Calcium channel blockers

Calcium channel blockers

Examples of such calcium channel blockers are shown in Figure 6.7. While nifedipine contains the dihydropyridine moiety (in red) after which the receptor has been named, verapamil does not, indicating that the receptor's name does not reflect any fundamental requirement of drug molecular structure.

We have seen before that calcium channels are not only im-portant in the contraction of the heart muscle but also in the generation of cardiac rhythm. The DHPR is present in both the pacemaker and the muscle cells of the heart mus-cle. This means that calcium channel blockers will not only reduce the contractility of the heart muscle cells but also slow down the rhythm. Slowing down the rhythm means increased duration of the interval between two contrac-tions (the diastole). The diastole is the only period during which the pressure within the heart tissue does not exceed the arterial blood pressure; therefore, only during the dias-tole the heart tissue itself is effectively perfused. Reduced contractility and prolonged pauses combine to improve the metabolic situation of heart muscle cells suffering from re-duced perfusion in occlusive disease ???

The DHPR is also found in vascular smooth muscle. While the mode of action of Ca⁺⁺ is somewhat different in smooth muscle than in striated muscle (cf. Figure 6.10b, below), it is still crucial for contraction, and as in heart muscle, flow of Ca ⁺⁺ across the plasma membrane is required. The DHPR in smooth muscle therefore constitutes an impor-tant drug target for calcium channel blockers as well, as they will decrease the vascular wall tension and, hence, the blood pressure. The DHPR subtypes in heart and smooth muscle differ, and some blockers act more strongly on ei-ther the smooth muscle (nifedipine) or the heart (vera-pamil).