Pharmacology - Calcium Channel Blockers and Nitrates Questions and Answers

CCBs mechanism inhibit Ca2+ influx through L-type (voltage gated) calcium channels (LTCC) CCBs actions act on Ca2+ entry into vascular smooth muscle (vasodilate), cardiac muscle (decrease force of contraction), SA nodal tissues (reduce contraction rate), AV node (decrease conduction velocity) Therapeutic Indications - Hypertension CCBs Dihydropyridines Therapeutic Indications - Arrhythmias CCBs Verapamil Therapeutic Indications - Angina CCBs Verapamil/Diltiazem Advantages with CCBs Do not induce bronchoconstriction or adversely affect lipid profiles Dihydropyridine CCB (dipine drugs) action vasodilator on arteriolar smooth muscle (not cardiac) Dihydropyridine CCB mechanism anti-hypertensive from vasodilation, reduced vascular resistance (afterload) so reduced MAP, little effect on venous beds. Directly bind to and stabilise inactivated channel state - more inactivated channels in arteriolar smooth muscle as depolarisations are longer than cardiac muscle Dihydropyridine CCB beware: drop in pressure causes reflex cardiac stimulation - tachycardia, increased inotropy, large increase in myocardial O2 demand so not good for angina Verapamil CCB action cardiac negative inotrope, reduces SA node automaticity, reduces AV node conduction velocity Verapamil CCB mechanism binds to open cardiac LTCC so relatively cardioselective, suppresses cardiac contractility and reduces LTCC channel recovery by interfering with Ca2+ binding - promotes inactivated channel conformation. Inhibition increases at higher HRs - more channels open