Calcium channel blockers causative agents

Calcium channel blockers cause more pronounced lowering of blood pressure in hypertensive patients than in normotensive individuals. Generally, all calcium channel blockers cause an immediate increase in PRA during acute treatment in patients having hypertension but PRA is normalized during chronic treatment despite the sustained decrease in blood pressure. These agents also do not generally produce sodium and water retention, unlike the conventional vasodilators. This is because they produce diuretic effects by direct actions on the kidney. 

CALCIUM CHANNEL BLOCKERS ANTIPLATELET AGENTS -ASPIRIN 1 antihypertensive effect with aspirin effect not noted with low-dose aspirin Aspirin may cause sodium retention and vasoconstriction at possibly both renal and endothelial sites Monitor BP closely when high-dose aspirin is prescribed... 

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. 

In addition to being used as antianginal and antiarrhythmic agents, calcium channel blockers are used to treat weak and moderate hypertension. These drugs prevent calcium ions from entering into the smooth muscle cells of peripheral vessels, and they cause relaxation of peripheral vessels, which leads to lowering of arterial blood pressure. In clinically used doses, calcium channel blockers relax smooth musculature of arteries and have little effect on veins. In doses that relax smooth musculature, calcium channel blockers have relatively little effect on cardiac contractility. 

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 inhibit the entrance of calcium into cardiac and smooth muscle cells of the coronary and systemic arterial beds. All calcium channel blockers are therefore vasodilators that cause a decrease in smooth muscle tone and vascular resistance. (See p. 187 for a description of the mechanism of action of this group of drugs.) At clinical doses, these agents affect primarily the resistance of vascular smooth muscle and the myocardium. [Note Verapamil mainly affects the myocardium, whereas nifedipine exerts a greater effect on smooth muscle in the peripheral vasculature. Diitiazem is intermediate in its actions.]... 

DISOPYRAMIDE CALCIUM CHANNEL BLOCKERS Risk of myocardial depression and asystole when disopyramide is co administered with verapamil, particularly in the presence of heart failure Disopyramide is a myocardial depressant like verapamil and can cause ventricular tachycardia, ventricular fibrillation or torsades de pointes Avoid co administering verapamil with disopyramide if possible. If single-agent therapy is ineffective, monitor PR, BP and ECG closely watch for heart failure... 

The effects of antihypertensive agents have been evaluated in patients taking ciclosporin. Collectively, dihydropyridine calcium channel blockers that do not affect ciclosporin blood concentrations substantially or at all (felodipine, isradipine, and nifedipine) are usually considered to be the drugs of choice. However, the risk of gingival hyperplasia with nifedipine, which ciclosporin also causes, should be borne in mind. Combination therapy with angiotensin-converting enzyme inhibitors or beta-blockers, or the use of other calcium channel blockers (verapamil or diltiazem) should also be considered, but careful monitoring of ciclosporin blood concentrations is recommended with the latter because they inhibit ciclosporin metabolism. 

Three landmark placebo-controlled clinical trials have established the benefits of both hypertension treatment and diuretic therapy. The Systolic Hypertension in the Elderly Program (SHEP), the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension), and the Medical Research Council (MRC) trial " showed significant reductions in stroke, myocardial infarction, and aU-cause cardiovascular disease and mortality with thiazide diuretic-based therapy versus placebo. These trials allowed for /3-blockers as add-on therapy for BP control. Newer agents (i.e., ACE inhibitors, angiotensin II receptor blockers [ARBs], and calcium channel blockers [CCBs]) were not available at the time of these studies. However, subsequent clinical trials have compared these newer antihypertensive agents (ACE inhibitors, ARBs, and CCBs) to diuretics." These data show similar effects, but most trials used a prospective, open-label, blinded end point (PROBE) study methodology that is... 

Eactors involved in precipitating decompensation have been evaluated prospectively in patients admitted to the hospital with heart faUure. ° These studies consistently show that noncompliance with drugs or diet is a common cause of heart failure exacerbation. Eor example, 43% of patients admitted with an acute decompensation of chronic heart failure were assessed as having dietary sodium excess, 34% had excess fluid intake (defined as >2.5 L/day), and about 24% had drug noncompliance that may have contributed to their decompensation (although not necessarily defined as the primary cause of decompensation). Use of inappropriate medications such as antiar-rhythmic agents or calcium channel blockers also was an important precipitant of exacerbations. 

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