课件：治疗冠心病药物.ppt

第19章 治疗冠心病药物Agents to treat CHD,coronary heart disease Background: IHD is the leading single cause of death in the US and is responsible for 1 of every 4.8 deaths. About half of the patients with IHD initially present with chronic stable angina. IHD manifests as an imbalance in myocardial oxygen supply and demand that results in myocardial hypoxemia. IHD is usually due to atherosclerotic disease of the coronary arteries (coronary heart disease CHD and coronary artery disease CAD)。,病因学Etiology,The exact pathogenesis of CAD is not clear, and no single theory adequately explains the atherosclerotic process. Two main explanations have been proposed: the lipid hypothesis and the chronic endothelial injury hypothesis. These explanations are probably interrelated and are certainly not mutually exclusive.,Risk Factors,Positive family history, particularly with onset before age 50 in same-sex parent Male gender Age Abnormalities in blood lipids/lipid metabolism, High Waist/Hip Ratio (Rexrode et al, 1998) Elevated blood homocysteine Elevated fibrinogen (Bielak et al, 2000) High ultra-sensitive C-reactive protein High levels of iron stores (Salonen et al, 1992) Low levels of selenium (Suadicani et al, 1992) Sedentary lifestyle/poor physical fitness,Cigarette smoking Alcohol abuse Diets high in animal fat and calories and low in fruits, vegetables, and fiber Diets low in polyunsaturated fatty acids Diets high in trans fats (Willett et al, 1993) Poor stress management High blood levels of insulin Decreased oxidative radical antioxidant capacity (ORAC) (Fazendas et al, 2000) Diabetes mellitus Hypertension Hypothyroidism Marital stress (Orth-Gomer, 2002),1动脉粥样硬化与冠心病 动脉粥样硬化是冠心病的病理基础。 胆固醇等脂质沉着在大中动脉血管壁，形成粥样斑块，尤其在动脉分叉处。在心外膜下中等动脉分支的内膜下胆固醇沉着，管腔内新月形隆起，表面为纤维帽，含增殖平滑肌、胶原、脂质及泡沫细胞，内膜下形成坏死区，含胆固醇结晶、胆固醇酯，钙盐等。 冠脉狭窄为偏狭窄，开始为新月形，狭窄50%为轻度，对供血影响不大，无明显症状；狭窄50%-70%为重度，供血大减，可出现心绞痛。若管腔被血栓迅速阻塞，可产生急性心肌梗死。 冠脉痉挛亦导致缺血性心脏病，可造成心绞痛（如变异型心绞痛），甚至心肌梗死。,2冠心病的临床分型及表现 冠心病共分为五型，分述如下： 隐匿型：病人无症状，仅心电图有缺血改变（包括运动试验），如T波低平，下降，S-T段压低等。 心绞痛（angina pectoris）：心绞痛的发生是由于心肌耗氧增加或供血不足，导致心肌氧供需失衡所致。 急性心肌梗死（acute myocardial infarction，AMI）：心肌严重缺血缺氧持续时间过长，导致心肌代谢和功能障碍，心肌细胞坏死。 心力衰竭及心律失常型：为长期心肌缺血导致心肌纤维化所致。表现为心脏扩大，心力衰竭及心律失常。 猝死型冠心病：因缺血心肌电生理紊乱引起严重心律失常所致的原发性心脏猝死。,通常将心绞痛分为稳定型心绞痛、不稳定型心 绞痛和变异型心绞痛三型，现根据WHO意见将心绞痛分为劳累性和自发性两类： 劳累性心绞痛：由体力活动、情绪激动、寒冷或其他增加心肌需氧量的活动诱发。又分为三种： 稳定型心绞痛（stable angina）：为最常见的一种类型。病情稳定一个月以上，静息时无症状，在劳累或情绪激动时发病，病情稳定，有规律性。心电图改变主要有S-T段压低，T波低平倒置等。 初发劳累性心绞痛：劳累性心绞痛病程在一个月以内。 恶化型劳累性心绞痛：同等程度劳累所诱发的心绞痛发作次数、严重程度及持续时间突然加重。 自发性心绞痛：包括变异型心绞痛（variant angina），较少见。主要由冠脉痉挛所致，在休息静止时发作。其特点为发作与心肌需氧量增加无明显关系，时间较长，程度较重，且不易为硝酸甘油缓解。心电图主要表现为S-T段抬高。 不稳定型心绞痛：包括初发劳累性，恶化型，及自发性心绞痛，易发生心肌梗死。,Pathophysiology,Myocardial ischemia reflects an imbalance between myocardial oxygen supply and demand. Myocardial oxygen demand is mainly determined by heart rate, the force of ventricular contraction, and ventricular wall tension, which is proportional to the ventricular volume and pressure. The myocardiums extraction of oxygen is nearly maximal in the resting state. Therefore, in the absence of anemia or systemic hypoxia, an increase in coronary blood flow is essentially the only mechanism available to compensate for increases in myocardial oxygen demand.,影响心肌耗氧量的影响,心肌收缩力 心室壁张力（与心室内压和心室半径乘积成正比） 心率和射血时间 通常用简便的方法来估算心肌耗氧量 二重乘积（心率收缩压，HRSBP） 三重乘积（心率收缩压射血时间(Q-T) ，HRSBPET）。 凡使心率加快，血压升高，心肌收缩加强及心室扩大的因素都可增加心肌氧耗。,Factors that Affect Myocardial Oxygen Demand,The major determinants of myocardial oxygen consumption include: ventricular wall stress heart rate inotropic state (contractility) Both preload and afterload affect the stress on the ventricular wall “double product“ (Heart Rate x Systolic Blood Pressure),Treatment,Lifestyle Measures counsel patients about smoking cessation , diet, regular exercise, and weight reduction Pharmacological treatment Pharmacological treatment of CAD can be divided into agents that prolong survival (eg, aspirin, statin drugs, ACE inhibitors, beta-blockers) and those that treat symptoms (eg, calcium channel blockers, nitrates).,2019/8/31,13,可编辑,抗血栓形成,Aspirin has been shown to decrease mortality and reinfarction after an MI. Administer aspirin immediately, which the patient should chew if possible upon presentation. Continue aspirin indefinitely unless an obvious contraindication, such as a bleeding tendency or an allergy, is present. Clopidogrel may be used as an alternative to aspirin in cases of aspirin resistance or allergy,Start all patients with suspected coronary artery disease (CAD) or ischemic heart disease (IHD) on aspirin (75 to 150 milligrams mg one time a day), unless contraindicated Aspirin reduces the risk of adverse cardiovascular events by 25% to 33% in patients with stable angina. Clopidogrel (75 mg a day) appears to be as effective as aspirin, but it is much more expensive; it is recommended for patients with contraindication(s) to aspirin,缓解心绞痛 Three categories of agents are used in the treatment of angina,1. Organic nitrates (reduce preload, reduce afterload, vasodilate coronary arteries, inhibit platelet aggregation) 2. Calcium channel blockers (reduce afterload, vasodilate coronary arteries, may inhibit platelet aggregation; some also decrease heart rate, decrease contractility),3. Beta-adrenergic antagonists (decrease heart rate, decrease contractility, decrease afterload due to decrease in cardiac output, may inhibit platelet aggregation),硝酸酯及亚硝酸酯,是缓解心绞痛的主要药物 增加氧供，改善侧支循环 降低心室内压，改善心内膜下心肌供血（此处常是缺血最严重的部位），舒张冠脉痉挛 减少氧耗 舒张外周静脉和动脉血管，降低心脏前后负荷，缩小心室容积 一般短效，可产生反射性心动过速,Beta-阻断剂,阻断交感对心脏的兴奋作用，减慢心率，抑制心肌收缩，降低氧耗量 对劳作型心绞痛效好，对变异性无效？ 可用于先兆心肌梗死和急性心肌梗死,钙拮抗剂,舒张动静脉血管，减轻后负荷和前负荷 冠脉解痉效果好，最适用于变异性心绞痛 要用长效药物，短效者可使血压波动过大，兴奋交感,Use beta-blockers as first-line anti-anginal therapy, unless contraindicated. Beta-blockers decrease myocardial oxygen demand by decreasing myocardial contractility, arterial (blood) pressure, and heart rate. Left ventricular perfusion is enhanced by the increased duration of diastole. Of all of the medications used in treating angina pectoris, only beta-blockers have conclusively been shown to reduce both clinical symptoms and cardiac events . However, emerging data suggest that angiotensin-converting enzyme (ACE) inhibitors and statins also reduce clinical symptoms and cardiac events .,combination therapy Beta-blockers and nitrates are frequently used together in patients with chronic stable angina, because their combined use appears to be more effective than monotherapy with either agent . The concurrent use of beta-blockers attenuates the tendency of nitrates to increase sympathetic tone and cause reflex tachycardia. The potential increase in left ventricular volume, end-diastolic pressure, and wall tension, and the potential decrease in heart rate with beta-blockers, are counteracted by the concurrent use of nitroglycerin.,对心肌梗死的治疗,冠脉血栓 心