Calcium Channel BlockersCalcium Channel Blockers － － CCalcium Antagonistsalcium Antagonists

Calcium Channel BlockersCalcium Channel Blockers － － CCalcium Antagonistsalcium Antagonists

Selectively affect voltage-dependeSelectively affect voltage-depende

nt calcium channels, inhibiting Cant calcium channels, inhibiting Ca2+2+ entering into cells. entering into cells.

Selectively affect voltage-dependeSelectively affect voltage-depende

nt calcium channels, inhibiting Cant calcium channels, inhibiting Ca2+2+ entering into cells. entering into cells.

Voltage-dependent calcium cVoltage-dependent calcium channels are classified into 6 shannels are classified into 6 subtypesubtypes ：：

〔〔 ClassificationClassification 〕〕 Selective calcium channel blockers:Selective calcium channel blockers:

ⅠⅠ Phenylalkylamines: VerapamilPhenylalkylamines: Verapamil

ⅡⅡ Dihydropyridines:Dihydropyridines: NifedipineNifedipine

ⅢⅢ Benzothiazepines:Benzothiazepines: Diltiazem Diltiazem

Non-selectiveNon-selective calcium channel blockecalcium channel blockers:rs:

ⅣⅣ FlunarizineFlunarizine

ⅤⅤ PrenylaminePrenylamine

ⅥⅥ Others: Perhexiline Others: Perhexiline

ⅠⅠ Selective effects on L-type calcium Selective effects on L-type calcium channelschannels ，， including 4 subcategoriesincluding 4 subcategories ：：

ⅠⅠ Selective effects on L-type calcium Selective effects on L-type calcium channelschannels ，， including 4 subcategoriesincluding 4 subcategories ：：

ⅠⅠaa Dihydropyridines:Dihydropyridines: nifeidipine 、 nicardipine 、 nitrendipine （尼群地平）、 amlodipine （氨氯地平）、 nimodipine

ⅠⅠbb DiltiazemDiltiazem ：： diltiazem （地尔硫卓） 、 clentiazem （克仑硫卓）

ⅠⅠcc Phenylalkylamines:Phenylalkylamines: verapamil ⅠⅠdd TiapamilTiapamil ：： tiapamil （噻烷丙胺）

(1)(1) T type: T type: Mibefradil Mibefradil （咪拉地尔） （咪拉地尔） (2)(2) N type: N type: Conotoxin Conotoxin （竽螺毒素）（竽螺毒素）(3)(3) P type: P type: Spider toxin Spider toxin （蜘蛛毒（蜘蛛毒

素）素）

(1)(1) T type: T type: Mibefradil Mibefradil （咪拉地尔） （咪拉地尔） (2)(2) N type: N type: Conotoxin Conotoxin （竽螺毒素）（竽螺毒素）(3)(3) P type: P type: Spider toxin Spider toxin （蜘蛛毒（蜘蛛毒

素）素）

Ⅱ Ⅱ Selective effects on other voltage-deSelective effects on other voltage-dependent calcium channelspendent calcium channels ：：

Ⅲ Ⅲ Non-selective calcium channel blockers:Non-selective calcium channel blockers:

Prenylamine （普尼拉明） Flunarizine （氟苯桂嗪）

Generations:Generations:

First First ：： Verapamil, Nifedipine, DiltiazemVerapamil, Nifedipine, Diltiazem

SecondSecond ：： NimodipineNimodipine 尼莫地平尼莫地平 , Nicardipine, Nicardipine 尼卡地平尼卡地平 , ,

FelodipineFelodipine 非洛地平非洛地平

Third Third ：： PranidipinePranidipine 普拉地平，普拉地平， AmlodipineAmlodipine 氨氯地平氨氯地平

L and T type are the main types in cL and T type are the main types in c

ardiovascular systemardiovascular system, , and and L typeL type is the is the

most important one, which involves maimost important one, which involves mai

nly in the nly in the contraction ofcontraction of cardiac and smcardiac and sm

ooth muscleooth muscle, , sinuatrial node pacingsinuatrial node pacing 窦窦房结率房结率 , and , and atrioventricular conductionatrioventricular conduction

房室间传导房室间传导 . .

Extracellular

III IV

II IIVIII

56

56

Out

In

I II III IV

The The 1C subunit of the L-type Ca1C subunit of the L-type Ca2+2+ channel channel is the pore-forming subunit is the pore-forming subunit

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

NH3+

NH3+

COO-

COO-

1C

NH3+

COO-

2

I II III IV

COO-

NH3+

Action ModeAction ModeResting State Open Resting State Open

StateStateResting State Open Resting State Open

StateState

Inactive State

A

I

AA

I

I

A: Activation Gate I: Inactivation Gate

VerapamilVerapamil DiltiazemDiltiazem NifedipineNifedipine

Action StateAction State Open Open OpenOpen InactiveInactive

Binding SiteBinding Site Inside Inside InsideInside OutsideOutside

Frequency-Frequency-dependentdependent YesYes YesYes NoNo

Cardiac cells rely on L-type CaCardiac cells rely on L-type Ca2+2+ channels for channels for the upstroke of the AP in slow response cellsthe upstroke of the AP in slow response cells

L-Type

Slow Response Cells(SA node, AV node)

Ca2+

Ca2+

40

3

Calcium Channel Blockers

ActionsActions

HeartHeart

negative inotropic effectnegative inotropic effect 负性肌力作用负性肌力作用 negativenegative frequencyfrequency 负性频率 负性频率 and and

negativenegative conductionconduction 负性传导作用负性传导作用：：obvious in obvious in sino-atrial node and atrioventricular nsino-atrial node and atrioventricular n

odeode

--rationale for treating supraventricular arrhythmiarationale for treating supraventricular arrhythmia

ActionsActions

HeartHeart

negative inotropic effectnegative inotropic effect 负性肌力作用负性肌力作用 negativenegative frequencyfrequency 负性频率 负性频率 and and

negativenegative conductionconduction 负性传导作用负性传导作用：：obvious in obvious in sino-atrial node and atrioventricular nsino-atrial node and atrioventricular n

odeode

--rationale for treating supraventricular arrhythmiarationale for treating supraventricular arrhythmia

smooth musclesmooth muscle

blood vesselblood vessel ：： dilate Adilate A>>V; obvious for V; obvious for spasmodic spasmodic

blood vessel;blood vessel; dilate dilate coronary vesselscoronary vessels 冠状血管冠状血管

other other smooth musclesmooth muscle: relax: relax

anti-artherosclerosisanti-artherosclerosis 抗动脉粥样硬化作用抗动脉粥样硬化作用

relieve relieve vein wall injury caused by calcium overloavein wall injury caused by calcium overloa

dd

increase increase compliancecompliance of of vessel wallvessel wall

inhibit inhibit lipid peroxidationlipid peroxidation and protect endothelial c and protect endothelial c

ellell

smooth musclesmooth muscle

blood vesselblood vessel ：： dilate Adilate A>>V; obvious for V; obvious for spasmodic spasmodic

blood vessel;blood vessel; dilate dilate coronary vesselscoronary vessels 冠状血管冠状血管

other other smooth musclesmooth muscle: relax: relax

anti-artherosclerosisanti-artherosclerosis 抗动脉粥样硬化作用抗动脉粥样硬化作用

relieve relieve vein wall injury caused by calcium overloavein wall injury caused by calcium overloa

dd

increase increase compliancecompliance of of vessel wallvessel wall

inhibit inhibit lipid peroxidationlipid peroxidation and protect endothelial c and protect endothelial c

ellell

nifedipine nifedipine increases intracellular cAMP, leadinincreases intracellular cAMP, leadin

g to a decrease of intracellular g to a decrease of intracellular cholesterincholesterin

RBCRBC: : relieve injury of RBC caused by calciurelieve injury of RBC caused by calciu

m overloadm overload

Inhibition of Inhibition of plateletplatelet activationactivation

KidneyKidney: : exclude sodium and exclude sodium and diuresisdiuresis

nifedipine nifedipine increases intracellular cAMP, leadinincreases intracellular cAMP, leadin

g to a decrease of intracellular g to a decrease of intracellular cholesterincholesterin

RBCRBC: : relieve injury of RBC caused by calciurelieve injury of RBC caused by calciu

m overloadm overload

Inhibition of Inhibition of plateletplatelet activationactivation

KidneyKidney: : exclude sodium and exclude sodium and diuresisdiuresis

Threapeutic usesThreapeutic usesanginaangina: : effective for all kindseffective for all kinds

arrhythmiaarrhythmia ：： especially caused by especially caused by supravesuprave

ntricularntricular and and after-depolarization triggered actiafter-depolarization triggered acti

vityvity 后除极触发活动后除极触发活动hypertensionhypertension

cerebrovascular diseasecerebrovascular disease peripheral angiospasmperipheral angiospasm,, prophylaxis of prophylaxis of artheroarthero

sclerosis, sclerosis, bronchial asthma, brow ache bronchial asthma, brow ache

Threapeutic usesThreapeutic usesanginaangina: : effective for all kindseffective for all kinds

arrhythmiaarrhythmia ：： especially caused by especially caused by supravesuprave

ntricularntricular and and after-depolarization triggered actiafter-depolarization triggered acti

vityvity 后除极触发活动后除极触发活动hypertensionhypertension

cerebrovascular diseasecerebrovascular disease peripheral angiospasmperipheral angiospasm,, prophylaxis of prophylaxis of artheroarthero

sclerosis, sclerosis, bronchial asthma, brow ache bronchial asthma, brow ache