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[Treatment of angina pectoris. New perspectives]
Insights
Future angina pectoris treatments target myocardial ischemia by addressing atherosclerosis, thrombosis, and inflammation. Novel drugs aim to modify the arachidonic acid cascade, inhibit platelet aggregation, and scavenge free radicals for improved cardiac function.
Area of Science:
- Cardiology
- Pharmacology
Context:
- Myocardial ischemia involves atherosclerosis, thrombosis, coronary spasm, and platelet aggregation.
- Endothelial dysfunction impacts coronary blood flow regulation.
- Current angina treatments reduce myocardial oxygen consumption.
Purpose:
- To explore novel pharmacological strategies for treating angina pectoris.
- To investigate drugs targeting the arachidonic acid cascade, thrombosis, and inflammation.
- To understand the pathophysiology of myocardial ischemia for developing new therapies.
Summary:
- Future angina treatments focus on modifying the arachidonic acid cascade (prostacyclin, thromboxane A2), using clot-specific thrombolytics, anticoagulants, free-radical scavengers, and anti-platelet agents.
- Drugs like trimetazidine offer a multi-target approach, preventing ATP depletion, inhibiting potassium leak, reducing free radicals, and modulating eicosanoid synthesis.
- Preventing atherosclerosis progression and modifying myocardial metabolism during ischemia are also key therapeutic avenues.
Impact:
- Advances in understanding myocardial ischemia pathophysiology.
- Development of new therapeutic agents for angina pectoris.
- Potential for improved patient outcomes through targeted pharmacological interventions.
Abstract:
Myocardial ischaemia results from complex interrelated processes involving progression of atherosclerosis, thrombosis, coronary spasm, platelet aggregation and local release of products from the arachidonic acid cascade. Endothelium-dependent responsiveness contributes to the local regulation of coronary blood flow, and the presence of endothelial damage may result in enhanced contraction of the smooth muscle. Drugs which have been used for the treatment of angina pectoris are able to reduce myocardial oxygen consumption. This concept will further be developed in the near future with beta-blocking agents with vasodilating properties, potent long acting nitrates (nicorandil), bradycardic agents (AQA 39 or AS-AH 208), and new calcium antagonists. However, future prospects in the treatment of angina pectoris include: drugs modifying the arachidonic acid cascade by increasing synthesis or release of prostacyclin (nafazatrom) or decreasing prostacyclin degradation (almitrine), or blocking thromboxane A2 synthetase (dazoxiben) or thromboxane A2 receptors (BM 13177) or, blocking the lipoxygenase pathway (nafazatrom) or prostacyclin analogues (iloprost); more clot-specific thrombolytic agents and new oral anticoagulant drugs; free-radical scavengers such as superoxide dismutase, catalase or peroxidase and drugs inhibiting xanthine-oxidase; anti-platelet drugs such as ticlopidine which blocks the fibrinogen receptors of platelets; drugs preventing the progression of atherosclerosis lesions such as nifedipine or verapamil in animals fed high-lipid diets; drugs which could modify myocardial metabolism during ischaemia. In this context, trimetazidine acts through prevention of ischaemia-induced decrease in ATP cellular storages, inhibition of potassium leak, decrease in free-radical production and thromboxane A2 synthesis and increase in prostacyclin synthesis. These new concepts provide an important contribution to the understanding of the pathophysiology of myocardial ischaemia. This explains the considerable development of pharmacological research for new agents in the treatment of angina pectoris.