Effect of Calcium-Channel Blockers on Cyclosporine Clearance and Use in Renal Transplant Patients

OBJECTIVE: To determine the effect of calcium-channel blockers (CCBs) on cyclosporine dose, clearance, and cost, and their effect on kidney graft function and survival in patients who underwent kidney transplant. DESIGN: A total of 176 adults receiving 177 transplants were studied retrospectively. Patients were stratified as follows: no CCB (n=57), diltiazem (n=13), nifedipine (n=37), and verapamil (n=70). Patients received cyclosporine 3–4 mg/kg by continuous infusion for 5 days followed by cyclosporine 10 mg/kg/d po to maintain initial whole blood concentrations of 300–400 ng/mL. Clearance of intravenously administered cyclosporine was calculated following at least 48 hours of the same dose by continuous infusion. The amount and cost of cyclosporine used during the first 10 days of oral therapy were also calculated. RESULTS: Patients receiving diltiazem, but not verapamil or nifedipine, had decreased clearance of intravenously administered cyclosporine compared with that of the mean control group. The mean clearance of intravenously administered cyclosporine ± SD in patients receiving no CCB was 5.1 ± 1.5 mL/min/kg, diltiazem was 3.7 ± 0.8 mL/min/kg, nifedipine was 6.4 ± 1.9 mL/min/kg, and verapamil was 5.2 ± 2.2 mL/min/kg. The amount and cost of 10 days of oral cyclosporine therapy was decreased in the verapamil group (5.7 ± 1.5 g and $257 ± 69) compared with that of the control group (6.7 ± 1.6 g and $304 ± 72) (p<0.001). There was no significant difference among the groups with respect to immediate graft function, 1-year serum creatinine concentration, or 1-year graft survival. CONCLUSIONS: Diltiazem decreased the clearance of intravenously administered cyclosporine. Although verapamil did not decrease the clearance of intravenously administered cyclosporine, it allowed a significant reduction in oral cyclosporine cost without apparent adverse effects on graft function. Further work is needed to determine the effect of CCBs on cyclosporine pharmacokinetics, especially with respect to their metabolism by gut and hepatic cytochrome P-450 enzymes, and their effect on patient outcome.

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Comparative study of anti-inflammatory property of calcium channel blocker and aspirin in albino rats

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20185157 ◽

2018 ◽

Vol 8 (1) ◽

pp. 21

Author(s):

Anjum Begum

Keyword(s):

Inflammatory Response ◽

Calcium Channel ◽

Calcium Channel Blockers ◽

Control Group ◽

Albino Rats ◽

Standard Group ◽

Channel Blockers ◽

Treatment Of Hypertension ◽

The Mean ◽

Anti Inflammatory

Background: Calcium channel blockers are being used in the treatment of hypertension, ischemic heart disease, cardiac arrhythmias etc. They act by blocking the slow calcium channels. Influx of calcium is an essential step in the release of histamine and 5HT from mast cells and in the synthesis and release of prostaglandins. They are the main mediators in the process of inflammation. The aim of the present study was to compare anti-inflammatory properties of calcium channel blockers and aspirin in albino rats.Methods: Present study was prospective intervention study carried out to compare anti-inflammatory properties of calcium channel blockers and aspirin in albino rats. Total 30 albino rats were used, and they were divided into 5 groups of 6 each. First group of rats was control group where normal saline was used. Second group was standard group where aspirin was used. Remaining three groups were test groups and given nifedipine, amlodipine and diltiazem respectively. Effects were observed and compared between the groups.Results: In carrageenan method, the anti-inflammatory response of Aspirin was significantly higher. Nifedipine response was <aspirin but >diltiazem. The response of amlodipine was not significantly > that of control percent inhibition. In histamine method, the anti-inflammatory response of aspirin was significantly highest. Anti-inflammatory response of nifedipine was < aspirin but > diltiazem. Diltiazem response was < nifedipine but > amlodipine. In formaldehyde method, aspirin inhibition was highest at 96.2% followed by nifedipine (90.7%), diltiazem (75.9%) and amlodipine (3.7%). In cotton wool pellet granuloma, the mean dry granuloma weight was least for aspirin and percent anti-inflammatory activity was significantly high.Conclusions: Calcium channel blockers (nifedipine, diltiazem) have shown comparable anti-inflammatory property with that of aspirin. Further clinical studies are required for confirmation.

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Impact of Calcium Channel Blockers on Aspirin Reactivity in Patients With Coronary Artery Disease

10.21203/rs.3.rs-932481/v1 ◽

2021 ◽

Author(s):

Afek Kodesh ◽

Eli Lev ◽

Dorit Leshem-Lev ◽

Alejandro Solodky ◽

Ran Kornowski ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Calcium Channel ◽

Calcium Channel Blockers ◽

Platelet Reactivity ◽

Aspirin Resistance ◽

Control Group ◽

Channel Blockers ◽

Artery Disease ◽

Stable Cad

Abstract Purpose: Calcium channel blockers (CCBs) do not reduce the risk of initial or recurrent myocardial infarction (MI) in patients diagnosed with stable coronary artery disease (CAD). The aim of this current study was to evaluate the association between CCBs and aspirin resistance in patients with CAD. Methods: Patients with stable CAD who were regularly taking aspirin (75-100 mg qd) for at least one month prior to enrollment in the study were included. The VerifyNow system was used for platelet function testing with high on-aspirin platelet reactivity (HAPR) defined as aspirin reaction units (ARU) >550. We compared patients treated with CCBs versus control group. Results: 503 patients with CAD were included in this study, 88 were treated with CCBs; Mean age (67.9±9.7 in the CCB group vs 66.5±11.4 in the control group, p=0.288), gender (77.3 male vs. 82.9%, p=0.214) and rates of diabetes mellitus (34.7 vs. 36.9%, p=.121) were similar. Rates of hypertension were higher in the CCB group (83.9 vs. 63.5%, p<0.01), but rates of past MI were lower (47.1 vs. 59.7%, p=0.039). The mean ARU was 465.4P70.0 for patients treated with CCBs versus 445.2u60.0 in controls (p=0.006). Similarly, 15.9% of CCB patients demonstrated HAPR compared to 7.0% (p=0.006). In a multivariate analysis, the administration of CCBs was independently associated with HAPR (OR- 1.72, 95% CI 1.04 – 8.91, p=0.047). Conclusions: Usage of CCBs is positively correlated with aspirin resistance. These findings may suggest an adverse pharmacologic effect of CCBs among patients with stable CAD treated with aspirin.

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Antiproteinuric effects of antihypertensive agents in non-diabetic hypertensive population

Open Medicine ◽

10.2478/s11536-008-0036-8 ◽

2008 ◽

Vol 3 (3) ◽

pp. 287-293

Author(s):

Zorica Jovic ◽

Vidojko Djordjevic ◽

Karin Vasic ◽

Snezana Cekic ◽

Jankovic Irena

Keyword(s):

Blood Pressure ◽

Calcium Channel ◽

Antihypertensive Drug ◽

Calcium Channel Blockers ◽

Ace Inhibitors ◽

Statistical Significance ◽

Antihypertensive Agents ◽

Channel Blockers ◽

Significant Difference ◽

Change In Mean

AbstractArterial hypertension and proteinuria are important factors associated with the progression of both diabetic and nondiabetic chronic kidney disease. The objective of the present study was to determine the influence of different antihypertensive drug groups on urinary albumin excretion (UAE) as related to blood pressure in non-diabetic population. Subjects (n=39) with chronic renal disease accompanied by mild to moderate hypertension and varying degrees of proteinuria were divided into 3 groups based on UAE values and placed on nonpharmacological and/or treatment with an antihypertensive drug regimen (consisting of one or more antihypertensive drugs [beta blocker, ACE inhibitor or calcium-channel blocker]) to achieve a target blood pressure ≤ 130/85 mmHg. Periodic UAE measurements were performed. A reduction was observed over time in most patients, however, it reached statistical significance only in the microalbuminuric group (P<0.01). Patients were further stratified into 5 groups depending on assigned therapy: 0, nonpharmacological treatment; 1-drug group 1; 12-drug groups 1 and 2; 13-drug groups 1 and 3; 123-all 3 drug groups (1-ACE inhibitors, 2-beta blockers, 3-calcium channel blockers). A statistically significant change in mean UAE values at the start and end of the study period in patients assigned to drug groups 12, 13, and 123 was achieved (P < 0.05). Also, there was a statistically significant difference in the average reduction of proteinuria under varying antihypertensive drug regimens (P < 0.05). In conclusion, in patients with hypertension, changes in UAE depend on initial UAE values and administered antihypertensive treatment. ACE inhibitors combined with calcium channel blockers resulted in a higher UAE reduction than other drug groups.

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Calcium channel blockers use and overall survival in pancreatic cancer patients receiving gemcitabine.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15756 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15756-e15756 ◽

Cited By ~ 1

Author(s):

Leszek Kraj ◽

Andrzej Śliwczyński ◽

Joanna Krawczyk-Lipiec ◽

Krzysztof Woźniak ◽

Anna Waszczuk-Gajda ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Calcium Channel ◽

Calcium Channel Blockers ◽

Rank Test ◽

Channel Blockers ◽

Test Results ◽

Log Rank Test ◽

Kaplan Meier ◽

Significant Difference

e15756 Background: Preclinical studies have shown that calcium channel blockers (CCB) may potentiate anticancer effect of chemotherapy via intra-cellular drug accumulation. Gemcitabine-based chemotherapy is commonly used in pancreatic cancer (PC) patients. The aim of this study was to determine whether CCB may affect overall survival (OS) in PC patients receiving gemcitabine-based chemotherapy. Methods: The retrospective cohort of PC patients treated with gemcitabine between 2007 and 2016 was identified in the Polish National Health Fund databases. Electronic records of prescriptions were searched to identify in this cohort patients receiving CCB (amlodipine, nitrendipine, felodipine, lacidipine). The primary endpoint was OS and it was determined by Kaplan-Meier methods and compared by the log-rank test. Results: In total 4628 PC patients treated with gemcitabine (median OS 7.7 months; 95% CI: 7.4-7.9) were identified. Among these 380 patients were prescribed any CCB. There was a significant difference (p < 0.001) in median OS between patients prescribed CCB (n = 380; OS 9.3 months; 95% CI: 7.8-11.0) and those who did not (n = 4214; OS 7.6 months; 95% CI: 7.3-7.8) with hazard ratio for death 0.70 (95% CI: 0.62-0.79). Notably, the survival curves tended to flatten in CCB group, with 24% of patients alive at 2 years (95% CI: 20-29%) and 15% alive at 5 years (95% CI: 11-19%), compared with 11% (95% CI: 10-12%) and 4% (95% CI: 4-5%) in controls respectively. Conclusions: The use of CCB in PC patients receiving gemcitabine-based chemotherapy was associated with improved OS. Further validation is needed to evaluate effectiveness of CCB-gemcitabine combinations in the management of PC.

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Drug–drug interaction of rivaroxaban and calcium channel blockers in patients aged 80 years and older with nonvalvular atrial fibrillation

Drug Metabolism and Personalized Therapy ◽

10.1515/dmdi-2020-0127 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Dmitry Sychev ◽

Karin Mirzaev ◽

Marina Cherniaeva ◽

Maria Kulikova ◽

Pavel Bochkov ◽

...

Keyword(s):

Atrial Fibrillation ◽

Drug Interaction ◽

Calcium Channel ◽

Calcium Channel Blockers ◽

Control Group ◽

Channel Blockers ◽

Nonvalvular Atrial Fibrillation ◽

Steady State Plasma Concentration ◽

Drug Drug Interaction ◽

Group 2

AbstractObjectivesFor revealing the peculiarities of the drug–drug interaction of rivaroxaban (substrate CYP3A4 and P-gp) and calcium channel blockers (CCBs) (verapamil – inhibitor CYP3A4 and P-gp and amlodipine – substrate CYP3A4) in patients 80 years and older with nonvalvular atrial fibrillation (NAF) we studied 128 patients.MethodsAll patients were divided into groups depending on the therapy taken: the 1st – rivaroxaban + amlodipine (n=51), the 2nd – rivaroxaban + verapamil (n=30), the control group – rivaroxaban without CCBs (n=47). A trough steady-state plasma concentration (Cmin,ss) of rivaroxaban, prothrombin time (PT) in the blood plasma and the event of clinically relevant non-major (CRNM) bleeding were assessed for each patient.ResultsPatient in group 2 had higher Cmin,ss of rivaroxaban, PT and CRNM than subjects in the control group (Me 73.8 [50.6–108.8] ng/mL vs. 40.5 [25.6–74.3] ng/mL; Me 14.8 [13.4–17.3] s vs. 13.8 [12.6–14.4] s; 34% vs. 13%, respectively, p<0.05 for all). When compared, the PT and complication rate in group 1 with the control group Cmin,ss of rivaroxaban were practically the same (p>0.05 for all).ConclusionsIn patients ≥80 years with NAF, the use of rivaroxaban in combination with verapamil may not be safe and can lead to CRNM bleeding.

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Blood Pressure Control and Antihypertensive Treatment Among Hemodialysis Patients—Retrospective Single Center Experience

Medicina ◽

10.3390/medicina57060590 ◽

2021 ◽

Vol 57 (6) ◽

pp. 590

Author(s):

Piotr Skonieczny ◽

Zbigniew Heleniak ◽

Marek Karowiec ◽

Stanisław Zajączkowski ◽

Leszek Tylicki ◽

...

Keyword(s):

Blood Pressure ◽

Calcium Channel ◽

Blood Pressure Control ◽

Calcium Channel Blockers ◽

Antihypertensive Treatment ◽

Pressure Control ◽

Hemodialysis Patients ◽

Channel Blockers ◽

Renin Angiotensin Aldosterone System ◽

The Mean

Background and Objectives: Hypertension affects at least 80% of hemodialysis patients. Inappropriate control of blood pressure is mentioned as one of the essential cardiovascular risk factors associated with development of cardiovascular events in dialysis populations. The aim of the cross-sectional, retrospective study was the evaluation of the antihypertensive treatment schedule and control of blood pressure in relation to the guidelines in the group of hemodialysis patients. Additionally, we assessed the level of decrease in blood pressure by each group of hypotensive agents. Materials and Methods: 222 patients hemodialyzed in a single Dialysis Unit in three distinct periods of time—2006, 2011, and 2016—with a diagnosis of hypertension were enrolled in the study. The analysis of the antihypertensive treatment was based on the medical files and it consisted of a comparison of the mean blood pressure results reported during the six consecutive hemodialysis sessions. Results: The mean values of blood pressure before hemodialysis were as follows: 134/77, 130/74, and 140/76 mmHg, after hemodialysis 124/74, 126/73, and 139/77 mmHg in 2006, 2011, and 2016 respectively. The goal of predialysis blood pressure control (<140/90) was achieved by up to 64.3% of participants in 2006 as compared to 49.4% in 2016. Additionally, the postdialysis goal (<130/90) reached 57.1% of the study population in 2006 as compared to 27.1% of patients in 2016. The differences in percentage of patients using single, double, triple, and multidrug therapy during observation were not statistically significant. The most often used drugs were ß-blockers, diuretics, and calcium channel blockers in all points of the study. Blockades of the renin–angiotensin–aldosterone system in 2006 and calcium channel blockers in 2011 and 2016 were the drugs with highest impact on lowering blood pressure. Conclusions: The goal of predialysis or postdialysis blood pressure control was achieved in a lower percentage of patients during the period of the study. Blockade of renin–angiotensin–aldosterone system and calcium channel blockers decrease the blood pressure significantly. It is necessary to achieve better control of blood pressure in prevention of cardiovascular incidents.

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Calcium Channel Blockers Are Associated with Nocturia in Men Aged 40 Years or Older

Journal of Clinical Medicine ◽

10.3390/jcm10081603 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1603

Author(s):

Satoshi Washino ◽

Yusuke Ugata ◽

Kimitoshi Saito ◽

Tomoaki Miyagawa

Keyword(s):

Blood Pressure ◽

Calcium Channel ◽

Calcium Channel Blockers ◽

Cross Sectional Study ◽

Channel Blockers ◽

Prescription Medications ◽

Normal Blood Pressure ◽

Cross Sectional ◽

Significant Difference ◽

Male Patients

Background: The associations of nocturia with hypertension and anti-hypertensive agents (AHTs) remain to be validated. Methods: This cross-sectional study examined whether blood pressure and/or frequently used classes of AHTs had consistent associations with nocturia. Methods: A total of 418 male patients aged ≥ 40 years were retrospectively assessed in terms of the International Prostate Symptom Score (IPSS), prescription medications, and blood pressure. Nocturia was evaluated using item 7 of the IPSS, and two or more episodes of nocturia per night was considered to indicate clinically important nocturia. Results: Patients taking calcium channel blockers (CCBs), but not other AHTs, experienced more episodes of nocturia than patients not taking AHTs (1.77 ± 1.07, 1.90 ± 1.19, and 1.48 ± 0.98 in CCBs alone, CCBs + other AHTs, and other AHTs alone, vs. 1.35 ± 1.08 in not taking AHTs; p = 0.014, p < 0.0001, and p = 0.91, respectively), whereas there was no significant difference in the number of nocturia episodes between patients with elevated and normal blood pressure. In multivariate analysis, CCB (odds ratio (OR) = 2.68, p < 0.0001) and age (OR = 1.06, p < 0.0001) were independently associated with clinically important nocturia. Conclusion: CCB was associated with nocturia, while AHTs other than CCBs and elevated blood pressure were not.

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Case—Control Studies of Cardiovascular Medications as Risk Factors for Clinically Diagnosed Depressive Disorders in a Hospitalized Population

The Canadian Journal of Psychiatry ◽

10.1177/070674379604100713 ◽

1996 ◽

Vol 41 (7) ◽

pp. 469-476 ◽

Cited By ~ 15

Author(s):

Scott B Patten ◽

Jeanne VA Williams ◽

Edgar J Love

Keyword(s):

Calcium Channel ◽

Calcium Channel Blockers ◽

Ace Inhibitors ◽

Depressive Disorders ◽

Case Control ◽

Control Group ◽

Channel Blockers ◽

Discharge Diagnosis ◽

Case Control Studies ◽

Β Blockers

Objective: Certain medications used in cardiovascular therapeutics may contribute to the etiology of substance-induced mood disorders. These medications include digoxin, angiotensin converting enzyme (ACE) inhibitors, β- blockers, and calcium channel blockers. The objective of this study was to evaluate associations between these drugs and clinical diagnoses of depressive disorders in a population of hospitalized patients. Method: Two case–control studies were conducted. For each study, subjects were selected from a health records data base maintained at the Calgary General Hospital. Selection of subjects in the first study was restricted to those receiving a discharge diagnosis of congestive heart failure and in the second study to subjects receiving a discharge diagnosis of hypertension. In each of these 2 studies, a single case group was selected along with 2 control groups: a psychiatric control group consisting of subjects receiving a psychiatric diagnosis other than a depressive disorder and a nonpsychiatric control group receiving no psychiatric diagnoses. Drug exposures and other variables were recorded from a chart review. Results: Exposures to digoxin, β- blockers, and calcium channel blockers were not associated with depressive diagnoses. An association was observed, however, for ACE inhibitors. An elevated odds ratio (OR) was observed in each case-control study and was stronger infernale subjects and subjects over the age of 65. Conclusions: This is the first reported epidemiological evidence of an association between ACE inhibitors and depressive disorders. The design of this study does not permit a determination of whether the observed association was causal. Additional studies are needed.

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Pathogenetic bases and efficacy of slow calcium channel blockers in the therapy of recurrent peptic ulcer disease associated with hypertension

Terapevticheskii arkhiv ◽

10.17116/terarkh201789210-14 ◽

2017 ◽

Vol 89 (2) ◽

pp. 10-14 ◽

Cited By ~ 3

Author(s):

L A Fomina ◽

V V Chernin

Keyword(s):

Peptic Ulcer ◽

Combination Therapy ◽

Peptic Ulcer Disease ◽

Calcium Channel ◽

Calcium Channel Blockers ◽

Clinical Symptoms ◽

Control Group ◽

Channel Blockers ◽

Blood Calcium ◽

Ulcer Disease

Aim. To clarify blood calcium concentrations (BCCs) as an indicator of the functional state of the calcium-regulating system in the concomitant course of recurrent peptic ulcer disease (PUD) and hypertension, by comparing with the severity of a ulcerous process, with changes in regional microcirculation, and with the functions of the stomach. To elucidate the pathogenetic justification for and clinical efficacy of slow calcium channel blockers (SCCBs) in the treatment of this comorbidity. Subjects and methods. In the case-control study, each patient with recurrent PUD and grade 1, Stage I hypertension (Group 1; n=23) corresponded to a recurrent PUD patient matched for sex, age, and ulcer site (Group 2, n=23). The complex of treatment for these patients included the SCCB nifedipine. A control group consisted of 56 recurrent PUD patients who received combination therapy without nifedipine. All the patients over time underwent clinical and endoscopic examinations and determinations of BCCs, indicators of gastric secretory and motor functions, and regional microcirculation in the gastroduodenal mucosal biopsy specimens. Results. Recurrent PUD was present with a reliable BCC increase that was more substantial when it was associated with hypertension. Calcium imbalance was accompanied by changes in regional microcirculation and gastric secretory and motor functional indicators forming an acid peptic factor, as well as by hypermotor dyskinesia, which were more pronounced in patients with comorbidity. Incorporation of a SCCB into a complex of therapy for recurrent PUD to eliminate the pathogenic effect of blood calcium contributed to more rapid arrest of the clinical symptoms of a recurrence, to elimination of acute-phase microcirculatory disorders in the gastroduodenal zone, and to the recovery of gastric functional indicators. Elevated blood pressure was ruled out during the therapy of concomitant diseases. Conclusion. Incorporation of a SCCB into the combination therapy of recurrent PUD associated with hypertension is pathogenetically sound and clinically effective.

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Effect of calcium channel blockers long-term use on blood level of luteinizing hormone and estradiol in rats

Kazan medical journal ◽

10.17816/kmj1521 ◽

2014 ◽

Vol 95 (3) ◽

pp. 389-392

Author(s):

A U Kazimova ◽

K G Garaeva

Keyword(s):

Luteinizing Hormone ◽

Calcium Channel ◽

Blood Level ◽

Calcium Channel Blockers ◽

Female Rats ◽

Control Group ◽

Blood Levels ◽

Channel Blockers ◽

High Doses

Aim. To define the effect of calcium channel blockers long-term use on blood level of luteinizing hormone and estradiol in female rats. Methods. 82 mature female outbreed rats were distributed to seven groups. The rats of the first (control) group were administered 0.2 ml of 0.9% saline intraperitoneally for 21 day. Instead of saline, 5 and 25 mg/kg of verapamil were used in rats of the second and third groups, 5 and 10 mg/kg of nifedipine - in rats of the 4th and 5th groups, 5 and 20 mg/kg of diltiazem - in rats of the 6th and 7th groups accordingly. Blood levels of luteinizing hormone and estradiol were determined by ELISA after animals were withdrawn from the study. Results. In rats treated with calcium channel blockers, a dose-dependent decrease of luteinizing hormone and estradiol blood levels were observed. High doses of verapamil (group 3) decreased the level of luteinizing hormones and estradiol by 50% compared to control group, high doses of diltiazem (group 7) - by 50%. Only minor changes were observed in rats who were administered nifedipine, even in high doses. Conclusion. Observed decrease of blood estradiol level indicate the influence of calcium channel blockers directly on ovarian function; decrease of blood luteinizing hormone level might by secondary due to positive feedback between the estradiol and luteinizing hormone secretion and reflect decreased estradiol blood level.

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