Types Of Calcium Channel Blockers Research Articles

Evaluation of ultra-early and dose-dependent edema and ultrastructural changes in the myocyte during anti-hypertensive drug delivery in the spontaneously hypertensive rat model.

BackgroundQuantifying dose-dependent ultra-early edema and ultrastructural changes in the myocyte after drug delivery is important for the development of new mixed calcium channel blockers (CCBs).Materials and methodsArterial cannulation was used to measure mean arterial pressure in real time; simultaneously, magnetic resonance imaging proton density mapping was used to quantify edema 5–55 min after the delivery of L-type CCBs, T- and L-type CCBs, and solvent to a spontaneously hypertensive rat model. Transmission electron microscopy was used to show ultrastructural changes in the myocyte.ResultsAnalysis of variance showed significant differences among the three groups in mean arterial pressure reduction (F = 246.36, P = 5.75E-25), ultra-early level of edema (ULE) (F = 175.49, P = 5.62E-22), and dose-dependent level of edema (DLE) (F = 199.48, P = 4.28E-23). Compared with the solvent’s mean arterial pressure reduction (2.65±6.56±1.64), ULE (1.16±0.09±0.02), and DLE (0.0010±0.0001±0.0000), post hoc tests showed that T- and L-type CCBs had better mean arterial pressure reduction (90.67±11.58±2.90, P = 1.06E-24 vs. 68.34±15.19±3.80, P = 1.76E-12), lower ULE (1.53±0.14±0.04, P = 4.74E-9 vs. 2.08±0.18±0.04, P = 2.68E-22), and lower DLE (0.0025±0.0004±0.0001, P = 1.14E-11 vs. 0.0047±0.0008±0.0002, P = 2.10E-11) than L- type CCBs. Transmission electron microscopy showed that T- and L-type CCBs caused fewer ultrastructural changes in the myocytes after drug delivery than L-type CCBs.ConclusionT- and L-type CCBs produced less ultra-early and dose-dependent edema, fewer ultrastructural changes in the myocyte, and a greater antihypertensive effect. Proton density mapping combined with arterial cannulation and transmission electron microscopy allowed for quantification of ultra-early and dose-dependent edema, antihypertensive efficacy, and ultrastructural changes in the myocyte. This is important for the evaluation of induced vasodilatory edema.

Coronary microvascular remodelling in low oxygen microenvironment: Role of cilnidipine, a dual L/N type calcium channel blocker

Background: People exposed to chronic sustained hypoxia (COPD) ultimately succumb to cardiovascular diseases. The heart is an obligate aerobic organ that requires a continuous supply of oxygen for its normal functions. Hence the structural and functional integrity of coronary microvasculature is very crucial for the normal functioning of the myocardium. Aims and Objectives: To assess the coronary microvascular remodelling in chronic sustained hypoxia exposure and its association with hypoxia signalling molecules. To study the role of cilnidipine, a unique calcium channel blocker (CCB) with dual L/N type calcium channel blocking actions with a documented cardioprotective role on chronic hypoxia-induced coronary microvascular remodelling. Methodology: 24 Wistar strain albino rats were randomly allocated into one of the four groups as follows - group 1, Control, (Normoxia, 21% O2); group 2, Chronic Hypoxia (CH) (10% O2, 90% N); group 3, Normoxia (21% O2) + Cilnidipine (Cil); group 4, Chronic Hypoxia (10% O2, 90% N) + Cilnidipine (CH+Cil). The intervention period was 21 days. Coronary microvascular remodelling was assessed by histopathological examination of the intramyocardial coronary artery. Normalised wall index (NWI) which is an indicator of arterial remodelling was calculated using histological images of coronary microvasculature using ImageJ software ( https://imagej.nih.gov/ij/ ). Hypoxia signalling molecules like vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (NOS3), nitric oxide (NO) were estimated in the serum and their correlation with NWI was determined. Results and Conclusion: Histopathological examination of intramyocardial coronary artery demonstrated moderate arteriosclerosis and congestion on CH exposure. NWI was significantly increased indicating an overall increase in wall thickness. NWI and VEGF and eNOS were positively correlated. Cilnidipine treatment ameliorated the chronic hypoxia-induced coronary microvascular remodelling. Hence chronic hypoxia-induced coronary microvascular remodelling may be an early subclinical culprit in the pathogenesis of CVDs in patients exposed to hypoxia. The present study also reiterates the cardioprotective role of cilnidipine while opening new avenues for its role in coronary microvasculature in chronic hypoxia exposure.

Methylene blue in the management of severe distributive shock in calcium channel blocker overdose

Introduction: Deliberate polypharmacy overdose is associated with an increasing proportion of admissions to the intensive care unit. Overdose on hemodynamic active substances such as calcium channel blockers can be fatal as it is associated with severe distributive shock. Methylene blue has drawn attention in critical care medicine for its use in the management of distributive shock, particularly in cases of anaphylaxis, septic shock, and shock following cardiac bypass surgery. We describe the use of methylene blue in the management of refractory shock due to calcium channel blocker (CCB) overdose. Case Report: We present a case of benzothiazepine type CCB overdose which leads to admission to the intensive care unit for the management of severe distributive shock. Conventional treatments including vasopressors and high dose insulin therapy were instituted, but despite these treatments the patient remained hypotensive. The decision was made to administer methylene blue following which the patient achieved hemodynamic stability and was successfully weaned off all vasopressors. Conclusion: This case report specifically focuses on the use of methylene blue in distributive shock secondary to CCB overdose. Currently there are no randomized control trials to support its use, and evidence is limited to observational studies including single case reports. In this case report we describe the mechanism of action of methylene blue and why we believe it makes for the perfect adjunct therapy in calcium channel blocker overdose.

Structural basis for efonidipine block of a voltage-gated Ca2+ channel

Efonidipine is a dual L-/T- type calcium channel blocker with a slow onset of action and a long lasting effect that exibihits antihypertensive and nephroprotective effects.differs from most other DHPs which can induce reflex tachycardia. Efonidipine reduces blood pressure without decreasing cardiac output and exerts organ-protective effects on the heart and kidney. In order to investigate how efonidipine block voltage-gated Ca2+ channel, we determined the crystal structure of CaVAb in complex with efonidipine at atomic resolution using x-ray crystallography. Our results reveal that efonidipine targets the central cavity of a model voltage-gated calcium channel underneath its selectivity filter and occlude the channel in an inactivated state. Binding of efonidipine does not break down the fourfold symmetry of the quaternary structure and its pore structure. Our work provides the structural basis for efonidipine block of a voltage-gated Ca2+ channel at the molecular level.

Use of calcium channel blockers in cardiovascular disease

Calcium channel blockers (CCBs) are widely used agents in the management of a number of cardiovascular indications, including hypertension, angina and supraventricular tachycardias. By inhibiting the movement of calcium into the cytoplasm via transmembrane calcium channels, they reduce vascular and myocardial contractility, and modulate the activity of pacemaker cells. There are important differences between the different types of calcium channel blockers, and a sound understanding of their mechanism of action is required to promote their safe, effective use. This article briefly describes calcium channel pharmacology, the mechanism of action of CCBs and their place in the therapy of cardiovascular disease.

S53. COMPARISON OF RALOXIFENE AND ISRADIPINE AS AN ADJUNCTIVE TREATMENT IN COGNITIVE DEFICITS OF PATIENTS WITH SCHIZOPHRENIA

BackgroundCognitive impairment is the most important feature of schizophrenia that leads to severe social and functional disability. Improving neurocognitive physiopathologic aspect of schizophrenia is a current challenge to identify the pathway to develop goal directed clinical interventions in practice. In the current study we investigated the effect of raloxifine as a selective estrogen modulator and isradipine as a voltage gated L type calcium channel blocker on the enhancement of schizophrenic patients’ cognitive deficits.MethodsWe designed a double blind randomized, parallel, placebo controlled clinical trials. 60 patients with schizophrenia randomized in 3 specific groups. The first group received isradipine 5 mg, the second raloxifine 60 mg and the third placebo for 6 consequent weeks, in the same shape capsules, 2 times a day, alongside treatment with the conventional antipsychotics. The initial and final lab tests, ECG, as well as cognitive tests in specific domains such as attention, processing speed, executive function and verbal memory were carried out.ResultsOur findings, revealed a remarkable association between adjunctive treatment of raloxifine in verbal memory deficits. moreover, isradipine treatment indicated significant improvement relative to placebo in verbal memory as well as attention dysfunction in some variables of the Stroop test. However, no effect was observed in processing speed and executive function deficits.DiscussionThe study provides the first evidence to our knowledge, which isradipine as a novel therapy was associated with improvement in verbal memory and attention, both related to hippocampal and cerebellar activity. Overall, further investigation is necessary to determine the various ways of the both drugs performance in the brain.

Azelnidipine is a useful medication for the treatment of heart failure preserved ejection fraction

ABSTRACTBackground: The optimal therapy in patients with heart failure preserved ejection fraction (HFpEF) and hypertension (HT) has not been revealed. The beta blocker (BB) and the renin angiotensin aldosterone system inhibitor (RAAS-I) are recommend as class IIa in patients with HFpEF. The calcium channel blocker (CCB), a major anti-hypertensive drugs in Japan, is also recommend as class IIa in patients with HFpEF. However, the difference between azelnidipine, an L type CCB, and cilnidipine, an N type CCB, is unclear. We investigated the difference between azelnidipine and cilnidipine in patients with HFpEF and HT. Methods: Twenty-five consecutive HFpEF patients treated with BB and RAAS-I from April 2013 to March 2015 were enrolled. Initially, cilnidipine was used, and then switched to azelnidipine. Age, gender, blood pressure (BP), heart rate (HR), blood tests, echocardiography, and cardiac-scintigraphy (123I-metaiodobenzylguanidine: MIBG) were measured before and after six months from azelnidipine administration. Results: There was no statistically significant difference in BP. B type natriuretic peptides were significantly reduced (pre-state: 195.4 ± 209.7 pg/ml and post-state: 140.7 ± 136.4 pg/ml, p = 0.050). In echocardiography, the TEI index tended to be decreased (pre-state: 0.47 ± 0.15 and post-state: 0.42 ± 0.08, p = 0.057). As for MIBG, there was no significant change in the heart/mediastinum ratio. However, the washout rate was significantly reduced (pre-state: 44.7 ± 12.2 and post-state: 40.7 ± 12.1, p = 0.011). In addition, there was no statistically significant change, although HR tended to decrease by switching to azelnidipine (pre-state: 62.7 ± 11.6 and post-state: 61.8 ± 16.5, p = 0.373). Conclusions: In patients with HT and HFpEF, azelnidipine improved the severity of HF and cardiac sympathetic nerve activity compared with cilnidipine.

Synthesis of new N3-substituted dihydropyrimidine derivatives as L-/T- type calcium channel blockers

Cardiovascular diseases (CVDs) are the main cause of deaths worldwide. Up-to-date, hypertension is the most significant contributing factor to CVDs. Recent clinical studies recommend calcium channel blockers (CCBs) as effective treatment alone or in combination with other medications. Being the most clinically useful CCBs, 1,4-dihydropyridines (DHPs) attracted great interest in improving potency and selectivity. However, the short plasma half-life which may be attributed to the metabolic oxidation to the pyridine-counterparts is considered as a major limitation for this class. Among the most efficient modifications of the DHP scaffold, is the introduction of biologically active N3-substituted dihydropyrimidine mimics (DHPMs). Again, some potent DHPMs showed only in vitro activity due to first pass effect through hydrolysis and removal of the N3-substitutions. Herein, the synthesis of new N3-substituted DHPMs with various functionalities linked to the DHPM core via two-carbon spacer to guard against possible metabolic inactivation is described. It was designed to keep close structural similarities to clinically efficient DHPs and the reported lead DHPMs analogues, while attempting to improve the pharmacokinetic properties through better metabolic stability. Applying whole batch clamp technique, five compounds showed promising L- and T- type calcium channel blocking activity and were identified as lead compounds. Structure requirements for selectivity against Cav1.2 as well against Cav3.2 are described.

Preadmission Use of Calcium Channel Blockers and Outcomes After Hospitalization With Pneumonia: A Retrospective Propensity-Matched Cohort Study.

In sepsis, an overwhelming immune response, as mediated by the release of various inflammatory mediators, can lead to shock, multiple organ damage, and even death. Pneumonia is the leading cause of sepsis. In animal septic models, sepsis could induce uncontrolled calcium (Ca) leaking, raising cytosolic Ca to a toxic level, causing irreversible cellular injuries and organ failure. All types of calcium channel blockers (CCBs), by inhibiting Ca influx, have been shown to decrease overall mortality in various septic animal models. However, to our best knowledge, no clinical study had been conducted to investigate the beneficial effect(s) of CCBs in sepsis. We conducted a retrospective propensity-matched cohort study after screening 2214 patients hospitalized for pneumonia from year 2012 to 2014 at our institution. We identified 387 preadmission CCB users and 387 nonusers by propensity score matching. Logistic regression analysis was then used to determine the association between preadmission CCB use and outcomes in pneumonia. Our study showed that the odds for development of severe sepsis was significantly lower in the CCB user group [odds ratio (OR), 0.466; 95% confidence interval (CI), 0.311-0.697; P = 0.002]. Preadmission CCB use was associated with a lower risk of contracting bacteremia (OR, 0.498; 95% CI, 0.262-0.99; P = 0.0327), lower risk of acute respiratory insufficiency (OR, 0.573; 95% CI, 0.412-0.798; P = 0.001), lower risk of intensive care unit admission (OR, 0.602; 95% CI, 0.432-0.840; P = 0.0028). In conclusion, our study suggested preadmission CCB use was associated with a reduction in the risks of development of respiratory insufficiency, bacteremia, and severe sepsis in patients admitted to the hospital with pneumonia.

On the top of ARB N/L typeCa channel blocker leads to less elevation of aldosterone.

The activation of the renin–angiotensin system (RAS) is one of the unfavourable characteristics of calcium channel blocker (CCB). N type calcium channel is thought to be involved in renin gene transcription and adrenal aldosterone release. Accordingly, N/L type CCB has a possibility of less elevation of plasma aldosterone concentrations (PAC) among CCBs. In a monotherapy study, we had already demonstrated that N/L type CCB leads to less activation of the RAS compared with L type CCB. The objective of this study is to substantiate the hypothesis that at the condition of additive administration on the top of an angiotensin receptor blocker (ARB), still N/L type CCB leads to less elevation of PAC compared with L type one. Subjects were 60 hypertensives administered with valsartan. As an open label study, amlodipine (L type) or cilnidipine (N/L type) were administered on the top of valsartan (ARB) in a cross-over manner. Results were as follows (valsartan+amlodipine compared with valsartan+cilnidipine): systolic blood pressure (SBP)/diastolic blood pressure (DBP) (mmHg): 132±10/76±10 compared with 131±10/77±9, P=0.95/0.48, plasma renin activity (PRA) (ng/ml·h): 2.41±2.67 compared with 2.00±1.50 P=0.20, PAC (pg/ml): 77.3±31.0 compared with 67.4±24.8, P<0.05, urinary albumin excretion (UAE) (mg/gCr): 105.9±216.1 compared with 73.9±122.2, P<0.05. Thus, PAC at cilnidipine was significantly lower than those at amlodipine in spite of the comparable BP reductions. Besides, UAE was significantly lower at cilnidipine. In conclusion, on the top of the ARB, it is suggested that cilnidipine administration might lead to less elevation of PAC and reduction in UAE compared with amlodipine.

Effect of nimodipine and flunarizine on neuromuscular function in mice

Background: Changes in the intracellular concentration of Ca2+ control a number of cellular and physiological processes, hormone secretion, and cell fate and gene expression. The objective of this study was to study the effect of L-type of calcium channel blocker nimodipine and T-type of calcium channel blocker funarizine on neuromuscular function in mice without pre-treatment by any other drug.Methods: The study was carried out following permission from the Institutional animal ethics committee. Healthy Swiss albino mice of either sex were selected by the strict inclusion and exclusion criteria and the grouping is done. Group A is control treated with normal saline; group B and C received two titrated doses of nimodipine while group D and E received two titrated doses of flunarizine. The animals were then observed for neuromuscular function and the Statistical analysis was done by using unpaired‘t’ test.Results: L-type calcium channel blocker nimodipine has dose dependent effect on locomotor activity on traction wire and while the T- type calcium channel blocker flunarizine has no effect on locomotor activity.Conclusions: Nimodipine has significant dose dependent depressant action on neuromuscular function while flunarizine has no effect on the above mentioned parameter.

Effect of L- type Calcium Channel Blocker Nimodipine and T-type Calcium Channel Blocker Flunarizine on Motor Control in Mice

Objective: To study the effect of L-type of Calcium channel blocker nimodipine and T-type of calcium channel blocker funarizine on locomotor activity in mice without pretreatment by any other drug. Materials and method: The study was carried out following permission from the Institutional animal ethics committee. Healthy Swiss albino mice of either sex were selected by the strict inclusion and exclusion criteria and the grouping is done. Group A is control treated with normal saline, Group B and C received two titrated doses of nimodipine while Group D and E received two titrated doses of flunarizine. The animals were then observed for motor control on inclined plane and the Statistical analysis was done by using unpairedt test. Results: L-type calcium channel blocker nimodipine has dose dependent effect on motor control on inclined plane while the T- type calcium channel blocker flunarizine has no effect on motor control. Conclusion: Nimodipine has significant dose dependent depressant action on motor control on inclined plane while flunarizine has no effect on the above mentioned parameter.

Cyclodextrine screening for the chiral separation of amlodipine enantiomers by capillary electrophoresis.

Amlodipine is a long acting, dihydropyridine type calcium channel blocker frequently used in the treatment of hypertension and coronary insufficiency. The calcium channel blocking activity resides primarily in the S-amlodipine enantiomer, while R-amlodipine is a potent inhibitor of smooth muscle cell migration. In this study capillary electrophoresis was applied for the enantiomeric separation of amlodipine using different native and derivatized; neutral and charged cyclodextrines as chiral selectors. The effects of pH and composition of the background electrolyte, concentration and type of chiral selector, capillary temperature, running voltage and injection parameters have been investigated. Stereoselective interactions were observed when using α-CD, β-CD, HP-β-CD, RAMEB, CM-β-CD and SBE-β-CD. Optimized separation conditions consisted on a 50 mM phosphate buffer, pH - 3.0, 20 mM RAMEB as chiral selector, + 25 kV applied voltage, 15°C temperature and UV detection at 238 nm. Using the optimized electrophoretic conditions we succeeded the chiral separation of amlodipine enantiomers in approximately 6 minute, the order of migration being R-amlodipine followed by S-amlodipine. The method was successfully applied for the determination of amlodipine enantiomers from commercially available pharmaceuticals. The linearity range, limits of detection and quantification, precision and accuracy were determined and the results obtained confirmed that the method was suitable for this purpose. It can be concluded that the proposed capillary electrophoresis methods can be useful for routine pharmaceutical applications with benefits of its effectivity, simplicity, short analysis time and low consumption of analytes, solvents and chiral selectors.

Evaluation of effects of T and N type calcium channel blockers on the electroencephalogram recordings in Wistar Albino Glaxo/Rij rats, an absence epilepsy model.

Objectives:It is suggested that excessive calcium entry into neurons is the main triggering event in the initiation of epileptic discharges. We aimed to investigate the role of T and N type calcium channels in absence epilepsy experimental model.Materials and Methods:Wistar Albino Glaxo/Rij (WAG/Rij) rats (12–16 weeks old) were randomly allocated into four groups; sham, mibefradil (T type calcium channel blocker), w-Conotoxin MVIIA (N type calcium channel blocker), and mibefradil + w-Conotoxin MVIIA. Beta, alpha, theta, and delta wave ratios of EEG recordings and frequency and duration of spike wave discharges (SWDs) were analyzed and compared between groups.Results:Beta and delta recording ratios in 1 μM/5 μl mibefradil group was significantly different from basal and other dose-injected groups. Beta, alpha, and theta recordings in 0.2 μM/5 μl w-Conotoxin MVIIA group was significantly different from basal and other dose-injected groups. In w-Conotoxin MVIIA after mibefradil group, beta, alpha, and theta recording ratios were significantly different from basal and mibefradil group. Mibefradil and w-Conotoxin MVIIA significantly decreased the frequency and duration of SWDs. The decrease of frequency and duration of SWDs in mibefradil group was significantly different from w-Conotoxin MVIIA group. The frequency and duration of SWDs significantly decreased in w-Conotoxin MVIIA after mibefradil group compared with basal, mibefradil, and w-Conotoxin MVIIA groups.Conclusions:We concluded that both T and L type calcium channels play activator roles in SWDs and have positive effects on frequency and duration of these discharges. These results are related with their central effects more than peripheral effects.

Cutting-edge Advancement in the Therapy of Glaucoma

Glaucoma is the second most prevalent eye condition, after cataracts, known to cause irreversible blindness in the world. Currently, the only modifiable risk factor for the progression of this disease is intraocular pressure (IOP). This article aims to evaluate the hypotensive potential of topical calcium channel blockers in glaucoma management, based on our current knowledge about this disease. A comprehensive literature search was conducted on Medline, PubMed, and Google Scholar databases in April 2013. Search temporal limits included articles published from 1996 to 2013 with the purpose of providing the most recent evidence. Studies were queried using the following keywords in various combinations: glaucoma, calcium channel blockers, glaucomatous optic neuropathy, neuroprotection, topical calcium channel blockers. The articles of high or medium clinical and preclinical relevance were selected for review. Multiple studies have shown the relevancy and effectiveness of topical calcium channel blockers as an alternative hypotensive therapy in glaucoma management. Taken into account that not all calcium channel blockers are equally effective, the challenge for future research will be to determine the best type of calcium channel blocker.

Calcium channel blockers for inhibiting preterm labour and birth.

Calcium channel blockers for inhibiting preterm labour and birth.

Calcium channel blockers in cardiovascular pharmacotherapy.

This paper summarizes the pharmacological properties of calcium channel blockers (CCBs), their established therapeutic uses for cardiovascular disorders and the current improvement of their clinical effects through drug combinations. Their identification resulted from study of small molecules including coronary dilators, which were named calcium antagonists. Further experiments showed that they reduced contraction of arteries by inhibiting calcium entry and by interacting with binding sites identified on voltage-dependent calcium channels. This led to the denomination calcium channel blockers. In short-term studies, by decreasing total peripheral resistance, CCBs lower arterial pressure. By unloading the heart and increasing coronary blood flow, CCBs improve myocardial oxygenation. In long-term treatment, the decrease in blood pressure is more pronounced in hypertensive than in normotensive patients. A controversy on the safety of CCBs ended after a large antihypertensive trial (ALLHAT) sponsored by the National Heart, Lung, and Blood Institute. There are two main types of CCBs: dihydopyridine and non-dihydropyridine; the first type is vascular selective. Dihydropyrines are indicated for hypertension, chronic, stable and vasospastic angina. Non-dihydropyridines have the same indications plus antiarrythmic effects in atrial fibrillation or flutter and paroxysmal supraventricular tachycardia. In addition, CCBs reduced newly formed coronary lesions in atherosclerosis. In order to reach recommended blood pressure goals, there is a recent therapeutic move by combination of CCBs with other antihypertensive agents particularly with inhibitors acting at the level of the renin-angiotensin system. They are also combined with statins. Prevention of dementia has been reported in hypertensive patients treated with nitrendipine, opening a way for further studies on CCBs' beneficial effect in cognitive deterioration associated with aging.

T-type Ca Channel Blockers in Patients with Chronic Kidney Disease in Clinical Practice

Chronic kidney disease (CKD) progressively increases the risk of cardiovascular disease (CVD) and end-stage renal disease (ESRD) in line with its severity. Recent studies have revealed that albuminuria and proteinuria in CKD are risk factors for both ESRD and CVD. Accordingly, reductions in albuminuria and proteinuria are associated with a trend in reduced renal death and cardiovascular events. Renin-angiotensin-aldosterone system inhibitors, including angiotensin converting enzyme inhibitors and angiotensin II receptor blockers are recommended as first-choice drugs for the treatment of hypertensive patients with CKD according to several guidelines. However, monotherapy is not sufficient to control blood pressure, particularly in patients with CKD, highlighting the need for combination drug therapy. Calcium channel blockers (CCBs) reduce blood pressure and are useful antihypertensive drugs. Three types of CCBs--the L-, T-, and Ntypes-- are in clinical use. In renal tissue, L-type calcium channels are present only in the afferent arterioles, while N-type and T-type calcium channels are located in both efferent and afferent arterioles. Therefore, CCBs that block either T-type or N-type calcium channels may exert renoprotective effects by dilating the efferent artery and protecting the glomerulus from hyperfiltration injury. It has been established that T-type CCBs exert a renal protective action by ameliorating glomerular microcirculation via vasodilatory activity on both afferent and efferent arterioles. Additionally, blockade of the T-type Ca channel suppresses inflammatory processes, renin-angiotensin-aldosterone system, and oxidative stress. Such effects of T-type CCBs seem to provide good efficacy in terms of the progression of renal outcome and the prevention of cardiovascular events in patients with CKD.

Use of Antihypertensive Medications and Breast Cancer Risk Among Women Aged 55 to 74 Years

Antihypertensive agents are the most commonly prescribed class of medications in the United States. Evidence regarding the relationship between different types of antihypertensives and breast cancer risk is sparse and inconsistent, and prior studies have lacked the capacity to assess impacts of long-term use. To evaluate associations between use of various classes of antihypertensive medications and risks of invasive ductal and invasive lobular breast cancers among postmenopausal women. Population-based case-control study in the 3-county Seattle-Puget Sound metropolitan area. Participants were women aged 55 to 74 years, 880 of them with invasive ductal breast cancer, 1027 with invasive lobular breast cancer, and 856 with no cancer serving as controls. Recency and duration of use of antihypertensive medications. Risks of invasive ductal and invasive lobular breast cancers. Current use of calcium-channel blockers for 10 or more years was associated with higher risks of ductal breast cancer (odds ratio [OR], 2.4; 95% CI, 1.2-4.9) (P= .04 for trend) and lobular breast cancer (OR, 2.6; 95% CI, 1.3-5.3) (P= .01 for trend). This relationship did not vary appreciably by type of calcium-channel blocker used (short-acting vs long-acting, dihydropyridines vs non-dihydropyridines). In contrast, use of diuretics, β-blockers, and angiotensin II antagonists were not associated with risk. While some studies have suggested a positive association between calcium-channel blocker use and breast cancer risk, this is the first study to observe that long-term current use of calcium-channel blockers in particular are associated with breast cancer risk. Additional research is needed to confirm this finding and to evaluate potential underlying biological mechanisms.

Calcium Channel Blockers as Initial Therapeutic Agents in Hypertension

Blood pressure (BP) control is central to health promotion and maintenance across the health care continuum. Optimal control has been associated with improved microvascular end organ outcomes, reduced morbidity and mortality, and improved quality of life. Calcium channel blockers (CCBs) are a frequently utilized first-line antihypertensive agent, either as a monotherapy or in combination, as advocated by the 2003 Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII). However, despite their ability to achieve BP parameters comparable to alternative agents, CCBs may be inducing heart failure (HF) pathology by a mechanism other than the well-known negative inotropic effects of nondihydropyridine CCBs and thus may be responsible for more incident HF than was previously thought. Review of current literature indicates that there is a strong association between all types of CCBs and incident HF, that this association is found in persons with and without preexisting myocardial dysfunction, that BP measurement alone is an insufficient measure of end organ preservation with CCB use, and that CCB-induced HF is more problematic with comorbid coronary disease, renal disease, and diabetes mellitus. Furthermore, current research suggests that these outcomes are a result of CCB-induced neurohormonal sympathetic activation, sustained CCB-generated nitric oxide production leading to inflammation and tissue destruction, and/or increased systemic calcification secondary to concurrent calcium supplementation. These findings suggest the pressing need for reevaluation of CCBs as first-line agents in treating hypertension and for possible revision of JNC VII hypertension guidelines.