Calcium Channel Blockers － C alcium Antagonists Calcium Channel Blockers － C alcium Antagonists Selectively affect voltage- dependent calcium channels, inhibiting Ca 2+ entering into cells. Selectively affect voltage- dependent calcium channels, inhibiting Ca 2+ entering into cells.

Voltage-dependent calcium channels are classified into 6 subtypes ： Voltage-dependent calcium channels are classified into 6 subtypes ：

〔 Classification 〕 Selective calcium channel blockers: Selective calcium channel blockers: Ⅰ Phenylalkylamines: Verapamil Ⅰ Phenylalkylamines: Verapamil Ⅱ Dihydropyridines: Nifedipine Ⅱ Dihydropyridines: Nifedipine Ⅲ Benzothiazepines: Diltiazem Ⅲ Benzothiazepines: Diltiazem Non-selective calcium channel blockers: Non-selective calcium channel blockers: Ⅳ Flunarizine Ⅳ Flunarizine Ⅴ Prenylamine Ⅴ Prenylamine Ⅵ Others: Perhexiline Ⅵ Others: Perhexiline

Ⅰ Selective effects on L-type calcium channels ， including 4 subcategories ： Ⅰ Selective effects on L-type calcium channels ， including 4 subcategories ： Ⅰ aDihydropyridines: Ⅰ a Dihydropyridines: nifeidipine 、 nicardipine 、 nitrendipine （尼群地平）、 amlodipine （氨氯 地平）、 nimodipine Ⅰ bDiltiazem ： Ⅰ b Diltiazem ： diltiazem （地尔硫卓） 、 clentiazem （克仑硫卓） Ⅰ cPhenylalkylamines: Ⅰ c Phenylalkylamines: verapamil Ⅰ dTiapamil ： Ⅰ d Tiapamil ： tiapamil （噻烷丙胺）

(1) T type: Mibefradil （咪拉地尔） (2) N type: Conotoxin （竽螺毒素） (3) P type: Spider toxin （蜘蛛毒素） (1) T type: Mibefradil （咪拉地尔） (2) N type: Conotoxin （竽螺毒素） (3) P type: Spider toxin （蜘蛛毒素） Ⅱ Selective effects on other voltage- dependent calcium channels ： Ⅲ Non-selective calcium channel blockers: Prenylamine （普尼拉明） Flunarizine （氟苯桂嗪）

Generations: Generations: First ： Verapamil, Nifedipine, Diltiazem Second ： Nimodipine 尼莫地平, Nicardipine 尼卡地平, Felodipine 非洛地平 Third ： Pranidipine 普拉地平， Amlodipine 氨氯地平

L and T type are the main types in cardiovascular system, and L type is the most important one, which involves mainly in the contraction of cardiac and smooth muscle, sinuatrial node pacing 窦房结率, and atrioventricular conduction 房室间传导.

Extracellular The  1C subunit of the L-type Ca 2+ channel is the pore-forming subunit

The expression and function of the  1C subunit is modulated by other smaller subunits

Action Mode Resting State Open State Inactive State A I A A I I A: Activation Gate I: Inactivation Gate

VerapamilDiltiazemNifedipine Action State OpenOpenInactive Binding Site InsideInsideOutside Frequency- dependent YesYesNo

Cardiac cells rely on L-type Ca 2+ channels for the upstroke of the AP in slow response cells L-Type Slow Response Cells (SA node, AV node) Ca Calcium Channel Blockers

Actions  Heart negative inotropic effect 负性肌力作用 negative inotropic effect 负性肌力作用 negative frequency 负性频率 and negative conduction 负性传导作用： negative frequency 负性频率 and negative conduction 负性传导作用： obvious in sino-atrial node and atrioventricular node -rationale for treating supraventricular arrhythmia Actions  Heart negative inotropic effect 负性肌力作用 negative inotropic effect 负性肌力作用 negative frequency 负性频率 and negative conduction 负性传导作用： negative frequency 负性频率 and negative conduction 负性传导作用： obvious in sino-atrial node and atrioventricular node -rationale for treating supraventricular arrhythmia

 smooth muscle blood vessel ： dilate A>V; obvious for spasmodic blood vessel; dilate coronary vessels 冠状血管 other smooth muscle: relax  anti-artherosclerosis 抗动脉粥样硬化作用 relieve vein wall injury caused by calcium overload relieve vein wall injury caused by calcium overload increase compliance of vessel wall increase compliance of vessel wall inhibit lipid peroxidation and protect endothelial cell inhibit lipid peroxidation and protect endothelial cell  smooth muscle blood vessel ： dilate A>V; obvious for spasmodic blood vessel; dilate coronary vessels 冠状血管 other smooth muscle: relax  anti-artherosclerosis 抗动脉粥样硬化作用 relieve vein wall injury caused by calcium overload relieve vein wall injury caused by calcium overload increase compliance of vessel wall increase compliance of vessel wall inhibit lipid peroxidation and protect endothelial cell inhibit lipid peroxidation and protect endothelial cell

nifedipine increases intracellular cAMP, leading to a decrease of intracellular cholesterin nifedipine increases intracellular cAMP, leading to a decrease of intracellular cholesterin  RBC: relieve injury of RBC caused by calcium overload Inhibition of platelet activation Inhibition of platelet activation  Kidney: exclude sodium and diuresis nifedipine increases intracellular cAMP, leading to a decrease of intracellular cholesterin nifedipine increases intracellular cAMP, leading to a decrease of intracellular cholesterin  RBC: relieve injury of RBC caused by calcium overload Inhibition of platelet activation Inhibition of platelet activation  Kidney: exclude sodium and diuresis

Threapeutic uses angina: effective for all kinds angina: effective for all kinds arrhythmia ： especially caused by supraventricular and after-depolarization triggered activity 后除极触发活动 arrhythmia ： especially caused by supraventricular and after-depolarization triggered activity 后除极触发活动 hypertension hypertension cerebrovascular disease cerebrovascular disease peripheral angiospasm, prophylaxis of artherosclerosis, bronchial asthma, brow ache peripheral angiospasm, prophylaxis of artherosclerosis, bronchial asthma, brow ache Threapeutic uses angina: effective for all kinds angina: effective for all kinds arrhythmia ： especially caused by supraventricular and after-depolarization triggered activity 后除极触发活动 arrhythmia ： especially caused by supraventricular and after-depolarization triggered activity 后除极触发活动 hypertension hypertension cerebrovascular disease cerebrovascular disease peripheral angiospasm, prophylaxis of artherosclerosis, bronchial asthma, brow ache peripheral angiospasm, prophylaxis of artherosclerosis, bronchial asthma, brow ache