BACKGROUND Heart failure with preserved ejection fraction(HFpEF)accounts for approximately half of heart failure cases and is associated with high morbidity and mortality.Beta-blockers(BB)and calcium channel blockers(...BACKGROUND Heart failure with preserved ejection fraction(HFpEF)accounts for approximately half of heart failure cases and is associated with high morbidity and mortality.Beta-blockers(BB)and calcium channel blockers(CCB)are commonly used for symptom control and comorbidity management,but their comparative effectiveness and safety remain unclear.AIM To compare the effectiveness and safety of BB vs CCB in patients with HFpEF using simulated real-world data and propensity score-matched analyses.METHODS Simulated data for 4000 HFpEF patients(2000 BB,2000 CCB)were generated based on distributions extracted from electronic medical records spanning 2014-2023.Inclusion criteria included adults with left ventricular ejection fraction≥50%and initiation of BB or CCB.Effectiveness outcomes encompassed mortality,heart failure hospitalizations,and changes in clinical parameters.Safety outcomes included bradycardia,hypotension,and drug discontinuation.Statistical analyses used t-tests,χ2 tests,Cox proportional hazards models for hazard ratios(HR),and incidence rate ratios(IRR)in R software.Propensity score matching(PSM)was performed to balance baseline characteristics,with outcomes reassessed in the matched cohort.RESULTS Baseline characteristics were largely balanced,with minor differences in sex,chronic kidney disease,systolic blood pressure,and left atrial volume index.BB demonstrated lower all-cause mortality(crude HR 0.78,95%CI:0.70-0.87,P=0.003),heart failure hospitalization(crude HR 0.86,95%CI:0.77-0.96,P=0.031),and composite endpoint(crude HR 0.85,95%CI:0.79-0.91,P<0.001)rates compared to CCB.IRR for heart failure hospitalizations and emergency visits favored BB.Safety profiles showed higher symptomatic bradycardia(9.2%vs 4.9%,P<0.001)and drug discontinuation(11.3%vs 9.3%,P=0.043)with BB,and higher hypotension(7.2%vs 11.5%,P<0.001)with CCB.Matched analyses showed all-cause mortality rates of 0.0622 per person-year for BB vs 0.0649 for CCB(HR 0.96,95%CI:0.85-1.08),heart failure hospitalization rates of 0.0751 vs 0.0888(HR 0.84,95%CI:0.75-0.94),and IRR for number of heart failure hospitalizations of 1.65 for CCB vs BB(95%CI:1.51-1.80,P<0.001).CONCLUSION BB may offer potential advantages in reducing mortality and hospitalizations in HFpEF compared to CCB,with distinct safety considerations.PSM confirmed these trends with reduced confounding.Personalized therapy is recommended,warranting prospective trials for validation.展开更多
Aim and Method A novel three-dimensional quantitative structure-activityrelationship (3D-QSAR) method, self-organizing molecular field analysis (SOMFA) , was used toinvestigate the correlation between the molecular pr...Aim and Method A novel three-dimensional quantitative structure-activityrelationship (3D-QSAR) method, self-organizing molecular field analysis (SOMFA) , was used toinvestigate the correlation between the molecular properties and a class of chromanol analogs asI_(Ks) blockers. Results The cross-validated correlation coefficient q^2 values (0.698) and noncross-validated correlation coefficient r^2 values (0.701) proved a good conventional statisticalcorrelation. Conclusion The final SOMFA model has therefore good predictive activity for the furthermolecular design of chromanol I_(Ks) potassium channel blockers.展开更多
In order to observe it blockers of sodium channel obsesses the neuroprotective effect on hippocampal CA 1 pyramidal cell under the condition of transient brain ischemia, the present experiment used 24 male Wistar rat...In order to observe it blockers of sodium channel obsesses the neuroprotective effect on hippocampal CA 1 pyramidal cell under the condition of transient brain ischemia, the present experiment used 24 male Wistar rats aged 9 months and divided them into four groups. Lidocaine and/or furosemide were injected introcerebroventicularlly (I.C.V). Stained with H E and accounted the CA 1 pyramidal cell numbers by computer in each group suggested following findings: Although 5 μl of 2% lidocaine was injected I.C.V, the results indicated lidocaine didn't have any blockade to pyramidal cell injuries in hippocampal CA 1 area (P<0 05). In the group medicated with 2 5μl of both 2% lidocaine and 2% furosemide, the results showed that the combined approach had a blockade to injuries of pyramidal cells compared with control group (P<0 01). The present experiment indicates that the combined blockade of lidocaine and furosemide injected I.C.V. to Na + channel can prevent the injuries from hippocampal neurons owing to ischemia.展开更多
Objective:This study was aimed at investigating whether the addition of nicorandil to a dihydropyridine calcium channel blocker(DHP-CCB)regimen might decrease the occurrence of major adverse cardiovascular events(MACE...Objective:This study was aimed at investigating whether the addition of nicorandil to a dihydropyridine calcium channel blocker(DHP-CCB)regimen might decrease the occurrence of major adverse cardiovascular events(MACE)in patients with coronary heart disease(CHD).Methods:A multicenter,retrospective,real-world study was conducted.Between August 2002 and March 2020,7413 eligible patients with CHD were divided into DHP-CCB plus nicorandil combination(n=1843)and DHP-CCB(n=5570)treatment groups.The primary outcome was MACE,defined as a composite of myocardial infarction,stroke,and all-cause mortality.Propensity score matching was used to adjust for confounding factors.Results:After propensity score matching,combination therapy,compared with DHP-CCBs alone,was associated with a lower risk of MACE(HR:0.80,95%CI:0.67–0.97).The combination group also had a lower risk of stroke(HR:0.55,95%CI:0.44–0.69),but not myocardial infarction(HR:1.21,95%CI:0.91–1.61)or all-cause mortality(HR:1.24,95%CI:0.63–2.44).Subgroup analysis revealed more prominent benefits of the combined treatment on MACE in patients with than without diabetes.Conclusions:The combination of nicorandil and DHP-CCBs may be more beneficial than DHP-CCBs alone in decreasing long-term risks of MACE and stroke in patients with CHD.展开更多
Alzheimer＇s disease is characterized by two pathological hallmarks： amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging Recent research shows that ...Alzheimer＇s disease is characterized by two pathological hallmarks： amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer＇s disease. Calcium channel blockers are effective therapeutics for treating Alzheimer＇s disease. This review provides an overview of the current research of calcium channel blockers involved in Alzheimer＇s disease theraov.展开更多
This study aimed to develop an evaluation index system for calcium channel blocker(CCB)drugs in medical institutions to support a scientific and evidence-based approach to their assessment and selection.In accordance ...This study aimed to develop an evaluation index system for calcium channel blocker(CCB)drugs in medical institutions to support a scientific and evidence-based approach to their assessment and selection.In accordance with the Management Guidelines for Comprehensive Clinical Evaluation of Drugs(2021 Trial Edition)and utilizing the Delphi method,we established a comprehensive evaluation index system for CCB drugs.Two rounds of online expert consultations were conducted,resulting in a finalized system comprising six primary indicators,23 secondary indicators,and 52 tertiary indicators.The average familiarity scores of experts were 0.83 and 0.79 across the two rounds,with judgment basis coefficients of 0.92 and 0.93,authority coefficients of 0.88 and 0.86,and credibility scores of 0.96 and 0.98,respectively.The developed evaluation index system exhibited robust credibility and wide applicability.It provided a structured framework to guide the selection and rational use of CCB drugs in medical institutions,thereby enhancing pharmacy service quality and facilitating optimized drug cost management.展开更多
Four calcium channel blockers, i.e. nifedipine, verapamil, cinnarizine and tetrandrine are currently available and used widely in treating cardiovascular diseases. To confirm the effects, if any, of calcium channel bl...Four calcium channel blockers, i.e. nifedipine, verapamil, cinnarizine and tetrandrine are currently available and used widely in treating cardiovascular diseases. To confirm the effects, if any, of calcium channel blockers on cirrhotic patients with portal hypertension, a study was performed on esophageal variceal pressure and rebleeding rate of esophageal varices after 2 years by using calcium channel blocker in 321 patients from some 23 hospitals. The results demonstrated that the calcium channel blockers could significantly reduce the esophageal variceal pressure and the portal blood flow in cirrhotic patients with portal hypertension. The proportion of patients with no recurrent gastrointestinal bleeding after 2 years medication of tetrandrine was 87.9% in tetrandrine group, significantly higher than those in the other 4 groups (P<0.05). It is suggested that tetrandrine should be more effective for cirrhotic patients with portal hypertension in preventing recurrent variceal bleeding.展开更多
Background:Hypertension is considered an important risk factor for the coronavirus disease 2019(COVID-19).The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system(RAAS)inhibitors,calcium chann...Background:Hypertension is considered an important risk factor for the coronavirus disease 2019(COVID-19).The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system(RAAS)inhibitors,calcium channel blockers(CCBs),and beta-blockers.The association between commonly used anti-hypertensive medications and the clinical outcome of COVID-19 patients with hypertension has not been well studied.Methods:We conducted a retrospective cohort study that included all patients admitted with COVID-19 to Huo Shen Shan Hospital and Guanggu District of the Maternal and Child Health Hospital of Hubei Province,Wuhan,China.Clinical and laboratory characteristics were extracted from electronic medical records.Hypertension and anti-hypertensive treatment were confirmed by medical history and clinical records.The primary clinical endpoint was all-cause mortality.Secondary endpoints included the rates of patients in common wards transferred to the intensive care unit and hospital stay duration.Logistic regression was used to explore the risk factors associated with mortality and prognosis.Propensity score matching was used to balance the confounders between different anti-hypertensive treatments.Kaplan-Meier curves were used to compare the cumulative recovery rate.Log-rank tests were performed to test for differences in Kaplan-Meier curves between different groups.Results:Among 4569 hospitalized patients with COVID-19,31.7%(1449/4569)had a history of hypertension.There were significant differences in mortality rates between hypertensive patients with CCBs(7/359)and those without(21/359)(1.95%vs.5.85%,risk ratio[RR]:0.32,95% confidence interval[CI]:0.13–0.76,χ^(2)=7.61,P=0.0058).After matching for confounders,the mortality rates were similar between the RAAS inhibitor(4/236)and non-RAAS inhibitor(9/236)cohorts(1.69% vs.3.81%,RR:0.43,95% CI:0.13–1.43,χ^(2)=1.98,P=0.1596).Hypertensive patients with beta-blockers(13/340)showed no statistical difference in mortality compared with those without(11/340)(3.82% vs.3.24%,RR:1.19,95% CI:0.53–2.69,χ^(2)=0.17,P=0.6777).Conclusions:In our study,we did not find any positive or negative effects of RAAS inhibitors or beta-blockers in COVID-19 patients with hypertension,while CCBs could improve prognosis.展开更多
Platelet activation plays an important role in thrombosis. Platelet glycoprotein Ⅱ b/Ⅲ a （ GPⅡ b/Ⅲ a ） is the receptor of fibrinogen. Platelet cross-linking with fibrinogen through GP Ⅱ b/Ⅲ a is the process of...Platelet activation plays an important role in thrombosis. Platelet glycoprotein Ⅱ b/Ⅲ a （ GPⅡ b/Ⅲ a ） is the receptor of fibrinogen. Platelet cross-linking with fibrinogen through GP Ⅱ b/Ⅲ a is the process of thrombosis. Ca^2＋ is an important intracellular second messenger in platelet activation. It has been reported that GP Ⅱ b/Ⅲ a receptors were involved in the calcium influx of activated platelet, and GP Ⅱ b/Ⅲ a receptor had characteristics of calcium channel or an adjacent calcium channel.展开更多
The usefulness of biopartitioning micellar chromatography （BMC） for predicting oral drug acute toxicity and apparent bioavailability was demonstrated. A logarithmic model （an LD50 model） and the second order polyn...The usefulness of biopartitioning micellar chromatography （BMC） for predicting oral drug acute toxicity and apparent bioavailability was demonstrated. A logarithmic model （an LD50 model） and the second order polynomial models （apparent bioavailability model） have been obtained using the retention data of the selective calcium channel blockers to predict pharmacological properties of compounds. The use of BMC is simple, reproducible and can provide key information about the acute toxicity and transport properties of new compounds during the drug discovery process.展开更多
The release of mediators from mast cells is a model for cell secretion and is an in-vitro index for immediate hypersensitivity reactions. Calcium influx is generally accepted to be the primary biochemicalevent in mast...The release of mediators from mast cells is a model for cell secretion and is an in-vitro index for immediate hypersensitivity reactions. Calcium influx is generally accepted to be the primary biochemicalevent in mast cell activation.We studied the effect of the calcium ionophore A 23187 and calcium channelblockers,nifedipine and verapamil, in triggering the activation of rat peritoneal mast cells.At suitableconcentration nifedipine and verapamil have had the inhibition effect in the IgE-dependent roaction.展开更多
Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy onhepatocarcinoma-bearing rats, and examine the action between calcium channel bloc...Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy onhepatocarcinoma-bearing rats, and examine the action between calcium channel blockers and cytotoxic drugs.Methods We adopted the method of subcapsular implantation of carcinoma tissues of walker-256 in the left liver lobe as a model of livercarcinoma-bearing rats. All experimental animals were divided into four groups. On the sixth day post implantation, in group A (controlgroup) 6 ml of saline was injected intraperitoneally once a day for 3 days. In group B (single chemotherapy group) 6 ml of 5-Fu 75 mg/kg was injected intraperitoneally once a day for 3 days. In group C (combination of treatment group) both 5-Fu (75 mg/kg) and verapamil(25 mg/kg) were administered simultaneously as in A and B. In group D (simple verapamil group) only 6 ml of verapamil (25 mg/kg)was administered as above.Results Compared with groups A, B and D, The volume of cancer and the contents of liver cancer DNA and protein were significantlyreduced. The rates of inhibiting cancer (89.9% in group C and 35.4% in group B) were significantly increased in group C. Group C hadsignificantly long survival time compared to groups A, B and D ( P < 0.05) . By light microscopy, a number of focal necroses were foundin cancer tissue in group C.Conclusion Calcium channel blockers can enhance the antineoplastic effect of 5-Fu intraperitoneal chemotherapy to liver cancer ; Theuse of verapamil can not increase the toxicity of 5-Fu.展开更多
The effects of hepatic ischemia/reperfusion (I/R) injuries on hepatocellular viability and store-operated calcium current (Isoc) in isolated rat hepatocytes and the effects of 2-APB on store-operated calcium current (...The effects of hepatic ischemia/reperfusion (I/R) injuries on hepatocellular viability and store-operated calcium current (Isoc) in isolated rat hepatocytes and the effects of 2-APB on store-operated calcium current (Isoc) in isolated rat hepatocytes after hepatic ischemia/reperfusion injuries were studied. Hepatic ischemia and reperfusion injury model was established and whole cell patch-clamp techniques were used to investigate the effects of 2-APB on Isoc. The results showed that ischemia/reperfusion injuries could significantly reduce hepatocellular viability and further increase Isoc in hepatocytes and 2-APB (20, 40, 60, 80, 100 μmol/L) produced a concentration-dependent decrease of Isoc with IC 50 value of 64.63±10.56 μmol/L (n=8). It was concluded that ischemia/reperfusion injuries could reduce hepatocellular viability, probably through increased Isoc in hepatocytes and 2-APB had a protective effect on ischemia/reperfusion-induced liver injury, probably though inhibiting Isoc.展开更多
The types of the voltage-dependent calcium channels （VDCCs） in human ejaculatory sperm and the effects of calcium channel blocker （CCB） on human sperm motility parameters in vitro were investigated. The human sper...The types of the voltage-dependent calcium channels （VDCCs） in human ejaculatory sperm and the effects of calcium channel blocker （CCB） on human sperm motility parameters in vitro were investigated. The human sperm motility parameters in vitro in response to the pharmacological agents nifedipine （NIF, inhibitor of L-type VDCC） and ω-conotoxin （GVIA, inhibitor of N-type VDCC） were compared and analyzed statistically. The results showed that NIF （1, 5, 10 μmol/L） could not only significantly affect human sperm＇s shape but also spermatozoa motility after incubated at least 10 rain in vitro （P〈0.001）. GVIA （0.1, 0.5 and 1 μmol/L） could just only significantly affect human sperm＇s progressive motility （a %＋b %） after incubated for 20 min in vitro （P〈0.01）, but they both could not significantly affect spermic abnormality rate. It is suggested that L-type VDCC, non L-type VDCCs and isoform of L-type VDCC exist in the cell membrane of human sperm solely or together, and they participate in the spermic physiological processes especially the spermic motility.展开更多
Objective:To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods:The spasmogenic and spasmolytic effects were evaluated on is...Objective:To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods:The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath.The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System.The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis,respectively.Results:The total phenolic and total flavonoids contents of the extract were(267.75±5.77)mg GAE/g and(73.86±6.01)mg QE/g,respectively.Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC_(50)value of 0.016 mg/m L,which was blocked by atropine(0.3μM).Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC_(50)value of 2.185 mg/mL.Furthermore,Argemone mexicana extract relaxed potassium(80 mM)-induced contractions(EC_(50):9.07 mg/mL),similar to a standard drug verapamil.The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract(1-5 mg/mL)and verapamil(0.1-1μM).In addition,the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks.Conclusions:Argemone mexicana shows cholinergic agonist and calcium channel blocker activities,as well as antiemetic effect.It may be used as a potential agent for treating gastrointestinal disorders.展开更多
Background As to abdominal aortic aneurysm （AAA） disease, our major challenge faced in clinical practice is effective drug therapies to prevent rupture of AAA. At present, there wasn’t definite evidence that other ...Background As to abdominal aortic aneurysm （AAA） disease, our major challenge faced in clinical practice is effective drug therapies to prevent rupture of AAA. At present, there wasn’t definite evidence that other drugs had a role in inhibiting AAA rupture except for beta blocker. In our study, we evaluated the role of calcium channel blocker （CCB） played in prevention of AAA rupture. Methods A total of 460 subjects with AAA, aged 29 to 89 years, at least twice admitted into our hospital from January 2000 to April 2010. All of them accepted ultrasound examination for scanning abdominal aortic aneurysm at each admission period. Results Our results revealed that AAA patients suffered from rupture took little CCB and beta-blockers. Treatment with CCB or beta blocker was negatively related to risk of rupture of abdominal aortic aneurysm, and drugs such as statins, angiotensin II receptor blocker （ARB） or angiotensin-converting enzyme inhibitor （ACEI） hadn’t positive or negative effect on AAA. C reactive protein level was lower in patients with taking CCB than those without CCB. Conclusions CCB therapy was negatively related to AAA rupture, and possibly was another kind of drug for.展开更多
Objective: to analyze the application value of calcium channel blocker in the treatment of coronary heart disease angina pectoris. Methods: a total of 100 cases of coronary heart disease patients with angina pectoris ...Objective: to analyze the application value of calcium channel blocker in the treatment of coronary heart disease angina pectoris. Methods: a total of 100 cases of coronary heart disease patients with angina pectoris admitted to our hospital from February 2019 to February 2020 were randomly divided into groups. Patients in the control group were treated with conventional methods, while patients in the observation group were additionally treated with calcium channel blockers. NBP, VAS score, left ventricular ejection fraction and overall outcome efficiency were compared between 2 groups before and after treatment. Results: before treatment, NBP, VAS score and left ventricular ejection fraction were compared between the two groups (P > 0.05). After treatment, NBP, VAS score of angina pectoris in the observation group was lower than that in the control group, while left ventricular ejection fraction was higher than that in the control group (P < 0.05). The total effective rate of observation group was 96.00% (48/50) higher than that of control group (80.00%, 40/50), P < 0.05. Conclusions: conventional drugs and calcium channel blockers have definite effects on coronary heart disease angina pectoris, which can improve cardiac function, relieve angina pectoris and improve serological indexes.展开更多
\ The effects of tetrandrine (Tet) on cytosolic free calcium ([Ca2+]i) in subcultured bovine aortic smooth muscle cells (SMC) were studied by Fura2 and ARCMMIC cation measurement system. Tet (1～100 μmol·L-1) ...\ The effects of tetrandrine (Tet) on cytosolic free calcium ([Ca2+]i) in subcultured bovine aortic smooth muscle cells (SMC) were studied by Fura2 and ARCMMIC cation measurement system. Tet (1～100 μmol·L-1) had no effect on the resting [Ca2+]i, but had inhibitory effects on [Ca2+]i elevation induced by high K+, 5HT, ATP, Ang II and NE in the presence of extracellular Ca2+. High concentration of Tet also inhibited Pheinduced [Ca2+]i elevation in absence of extracellular Ca2+. Tet (1～100 μmol·L-1) inhibited KCl (60 mmol·L-1) induced [Ca2+]i elevation in dosedependent manner, the IC50 value was 9.2 (95% confidence limits: 5.7～14.9) mmol·L-1. The results suggested that Tet had blocking effects on both VOC and ROC in bovine aortic SMC. It appears that the mechanisms of blocking effect of Tet on ROC might be primarily due to its Ca2+ entry blocking effects.展开更多
Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factor...Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis, both of which require effective treatment. Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission. Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades. Alverine citrate, a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to calcium, and it is a selective 5-HT<sub>1A</sub> receptor antagonist. Alverine, in combination with simethicone, has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control; nevertheless, in recent placebo-controlled studies, mebeverine did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed from the GI tract, where it acts locally as an L-type calcium channel blocker, an antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has effectively reduced pain and improved defecation alterations in placebo-controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract. Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients. Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety profiles. T-type calcium channel blockers can abolish visceral hypersensitivity in animal models, which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS.展开更多
文摘BACKGROUND Heart failure with preserved ejection fraction(HFpEF)accounts for approximately half of heart failure cases and is associated with high morbidity and mortality.Beta-blockers(BB)and calcium channel blockers(CCB)are commonly used for symptom control and comorbidity management,but their comparative effectiveness and safety remain unclear.AIM To compare the effectiveness and safety of BB vs CCB in patients with HFpEF using simulated real-world data and propensity score-matched analyses.METHODS Simulated data for 4000 HFpEF patients(2000 BB,2000 CCB)were generated based on distributions extracted from electronic medical records spanning 2014-2023.Inclusion criteria included adults with left ventricular ejection fraction≥50%and initiation of BB or CCB.Effectiveness outcomes encompassed mortality,heart failure hospitalizations,and changes in clinical parameters.Safety outcomes included bradycardia,hypotension,and drug discontinuation.Statistical analyses used t-tests,χ2 tests,Cox proportional hazards models for hazard ratios(HR),and incidence rate ratios(IRR)in R software.Propensity score matching(PSM)was performed to balance baseline characteristics,with outcomes reassessed in the matched cohort.RESULTS Baseline characteristics were largely balanced,with minor differences in sex,chronic kidney disease,systolic blood pressure,and left atrial volume index.BB demonstrated lower all-cause mortality(crude HR 0.78,95%CI:0.70-0.87,P=0.003),heart failure hospitalization(crude HR 0.86,95%CI:0.77-0.96,P=0.031),and composite endpoint(crude HR 0.85,95%CI:0.79-0.91,P<0.001)rates compared to CCB.IRR for heart failure hospitalizations and emergency visits favored BB.Safety profiles showed higher symptomatic bradycardia(9.2%vs 4.9%,P<0.001)and drug discontinuation(11.3%vs 9.3%,P=0.043)with BB,and higher hypotension(7.2%vs 11.5%,P<0.001)with CCB.Matched analyses showed all-cause mortality rates of 0.0622 per person-year for BB vs 0.0649 for CCB(HR 0.96,95%CI:0.85-1.08),heart failure hospitalization rates of 0.0751 vs 0.0888(HR 0.84,95%CI:0.75-0.94),and IRR for number of heart failure hospitalizations of 1.65 for CCB vs BB(95%CI:1.51-1.80,P<0.001).CONCLUSION BB may offer potential advantages in reducing mortality and hospitalizations in HFpEF compared to CCB,with distinct safety considerations.PSM confirmed these trends with reduced confounding.Personalized therapy is recommended,warranting prospective trials for validation.
文摘Aim and Method A novel three-dimensional quantitative structure-activityrelationship (3D-QSAR) method, self-organizing molecular field analysis (SOMFA) , was used toinvestigate the correlation between the molecular properties and a class of chromanol analogs asI_(Ks) blockers. Results The cross-validated correlation coefficient q^2 values (0.698) and noncross-validated correlation coefficient r^2 values (0.701) proved a good conventional statisticalcorrelation. Conclusion The final SOMFA model has therefore good predictive activity for the furthermolecular design of chromanol I_(Ks) potassium channel blockers.
文摘In order to observe it blockers of sodium channel obsesses the neuroprotective effect on hippocampal CA 1 pyramidal cell under the condition of transient brain ischemia, the present experiment used 24 male Wistar rats aged 9 months and divided them into four groups. Lidocaine and/or furosemide were injected introcerebroventicularlly (I.C.V). Stained with H E and accounted the CA 1 pyramidal cell numbers by computer in each group suggested following findings: Although 5 μl of 2% lidocaine was injected I.C.V, the results indicated lidocaine didn't have any blockade to pyramidal cell injuries in hippocampal CA 1 area (P<0 05). In the group medicated with 2 5μl of both 2% lidocaine and 2% furosemide, the results showed that the combined approach had a blockade to injuries of pyramidal cells compared with control group (P<0 01). The present experiment indicates that the combined blockade of lidocaine and furosemide injected I.C.V. to Na + channel can prevent the injuries from hippocampal neurons owing to ischemia.
文摘Objective:This study was aimed at investigating whether the addition of nicorandil to a dihydropyridine calcium channel blocker(DHP-CCB)regimen might decrease the occurrence of major adverse cardiovascular events(MACE)in patients with coronary heart disease(CHD).Methods:A multicenter,retrospective,real-world study was conducted.Between August 2002 and March 2020,7413 eligible patients with CHD were divided into DHP-CCB plus nicorandil combination(n=1843)and DHP-CCB(n=5570)treatment groups.The primary outcome was MACE,defined as a composite of myocardial infarction,stroke,and all-cause mortality.Propensity score matching was used to adjust for confounding factors.Results:After propensity score matching,combination therapy,compared with DHP-CCBs alone,was associated with a lower risk of MACE(HR:0.80,95%CI:0.67–0.97).The combination group also had a lower risk of stroke(HR:0.55,95%CI:0.44–0.69),but not myocardial infarction(HR:1.21,95%CI:0.91–1.61)or all-cause mortality(HR:1.24,95%CI:0.63–2.44).Subgroup analysis revealed more prominent benefits of the combined treatment on MACE in patients with than without diabetes.Conclusions:The combination of nicorandil and DHP-CCBs may be more beneficial than DHP-CCBs alone in decreasing long-term risks of MACE and stroke in patients with CHD.
基金supported by the National Natural Science Foundation of China, No. 81171206
文摘Alzheimer＇s disease is characterized by two pathological hallmarks： amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer＇s disease. Calcium channel blockers are effective therapeutics for treating Alzheimer＇s disease. This review provides an overview of the current research of calcium channel blockers involved in Alzheimer＇s disease theraov.
文摘This study aimed to develop an evaluation index system for calcium channel blocker(CCB)drugs in medical institutions to support a scientific and evidence-based approach to their assessment and selection.In accordance with the Management Guidelines for Comprehensive Clinical Evaluation of Drugs(2021 Trial Edition)and utilizing the Delphi method,we established a comprehensive evaluation index system for CCB drugs.Two rounds of online expert consultations were conducted,resulting in a finalized system comprising six primary indicators,23 secondary indicators,and 52 tertiary indicators.The average familiarity scores of experts were 0.83 and 0.79 across the two rounds,with judgment basis coefficients of 0.92 and 0.93,authority coefficients of 0.88 and 0.86,and credibility scores of 0.96 and 0.98,respectively.The developed evaluation index system exhibited robust credibility and wide applicability.It provided a structured framework to guide the selection and rational use of CCB drugs in medical institutions,thereby enhancing pharmacy service quality and facilitating optimized drug cost management.
文摘Four calcium channel blockers, i.e. nifedipine, verapamil, cinnarizine and tetrandrine are currently available and used widely in treating cardiovascular diseases. To confirm the effects, if any, of calcium channel blockers on cirrhotic patients with portal hypertension, a study was performed on esophageal variceal pressure and rebleeding rate of esophageal varices after 2 years by using calcium channel blocker in 321 patients from some 23 hospitals. The results demonstrated that the calcium channel blockers could significantly reduce the esophageal variceal pressure and the portal blood flow in cirrhotic patients with portal hypertension. The proportion of patients with no recurrent gastrointestinal bleeding after 2 years medication of tetrandrine was 87.9% in tetrandrine group, significantly higher than those in the other 4 groups (P<0.05). It is suggested that tetrandrine should be more effective for cirrhotic patients with portal hypertension in preventing recurrent variceal bleeding.
基金supported by grants from the Natural Science Foundation of Shanghai(No.15ZR1412300)Three-Year Action Plan for Strengthening Public Health System in Shanghai(2020–2022)Key Discipline Con-struction Project(No.GWV-10.1-XK05).
文摘Background:Hypertension is considered an important risk factor for the coronavirus disease 2019(COVID-19).The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system(RAAS)inhibitors,calcium channel blockers(CCBs),and beta-blockers.The association between commonly used anti-hypertensive medications and the clinical outcome of COVID-19 patients with hypertension has not been well studied.Methods:We conducted a retrospective cohort study that included all patients admitted with COVID-19 to Huo Shen Shan Hospital and Guanggu District of the Maternal and Child Health Hospital of Hubei Province,Wuhan,China.Clinical and laboratory characteristics were extracted from electronic medical records.Hypertension and anti-hypertensive treatment were confirmed by medical history and clinical records.The primary clinical endpoint was all-cause mortality.Secondary endpoints included the rates of patients in common wards transferred to the intensive care unit and hospital stay duration.Logistic regression was used to explore the risk factors associated with mortality and prognosis.Propensity score matching was used to balance the confounders between different anti-hypertensive treatments.Kaplan-Meier curves were used to compare the cumulative recovery rate.Log-rank tests were performed to test for differences in Kaplan-Meier curves between different groups.Results:Among 4569 hospitalized patients with COVID-19,31.7%(1449/4569)had a history of hypertension.There were significant differences in mortality rates between hypertensive patients with CCBs(7/359)and those without(21/359)(1.95%vs.5.85%,risk ratio[RR]:0.32,95% confidence interval[CI]:0.13–0.76,χ^(2)=7.61,P=0.0058).After matching for confounders,the mortality rates were similar between the RAAS inhibitor(4/236)and non-RAAS inhibitor(9/236)cohorts(1.69% vs.3.81%,RR:0.43,95% CI:0.13–1.43,χ^(2)=1.98,P=0.1596).Hypertensive patients with beta-blockers(13/340)showed no statistical difference in mortality compared with those without(11/340)(3.82% vs.3.24%,RR:1.19,95% CI:0.53–2.69,χ^(2)=0.17,P=0.6777).Conclusions:In our study,we did not find any positive or negative effects of RAAS inhibitors or beta-blockers in COVID-19 patients with hypertension,while CCBs could improve prognosis.
文摘Platelet activation plays an important role in thrombosis. Platelet glycoprotein Ⅱ b/Ⅲ a （ GPⅡ b/Ⅲ a ） is the receptor of fibrinogen. Platelet cross-linking with fibrinogen through GP Ⅱ b/Ⅲ a is the process of thrombosis. Ca^2＋ is an important intracellular second messenger in platelet activation. It has been reported that GP Ⅱ b/Ⅲ a receptors were involved in the calcium influx of activated platelet, and GP Ⅱ b/Ⅲ a receptor had characteristics of calcium channel or an adjacent calcium channel.
基金Project supported by the National Natural Science Foundation of China （No. 20375010）, Natural Science Foundation of Hebei Province （No. 202096）, Bairen Project of Chinese Academy of Sciences, and the Excellent Teacher Program and the Specialized Research Fund for the Doctoral Program of Higher Education.Acknowledgements The authors wish to thank professor Yang LIANG and Yongjian ZHANG for a generous gift of m-nisoldipine, nisoldipine and nicardipine.
文摘The usefulness of biopartitioning micellar chromatography （BMC） for predicting oral drug acute toxicity and apparent bioavailability was demonstrated. A logarithmic model （an LD50 model） and the second order polynomial models （apparent bioavailability model） have been obtained using the retention data of the selective calcium channel blockers to predict pharmacological properties of compounds. The use of BMC is simple, reproducible and can provide key information about the acute toxicity and transport properties of new compounds during the drug discovery process.
文摘The release of mediators from mast cells is a model for cell secretion and is an in-vitro index for immediate hypersensitivity reactions. Calcium influx is generally accepted to be the primary biochemicalevent in mast cell activation.We studied the effect of the calcium ionophore A 23187 and calcium channelblockers,nifedipine and verapamil, in triggering the activation of rat peritoneal mast cells.At suitableconcentration nifedipine and verapamil have had the inhibition effect in the IgE-dependent roaction.
文摘Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy onhepatocarcinoma-bearing rats, and examine the action between calcium channel blockers and cytotoxic drugs.Methods We adopted the method of subcapsular implantation of carcinoma tissues of walker-256 in the left liver lobe as a model of livercarcinoma-bearing rats. All experimental animals were divided into four groups. On the sixth day post implantation, in group A (controlgroup) 6 ml of saline was injected intraperitoneally once a day for 3 days. In group B (single chemotherapy group) 6 ml of 5-Fu 75 mg/kg was injected intraperitoneally once a day for 3 days. In group C (combination of treatment group) both 5-Fu (75 mg/kg) and verapamil(25 mg/kg) were administered simultaneously as in A and B. In group D (simple verapamil group) only 6 ml of verapamil (25 mg/kg)was administered as above.Results Compared with groups A, B and D, The volume of cancer and the contents of liver cancer DNA and protein were significantlyreduced. The rates of inhibiting cancer (89.9% in group C and 35.4% in group B) were significantly increased in group C. Group C hadsignificantly long survival time compared to groups A, B and D ( P < 0.05) . By light microscopy, a number of focal necroses were foundin cancer tissue in group C.Conclusion Calcium channel blockers can enhance the antineoplastic effect of 5-Fu intraperitoneal chemotherapy to liver cancer ; Theuse of verapamil can not increase the toxicity of 5-Fu.
基金This project was supported by the National Natural Sci ence Foundation of China (No. 30270532), the Trans Cen tury Excellent Talent Development Plan Fund of Ministry ofEducation of China (Official Letter No. 2002 48) and Shu guang Program Project of Shanghai Educational Committee(No. 02SG20).
文摘The effects of hepatic ischemia/reperfusion (I/R) injuries on hepatocellular viability and store-operated calcium current (Isoc) in isolated rat hepatocytes and the effects of 2-APB on store-operated calcium current (Isoc) in isolated rat hepatocytes after hepatic ischemia/reperfusion injuries were studied. Hepatic ischemia and reperfusion injury model was established and whole cell patch-clamp techniques were used to investigate the effects of 2-APB on Isoc. The results showed that ischemia/reperfusion injuries could significantly reduce hepatocellular viability and further increase Isoc in hepatocytes and 2-APB (20, 40, 60, 80, 100 μmol/L) produced a concentration-dependent decrease of Isoc with IC 50 value of 64.63±10.56 μmol/L (n=8). It was concluded that ischemia/reperfusion injuries could reduce hepatocellular viability, probably through increased Isoc in hepatocytes and 2-APB had a protective effect on ischemia/reperfusion-induced liver injury, probably though inhibiting Isoc.
文摘The types of the voltage-dependent calcium channels （VDCCs） in human ejaculatory sperm and the effects of calcium channel blocker （CCB） on human sperm motility parameters in vitro were investigated. The human sperm motility parameters in vitro in response to the pharmacological agents nifedipine （NIF, inhibitor of L-type VDCC） and ω-conotoxin （GVIA, inhibitor of N-type VDCC） were compared and analyzed statistically. The results showed that NIF （1, 5, 10 μmol/L） could not only significantly affect human sperm＇s shape but also spermatozoa motility after incubated at least 10 rain in vitro （P〈0.001）. GVIA （0.1, 0.5 and 1 μmol/L） could just only significantly affect human sperm＇s progressive motility （a %＋b %） after incubated for 20 min in vitro （P〈0.01）, but they both could not significantly affect spermic abnormality rate. It is suggested that L-type VDCC, non L-type VDCCs and isoform of L-type VDCC exist in the cell membrane of human sperm solely or together, and they participate in the spermic physiological processes especially the spermic motility.
文摘Objective:To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods:The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath.The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System.The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis,respectively.Results:The total phenolic and total flavonoids contents of the extract were(267.75±5.77)mg GAE/g and(73.86±6.01)mg QE/g,respectively.Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC_(50)value of 0.016 mg/m L,which was blocked by atropine(0.3μM).Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC_(50)value of 2.185 mg/mL.Furthermore,Argemone mexicana extract relaxed potassium(80 mM)-induced contractions(EC_(50):9.07 mg/mL),similar to a standard drug verapamil.The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract(1-5 mg/mL)and verapamil(0.1-1μM).In addition,the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks.Conclusions:Argemone mexicana shows cholinergic agonist and calcium channel blocker activities,as well as antiemetic effect.It may be used as a potential agent for treating gastrointestinal disorders.
文摘Background As to abdominal aortic aneurysm （AAA） disease, our major challenge faced in clinical practice is effective drug therapies to prevent rupture of AAA. At present, there wasn’t definite evidence that other drugs had a role in inhibiting AAA rupture except for beta blocker. In our study, we evaluated the role of calcium channel blocker （CCB） played in prevention of AAA rupture. Methods A total of 460 subjects with AAA, aged 29 to 89 years, at least twice admitted into our hospital from January 2000 to April 2010. All of them accepted ultrasound examination for scanning abdominal aortic aneurysm at each admission period. Results Our results revealed that AAA patients suffered from rupture took little CCB and beta-blockers. Treatment with CCB or beta blocker was negatively related to risk of rupture of abdominal aortic aneurysm, and drugs such as statins, angiotensin II receptor blocker （ARB） or angiotensin-converting enzyme inhibitor （ACEI） hadn’t positive or negative effect on AAA. C reactive protein level was lower in patients with taking CCB than those without CCB. Conclusions CCB therapy was negatively related to AAA rupture, and possibly was another kind of drug for.
文摘Objective: to analyze the application value of calcium channel blocker in the treatment of coronary heart disease angina pectoris. Methods: a total of 100 cases of coronary heart disease patients with angina pectoris admitted to our hospital from February 2019 to February 2020 were randomly divided into groups. Patients in the control group were treated with conventional methods, while patients in the observation group were additionally treated with calcium channel blockers. NBP, VAS score, left ventricular ejection fraction and overall outcome efficiency were compared between 2 groups before and after treatment. Results: before treatment, NBP, VAS score and left ventricular ejection fraction were compared between the two groups (P > 0.05). After treatment, NBP, VAS score of angina pectoris in the observation group was lower than that in the control group, while left ventricular ejection fraction was higher than that in the control group (P < 0.05). The total effective rate of observation group was 96.00% (48/50) higher than that of control group (80.00%, 40/50), P < 0.05. Conclusions: conventional drugs and calcium channel blockers have definite effects on coronary heart disease angina pectoris, which can improve cardiac function, relieve angina pectoris and improve serological indexes.
文摘\ The effects of tetrandrine (Tet) on cytosolic free calcium ([Ca2+]i) in subcultured bovine aortic smooth muscle cells (SMC) were studied by Fura2 and ARCMMIC cation measurement system. Tet (1～100 μmol·L-1) had no effect on the resting [Ca2+]i, but had inhibitory effects on [Ca2+]i elevation induced by high K+, 5HT, ATP, Ang II and NE in the presence of extracellular Ca2+. High concentration of Tet also inhibited Pheinduced [Ca2+]i elevation in absence of extracellular Ca2+. Tet (1～100 μmol·L-1) inhibited KCl (60 mmol·L-1) induced [Ca2+]i elevation in dosedependent manner, the IC50 value was 9.2 (95% confidence limits: 5.7～14.9) mmol·L-1. The results suggested that Tet had blocking effects on both VOC and ROC in bovine aortic SMC. It appears that the mechanisms of blocking effect of Tet on ROC might be primarily due to its Ca2+ entry blocking effects.
文摘Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis, both of which require effective treatment. Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission. Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades. Alverine citrate, a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to calcium, and it is a selective 5-HT<sub>1A</sub> receptor antagonist. Alverine, in combination with simethicone, has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control; nevertheless, in recent placebo-controlled studies, mebeverine did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed from the GI tract, where it acts locally as an L-type calcium channel blocker, an antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has effectively reduced pain and improved defecation alterations in placebo-controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract. Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients. Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety profiles. T-type calcium channel blockers can abolish visceral hypersensitivity in animal models, which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS.
