For patients with severe PAD or those with vasospastic (Prinzmetal s) angina, wors- ening symptoms due to vasoconstriction from unopposed alpha-adrenergic activity can be avoided by using beta blockers with alpha-adrenergic blocking (eg, labetalol or carvedilol) or direct vasodilator (eg, nebivolol) properties. 4.4.3.1.2. Calcium Channel Blockers. If adverse effects or contraindications limit the use of beta blockers, calcium channel blockers are recommended for relief of anginal symptoms. These agents noncompetitively limit calcium ion influx through voltage-dependent L-type calcium channels, resulting in negative inotropic effects, cardiac pacemaker depression, slowing conduction, and smooth muscle relax- ation. There are 3 classes of calcium channel blockers: the dihydropyridines (eg, nifedipine) and 2 types of nondihydro- pyridines, the phenylalkylamines (eg, verapamil) and the benzothiazepines (eg, diltiazem). All classes improve myo- cardial oxygen supply by decreasing coronary vascular resis- tance and augmenting epicardial conduit vessel and systemic arterial blood flow. Myocardial demand is decreased by a reduction in myocardial contractility, systemic vascular resis- tance, and arterial pressure. However, the phenylalkylamines and, to a lesser extent, the benzothiazepines also depress cardiac pacemaker rate and slow conduction. This depressant effect can cause sinus bradycardia or can worsen preexisting conduction defects, leading to heart block. Myocardial con- tractile depression also is a common feature, although the degree is variable according to drug class. 