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CHANGES IN THE CARDIOVASCULAR SYSTEM THAT OCCUR WITH
THE COMBINED USE OF ANTIHYPERTENSION DRUGS
Akhundzhonova Khakima Abdumannabovna
International Medical University "CAMU"
Assistant of the Faculty of "Medical".
https://doi.org/10.5281/zenodo.13881314
Abstract:
In this article, the analysis of literature data on the clinical
efficacy and safety of antihypertensive drugs shows that there is a significant
difference between original and generic drugs, both in therapeutic equivalence
and in the frequency and severity of adverse reactions caused by them.
Key words:
arterial hypertension, antihypertensive drugs, original drug,
generic, therapeutic equivalence, side effects.
Arterial hypertension (AH) is a long-term increase in blood pressure (BP)
above 140/90 mm Hg. Art. arterial hypertension (systolic and diastolic blood
pressure, respectively) in people who do not receive adequate antihypertensive
therapy.
Hypertension is one of the leading risk factors for the development of
cardiovascular and cerebrovascular diseases, the main cause of high mortality
and disability in all countries, and the most common heart disease. The
prevalence of hypertension is high throughout the world, 20-30% of the adult
population in developed countries suffer from it. [4,5]
In Uzbekistan, hypertension occurs in 30-40% of the elderly population,
and in people over 60 years old - up to 60-70%. The main types of arterial
hypertension are essential hypertension of unknown etiology, which accounts
for 90-95% of patients with hypertension, or arterial hypertension, and
secondary hypertension - symptomatic, the cause of which may be kidney
pathology (kidney damage), renal parenchyma, adrenal glands. glands
(pheomocytoma, hyperaldosteronism), large vessels (renal artery stenosis,
coarctation of the aorta). Isolated systolic hypertension is also distinguished, in
which systolic blood pressure exceeds 160, and diastolic blood pressure is less
than 90 mm Hg. Art. This form of hypertension occurs mainly in the elderly and
is caused by a decrease in vascular elasticity. Adequate treatment of arterial
hypertension should lead to a decrease in pressure to target values (140/90 mm
Hg, in diabetes mellitus and kidney pathology - 130/80). The prognosis of
hypertension depends not only on blood pressure. Of great importance are: the
presence of concomitant risk factors: age, family history of early cardiovascular
diseases, smoking, high cholesterol and lipid spectrum disorder in the blood
THEORETICAL ASPECTS IN THE FORMATION OF
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plasma, physical inactivity; weight gain; abdominal obesity, diabetes mellitus
(DM), high doses of alcohol; the degree of damage to target organs and the
presence of concomitant clinical conditions [7].
The main goal of hypertension treatment is to reduce mortality from
cardiovascular diseases. Antihypertensive therapy strategies are developed to
prevent damage to target organs and death associated with hypertension. In
patients with high blood pressure, the greatest risk of developing myocardial
infarction or stroke occurs when antihypertensive therapy is discontinued (even
temporarily). According to a meta-analysis of many clinical studies, a decrease in
systolic blood pressure by 12–13% leads to a decrease in cardiovascular
complications by 21–37%. Adequate, regular antihypertensive therapy reduces
mortality in patients: from myocardial infarction - by 15–20%, from stroke - by
40–50%. This explains the need for timely and justified treatment [6,7].
According to leading world experts, treatment of arterial hypertension
should be as early and intensive as possible. Therefore, effective treatment often
requires a combination of two or more antihypertensive drugs even in the early
stages of the disease. Combined low doses of drugs are used in therapy, which
reduces the risk of side effects; Acts simultaneously on various mechanisms of
arterial hypertension, which increases the effectiveness of treatment; In
addition, a fixed combination of two or more drugs allows for combination
therapy with one tablet, which is more convenient for the patient [2,6]. The main
groups of drugs for the treatment of arterial hypertension: First-line drugs
(main): angiotensin-converting enzyme inhibitors; beta-blockers (BB); calcium
channel blockers (Ca2+ antagonists); diuretics; angiotensin receptor blockers;
Second-line drugs (alternative): alpha-blockers; A2-adrenergic receptor
agonists and imidazoline receptors (central neurotropic agents, central
sympatholytics), direct renin inhibitors.
Features of the main groups of antihypertensive drugs AAF inhibitors:
more effective in young people; improve quality of life; organoprotective action
(cardio-, nephrovasoprotective); prevention of diabetic nephropathy; slowing
down the development of addiction; positive metabolic effects: improved
glucose metabolism, increased sensitivity of peripheral tissues to insulin, does
not affect lipid metabolism, urea or creatinine levels; no withdrawal syndrome;
But! May cause cough in 11.5% of cases - with captopril, in 24.7% of cases - with
enalapril, as a result of irritation of the afferent fibers of the vagus nerve of the
upper respiratory tract due to impaired bradykinin metabolism may increase.
Potassium levels in the blood and pathways that cause renal failure [5,6]. Beta-
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blockers (BB): their effectiveness is high, especially in young people; they reduce
mortality from coronary heart disease in non-smokers; reduction in the
incidence of coronary heart disease and its development; reduction in mortality
from myocardial infarction; But! may reduce high-density lipoprotein levels;
causes sexual dysfunction in men; may have a negative effect on cognitive
functions (lipophilic beta-blockers); peripheral vasoconstriction, bronchospasm
(non-selective beta-blockers); high doses - bradycardia and heart failure. They
cause withdrawal syndrome. Inexpensive drugs are available (propranolol).
Thiazide diuretics: currently, diuretics occupy one of the leading positions
among modern drugs for the long-term treatment of arterial hypertension; more
effective in elderly patients; reduce the risk of stroke in smokers and non-
smokers; delay the release of calcium and prevent pathological fractures in
osteoporosis; high doses (dichlorothiazide above 25 mg) can reduce the amount
of potassium in the plasma, cause impotence, increase the level of total
cholesterol and low-density lipoproteins, glucose and urea, therefore they are
not indicated for patients with hypokalemia, diabetes mellitus, gout. ; Important:
low doses of hydrochlorothiazide and thiazide-like diuretics used to treat
arterial hypertension (hydrochlorothiazide 12.5-25 mg) have a satisfactory
safety profile, do not have a clinically significant effect on carbohydrate, lipid,
purine and electrolyte metabolism and are well tolerated. received. patients,
which allows for long-term therapy. Indapamide, unlike other thiazide and
thiazide-like diuretics, has a minimal effect on potassium and uric acid levels,
has virtually no effect on plasma glucose concentrations, does not impair the
sensitivity of peripheral tissues to insulin, and is therefore the safest drug for
treating hypertension in patients with diabetes mellitus and has a mild diuretic
effect. Calcium channel blockers: very effective in treating hypertension,
especially in the elderly; effective in ischemic heart disease, but virtually useless
in post-infarction cardiosclerosis; their advantages include lowering systolic
blood pressure and diastolic blood pressure without causing orthostatic
hypotension; metabolically neutral - does not affect the lipid profile,
carbohydrates, purine metabolism, or electrolyte balance); has antiplatelet
activity; has a cardioprotective effect (more pronounced in verapamil and
diltiazem); possible side effects associated with vasodilation - headache,
dizziness, fever hot flashes, palpitations, temporary hypotension, peripheral
edema of the legs, ankles, elbows - more typical for short-acting nifedipine;
bradycardia, rare cases of heart failure (verapamil).
THEORETICAL ASPECTS IN THE FORMATION OF
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When prescribing drugs, the following main factors should be taken into
account: drug efficacy, impact on quality of life, metabolism, drug price and its
pharmacoeconomic and quality indicators, due to which its origin is very large.
It is important whether the drug is original or reproduced (generic).
Generic drug - a generic drug replaced by a patented analogue (original
drug) and released on the market after the expiration of the patent, protection of
the original copy. Specific features of generics: obtaining a copy of the original
drug, since the patent holder provides incomplete information about the
original; low quality, efficiency and safety indicators; entering the market after
the expiration of the patent protection of the original drug; lack of preclinical
and clinical studies; usually uninformed instructions; circulation is permitted on
the basis of a reduced volume of registration data and bioequivalence
assessment data; production is not always carried out in accordance with GMP
rules; low cost per package. Generics are produced by pharmaceutical
companies in Eastern Europe, Asia, Latin America, the CIS, including the Russian
Federation. There are tens of thousands of manufacturers of generic drugs
worldwide, operating in various economic and regulatory conditions. Therefore,
the "cheapness" of a generic often leads to large additional costs for the patient
to administer a larger dose of an ineffective generic, treat unwanted side effects
and compensate for a more severe clinical condition [1]. Thus, in a randomized
study, the effectiveness of several generics of enalapril (Enap, Ednita, Invoril,
Envas and Enam) was compared with the original drug Renitec and it was
shown that some of them may require certain doses to achieve the effect. almost
3 times higher than the original dose of the drug. In addition,
pharmacoeconomic studies of enalapril preparations have shown that a course
of treatment, for example, with the "cheap" Enap is significantly more expensive
than treatment with the original drug Renitek. When studying the efficacy and
safety of generics, Indapamide showed a tendency to increase blood pressure in
the first 6-7 hours and 17-19 hours after their use, did not normalize the
circadian rhythm of blood pressure and had a pronounced negative trend. effect
on electrolytes. Metabolism is not typical for the original indapamide [3]. When
comparing the original drug Bisoprolol with one of its generics in patients with
arterial hypertension stage 1-2, it was found that the generic significantly
reduces systolic and diastolic blood pressure, but this decrease was significantly
less (by 3-4 mm Hg) than the decrease in blood pressure under the influence of
the original drug. At first glance, such drugs can be interpreted as
therapeutically equivalent, but in arterial hypertension, the frequency of
THEORETICAL ASPECTS IN THE FORMATION OF
PEDAGOGICAL SCIENCES
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54
achieving target blood pressure values with the use of the original drug was
more than 20% higher than with general use. A randomized, double-blind
comparative study of the original drug amlodipine (Norvasc) and one of its
many generics, Cardiopin, in patients with mild to moderate arterial
hypertension showed that there are no statistically significant differences in
div weight in the disease. A hypotensive effect of both drugs was found, but
there was a slight tendency to decrease diastolic blood pressure 6 weeks after
the start of treatment with Norvasc. This. Cardiopin is the only generic
amlodipine that has been fully studied for other generics, without a direct
comparison of therapeutic equivalence with the original drug [4,5].
Thus, when choosing a drug, two questions arise:
1) What should I prescribe - the original drug or a generic? 2) If the choice
is made in favor of a generic, which manufacturer should be preferred? If you
can afford to buy an original drug, it is better to buy the original version. If you
have a choice between several generics, it is better to buy a drug from a trusted
manufacturer.
In the future, original drugs will take a leading place in the pharmacotherapy of
complex cardiovascular diseases, including hypertension. The best option for
generics are generics produced in Eastern Europe, since these are mainly
modern drugs with a patent protection period of no more than 5 years. Generics
produced in Russia and Asia are usually outdated, because ... Their patent
protection expired 10-15 years ago
References:
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safety of Bisogamma and Concor for the treatment of arterial hypertension //
Farmateka. - 2008. - No. 12 (166). - B.81-89.
3. Kutishchenko N.P., Yakusevich V.V., Deev A.D. The level of therapeutic
equivalence of the original indapamide and generic indapamide in patients with
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