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Download Calcium Channel Blockers - C alcium Antagonists Calcium Channel Blockers - C alcium Antagonists Selectively affect voltage- dependent calcium channels,

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  • Calcium Channel Blockers Calcium Antagonists Selectively affect voltage-dependent calcium channels, inhibiting Ca2+ entering into cells.

  • Voltage-dependent calcium channels are classified into 6 subtypes

  • Classification Selective calcium channel blockers: Phenylalkylamines: Verapamil Dihydropyridines: Nifedipine Benzothiazepines: Diltiazem Non-selective calcium channel blockers: Flunarizine Prenylamine Others: Perhexiline

  • Selective effects on L-type calcium channelsincluding 4 subcategories a Dihydropyridines: nifeidipinenicardipine nitrendipineamlodipinenimodipineb Diltiazem diltiazem clentiazemc Phenylalkylamines: verapamil d Tiapamiltiapamil

  • (1) T type: Mibefradil (2) N type: Conotoxin(3) P type: Spider toxin Selective effects on other voltage-dependent calcium channels Non-selective calcium channel blockers:Prenylamine Flunarizine

  • Generations:First Verapamil, Nifedipine, DiltiazemSecondNimodipine, Nicardipine, FelodipineThird PranidipineAmlodipine

  • 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, and atrioventricular conduction.

  • ExtracellularThe 1C subunit of the L-type Ca2+ channel is the pore-forming subunit

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

  • Action ModeResting State Open State

    Inactive StateAIAAIIA: Activation Gate I: Inactivation Gate

  • VerapamilDiltiazemNifedipineAction StateOpen OpenInactiveBinding SiteInside InsideOutsideFrequency-dependentYesYesNo

  • Cardiac cells rely on L-type Ca2+ channels for the upstroke of the AP in slow response cellsL-TypeSlow Response Cells(SA node, AV node)Ca2+Ca2+ Calcium Channel Blockers

  • Actions Heart negative inotropic effect negative frequency and negative conductionobvious in sino-atrial node and atrioventricular node-rationale for treating supraventricular arrhythmia

  • smooth muscleblood vesseldilate A>V; obvious for spasmodic blood vessel; dilate coronary vesselsother smooth muscle: relax anti-artherosclerosis relieve vein wall injury caused by calcium overload increase compliance of vessel wall inhibit lipid peroxidation and protect endothelial cell

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

  • Threapeutic usesangina: effective for all kinds arrhythmiaespecially caused by supraventricular and after-depolarization triggered activityhypertensioncerebrovascular diseaseperipheral angiospasm, prophylaxis of artherosclerosis, bronchial asthma, brow ache

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