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Volume 2 Issue 12 (2022): EJAR
Volume 2 Issue 12 (2022): EJAR
CLINICAL PHARMACOLOGICAL APPROACH TO THE USE
OF ANTIANGINAL DRUGS IN THE TREATMENT OF
MYOCARDIAL INFARCTION
Rasulov Boburjon Abdukakhorovich
Assistant intern at the Department of "Pharmacology, clinical
pharmacology and medical biotechnologies", ASMI
https://doi.org/10.5281/zenodo.14557087
ARTICLE INFO
ABSTRACT
Received: 19
th
December 2024
Accepted: 25
th
December 2024
Online: 26
th
December 2024
,
A brief description of modern antianginal drugs presented
in the latest revision of the European Society of Cardiology
recommendations is given. Angina pectoris is the most
common form of chronic coronary insufficiency, the
treatment of which consists in reducing the number,
duration and severity of attacks of anginal pain, as well as
improving the prognosis: preventing the development of
such cardiovascular complications as acute myocardial
infarction, life-threatening rhythm disturbances and
chronic heart failure.
KEYWORDS
Angina pectoris, drug therapy,
antianginal drugs, history of
development, mechanism of
action.
INTRОDUСTIОN
Impressive successes in the treatment of coronary heart disease in recent years, caused
primarily by the widespread introduction of surgical and endovascular methods of restoring
blood supply to the heart in clinical practice, have relegated the use of pharmacological
antianginal therapy to the background. Nevertheless, the clinic continues to experience a need
for drugs with anti-ischemic properties. This mainly applies to the group of patients with
angina pectoris, for whom myocardial revascularization cannot be performed for various
reasons, including technical ones. In this regard, it should be noted that the number of
patients with diabetes mellitus is constantly increasing [1], whose angina, in addition to
atherosclerotic lesions of the epicardial arteries, may be caused by the presence of diabetic
myocardial microangiopathy. It should also be emphasized that more than 25% of patients
after successful coronary artery angioplasty experience recurrent attacks of anginal chest
pain within 5 years [2]. In addition, today we are still unable to fully satisfy all the needs for
myocardial revascularization. Thus, clinical interest in antianginal drug therapy remains. To a
certain extent, this is confirmed by the attention paid to this section in the latest
recommendations of the European Society of Cardiology for the diagnosis and treatment of
chronic coronary syndrome [3].
M
А
T
Е
RI
А
LS
А
ND M
Е
TH
О
DS
Changes in the understanding of the pathogenetic features of some diseases, the use of
methods for objective evaluation of drug effectiveness, and the introduction of evidence-
based medicine principles into clinical practice have had a significant impact on treatment
tactics in cardiology, including pharmacotherapy of chronic coronary syndrome. Treatment of
angina involves reducing the number, duration, and severity of attacks of angina chest pain
and improving the prognosis - preventing cardiovascular complications. Without dwelling on
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the issues of secondary prevention of coronary heart disease, in this review we focus on drug
therapy for transient myocardial ischemia aimed at alleviating the condition of patients. In
this regard, of particular interest is the analysis of the formation of our ideas about the
mechanisms of action of drugs that cause an anti-ischemic effect in patients with angina,
which will allow us to establish the main trends in the development of the pharmacology of
cardiovascular pathology.
R
Е
SULTS
А
ND DIS
С
USSI
О
N
The search for new antianginal drugs was directed towards developing preparations
that enhance coronary blood flow. Following this trend, in the 1970s, preparations with
vasodilatory properties were proposed and widely used for the treatment of coronary
insufficiency. Carbocromen (intensain, intensordin) gained great popularity among clinicians;
in addition to its ability to enhance coronary blood flow, according to researchers, it had a
stimulating effect on collateral circulation and prevented platelet aggregation [4, 5].
Dipyridamole (curantil, persantin, antistenocardin) was no less widespread. In addition to its
vasodilatory effect, it was also found to have antithrombotic properties [2]. However, as
clinical experience accumulated, conflicting data began to appear. Thus, the occurrence of
angina attacks was noted with its rapid intravenous administration, which was interpreted as
the development of the syndrome of "stealing" the ischemic zone of the myocardium. This
circumstance excluded the use of dipyridamole as an antianginal agent. However, it became
possible to use it for diagnostic purposes - in the so-called "curantyl test" to detect myocardial
ischemia. Difril (corontin, falicor) can be attributed to the number of very popular drugs of the
second half of the last century. However, clinical studies by L.A. Myasnikov et al. questioned
its effectiveness in patients with angina [3]. The same pharmacological group included such
drugs as lidoflazine, ditrimin, a phenothiazine derivative - chloracizine, and diethiphene,
which is close to sinestrol [3]. Of the vasodilators, purine derivatives were used - euphyllin,
theophylline. It should be noted, however, that the use of euphyllin was associated with a
number of serious side effects due to its ability to cause tachycardia, increase heart function
and increase myocardial oxygen consumption. Cases of death after intravenous
administration of the drug in acute myocardial infarction have been described [4]. In the
1970s, isoquinoline derivatives - papaverine, no-shpa - did not lose their significance as
antianginal agents; they were used routinely per os to prevent angina attacks and parenterally
to relieve angina attacks. Antianginal properties were attributed to amiodarone [4]. Very
modest, if not to say dubious, anti-ischemic properties, but the unconditional antiarrhythmic
effect served as the basis for transferring amiodarone to the group of antiarrhythmic agents,
where it currently resides. During the described period, attempts were made to use beta-
adrenergic stimulants to increase coronary blood flow. Such substances included oxyphedrine
(ildamen) and nonachlazine, which has better tolerability, the use of which was recommended
for the treatment of severe forms of coronary heart disease [5]. In the recommendations for
the treatment of coronary heart disease in the 1970s, one can find mention of the
anticholinergic platifillin and the ganglionic blocker quaterone [2]. Among the medications
that have been attributed antianginal properties, we find monoamine oxidase inhibitors that
affect the adrenergic innervation of the heart
–
ipraside, nialamide, the antidepressant action
of which is combined with dilation of the coronary vessels [4]. Since the 1960s, calcium
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antagonists have been included in the arsenal of antianginal agents. The first representative of
this group was verapamil (isoptin), which has not only a coronary dilator, but also an
antiarrhythmic effect.
Analyzing the medications used to treat chronic coronary insufficiency in the second half
of the last century, attention is drawn to a large number of preparations of plant origin:
salsolin is an alkaloid isolated from Central Asian saltwort, khellin is extracted from the seeds
of ammi dentata, pasticin is contained in parsnip seeds, orangelin is obtained from the roots of
mountain knotweed, dimidine is isolated from the roots of Siberian inflated fruit, daukarin is a
preparation from carrot seeds, anetine is from fragrant dill [3]. All of them, to varying degrees,
have an antispasmodic effect and moderately dilate the coronary arteries. However, no
objective confirmation of their ability to cause an anti-ischemic effect in patients with
coronary heart disease was found. Atherosclerotic narrowing of the coronary arteries limits
the potential for coronary blood flow growth. At the same time, it is known that when
myocardial ischemia occurs, as a result of a discrepancy between the metabolic demands of
the myocardium and its blood supply, powerful self-regulation mechanisms are immediately
activated, aimed at increasing blood flow. Under these conditions, the role of pharmaceuticals
that have a vasodilatory effect is minimal, at least in cases where vasospasm does not
dominate in the pathogenesis of myocardial ischemia. Understanding this led to a revision of
the traditional idea that coronary vasodilator drugs should form the basis of therapy for
chronic coronary insufficiency and changed the direction of pharmacological action. The
attention of researchers focused on the myocardium: changes in its metabolism,
cardiodynamics, accompanied by more economical oxygen consumption. Despite some
negative aspects of pharmacodynamics (reduced coronary blood flow, decreased inotropic
function of the myocardium, limited cardiac output, development of bradycardia, etc.), beta-
blockers (propranolol) have become increasingly widespread, without, however, occupying
leading positions in the treatment of angina. A wide range of pharmacological action,
including the effect on the hemostasis system, antiplatelet, fibrinolytic, antisclerotic and
antianginal effects of the antibradykinin agent - anginine, contributed to its popularity in the
treatment of angina pectoris, especially in combination with obliterating atherosclerosis of
the peripheral arteries [4]. In order to influence the metabolism of the myocardium, the use of
anabolic steroids - methandrostenolone, retabolil was recommended. It was believed that
anabolic drugs prevent the development of hypercholesterolemia, improve the potassium
balance in the div, increase the content of glycogen, ATP, and creatinine [5]. In practical
recommendations of that time, one can find references to drugs that, as a result of influencing
the metabolic processes of the heart muscle, are capable of optimizing its energy balance and,
at least theoretically, reducing the frequency of chest pain attacks in patients with angina. The
drug with the indicated effect included the anaerobic glycolysis activator pyridoxinol
glyoxylate, better known as glyosys [3].
The above leads to the conclusion that among the characteristic features of conservative
therapy of chronic coronary insufficiency of the 2nd half of the last century, one can single out
a significant number of drugs used, mostly with antispasmodic, coronary dilator properties,
from different pharmacological groups, having different chemical structures and differing in
the mechanism of action. In this regard, the statement of A.P. Chekhov involuntarily comes to
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mind: "If a lot of remedies are supposed to be used against some disease, then the disease is
incurable." With the introduction of methods for objective evaluation of the effectiveness of
drugs into clinical practice, a significant number of them, having demonstrated their
ineffectiveness, were excluded from clinical use. The methods of objectively assessing the
effectiveness of drug treatment for patients with angina include: paired bicycle ergometric
tests, repeated Holter ECG monitoring, isotope studies of myocardial perfusion, stress
echocardiography.
СО
N
С
LUSI
О
N
Thus, the development of antianginal pharmacotherapy has come a long way,
characterized by the search for the main factors of effective pharmacodynamics. The following
can be attributed to the features of modern antianginal pharmacotherapy:
reduction in the number of pharmacological groups due to the exclusion of drugs with
unproven or low effect;
improvement of the pharmacological properties of known drugs;
revision of the antianginal significance and clinical value of the drugs used;
significant increase in generic forms;
widespread use of combination dosage forms combining several drugs with different
mechanisms of action.
References:
1.
Shestakova M.V., Vikulova O.K., Zheleznyakova A.V., Isakov M.A., Dedov I.I. Epidemiology
of diabetes mellitus in the Russian Federation: what has changed over the past decade?
Therapeutic archive. 2019;(10):4
–
13.
2.
Berger P. Ranolazine and Other Antianginal Therapies in the Era of the Drug-Eluting
Stent. JAMA. 2014;291(3):365
–
367. https://doi.org/10.1001/jama.291.3.365.
3.
Knuuti J. 2019 ESC Guidelines for the diagnosis and treatment of chronic coronary
syndrome. Russian journal of cardiology. 2020;(2):119
–
182. https://doi.org/10.15829/1560-
4071-2020-2-3757.
4.
Gritsyuk AI (ed.). Medicines in clinical cardiology. Kyiv: Health; 2017. 296 p.
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Metelitsa VI Prevention of ischemic heart disease. Therapeutic archive. 2014;(1):14
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