Treatment of Angina Pectoris [æn‘dʒaɪnə] [’pektəris] 心绞痛治疗

1 Introduction Definition of angina pectoris: Angina pectoris denotes chest pain caused by accumulation of metabolites resulting from myocardial ischemia /is'ki:miə/心肌缺血.

Physiologic Anatomy of the Coronary Blood Supply

Causes of Angina

心绞痛分型 Classification of Angina 1) Stable Angina (Exertional Angina, Effort Angina) Features: Presents typically after some activity (running, walking, etc.) with minimal or non-existent symptoms at rest. Pathological basis： Coronary atherosclerotic [,æθərəusklə‘rɔtik]动脉粥样硬化的 stenosis /sti'nəusis/狭窄

2) Unstable angina Features: 1 It occurs at rest (or with minimal exertion)； 2 It is severe and of new onset; 3 It occurs with a crescendo /kri'ʃendəu/渐强的 pattern. Pathological basis ： Reduction of coronary flow due to transient platelet aggregation, or coronary thrombosis [θrɔm'bəusis]血栓形成

3) Variant Angina (Microvascular Angina)： Features: It occurs at any condition Pathological basis: Spasm /'spæzəm/痉挛 of the coronary artery.

Treatment of Angina-Vascular Recanalization 1978 Gruzentig

Treatment of Angina-Coronary Bypass Operation

Treatment of Angina-Antianginal Agents

2 Antianginal agents Nitrovasodilators: β Adrenergic Receptor Antagonists Ca2+ Channel Antagonists Common mechanism: Improving the balance of myocardial oxygen supply and demand: increasing supply by dilating the coronary vasculature or decreasing demand by reducing cardiac work.

2.1 Nitrates Nitroglycerin /,naitrə'ɡlisərin/硝酸甘油 Mechanism of action: These agents are prodrugs that are sources of nitric oxide (NO), which increases intracellular levels of cyclic GMP. In turn, this promotes the dephosphorylation of the myosin light chain and the reduction of intracellular Ca2+ and leads to the relaxation of smooth muscle cells in a broad range of tissues. The NO-dependent relaxation of vascular smooth muscle leads to vasodilation.

1 Hemodynamic Effects Cardiovascular Effects Decreasing both preload and afterload as a result of respective dilation of venous capacitance /kə'pæsitəns/容量 and arteriolar [ɑ:,tiəri'əulə]小动脉的 resistance vessels. Low dose: Dilating the veins more than the arterioles [ɑ:'tiəriəu]小动脉: decreasing left and right ventricular chamber size and end-diastolic pressures but results in little change in systemic vascular resistance. Higher doses: Causing further venous pooling and may decrease arteriolar resistance as well; Causing activation of compensatory sympathetic reflexes: reflex tachycardia

2 Effects on Total and Regional Coronary Blood Flow: Dilating coronary arteries and thereby increasing coronary blood flow; Redistribution of blood flow to subendocardial心内膜下的 tissues.

Aorta Myocardial Ischemia After Nitroglycerin Treatment B A Aorta B A Large Epicardial Vessels Ischemic Region Non-ischemic Region Resistance Vessels

Tolerance Intermittent treatment provides reproducible cardiovascular effects; Frequently repeated or continuous exposure to high doses of organic nitrates leads to a marked attenuation in the magnitude of most of their pharmacological effects.

Toxicity and Untoward Responses Headache; Transient dizziness, weakness, and other manifestations associated with postural hypotension may develop, particularly if the patient is standing immobile, and may progress occasionally to loss of consciousness; Drug rash 药疹.

Therapeutic Uses 1 Angina: Sublingual /sʌb'liŋɡwəl/舌下的 Administration: Onset of action is within 1 to 2 minutes, but the effects are undetectable by 1 hour after administration 2 Congestive Heart Failure: to relieve pulmonary congestion and to increase cardiac output; 3 Acute Myocardial Infarction: to relieve ischemic pain.

2.2 Ca2+ Channel Antagonists Mechanism of action Inhibiting Ca2+ channel function

Cardiovascular Effects 1) Relaxation of arterial vessels, decreasing afterload; 2) Producing direct negative inotropic [,inə‘trɔpɪk] 负性肌力作用 and chronotropic [,krɔnə‘trɔpɪk] effects 负性频率作用 in the heart. 3) Decreasing coronary vascular resistance and increasing coronary blood flow.

Pulmonary edema in heart failure

Therapeutic Uses Angina: Variant Angina, Exertional Angina, Unstable Angina; Myocardial Infarction; Other Uses: arrhythmia, hypertension etc.

2.3 β Adrenergic Receptor Antagonists Mechanism of action Decreasing myocardial oxygen consumption, due to: 1) Negative chronotropic effect (particularly during exercise); 2) Negative inotropic effect; 3) Reduction in arterial blood pressure (particularly systolic pressure)

Therapeutic Uses Exertional angina Unstable Angina; Myocardial Infarction: improving mortality in MI

2.4 Combination Therapy Nitrates and β Adrenergic Receptor Antagonists: β Adrenergic receptor antagonists: Blocking the baroreceptor [,bærəri'septə] 压力感受器-mediated reflex tachycardia and positive inotropic effects associated with nitrates; Nitrates: Attenuating the increase in left ventricular end-diastolic volume (by increasing venous capacitance) and alleviating the increase in coronary vascular resistance associated with β adrenergic receptor blockade.

Supplementary reading Antianginal agents may provide prophylactic [,prɔfi'læktik, ,prəu-]] 预防的 or symptomatic [sɪm(p)tə’mætɪk]有症状的 treatment, but β adrenergic receptor antagonists also reduce mortality apparently by decreasing the incidence of sudden cardiac death associated with myocardial ischemia and infarction. The treatment of cardiac risk factors can reduce the progression or even lead to the regression of atherosclerosis [,æθərəʊsklɪə‘rəʊsɪs]动脉粥样硬化. Aspirin is used routinely in patients with myocardial ischemia, and daily aspirin use reduces the incidence of clinical events. Other antiplatelet agents such as oral clopidogrel and intravenous anti-integrin drugs such as abciximab, tirofiban, and eptifibatide have been shown to reduce morbidity in patients with angina who undergo coronary artery stenting. Lipid-lowering drugs such as the statins reduce mortality in patients with hypercholesterolemia [,haɪpəkə,lɛstərə’limiə] 高脂血症 with or without known coronary artery disease. Angiotensin-converting enzyme (ACE) inhibitors also reduce mortality in patients with coronary disease. Coronary artery bypass surgery and percutaneous [,pə:kju:'teiniəs]经皮的 coronary interventions such as angioplasty [,ændʒɪo’plæsti] 血管成形术and coronary artery stent deployment can complement pharmacological treatment. In some subsets of patients, percutaneous or surgical revascularization may have a survival advantage over medical treatment alone. Intracoronary drug delivery using drug-eluting coronary stents represents an intersection of mechanical and pharmacological approaches in the treatment of coronary artery disease. Novel therapies that modify the expression of vascular or myocardial cell genes eventually may become an important part of the therapy of ischemic heart disease.

大纲要求 Objective and requirements Be familiar with the classification of antianginal drugs; Master the effects, mechanisms, indications, and adverse effects of various antianginal drugs. Teaching contents (1) Pathological causes and types of angina pectoris. (2) Antianginal effects, mechanisms, clinical uses, and adverse effects of nitroglycerin, calcium channel blocking drug verapamil, and β receptor blocker propranolol.

Essential vocabulary Angina pectoris/variant angina/exertional angina/unstable angina Myocardial ischemia Coronary atherosclerotic stenosis Antianginal agents Hemodynamic effects Sublingual administration Myocardial infarction