Calcium antagonists
Section snippets
Effects on arterial pressure
Calcium antagonists lower cytosolic free calcium concentration mainly through a reduction of transmembranous calcium influx and are potent arteriolar vasodilators.10 They also reduce angiotensin II—mediated vasoconstriction and decrease angiotensin II stimulatory effect on adrenal biosynthesis and secretion of aldosterone.11 In addition, there is evidence that some of the dihydropyridines (nifedipine and nicardipine) may interfere with α-adrenoceptor—mediated vasoconstriction.12 Unlike other
Lipids
Dyslipidemia and hypertension—2 disorders that frequently coexist in the same patient—are both risk factors for cardiovascular morbidity and mortality.
Unlike diuretics and β-blockers that adversely affect lipid profile, calcium antagonists have little effect on blood lipids.36 Pasanisi et al37 showed that calcium antagonists enhance triglyceride removal, possibly by stimulating the secretion of lipoprotein lipase. Alternatively, calcium antagonists could remove triglycerides by vasodilation and
Antiatheromatous effects of calcium antagonists
Hypertension is a risk factor for the development of atherosclerosis and its complications. Several calcium-dependent processes, such as platelet aggregation, monocyte adhesion, release of growth factors, cell proliferation and migration, protein and collagen secretion and synthesis, and endothelial necrosis, are involved in the formation of the atherosclerotic lesion. Because calcium plays a key role in the genesis of atherosclerosis, it is possible that interference with the calcium
Effects on left ventricular mass and myocardial fibrosis
Left ventricular hypertrophy (LVH) has been identified as one of the strongest pressure-independent risk factors for sudden death, acute myocardial infarction, congestive heart failure, and other cardiovascular morbidity and mortality.79, 80, 81, 82, 83, 84, 85, 86, 87, 88 Although it is unclear whether a reduction in LVH confers benefit over and above the benefit of lowering blood pressure per se, the effects of various antihypertensive agents on LVH have come under scrutiny.
Not all
Renal effects
Renal function deteriorates with age. This age-related loss of renal function is accelerated when blood pressure is elevated.243 In experimental models of chronic renal disease, calcium antagonists slowed the progression of renal damage.244 Studies using the isolated perfused hydronephrotic rat kidney model demonstrated that calcium antagonists preferentially vasodilate the preglomerular vessels, thereby augmenting glomerular filtration rate. The clinical implication of these observations has
Effects of calcium antagonists on cardiovascular outcomes
Recent prospective randomized studies attested to the beneficial effects of calcium antagonists in hypertensive patients3, 4, 5, 6, 7, 8, 9, 65, 74, 261, 262, 263, 264 (Table 3). In prospective, randomized, double-blind, placebo-controlled trials, calcium antagonist—based therapy reduced major cardiovascular events and cardiovascular death significantly in elderly hypertensive patients.3, 261, 262 Active treatment with calcium antagonist reduced the total rate of stroke by 38% to 42% and the
Drug interaction
The potential for drug interactions with calcium antagonists should be taken into consideration. Because calcium antagonists are most likely prescribed for patients with cardiovascular diseases, interactions with other cardiovascular agents are particularly important. Verapamil and nitrendipine may increase digoxin levels by 40% to 90%, α-blockers may cause excessive hypotension when coadministered with calcium antagonists, and, similarly, guanidine may cause excessive hypotension when
Side effects
The main side effects of the nondihydropyridine calcium antagonists include constipation, bradycardia, and even AV block and worsening of congestive heart failure. For the dihydropyridines the main side effects include flushing, headache, leg edema, gingival hypertrophy, and tachycardia—all of which are not life-threatening.27
To date, pedal edema remains the most frequent troublesome adverse effect of the dihydropyridines. However, this side effect is less common with agents of the third
Conclusions
By definition, all antihypertensive drugs, including calcium antagonists, lower arterial pressure. However, apart from lowering arterial pressure, calcium antagonists have a variety of beneficial effects in patients with hypertensive heart disease; they reduce LVM and improve its sequelae, such as ventricular dysrhythmias, impaired filling and contractility, and myocardial ischemia. Certain calcium antagonists have been shown to reduce the reinfarction rate and to have the potential for
Dr reiffel’s clinical pearls
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Verapamil, diltiazem, and the dihydropyridines are each negatively inotropic in vitro, but in vivo their inotropic effects reflect a balance between their direct effects and the effects of reflex sympathetic actions subsequent to their vasodilating actions. All are both peripheral and coronary vasodilators; all can be used for hypertension (calcium channel blockers are more effective for this in older patients, as are ACE inhibitors), for reduction of angina pectoris, for Raynaud syndrome
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Cited by (112)
Fluorophosphoric Acid Promoted Formation of Imines of Sulfonamides and Dihydropyridines at Room Temperature
2024, Organic Preparations and Procedures InternationalImpaired Ca<inf>V</inf>1.2 inactivation reduces the efficacy of calcium channel blockers in the treatment of LQT8
2022, Journal of Molecular and Cellular CardiologyCitation Excerpt :DHPs are known to act at the interface between domains III and IV of the pore domain [14,15], while PAAs and BZTs act at an overlapping site on the intracellular side of the selectivity filter [16]. Among these, the PAA verapamil is widely used in the treatment of cardiac arrhythmias [17], while DHPs such as amlodipine and nimodipine are a first-line therapy for hypertension [18]. In addition, all currently approved CCBs are state-dependent blockers and exhibit use-dependence [19,20], where sustained or repeated depolarization leads to increased drug block.
Participation of membrane calcium channels in erythropoietin-induced endothelial cell migration
2018, European Journal of Cell BiologyCitation Excerpt :Inhibition of these voltage-dependent channels in vascular smooth muscle cells as well as in cardiomyocytes not only results in coronary and peripheral artery vasodilation, but also in decreased cardiac contractility. Stemming from this, the clinical use of calcium antagonists has been demonstrated to successfully prevent stroke, ischemic heart disease and mortality in hypertensive patients (Grossman and Messerli, 2004). According to their chemical structure, calcium antagonists may be classified as phenilalkylamine, benzothiazepine and dihydropyridine drugs.
Calcium Channel Blockers
2018, Hypertension: A Companion to Braunwald's Heart DiseaseEffect of the human therapeutic drug diltiazem on the haematological parameters, histology and selected enzymatic activities of rainbow trout Oncorhynchus mykiss
2016, ChemosphereCitation Excerpt :Calcium channel blockers are prescribed to reduce heart rate and force of contraction. They also cause vasodilatation, leading to reduction in blood pressure (Grossman and Messerli, 2004; Lüllmann et al., 2002). The metabolism of diltiazem in mammals is well documented (Homsy et al., 1995; Molden et al., 2002a).