1、心血管药物Cardiovascular drugsHeart Disease FactsHeart disease is the leading cause of death for both men and women. More than half of the deaths due to heart disease in 2009 were in men.About 600,000 Americans die from heart disease each yearthats 1 in every 4 deaths.1Coronary heart disease is the most
2、common type of heart disease, killing more than 385,000 people annually.In the United States, someone has a heart attack every 34 seconds. Each minute, someone in the United States dies from a heart disease-related event.Heart disease is the leading cause of death for people of most racial/ethnic gr
3、oups in the United States, including African Americans, Hispanics, and whites. For Asian Americans or Pacific Islanders and American Indians or Alaska Natives, heart disease is second only to cancer.Coronary heart disease alone costs the United States $108.9 billion each year. This total includes th
4、e cost of health care services, medications, and lost productivity.High blood pressure, high LDL cholesterol, and smoking are key heart disease risk factors for heart disease. About half of Americans (49%) have at least one of these three risk factors.Several other medical conditions and lifestyle c
5、hoices can also put people at a higher risk for heart disease, including:DiabetesOverweight and obesityPoor dietPhysical inactivityExcessive alcohol useRisk Factors心血管药物Cardiovascular drugs1. 强心药 Cardiotonic agents2. 抗心绞痛药 Antianginal drugs3. 抗心率失常药 Antiarrhythmic drugs4. 抗高血压药 Antihypertensive drug
6、s5. 抗高脂蛋白血症 Antihyperlipoproteinemic drugs+_+_+_+_+_+_+_+_+_+_+_+_+_+_+_+_+Na+, K+-ATPaseATP Na+K+Ca+Cl-Na+K+K+mv-100-80-60-40-200+2043210-心肌细胞膜电位与离子转运零电位阈电位静息电位动作电位(actionpotential duration)细胞膜0相：除极，Na+快速内流1相：快速复极初期，K+短暂外流2相：Ca2+及少量Na+经慢通道内流，K+外流3相：快速复极末期，K+外流4相：静息期复极过程膜电位恢复到-60-50mV时，细胞才对刺激产生动作电位。
7、之前为Effective Refractory Period (ERP).ERP大：心肌不起反应的时间长不易发生快速性心律失常药物：影 心肌细胞膜的 通道， 流。I. 强心药 Cardiotonic agents / 正性肌力药 Inotropic agents 慢性 性心 (Congestive Heart Failure, CHF)发 ：心肌 性心肌 ， 性心 性肌 药 心肌 性 药 currency1“fi前 fl 心药 膜Na+，K+-ATP“性的 心 -激动 PDE(”“) 肌 对Ca2+ 性的药强心苷类 Cardiac glycosidesH3CO OO OH3COHHHO OH3
8、CO OH3COHHOOHOHHOHCH3H3CH3CO OO OH3C OHHHO OH3CO OH3COHHOOHOHH Digitoxin Digoxin 抑制心肌 胞膜 合的细 Na+,K+-ATPase（逆 度梯度主 动currency13Na+出 胞外，细 2K+入 胞 ）使 胞 细 内 细 内Na+增多，K+ 少， 经Na+-Ca2+ 向交 一步 致 细胞内Ca2+增加，使心肌收 加强。缩 Ca2+是 心肌发 -收 偶 的 物 ，胞 游离 内 Ca2+能和心肌 蛋白钙troponin 合，解除原肌球蛋白结 tropomyosin对actin和肌球蛋白myosin相互作用的抑制，使
9、actin在 滑 ，化 能 间 动 机械能 强心 中毒引 心律紊 ，可用 防止或 解。 发 F 60 80 药：0.51.5ng/m 药：2ng/mlnarrow therapeutic inde OHOOHCH3CO OO OH3C OHHO OOOCH3HOHHOHOHOHOHOHOH3CO OO OH3C OHHHO OH3CO OH3COH OHOHHOHCH3HOHO HOHOO C Lanatoside C K Strophanthin K ConvallatoxinO OOHCH3COHHOHO OHOHOH3COHH ：1,4- 性, 少， 心作 溶性小， 性肌 作 弱，脂溶性
10、增 ，易 CNS， 枢副作 五 环（植物）cardenolide六 环（动物）bufadienolide3：多为D-glucose, D-digito ose, -Rhamnose, D-Cymarose; 常见糖苷基OHOHOHOHOOHO OHH3COHHOO OHH3COCH3HOO OHH3CHOHO OH-D- -D-L- -D-甾核立体构象：顺反顺OHCH3HCH3HOHHHcis-trans-cis19181716151413121110 987654321ABCD通常3位有OH， ，currency1为型则失通常14位有OH，若脱 （8,14 or14,15）则失。C14应保持sp3杂在甾核的其它位置上可引入OH通常10，13有个甲 ，称19-CH3和18-CH319-CH3氧为19-CH2OH 19-CHO，性升 若氧为19-COOH，则性大大fi19-CH3脱除，性大大fi
