鈣通道阻滯藥物-2011-03-30

1、Calcium channel blockers（鈣通道阻滯藥）（鈣通道阻滯藥）Xiaoping Chen （陳小平）（陳小平）Department of pharmacology, CSUEmail: Calcium channel blockers(Calcium antagonist, 鈣拮抗劑鈣拮抗劑)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: 總鈣離子內(nèi)流總鈣離子內(nèi)流Ca : 單一鈣離子通道鈣內(nèi)流單一鈣離子通道鈣內(nèi)流n: 通道數(shù)目通道數(shù)目p: 開放概率開放概率+Calcium channel blockersCalcium channelBlockers-II. Pharmacological actions鈣通道阻滯藥對心臟及對血管鈣通道阻滯藥對心臟及對血管作用的選擇性作用的選擇性2.負性頻率作用及負性傳導(dǎo)作用（負性頻率作用及負性傳導(dǎo)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心絞痛（心絞痛（angina）變異型心絞痛（variant angina）: 舒張大的冠狀動脈，首選；勞力型心絞痛（angina of effort）: BP , afterload, oxygen demand2. Supraventricular arhythmia (室上室上性心動過速性心動過速) Use-dependence: channels being used frequently are more

4、susceptible to block3. Hypertension (高血壓高血壓)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 +動物實驗動物實驗: 心律失常發(fā)生心律失常發(fā)生, MI梗死面積梗死面積人類人類: 不能阻止不能阻止MI的發(fā)展，也不可降低其死亡率的發(fā)展，也不可降低其死亡率MI時存在鈣超載時存在鈣超載: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?。ǚ屎裥托募〔。╤ypertrophic myocardiopathy）Contraindications (禁忌證): left heart failure, sick sinus syndrome (病竇綜合癥), atrioventricular block（房室傳導(dǎo)阻滯） 7. 動脈粥樣硬化動脈粥樣硬化（atherosclerosis, AS）：）：Prevent or attenuate the development of AS8. 血管性疾?。ㄑ苄约膊。╲ascular disea

6、se）IV. PharmacokineticsV. Adverse reaction and interactions of drugs藥物相互作用（藥物相互作用（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 (維拉帕米維拉帕米 / Isoptin, 異博定異博定)l Negative inotropic effect (負性肌力作用負性肌力作用)Blocks calcium channel; activates phosphodiesterase; inhibits the function of systolic proteinsl Negative chronotropic effect (負性頻率作用負性頻率作用)l P-R interval (間期間期) dose dependentl Vasodilation (血管擴張血管擴張) Resistant vessels and coronary artery Reflex sympathetic activity is mild