseases. So, when you take the drug, you can significantly expand, we prepare varto buti to a reduced vice, since you have є before new schilosti.

Overvoltage of preparations and efficiency

• Direct analogs for this type of leads Practically dumb, tse means that it’s not a matter of getting it wrong, ale to wind for such minds the stench of a masu perevag.
• Naygolovnishim є those For an additional drug, you can take it, as I will help you for the symptoms of symptoms, so if you need a trivial therapy, angibitorium ACE, a universal lykarskiy zasob.
• Infection on the market Combination of ACE inhibitors, both as a diuretic and antihypertensive.
• Liks є we shorten advancing through the great heart disease in porous with antihypertensive diseases. This is a great effect, as well as at once with the therapy I will give a prophylactic and polish training. Strongly increase the ability of the clitin to cling to glucose, in case of diabetic diabetes, it can help to reduce the amount of insulin.
• New generation of lykarsky zasobiv can be victorious in case of serious problems with nirkas, which is an unbeatable challenge for people who can deprive one nirku of any serious pathology with given organs.

Prices for drugs

Given a group of lykarsky zasobіv can be known in a great pharmacy, prices will be found in every place, and also from the trade mark, which represents the drug.

According to all Russian prices, there may be slight changes, the axis is close to the number of the most popular types:

• renepril cost of 50 rubles for 20 tablets;
• parnavel mau partiality from 200 to 400 rubles for 30 pieces (for a view from the first lika maє bolsh triva diyu);
• monopril the cost of up to 450 rubles for 28 tablets
• ampilan the price is up to 200 rubles for 30 pieces (to get stuck in case of complex treatment of hypertension, ischemic ailments of the heart, it can be caught in case of damaged robots);
• hood the cost is up to 200 rubles for 40 pieces (to be stuck with a slight override of hypertension and for the suppression of attacks, as in the case of a one-time stagnation of non-victories of side effects).

Just vibrate the drug to a more suitable drug, it is not possible for you to develop any side effects, as it may appear if you do not have, if you control the intake, you can replace the drug for the smallest, more incoming one.

We need drugs to help solve the problem with hypertensive and other ill-gotten children, but for that purpose, they do not let them get away with it, you need to be sure to get a professional visit.

At home prophylactics of greater ailments include: training immunity, physical employment, regular maintenance, taking medications, and polishing the body. In case of ailments, it is even more important not to engage in self-abuse, it is necessary to immediately eat at the reception to the doctor, dal, and his recommendation.

The pharmacodynamic effect of ACE inhibitors is related to ACE blockages, which converts angiotensin I into angiotensin II in the blood and tissues, so that it can lead to the loss of freshwater and neurohumoral neurohumoral diseases in the middle of the second, as well as

A large number of ACE ingibitors є by spills (except captopril, lizinopril), which are active metabolites. Razrіznyayutsya іngіbіtory ACE affinity to ACE, injected on the fabric of the RAAS, lipophilicity, eliminatsії shlakhami.

The main pharmacodynamic effect is hemodynamic, of dressing with peripheral arterial and venous vasodilation, as in the case of other vasodilators it is not supervised to increase heart rate through a decrease in activity. Nirkovy effects of ACE inhibitors are associated with dilatation of glomeruli arterioles in the development of natriuresis and absorbed calories as a result of a decrease in aldosterone secretion.

Hemodynamic effects of the ACE are at the heart of the hypotensive activity; in ailments due to congestive heart failure - in a decrease in the dilatation of the heart and an increase in the heart wikidu.

Іngіbіtory ACE nadayut organoprotective (cardio-, vaso- and nephroprotective) diu; pleasantly infuse into carbohydrate exchange (change insulin resistance) and daily exchange (increase the level of LPVShch).

Angibitories of ACE become stagnant for the treatment of arterial hypertension, dysfunction of the louse and heart failure, vikoristovy in case of myocardial infarction, diabetes mellitus, nephropathy therapy.

Class-specific side effects manifest - cough, hypotonia of the first dose and angioedema, azotemia.

Key words: angiotensin II, angiotensin ACE, hypotensive action, organoprotective action, cardioprotective action, nephroprotective action, pharmacodynamics, pharmacokinetics, side effects, drug reactions.

BUDOVA I FUNCTION OF RENIN-ANGIOTENZINALDOSTERONE SYSTEMS

The renin-angiotensin-aldosterone system (RAAS) is a more important humoral inflow into the heart-vascular system and take part in the regulation of the arterial grip. Central Lanka RAAS Je angіotenzin II (AT11) (Scheme 1) yaky volodіє bearing-down direct vasoconstrictor dієyu perevazhno on arterії i oposeredkovanim dієyu CNS vivіlnennyam kateholamіnіv of nadnirkovih zaloz i viklikaє zbіlshennya OPSS, stimulyuє sekretsіyu aldosterone i only be sold to zatrimki rіdini i pіdvischennya ( BCC), stimulates catecholamines (norepinephrine) and other neurohormones from a pretty end. The injection of AT11 on the level of the arterial grip will help to improve the tone of the sudin, as well as for the additional structural overwhelming and remodeling of the heart and the sudin (Table 6.1). Zokrem, ATII є is also a growth factor (or a growth modulator) for cardiomyocytes and smooth blood cells.

Scheme 1. Budova-angiotensin-aldosterone system

Functions of the largest forms of angiotensin. Angiotensin I is of little importance in the RAAS system, as it quickly transforms into ATP, in addition, its activity is 100 times less than that of ATP. Angiotensin III diє is similar to ATP, ale and pressor activity is 4 times weaker than ATP. Angiotensin 1-7 is accepted in the course of converting to angiotensin I. For the functions of ATP it is important to consider the type of ATP: it is not a vicious pressor action, but navpaki, to reduce the stimulation of the arterial prostate of a hypertension, a secretion

RAAS to rob the regulating inflow to the nirk function. ATP wiklikє a straining spasm to bring arterioles and a decrease in the grip in the capillaries of the glomerulus, a decrease in the filtration in the nephron. As a result of a decrease in filtration, sodium reabsorption in the proximal nephron is reduced, so that sodium concentration in the distal tubules is increased to an increase and the activation of Na-sensitive receptors in the brain beaches. for fur

To the heart of the ringing sound, the price is to support the galvanizing of the renin and the improvement of the glomerular filtration.

The function of the RAAS is linked with aldosterone and for the additional mechanism of the vocal ring. Aldosterone is the most important regulator for the maintenance of the birth and homeostasis of calories. Aldosterone does not deteriorate directly on the secretion of renin and ATP; it is only possible to intervene by pouring through sodium into the organisms. In regulating the secretion of aldosterone, ATP and electrolyte take on the role of ATP, while ATP stimulates, and sodium and calcium - to change its awareness.

Homeostasis of electrolytes in tight dressings with the activity of the RAAS. Natriy and kaliy not only infuse the activity of the renin, but change the sensitivity of the fabric to the ATP. At the same time in the regulation of activity

Renin has a great role to play with sodium, and in the regulation of the secretion of aldosterone - calcium and sodium may, however, be added.

Physiological activation of the RAAS helps to prevent in case of a deficiency of an antihypertensive, meaning a decrease in an arterial pressure, as a result of a decrease in a hypertension in conditions, due to the activity of a sympathetic and urethy nervous system,

A number of heart-and-heart problems can be diagnosed with pathological stimulation of the RAAS, spine, with hypertension, congestive heart failure, myocardial infarction.

In the Danish hour of sight, PAC functions not only in plasma (endocrine function), but in bagatio tissues (brain, vertebral column, heart, nirkah, supra-nirkovy vals, legends). The tissue of the system can be practically independent of the plasma, on the cell line (paracrine regulation). In addition, they develop short-line effects of ATII, enriching the visibly circulating fraction in the systemic blood flow, and the progressive effects, regulated through the tissues of the RAS and injecting onto the structurally-adaptive mechanisms of the organisms (6.2

Table 6.2

Development of factions of RAAS and efects

The key enzyme RAAS is an angiotensin-converting enzyme (ACE), which will prevent the conversion of ΑTI into ATII. The main number of ACE is present in the systemic blood flow, without providing coverage of circulating ATII and short-term geodynamic effects. Reincarnation of AT in ATII in tissues can be found not only for the additional ACE, but also

tami (khimazi, endoperoxides, cathepsin G і ін.); Vvazhayut, so їm to establish a provid role in the function of the fabric of the RAS and the development of trivial effects in the model of the function and structure of organ-targets.

ACE is identical to the enzyme kinase II, which takes part in the degradation of bradykinin (Scheme 1). Bradykinin is a straining vasodilator, which takes a part in the regulation of microcirculation and ionic transport. Bradykinin is even a short period of life and is present in blood (tissues) in low concentrations; This is due to the fact that the muscle hormone (paracrine) is shown to be effective. Bradykinin spirits increase the internal calcium Ca 2 +, which is a cofactor for NO-synthetase, while taking part in the endothelial relaxant factor (nitrogen oxide or NO). Endothelial relaxation factor, which is a blockage of rapid muscle mass and thrombocyte aggregation, as well as an inhibitor of mitosis and proliferation of smooth muscles, which will prevent antiatherogenic activity. Bradykinin also stimulates synthesis in the endothelium of Sudin PGE 2 i PGI 2 (Prostacyclin) - vasodilators and platelet antiplatelet agents.

In such a rank, bradykinin and the whole kinin system is the counterpart for the RAAS. Blocking ACE potentially increases kinin levels in the tissues of the heart and vertebral column, which will prevent antiproliferative, antiischemic, antiatherogenic and antiplatelet effects. Kіnіnіyuyut increase in blood flow, dіuresis and natriyuresis without a change in the speed of glomerular filtration. PG E 2 i PGI 2 also may diuretic and natriyuretichesky day and increase nirkovy blood circulation.

The key enzyme RAAS is an angiotensin-converting enzyme (ACE), which will prevent ATI from converting to ATII, and also take part in the degradation of bradykin.

MECHANIZM DIЇ І PHARMACOLOGIA INGIBITORIV APF

Pharmacodynamic effects of ACE inhibitors are linked to ACE blockages and changes in the establishment of ATS in blood and tissues

Usunennyam of freshwater and other neurohumoral effects. At the same time, due to the mechanism of the vocal ring, the level of renin plasma and ATI can be reduced, and also the level of aldosterone can be transiently reduced. The Angibitories of the APF outdid the ruinous bradikinin, which will additionally and at the same time give rise to the deterioration effect.

There are a number of important characteristics for the distribution of preparations of the whole group (Table 6.3):

1) Khimichnu Budov (presence of Sff-group, carboxylic group, phosphor-containing);

2) likarska activity (drug abo prodrug);

3) infusion onto fabrics of RAAS;

4) pharmacokineticlasticity (lipophilicity).

Table 6.3

Characteristics of ingibitoriv ACE

The nature of the growth in fabrics (fabric specificity) of the ACEs is found at the stage of lipophilicity, which increases the penetration in the tissue, and as a result of the connection with the fabrics of the APF. Vivid power of action (affinity) of ingibitoriv APF doslidzhena in vitro. The data about the relative strength of the APF іngіbіtorіv іngіbіtorіv are presented below:

Kvіnaprilat = benazeprilat = Trandaloprilat = Cylazaprilat = Ramіprilat = Perindoprilat> Lisinopril> Enalaprilat> fosinoprilat> Captopril.

The power of the connection from the APF is not only the power of the action of the APF, but the triviality of the action.

Farmakodinamіchnі efekta іngіbіtorіv Je classes ACE-spetsifіchnimi pov'yazanі i s i blokuvannyam ACE zmenshennyam utvorennya ATP in krovі i tkaninah at usunennі presornih i іnshih neurohumoral Yogo efektіv and takozh of Poperedjennia ruynuvannya bradikіnіnu scho spriyaє utvorennyu vazodilatuyuchih faktorіv (PG, NO), additional vasodilatation effect.

PHARMACODYNAMIKA INGIBITORIV APF

The main pharmacodynamic effect of ACE ingibitoria is hemodynamic effect of arterial and venous vasodilation, which develops as a result of folding changes in neurohumoral regulation of the cardiovascular system. The mechanism of the stench is fundamentally derived from both direct vasodilators and antagonists of calcium, which go directly to the vertebral wall, as well as from the vasodilators of the receptor β-adrenergic receptor. Smell change the OPSS, increase the heart wikid and do not infuse on the heart rate very quickly as a result of the use of stimulating ATP on the SAS. The hemodynamic effect of the ACE inhibitions is spontaneous to occur independently of the activity of the renin in the blood. The vasodilating effect of ACE ingibitoria manifests itself in the changes in the regional blood flow in the organs and tissues of the brain, heart, nirok. In the tissue of nirok ingіbіtori APF, they expand the development of the arterioles of the glomeruli and reduce the internal glomerular hypertension. The stench will also reduce the amount of calories and reduce the secretion of aldosterone.

Hemodynamic Effects INGIBITORIV APF LIE IN THE BASIS OF THE NINTH Hypotensive Activities

The hypotensive effect of reasoning is not only a decrease in ATP education, but rather a reduction in the degradation of bradikin, which is a potential endothelium relaxation of smooth muscles of sudin, through the elucidation of the vasodilating factor of prostate cancer.

For a large number of ACE inhibitors, the hypotensive cycle should be repaired after 1-2 years, the maximum effect will develop in the middle after 2-6 years, the triviality of the day reaches 24 years (for the most short-lived three years - the captopril, and 6-12 years old) ). The speed of the hemodynamic effect of the inflammation is directly injected into the tolerance and variation of the hypotonia "first dose".

Table 6.4

The triviality of the hypotensive action of the Angibitorium

Rospodil hypotensive effect of angibitoris ACE in the hour does not depend on the exact form of pharmacokinetics, at all, not all drugs, to use a trivial type, are characterized by a high index T / p (Table 6.5).

Table 6.5

Stall T / p Ingibitoriv APF

Angiophilia ACE to reduce the development of norepinephrine and the reactivity of the vasoconstrictor vasoconstrictor sympathetic activation; In ailments іz zastіynoyu Sertsevy nedostatnіstyu znizhennya periferichnoї sistemnoї rezistentnostі (pіslyanavantazhennya) legenevoї sudinnoї rezistentnostі i kapіlyarnogo vise (perednavantazhennya) Veda to znizhennya dilatatsії porozhnin sericite, polіpshennyu dіastolіchnogo napovnennya, pіdvischennya Sertsevy vikidu i zbіlshennya tolerantnostі to fіzichnogo navantazhennya. In addition, the neurohumoral effects of the ACE ingibitorіv control the remodeling of the heart and sudin.

The managers of the blocking of neurohumoral effects ATII ingibitorium of ACE produce an organoprotective effect: cardioprotective, vasoprotective and nephroprotective; the stench wicks a number of friendly metabolic effects, turning into carbohydrate and lipid metabolism. Potential effects of ACE ingibitoriv are presented in table. 6.6.

ACE inhibitors develop a cardioprotective effect, suffer from HLS regression, undergo remodeling, ischemic and reperfusion myocardial regeneration. Cardioprotective effect є class-specific for all ACE intellectuals and sensations, from one side, trophic activity AT11 on the myocardium, and on the other hand, modulation of sympathetic activity, so important AT11

Table 6.6

Pharmacodynamic Effects of Ingibitoriv ACE

katecholamіnіv, and іngіbuvannya ATP to bring to the reduction of the pretty one in the heart and the judgment. In healthy cardioprotective effects in ACE ingibitors, it is not easy to have kinin. Bradykinin and prostaglandins for anti-ischemic diseases, dilatation of capillaries and growth

delivery of acidic myocardium to improve microcirculation, improve the metabolism and pumping function of the myocardium on the basis of HLS regression in the postinfarction period.

The role of antihypertensive drugs in the reduction of hypertension before the lower classes of antihypertensive drugs is important, and moreover, there is a difference in hypotensive effect and regression of hypertension.

Angіbіtori ACE have a vasoprotective effect, skating effect of ATII on the AT 1 receptor of sudin, from one side, from the second side, activating the bradykіnіnu system, reducing the endothelial function on smoothing and providing vascular antiproliferation

The anti-atherogenic effect may be anti-atherogenic in the mechanism of anti-proliferative and anti-gravity effects on the cells of smooth mucous membranes of the sudin and monocytes, the reduction of the antioxidant formation of the collagenous matrix, antioxidant. Additional anti-atherogenic effect of potential for ACE inhibitors of endogenous fibrinolysis and antiplatelet effect (galvanization of platelet aggregation); reduction of atherogenicity of plasmas (reduction of LPVShch and triglycerides and reduction of LPVShch); the stench poperezhayut rozryv atherosclerotic plaques and atherothrombosis. Anti-atherogenic power in clinical prescripts is shown for ramipril, quinapril.

Angibitorium ACE may have an important nephroprotective effect, which can lead to a progression of nircum deficiency and a decrease in proteinuria. Nephroprotective effect is class-specific and characteristic for all drugs. Dilatation of the overly important arteries of the glomerulus superficially leads to a decrease in the intraglomerular filtration pressure, the filtration fraction and the hypertension, as a result of the decrease in the hypotension Renal efficacy, which is sensitive to the high sensitivity of nirkovy vessels to the vasodilator effect of the angibitorium ACE, is manifested earlier, lower than the decrease in OPSS, and less often the hypotensive effect is often delayed. In the mechanism of antiproteinuric effect of the ingibitoriv ACE, lie the prototype on the basal membrane of the glomerulus and antiproliferative effect

on the mesangial cell of the glomerulus, which reduces the penetration for medium and high molecular weight proteins. In addition, the ACE inhibitors assimilate the trophic effects of ATII, which stimulate the growth of mesangial clitins, the production of collagen and the epidermal factor by them, the growth of nephrosclerosis, accelerate the development of nephrosclerosis.

It has been established that the lipophilicity of the ACE ingibitors is lumpy on the tissues of the RAS, and, possibly, organoprotective effects (Table 6.8).

The operational pharmacokinetics of ACE ingibitors is presented in table. 6.9.

The specific pharmacokinetic peculiarity of the greater number of ingibitoriv ACE (except captopril and lizinopril) є

Table 6.8

Index of lipophilicity of the active forms of the main ingibitoriv ACE

Note. Negatively significant in relation to the hydrophilicity.

changes in metabolism in the liver, including presystemic, which lead to the establishment of active metabolites and supervise a significant individual variability. Such pharmacokinetics robbing the ACE inhibitors similar to "prodrugs", the pharmacological process of which is accepted in the middle of the process is established in the liver of active metabolites. Russia has registered a parenteral form of enalaprilu - a synthetic analogue of enalaprilat, which is used to treat hypertensive crises.

The maximum concentration of ACE ingibitors is reached in blood plasma after 1-2 years and is infused into the rapidity of hypotonia development. The ingibitories of the ACE are associated with a high level of connection with the plasma beads (70-90%). The period of time is variable: from 3 years to 24 years and more, if the pharmacokinetics is less infused on the duration of the hemodynamic effect. I see three phases of early

not a widespread decrease, which shows the stage of growth (T 1/2 a); the cob phase of elimination, which represents the elimination of unconnected tissue ACE fractions (T 1/2 b); The trial is the thermal phase of elimination, which represents the elimination of the dissociated fraction of active metabolites from the complex with ACE, which can reach 50 hours (for ramipril) and the start of the dose interval.

The drugs need to be metabolized from the statements of glucuronides (like lisinopril and Cylazapril). Most importantly, may the way of the elimination of the Ingibitoriv APF:

overly nirkovy (ponad 60%) - lizinopril, tsilazapril, enalapril, quinapril, perindopril; biliarny (spirapril, trandolapril) for any reason. Biliary ecology is an important alternative to nirk elimination, especially if there is a chronic nirk deficiency.

Shown

arterial hypertension(Table 6.9). Angіbіtori ACE nadayut a hypotensive effect practically in all forms of hypertension, directly in the activity of renin plasmas. Baroreflexes and cardiovascular reflexes do not fluctuate, the day is orthostatic hypotonia. The whole class of drugs is delivered up to drugs in the 1st row in the blood pressure test. Monotherapy is effective in 50% of patients with arterial hypertension. In addition to hypotensive diseases, angibitories of ACE in ailments with hypertension, they reduce the risk of heart-bladder acceleration (perhaps, more, less hypotensive drugs). Іngіbіtory ACE є with Vibor preparations in case of hypertension and diabetes mellitus through a significant decrease in the heart-vascular rhizic.

Dysfunction of the systole of the lingering worm and chronic heart failure. Angibitories of ACE should indicate all ailments due to the dysfunction of the louse, regardless of the presence of symptoms of heart failure. Angibitories of the APF advance and improve the development of CHF, reduce the risk of HIM and rapid death, and reduce the need for hospitalization. ACE Іngіbіtorіy to change the dilatation of the lіvnuyu shlunochka and overshoot the remodeling of the myocardium, to change the cardiosclerosis. The effectiveness of the ACE Ingibitor is to cope with the severity of the dysfunction of the little one.

Gostriy myocardial infarction. Stagnation of ACE in the early term with a state of myocardial infarction to reduce the mortality of ailments. Particularly effective ACE testing on the background of AG, a diabetic and high-risk patients.

Diabetes mellitus and diabetic nephropathy. All APF іngіbіtorіs contribute to the progression of nirok in case of type I and II type diabetics, right away from the arterial vise. Angibitories of ACE contribute to the progress of chronic nephropathy in patients with other nephropathies. Trivale of the reduction of the incidence of diabetes and heart disease

Table 6.9

Shown before the designation of ingibitoriv ACE

quickening. Stagnation of ACE inhibitors is accompanied by a lower incidence of new diagnoses of diabetes mellitus, less hypotensive drugs (diuretics, β-adrenergic blockers, calcium antagonists).

Prototype

Angibitoria ACE contraindications in ailments with bilateral stenosis of the nirkovy arteries or stenosis in the United Kingdom, as well as for transplantation of nirka (risik development of nirkova deficiency); in ailments with a pronounced nirkova deficiency; hyperkalієmії; with severe aortic stenosis (with hemodynamic damage); in case of angioedema, including when there is a congestion of whether it is from ingibitoriv ACE.

Angibitorium ACE contraindicated in vaginosis. Stagnation of the ACE іngіbіtorіv before the hour of vagіtnostі produce up to embryotoxic effects: in the first trimester of the description of malformations of the heart, sudin, nirok, brain; in the II and III trimesters - to produce the fetus to hypotension, hypoplasia of the cranial cysts, non-malignant deficiencies, anuria and death to the fetus, that the ACE inhibitors are guilty of being hunted right away.

Protection is required for autoimmune diseases, collagenosis, especially systemic chervonia vovchak or scleroderma

(To improve the development of neutropenia and agranulocytosis); depression of the cystic brain.

The principles of supplementation. Dose of antibiotics APF is of its own specialty, tying up the therapy of the affected hemodynamic (hypotensive) effect and transferring the fixation of the dose titration method - keeping the onset of the onset of the low dose of the drug It is important to achieve the target dosage for the treatment of hypertension, CHF, and nephropathy, so that in the same doses, the maximum organoprotective effect of the ACE inhibitors is promoted.

Table 6.10

Dose ingibitoriv APF

Pobichna diya ІNGІBITORІV APF

Angibitories of ACE, which are very sensitive to the mechanism of a device linked to nonselective blocking of the ACE enzyme, may be of the same class-specific side effects (PE). Up to class-specific

kim PE ingibitoriv APF to be considered: 1) the most part - hypotension, cough, visip, hypercalcemia; 2) fewer parts - angioedema, blood loss, relish and deterioration of the function of nirok (spine, in ailments with bilateral stenosis of nirc arteries and with congestive heart deficiency, which can be recognized by diuretics).

The hypotonia of the "first dose" and the tied with her to the tampering of the power of all the angibitors of the APF; stench є a manifestation of a hemodynamic effect (frequency up to 2%, with heart failure - up to 10%). Particularly part of the reception of the first dose, in the lithium ailments, in the ailments with high activity of renin plasmas, with chronic heart failure, with giponatriya and one-hour reception of diuretics. To reduce the incidence of hypotonia "first dose", it is recommended to titrate more doses of drugs.

Cough - class-specific PE ingibitoriv ACE; the frequency of this incidence varies widely from 5 to 20%, more often not to stay in the dose of the drug, mainly to develop in women. Mechanism of development of cough dressings with the activation of the kinin-callicrein system and in the case of ACE blocking. At the same time, in the bronchial system, bradykinin and activation of pro-fired peptides (for example, substance P, neuropeptide Y), as well as histamine, can accumulate in the bronchial tubes and provoke a cough. Coughing up ACE ingibitors will increase my cough.

Hyperkalinemia (food 5.5 mmol / l) є the result of a change in the secretion of aldosterone;

Shkirny visip and angioeurotic nabryak (nabryak Kvinke) knitted from zbіlshennyam rіvnya bradykininu.

The impairment of the function of nirok (increase in creatine and excess nitrogen in the blood plasma) can be promoted to the ear of treatment by the ACE inhibitors, to be of a transient nature. Significant increase in creatine in blood plasma can be prevented in ailments with CHF and stenosis of nirkovy arteries, which is supervised by high activity of renin plasma and spasm of eferent arterioles; in all kinds of vipadki it is necessary to administer the preparation.

Neukopenia, thrombocytopenia and agranulocytosis occur rarely (less than 0.5%).

Table 6.11

Likarski vzaєmodії Ingіbіtorіv APF

Likarski Vzaєmodia

Іngіbіtori ACE do not lose pharmacokinetic interactions; all licarsky interactions with them are set up to pharmacodynamic.

Angibitorium ACE interacts with non-steroidal anti-pyretic drugs, diuretics, drugs, hypotensive drugs (Table 6.11). The combination of ACE inhibitors with diuretics and other hypotensive diseases can lead to a hypotensive effect, while the hypotensive effect can be increased for the potency of hypotensive activity of an inhibitor. In case of alcohol congestion with non-steroidal anti-inflammatory diseases (including aspirin in antiplatelet doses of less than 150 mg / add), it can lead to weakening of the hypotensive effect of the APF in the case of synonyms of retardation. Kaliyzberіgayuchі diuretics and іnshі Up to + -styat kosti (for example, KCl, food additives in calories) can increase the development of hyperkaliєmii. Estrogen drugs can change the hypotensive effect of the ACE ingibitors. Safety is required in case of alcohol intake of drugs, which may cause melodepressive activity.

Table 6.12

Pharmacokinetics of ingibitoriv ACE