Download Calcium Channel Blockers: Action, Usage, and Classification and more Study notes Acting in PDF only on Docsity! 1 DRUG CLASSES Calcium channel blockers (CCBs) or calcium antagonists, are among the most widely used drugs in cardiovascular medicine with roles not only in hypertension but also in angina and (for some CCBs) tachyarrhythmias. Examples Amlodipine Diltiazem Felodipine Isradipine Lacidipine Lercanidipine Nicardipine Nifedipine Nisoldipine Verapamil Mechanism of action CCBs promote vasodilator activity (and reduce blood pressure) by reducing calcium influx into vascular smooth muscle cells by interfering with voltage-operated calcium channels (and to a lesser extent receptor-operated channels) in the cell membrane. Interference with intracellular calcium influx is also important in cardiac muscle, cardiac conduction tissue and gastrointestinal smooth muscle. In cardiac tissues, CCBs have potential for negative inotropic, chronotropic and dromotropic activity while the gastrointestinal effects predispose to constipation. These effects vary with different agents according to ability to penetrate cardiac and other tissues, relative affinity for calcium channels in different tissues and the influence of reflux cardiac stimulation secondary to peripheral vasodilation. CALCIUM CHANNEL BLOCKERS 2 Although often considered as a single class, CCBs can be subdivided according to structural and functional distinctions. Dihydropyridine derivates : amlodipine, felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nisoldipine Phenylalkylamine : verapamil Benzothiazepine derivative : diltiazem Dihydropyridine derivatives have pronounced peripheral vasodilated properties and intense reflex cardiac stimulation overcomes any direct cardiac effects. Verapamil and diltiazem are also vasodilators but the balance of actions is such that these drugs have noticeable cardiac effects including reduced heart rate (rate-limiting CCBs). Pharmacokinetics Most CCBs have low and variable oral bioavailability because of extensive first-pass metabolism. Half-life is relatively short (< 12 hours). The exception is amlodipine which, although extensively metabolised, has a substantially longer half-life (> 40 hours). Diltiazem and verapamil tend to inhibit drug metabolism. This enzyme inhibitory effect is a potential source of drug interactions e.g. with ciclosporin. Adverse effects Dihydropyridines - headache and flushing due to peripheral vasodilation - tachycardia and palpitation secondary to reflex activation of the sympathetic nervous system Particularly with rapid-onset and short-acting agents Usually declines with time - swelling of ankles and occasionally hands due to disturbance of haemodynamics of microcirculation (preferential pre-capillary arteriolar vasodilation) Long-term effect Can arise many months after treatment initiated and may be more common with long-acting agents Rate-limiting CCBs - bradycardia and atrio-ventricular conduction delay due to direct cardiac effects - constipation with verapamil Early onset vasodilator effects less than with dihydropyridines
