THE ADVANTAGES OF SYDNONIMINES COMPARED TO NITRATES IN THE TREATMENT OF PATIENTS WITH ISCHEMIC HEART DISEASE AND CORONARY INSUFFICIENCY

Abstract

One of the primary challenges in treating patients with coronary artery disease and coronary insufficiency using nitrates is the development of tolerance. Nitrate tolerance is a condition in which the duration and intensity of anti-anginal and anti-ischemic effects decrease, despite maintaining a high concentration of the drug in the blood. In cases of developing tolerance, a continual increase in the nitrate dose is necessary to achieve the previous effect. To eliminate developed nitrate tolerance, discontinuing nitrates for 3-5 days is typically sufficient. Currently, molsidomine is employed as an alternative to nitrates, with sydnonimines emerging as a noteworthy substitute. Among sydnonimines, molsidomine (marketed as Sydnopharm, Dilasidom, Corvaton) stands out as the most effective. Despite its chemical distinction from nitrates, molsidomine operates through a similar mechanism. Functioning as a nitric oxide donor, this antianginal drug avoids the development of tolerance even with prolonged use. Molsidomine, akin to nitrates, acts as a vasodilator, exhibiting efficacy as an anti-ischemic and anti-anginal medication when administered in appropriate doses. Upon entering the human body, molsidomine undergoes hepatic metabolism, transforming into an active derivative compound known as SIN-1. This metabolite, upon entering the bloodstream, further converts into an active form (SIN-1A). From this active metabolite, the nitric oxide (NO) group is released, influencing the activation of guanylate cyclase. This activation prompts guanosine triphosphate to convert into cyclic guanosine triphosphate, ultimately contributing to the synthesis of proteins that bind calcium. This cascade of events results in the vasodilatory effect of molsidomine. Indications for molsidomine include stable angina pectoris, acute coronary syndrome, early post-infarction angina, congestive heart failure, portal hypertension, pulmonary hypertension, and Aerz's disease. Possible side effects following the therapy with molsidomine (dizziness, headache, and diplopia) occur much less frequently compared to nitrates. After using nitrates, such a side effect as methemoglobinемia may occur. Therapy with molsidomine does not lead to the development of this side effect.