钙通道阻滞药物-2011-03-30

1、Calcium channel blockers（钙通道阻滞药）（钙通道阻滞药）Xiaoping Chen （陈小平）（陈小平）Department of pharmacology, CSUEmail: Calcium channel blockers(Calcium antagonist, 钙拮抗剂钙拮抗剂)Physiological roles of Ca2+Sources of intracellular free calcium+Classification of calcium channelsL-type calcium channel and mechanism of drug

2、actionMenbraneOutsideInsideDHP: Dihydropyridine; PAA: PhenylalkylaminesOIRCa2+i = Ca n pCa2+i: 总钙离子内流总钙离子内流Ca : 单一钙离子通道钙内流单一钙离子通道钙内流n: 通道数目通道数目p: 开放概率开放概率+Calcium channel blockersCalcium channelBlockers-II. Pharmacological actions钙通道阻滞药对心脏及对血管钙通道阻滞药对心脏及对血管作用的选择性作用的选择性2.负性频率作用及负性传导作用（负性频率作用及负性传导作用（ne

3、gative chronotropic and negative conductive action）引起反射性心率加快引起反射性心率加快III. Therapeutic usesn心绞痛（心绞痛（angina）变异型心绞痛（variant angina）: 舒张大的冠状动脉，首选；劳力型心绞痛（angina of effort）: BP , afterload, oxygen demand2. Supraventricular arhythmia (室上室上性心动过速性心动过速) Use-dependence: channels being used frequently are more

4、susceptible to block3. Hypertension (高血压高血压)4.心肌梗死（心肌梗死（myocardium infarction, MI）calcium influx , overload activation of ATP consuming enzymes energy tores susceptibility to damage +动物实验动物实验: 心律失常发生心律失常发生, MI梗死面积梗死面积人类人类: 不能阻止不能阻止MI的发展，也不可降低其死亡率的发展，也不可降低其死亡率MI时存在钙超载时存在钙超载:energy stores Ischemia5. 充

5、血性心力衰竭（充血性心力衰竭（congestive heart failure）6. 肥厚型心肌病（肥厚型心肌病（hypertrophic myocardiopathy）Contraindications (禁忌证): left heart failure, sick sinus syndrome (病窦综合症), atrioventricular block（房室传导阻滞） 7. 动脉粥样硬化动脉粥样硬化（atherosclerosis, AS）：）：Prevent or attenuate the development of AS8. 血管性疾病（血管性疾病（vascular disea

6、se）IV. PharmacokineticsV. Adverse reaction and interactions of drugs药物相互作用（药物相互作用（drug interactions ）:l Pharmacokinetics: dioxin concentration; cimetidine t1/2, quinidine concentrationl Pharmacodynamics: hypotensive effects of nitrates and prazosin, atrioventricular blockade with -AR blockersVI. Cla

7、ssification of CCBsA. ActionsNifedipine (硝苯地平硝苯地平)2. 正性肌力作用（正性肌力作用（positive inotropic effect） B. Therapeutics usesC. Adverse reactions：D. ContraindicationsBe Cautious in HF and unstable angina Nitrendipine (尼群地平尼群地平)Nisodipine (尼索地平尼索地平)Nicardipine (尼卡地平尼卡地平)Nimodipine (尼莫地平尼莫地平)Amlodipine (氨氯地平氨氯地平

8、)Verapamil (维拉帕米维拉帕米 / Isoptin, 异博定异博定)l Negative inotropic effect (负性肌力作用负性肌力作用)Blocks calcium channel; activates phosphodiesterase; inhibits the function of systolic proteinsl Negative chronotropic effect (负性频率作用负性频率作用)l P-R interval (间期间期) dose dependentl Vasodilation (血管扩张血管扩张) Resistant vessels and coronary artery Reflex sympathetic activity is mild