3. Three Classes of CCBs Chemical Type Chemical Names Brand Names Phenylalkylamines verapamil Calan, Calna SR, Isoptin SR, Verelan Benzothiazepines diltiazem Cardizem CD, Dilacor XR 1,4-Dihydropyridines Nifedipine nicardipine isradipine felodipine amlodipine Adalat CC, Procardia XL Cardene DynaCirc Plendil Norvasc
4.
5.
6. The Three Classes of CCBs Bind to Different Sites 1,4- Dihydropyridines (nifedipine) Phenylalkylamines (verapamil) Benzothiazepines (diltiazem) Ca 2+ pore - - - - + + -
7.
8.
9. Why Do CCBs Act Selectively on Cardiac and Vascular Muscle?
10. N-type and P-type Ca 2+ channels mediate neurotransmitter release in neurons postsynaptic cell Ca 2+ Ca 2+ Ca 2+ Ca 2+ Ca 2+
11. Skeletal muscle relies on intracellular Ca 2+ for contraction Myofibril Plasma membrane Transverse tubule Terminal cisterna of SR Tubules of SR Triad T SR
12. Cardiac cells rely on L-type Ca 2+ channels for contraction and for the upstroke of the AP in slow response cells Contractile Cells (atria, ventricle) L-Type Ca 2+ Ca 2+ Ca 2+ Slow Response Cells (SA node, AV node) L-Type Ca 2+ Ca 2+
13. Vascular smooth muscle relies on Ca 2+ influx through L-type Ca 2+ channels for contraction (graded, Ca 2+ dependent contraction) L-Type Ca 2+
14.
15.
16. Differential effects of different CCBs on CV cells AV SN AV SN Potential reflex increase in HR, myocardial contractility and O 2 demand Coronary VD Dihydropyridines: Selective vasodilators Non -dihydropyridines: equipotent for cardiac tissue and vasculature Heart rate moderating Peripheral and coronary vasodilation Reduced inotropism Peripheral vasodilation