Calcium channel blockers incidence

The calcium channel blockers have been associated with both prolonged pregnancy and decreased neonatal morbidity.36,42 when compared with P-mimetics (e.g., terbutaline) and magnesium, they show better neonatal outcome and a lower incidence of serious maternal side effects.42 Potential minor maternal adverse effects include headache, flushing, dizziness, and transient hypotension.41... 

In a meta-analysis of megatrials of simvastatin, the overall incidence of myopathy was 0.025% the same proportion of those with myositis had used calcium channel blockers as the proportion overall, suggesting that there is no important interaction between these two groups of drugs (32). 

Vasodilatory calcium channel blockers have been reported to improve exercise tolerance in some preliminary studies. A multicenter, randomized, placebo-con-trolled trial was therefore performed in 437 patients with mild to moderate heart failure to assess the effects of amlodipine 10 mg/day in addition to standard therapy (5). Over 12 weeks amlodipine did not improve exercise time and did not increase the incidence of adverse events. 

Because of effects on smooth muscle, the calcium channel blockers (particularly verapamil (96) but also diltiazem) can cause constipation. This may be due to colonic motor activity inhibition (97). Gastroesophageal reflux can also occur, and the calcium channel blockers should be avoided in patients with symptoms suggestive of reflux esophagitis (98). Calcium channel blockers (verapamil, diltiazem, and nifedipine) can also be associated with an increased incidence of gastrointestinal bleeding, as reported in a prospective cohort study in 1636 older hypertensives, with a relative risk of 1.86 (95% Cl = 1.22, 2.82) compared with beta-blockers (7). However, this finding was not confirmed in other retrospective studies (13,99,100). 

Manidipine is a dihydropyridine calcium channel blocker that can be given once a day for hypertension. In a comparison of manidipine 10 mg/day and amlodipine 5 mg/day in a multicenter, randomized, double-blind study in 530 patients with mild-to-moderate hypertension, the two drugs had comparable antihypertensive effects, but manidipine was associated with a significantly lower incidence of ankle edema (1). Nevertheless, adverse events caused withdrawal from treatment in a similar number of patients, 23 with manidipine and 26 with amlodipine. 

Calcium chaimel blockers traditionally have been the first-line agents to treat hypertension after transplantation. In addition to their ability to control blood pressure, calcium channel blockers may ameliorate the nephrotoxic effects of CSA, improve renal hemodynamics, decrease the incidence of delayed graft function and development of allograft atherosclerosis, and provide some immunosuppression. Calcium channel blockers, however, also may contribute to gingival hyperplasia that is often associated with CSA-based immunosuppression. CYP 3A4 interactions with CSA and TAC are of concern with this class of medications, particularly with dil-tiazem, verapamil, and nicardipine, and CSA or TAC concentrations must be monitored to ensure proper dosage adjustments. 

B. Monotherapy It has been found in large clinical studies that many patients do well on a single drug (eg, an ACE inhibitor, calcium channel blocker, or alpha -blocker). This approach to the treatment of mild and moderate hypertension has become more popular than stepped care because of its simplicity, better patient compliance, and—with modern drugs—a relatively low incidence of toxicity. 

Terazosin. Retrospective analysis of a large multinational study in patients given terazosin 5 or 10 mg daily found that terazosin only affected the blood pressure of patients taking calcium-channel blockers (am-lodipine, felodipine, flunarizine, isradipine and nifedipine) if the blood pressure was uncontrolled. No change in blood pressure was seen in those with normal blood pressure (i.e. those without hypertension and those with hypertension controlled by calcium-channel blockers). The most common adverse effect in the 10-week terazosin phase was dizziness, and the incidence of this appeared to be lower in those taking antihypertensives (13 to 16%) than those not taking anti hypertensives (21 to 25%). ... 

Information seems to be limited but the interaction would appear to be established and clinically important, although its incidence is probably low. Anticipate the need to reduce the felodipine or verapamil dosage if erythromycin or clarithromycin, or possibly also telithromycin, is added. Nifedipine may also interact. Other reports suggests that the cardiac toxicity of erythromycin may be increased by verapamil, and diltiazem, and the authors of one of these reports consider that erythromycin should not be used with CYP3A4 inhibitors (that is diltiazem and verapamil). There seem to be no reports of interactions between any of the other calcium-channel blockers and macrolides. However, because of the theoretical possibility of an interaction, many of the manufacturers of calcium-channel blockers warn of the possibility of increased plasma levels and the need to either avoid use with macrolides such as erythromycin, or troleandomycin, or to monitor and reduce doses where necessary. 

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