Calcium channel blockers, specific

Calcium Channel Blockers. Because accumulation of calcium is one of the facets of the mote involved process leading to atherosclerosis, it would foUow that the antihypertensive calcium channel blockers might be effective in preventing atheroma. Both verapamil (Table 1) and nifedipine (Table 3) have been shown to stimulate the low density Upoprotein (LDL) receptor (159). This specific receptor-mediated pathway could theoretically improve Upid metaboUsm in the arterial wall, and thereby prove antiatherogenic. These effects have been proven in animals. 

Systemic and coronary arteries are influenced by movement of calcium across cell membranes of vascular smooth muscle. The contractions of cardiac and vascular smooth muscle depend on movement of extracellular calcium ions into these walls through specific ion channels. Calcium channel blockers, such as amlodipine (Norvasc), diltiazem (Cardizem), nicardipine (Cardene), nifedipine (Procardia), and verapamil (Calan), inhibit die movement of calcium ions across cell membranes. This results in less calcium available for the transmission of nerve impulses (Fig. 41-1). This drug action of the calcium channel blockers (also known as slow channel blockers) has several effects on die heart, including an effect on die smooth muscle of arteries and arterioles. These drug dilate coronary arteries and arterioles, which in turn deliver more oxygen to cardiac muscle. Dilation of peripheral arteries reduces die workload of die heart. The end effect of these drug is the same as that of die nitrates. 

ACE inhibitors and angiotensin-receptor blockers (ARB) have definite benefits in patients with nephropathy and are believed to have renoprotective effects in most patients. Due to their ability to cause an initial bump in serum creatinine, these agents should be used cautiously when employed in combination with the calcineurin inhibitors. The dihydropyridine calcium channel blockers have demonstrated an ability to reverse the nephrotoxicity associated with cyclosporine and tacrolimus (Table 52-8). In general, antihypertensive therapy should focus on agents with proven benefit in reducing the progression of cardiovascular disease and should be chosen on a patient-specific basis.55 See Chapter 2 for further recommendations for treating HTN. 

Klotz U. (2006) Ziconotide — a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain — a short review. Int J Clin Pharmacol Ther 44 478—483. 

The pharmacokinetic properties of these drugs are set forth in Table 12-5. The choice of a particular calcium channel-blocking agent should be made with knowledge of its specific potential adverse effects as well as its pharmacologic properties. Nifedipine does not decrease atrioventricular conduction and therefore can be used more safely than verapamil or diltiazem in the presence of atrioventricular conduction abnormalities. A combination of verapamil or diltiazem with 3 blockers may produce atrioventricular block and depression of ventricular function. In the presence of overt heart failure, all calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect. Amlodipine, however, does not increase the mortality of patients with heart failure due to nonischemic left ventricular systolic dysfunction and can be used safely in these patients. 

The calcium channel blockers currently used to treat angina pectoris are listed in Table 22-3. Although the chemistry and exact mechanism of action of each drug are somewhat distinct, all of these agents exert their effects by limiting calcium entry into specific cardiovascular tissues. Certain calcium channel blockers are said to be selective if they affect vascular smooth muscle, but have little or no affect on the heart. Nonselective calcium channel blockers affect the vasculature and inhibit calcium entry into cardiac muscle cells. Individual agents are discussed below. 

Calcium channel blockers can also be given to treat stable angina, especially if beta blockers are not tolerated or are contraindicated in specific patients.13 These drugs decrease cardiac workload directly by limiting calcium entry into myocardial cells and indirectly by producing peripheral vasodilation, thus decreasing cardiac preload and afterload.47 Hence, cal-... 

Class IV drugs have a selective ability to block calcium entry into myocardial and vascular smooth-muscle cells. These drugs inhibit calcium influx by binding to specific channels in the cell membrane.12,15 As discussed previously, calcium entry plays an important role in the generation of the cardiac action potential, especially during phase 2. By inhibiting calcium influx into myocardial cells, calcium channel blockers can alter the excitability and conduction of cardiac tissues. 

Calcium channel blockers bind specifically to receptor sites associated with the voltage-dependent calcium channels [31,32]. These blockers inhibit calcium uptake [33,34] and block smooth muscle contraction [35,36]. All these three activities of calcium channel blockers have been found to be mutually correlated. For ten known calciiun channel blockers (Table 4), Papaionnou et al. [37] derived the correlations ... 

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