This document summarizes calcium channel blocking drugs (CCBs). It discusses their binding sites on the L-type calcium channel, their three classes and differing mechanisms of action, including increasing the time calcium channels are closed. It lists the three classes of CCBs, their chemical names, and hemodynamic effects. It also covers the pharmacokinetics, adverse effects, and clinical uses of CCBs, which include angina, hypertension, and treating various arrhythmias. CCBs improve cardiac function by reducing afterload, increasing oxygen supply, decreasing preload, and normalizing heart rate.

1. Calcium Channel Blocking Drugs<br />CCB binding sites:<br />The α1C subunit of the L-type Ca++ channel is the pore forming subunit<br />The expression and function of the α1C subunit is modulated by other smaller subunits<br />The three classes of CCB’s binds to different sites<br />The different binding sites of CCB’s result in differing pharmacological actions<br />Use dependent binding (in cardiac cells – Verapamil, Diltiazem)<br />Voltage dependent binding ( in smooth muscle – Nifedipine)<br />Mechanism of action<br />Increase the time that Ca++ channels are closed<br />Relaxation of arterial smooth muscle but not much effect on the venous smooth muscle<br />Significant reduction in afterload but not preload <br />Three classes of CCB’s<br />CHEMICAL TYPE CHEMICAL NAMES <br />Phenylalkylamines Verapamil <br />Benzothiazepines Diltiazem<br />1,4-Dihydropyridines Nifedipine, Amlodipine , Felodipine , Nicardipine <br />Haemodynamic effects of CCB’s<br />All CCB’s causes peripheral & coronary vasodilation -> reduce after load<br />Non-dihydropryridines reduce the AV conduction, heart rate and contractility of the heart<br />Pharmacokinetics: all CCB’s have >90% oral absorption and highly bound to plasma protein (>90%)<br />Adverse effects: hypotension, peripheral edema, headache, non-dihydropyridines - constipation, worsening of CHF, AV block<br />Clinical uses of CCB’s<br />Angina pectoris<br />Hypertension<br />Treatment of Supraventricular arrhythmias<br />Atrial flutter<br />Atrial fibrillation<br />Paroxysmal SVT<br />CCB’s improve cardiac function by<br />reducing cardiac after load <br />increasing O2 supply<br />decreasing cardiac preload<br />normalizing heart rate in patients with supraventricular tachycardia <br />increasing total peripheral resistance<br />Correct : A, B, D<br />