Dihydropyridine Calcium Channel Blocker Research Articles

#838 Comparison of the incidence of proteinuria and eGFR change between febuxostat and topiroxostat users

Abstract Background and Aims Febuxostat and topiroxostat are novel non-purine selective xanthine oxidoreductase (XOR) inhibitors, commonly available for the treatment of hyperuricemia in Japan. The previous studies suggested that febuxostat and topiroxostat might have renoprotective effects. It is important to compare febuxostat with topiroxostat on the renoprotective effects for the selection of the XOR inhibitors in clinical settings. However, comparative data between febuxostat and topiroxostat on renal function and proteinuria are limited. Therefore, the present study aimed to compare renal function and proteinuria between febuxostat and topiroxostat. Method We conducted a retrospective cohort study using databases provided by DeSC Healthcare Inc. (Tokyo, Japan). We identified 17,446 individuals (11.8% women; mean age 67.4 years) without estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, a history of cardiovascular disease and proteinuria at baseline. The claims database includes all inpatient, outpatient, and pharmacy claims received from insurers during the study period. The use of febuxostat and topiroxostat was defined as having claims of dispensing (or prescribing) febuxostat and topiroxostat within 1 year before the baseline health check-up, respectively. Analyses were performed for the individuals with eGFR <60 mL/min/1.73 m2 and those with eGFR ≥60 mL/min/1.73 m2 separately. The Cox proportional hazard model was used to assess the adjusted hazard ratio (HR) for the incidence of proteinuria in the topiroxostat users compared with the febuxostat users. We calculated the annual rate of eGFR change as the slope of the linear regression between eGFR and year for each participant. Changes in eGFR were compared between the febuxostat users and the topiroxostat users using multiple regression analysis. We performed stratified analyses according to sex, age (<75 and ≥75 years), body mass index (BMI) (<25 and ≥25 kg/m2), hypertension, and diabetes mellitus. Covariates included sex, age, BMI, current smoker, current drinker, diabetes mellitus, dyslipidemia, systolic blood pressure, use of angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, dihydropyridine calcium channel blocker, or the other antihypertensive drugs, serum uric acid level, and baseline eGFR. Results During a mean follow-up of 1.79 years, 1,433 participants developed proteinuria. In the non-diabetic individuals with eGFR ≥60 mL/min/1.73 m2, the fully adjusted HRs (95% confidence interval, p-value) for the incidence of proteinuria in the topiroxostat users compared with in the febuxostat users were 0.60 (0.40–0.91, p= 0.016). We found a significant interaction between diabetes mellitus and the use of topiroxostat on the incidence of proteinuria. No significant differences were observed in eGFR change between the two treatment groups with eGFR <60 and ≥60 mL/min/1.73 m2. When we evaluated the eGFR change between the two groups with eGFR <60 and ≥60 mL/min/1.73 m2 using the eGFRCKD-EPI, we found no significant differences in eGFR change between the two groups with eGFR <60 and ≥60 mL/min/1.73 m2. Conclusion The topiroxostat prevalent-users had a lower risk of the incidence of proteinuria than the febuxostat prevalent-users in the non-diabetic individuals with eGFR ≥60 mL/min/1.73 m2. Our findings suggested that topiroxostat might be more effective than febuxostat in preventing proteinuria in non-diabetic individuals with eGFR ≥60 mL/min/1.73 m2.

A new three-dimensional (3D) molecularly imprinted polymer fluoroprobe based on green-red dual-emission signals of carbon quantum dots and self-polymerization of dopamine (CDs@PDA-MIPs) for sensitive detection of nifedipine.

Nifedipine (NIF), as one of the dihydropyridine calcium channel blockers, is widely used in the treatment of hypertension. However, misuse or ingestion of NIF can result in serious health issues such as myocardial infarction, arrhythmia, stroke, and even death. It is essential to design a reliable and sensitive detection method to monitor NIF. In this work, an innovative molecularly imprinted polymer dual-emission fluorescent sensor (CDs@PDA-MIPs) strategy was successfully designed for sensitive detection of NIF. The fluorescent intensity of the probe decreased with increasing NIF concentration, showing a satisfactory linear relationship within the range 1.0 × 10-6M ~ 5.0 × 10-3M. The LOD of NIF was 9.38 × 10-7M (S/N = 3) in fluorescence detection. Theapplication of the CDs@PDA-MIPs in actual samples such as urine and Qiangli Dingxuan tablets has been verified, with recovery ranging from 97.8 to 102.8% for NIF. Therefore, the fluorescent probe demonstrates great potential as a sensing system for detecting NIF.

Evaluation of the Efficacy and Safety of Nicardipine versus Clevidipine for Blood Pressure Control in Hypertensive Crisis

BackgroundHypertensive crisis is an acute increase in blood pressure greater than 180/120 mmHg. A titratable antihypertensive agent is preferred to acutely lower blood pressure in a controlled way and prevent an abrupt overcorrection. Nicardipine and clevidipine are both dihydropyridine calcium channel blockers that provide unique benefits for blood pressure control. ObjectiveThe purpose of this study was to compare the efficacy and safety of nicardipine or clevidipine for blood pressure control in the setting of hypertensive crisis. MethodsThis was a single-center, retrospective cohort study. Eligible patients received either nicardipine or clevidipine for the treatment of hypertensive crisis. The primary outcome was achievement of 25% reduction in mean arterial pressure (MAP) at 1 hour. The secondary outcome was achievement of a systolic blood pressure (SBP) of < 160 mmHg at 2-6 hours from the start of the infusion. ResultsThis study included a total of 156 patients with 74 in the nicardipine group and 82 in the clevidipine group. The SBP on admission and at the start of the infusion was similar between groups. There was no difference between groups in achieving a 25% reduction in MAP at one hour. Nicardipine achieved a SBP goal of < 160 mmHg at 2-6 hours significantly more often than the clevidipine group (89.2% vs 73.2%; p-value 0.011). ConclusionThere is no difference between agents for initial blood pressure control in the treatment of hypertensive crisis. Nicardipine showed more sustained SBP control with a lower risk of rebound hypertension and a significant cost savings as compared to clevidipine.

Characteristics associated with responsiveness to isometric handgrip training in medicated hypertensive patients: secondary data analysis.

Isometric handgrip training (IHT) has been shown to reduce blood pressure (BP) in hypertensive patients. However, factors that predict responsiveness to IHT are largely unknown. The aim of this study was to investigate the patient characteristics associated with the antihypertensive response to IHT using a recommended statistical approach for evaluating interindividual responses. Data from four randomized controlled trials were joined, totaling 81 patients undergoing IHT (48.8% women; 60 ± 11 years) and 90 control patients (45.6% women; 62 ± 12 years). IHT consisted of 4 × 2 min isometric contractions at 30% of maximal voluntary contraction, performed three times/week for 8-12 weeks. BP was measured at baseline and following IHT and control interventions. The interindividual variation was assessed by the standard deviation of the individual responses (SDir), and linear regression analyses were conducted to explore response predictors. IHT significantly decreased both SBP (-5.4; 95% confidence interval (CI) -9.5 to -1.3 mmHg) and DBP (-2.8; 95% CI -5.1 to -0.6 mmHg). The interindividual variation of BP change was moderate for systolic (SDir = 5.2 mmHg, 0.30 standardized units) and low for diastolic (SDir = 1.7 mmHg, 0.15 standardized units). Sex, age, and BMI were not associated with the antihypertensive effect of IHT. However, a higher baseline SBP (b = -0.467, P < 0.001) and absence of dihydropyridine calcium channel blockers use (b = 0.340, P = 0.001) were associated with greater BP reductions. IHT reduced BP in medicated hypertensive patients regardless of age, sex, and BMI. Patients with a higher baseline SBP and those not prescribed dihydropyridine calcium channel blockers were more responsive to IHT.

Dihydropyridine Calcium Channel Blockers and Kidney Outcomes.

Early trials of dihydropyridine calcium channel blockers (DCCBs) suggest a detrimental effect on intraglomerular pressure and an association with albuminuria. We sought to evaluate the associations of DCCB initiation with albuminuria and kidney failure with replacement therapy (KFRT) and to determine whether renin-angiotensin system (RAS) blockade modified these associations. We conducted a target trial emulation study using a new user, active comparator design and electronic health record data from Geisinger Health. We included patients without severe albuminuria or KFRT who were initiated on a DCCB or thiazide (active comparator) between January 1, 2004, and December 31, 2019. Using inverse probability of treatment weighting, we performed doubly robust Cox proportional hazards regression to estimate the association of DCCB initiation with incident severe albuminuria (urine albumin to creatinine ratio > 300 mg/g) and KFRT, overall and stratified by RAS blocker use. There were 11,747and 26,758 eligible patients initiating a DCCB and thiazide, respectively, with a weighted baseline mean age of 60 years, systolic blood pressure of 143 mm Hg, and eGFR of 86 mL/min/1.73 m2, and with a mean follow-up of 8 years. Compared with thiazides, DCCBs were significantly associated with the development of severe albuminuria (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.16-1.43), with attenuation of risk in the presence of RAS blockade (P for interaction < 0.001). The risk of KFRT was increased among patients without RAS blockade (HR, 1.66; 95% CI, 1.19-2.31), but not with RAS blockade (P for interaction = 0.005). DCCBs were associated with increased risk of albuminuria and, in the absence of RAS blockade, KFRT. These findings suggest coupling DCCB therapy with RAS blockade may mitigate adverse kidney outcomes.

Dissolving microneedles loaded with nimodipine for prevention of sleep disorders at a high altitude

Sleep disorders are one of the most common acute reactions on the plateau, which can cause serious complications. However, there is no effective and safe treatment currently available. Nimodipine (NMD) is a dihydropyridine calcium channel blocker with neuroprotective and vasodilating activity, mainly used for the treatment of ischemic brain injury. Commercial oral or injectable NMD formulations are not a good option for central neuron diseases due to their poor brain delivery. In this study, nimodipine dissolving microneedles (NDMNs) were prepared for the prevention of sleep disorders caused by hypoxia. NDMNs were composed of NMD and polyvinyl pyrrolidone (PVP) K90 with a conical morphology and high rigidity. After administration of NDMNs on the back neck of mice, the concentration of NMD in the brain was significantly higher than that of oral medication as was confirmed by the fluorescent imaging on mouse models. NDMNs enhanced cognitive function, alleviated oxidative stress, and improved the sleep quality of mice with high-altitude sleep disorders. The blockage of calcium ion overloading may be an important modulation mechanism. NDMNs are a promising and user-friendly formulation for the prevention of high-altitude sleep disorders.

Amlodipine-Induced Gingival Enlargement – A Case Report

One of the etiological factors for Gingival Enlargement is administration of certain drugs like calcium channel blockers, anticonvulsants, and immunosuppressant. The drug that is been commonly used for the management of portal hypertension is calcium channel blockers. Among the various drugs in calcium channel blockers, the occurrence of drug-induced gingival enlargement is high with the use of nifedipine drug whereas the occurrence of gingival enlargement due to the usage of amlodipine drug is a very rare phenomenon. Amlodipine is a third-generation drug belonging to dihydropyridine calcium channel blocker that has been used for its longer duration of action. Treatment for drug-induced gingival enlargement includes referral of patients to their physician for possible drug substitution or alteration in dosage of drug, periodontal therapy that includes oral prophylaxis followed by gingivectomy or gingivoplasty, and maintenance care. In this study, we report a case of gingival enlargement in a 44-year-old female patient taking amlodipine drug for a period of six months and nonsurgical and surgical management of amlodipine-induced gingival enlargement in the patient.

Comparative Bioequivalence and Food Effect of Two Formulations of 30-mg Nifedipine Controlled-Release Tablets in Healthy Chinese Adults.

Nifedipine is a potent antihypertensive medication classified as a dihydropyridine calcium channel blocker. The objective of this trial was to assess the bioequivalence of a 30-mg nifedipine controlled-release tablet and a reference drug in a cohort of healthy Chinese individuals. Two independent open-label, randomized, single-dose, crossover studies were conducted, 1 under fasting conditions (N = 44, with 1 participant dropping out midway) and the other under fed conditions (N = 44, with 4 participants dropping out midway). Plasma concentrations of nifedipine were determined using liquid chromatography-mass spectrometry, and pharmacokinetic (PK) parameters were calculated using noncompartmental analysis with Phoenix WinNonlin 8.0 software. In both fasting and fed studies, reasonable bioequivalence was observed for the PK parameters of both the test product and the reference drug. A good safety profile was demonstrated for both the test product and reference drug, with no serious adverse events reported, and both were similarly well tolerated. An important observation with food coadministration was that systemic exposure to nifedipine (based on area under the curve, AUC0-∞) was reduced by approximately 12%. The bioequivalence of the test product and reference drug under fasting/fed conditions in healthy subjects in China was demonstrated by the study results.

Implementation of Microcirculation Examination in Clinical Practice-Insights from the Nationwide POL-MKW Registry.

Background and Objectives: The assessment of coronary microcirculation may facilitate risk stratification and treatment adjustment. The aim of this study was to evaluate patients' clinical presentation and treatment following coronary microcirculation assessment, as well as factors associated with an abnormal coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) values. Materials and Results: This retrospective analysis included 223 patients gathered from the national registry of invasive coronary microvascular testing collected between 2018 and 2023. Results: The frequency of coronary microcirculatory assessments in Poland has steadily increased since 2018. Patients with impaired IMR (≥25) were less burdened with comorbidities. Patients with normal IMR underwent revascularisation attempts more frequently (11.9% vs. 29.8%, p = 0.003). After microcirculation testing, calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors were added more often for patients with IMR and CFR abnormalities, respectively, as compared to control groups. Moreover, patients with coronary microvascular dysfunction (CMD, defined as CFR and/or IMR abnormality), regardless of treatment choice following microcirculation assessment, were provided with trimetazidine (23.2%) and dihydropyridine CCBs (26.4%) more frequently than those without CMD who were treated conservatively (6.8%) and by revascularisation (4.2% with p = 0.002 and 0% with p < 0.001, respectively). Multivariable analysis revealed no association between angina symptoms and IMR or CFR impairment. Conclusions: The frequency of coronary microcirculatory assessments in Poland has steadily increased. Angina symptoms were not associated with either IMR or CFR impairment. After microcirculation assessment, patients with impaired microcirculation, expressed as either low CFR, high IMR or both, received additional pharmacotherapy treatment more often.

Evaluating Provider and Pharmacy Discordance in Potential Calcium Channel Blocker-Loop Diuretic Prescribing Cascade.

Prescribing cascades occur when a drug-induced adverse event is treated with a new medication. Identifying clinical scenarios in which prescribing cascades are more likely to occur may help determine ways to prevent prescribing cascades. To understand the extent to which discordant providers and discordant pharmacies contribute to the dihydropyridine calcium channel blocker (DH CCB)-loop diuretic prescribing cascade. A retrospective cohort study using Medicare Fee-For-Service data (2011-2018) of adults aged ≥ 66 years. Patients who initiated DH CCB with subsequent initiation of loop diuretic (DH CCB-loop diuretic dyad) within 90 days or patients who initiated angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) with subsequent initiation of a loop diuretic (ACEI/ARB-loop diuretic dyad; control). The primary outcomes were provider and pharmacy discordance for prescribing cascades and control drug pairs. Baseline clinical and socio-demographic characteristics were balanced using inverse probability of treatment weighting with propensity scores. Overall, we identified 1987 DH CCB-loop diuretic dyads and 3148 ACEI/ARB-loop diuretic dyads. Discordant providers occurred in 64% of DH CCB-loop diuretic dyads and 55% of ACEI/ARB-loop diuretic dyads, while discordant pharmacies occurred in 19% of DH CCB-loop diuretic dyads and 16% of ACEI/ARB-loop diuretic dyads. After adjustment, the risk of having discordant providers was 20% {Relative Risk (RR) 1.20 [95% confidence interval (CI), 1.14-1.26]} higher in the DH CCB-loop diuretic dyad compared with the ACEI/ARB-loop diuretic dyad. Moreover, pharmacy discordance was 17% (RR 1.17 [95% CI 1.02-1.33]) higher. Our findings suggest that discordant providers and discordant pharmacies were more commonly involved in the potentialprescribing cascade when compared with a similar control dyad of medications. Opportunities for enhanced care coordination and medication reconciliation should be explored to prevent unnecessary polypharmacy.

Seasonal variation in ambulatory blood pressure control in patients on clinic blood pressure-guided antihypertensive treatment.

We investigated seasonal variation in ambulatory blood pressure control in hypertensive patients on clinic blood pressure-guided antihypertensive treatment. The study participants were hypertensive patients enrolled in an 8-week therapeutic study. Antihypertensive treatment was initiated with long-acting dihydropyridine calcium channel blockers amlodipine 5 mg/day or the gastrointestinal therapeutic system (GITS) formulation of nifedipine 30 mg/day, with the possible up-titration to amlodipine 10 mg/day or nifedipine-GITS 60 mg/day at 4 weeks of follow-up. The proportion of up-titration to higher dosages of antihypertensive drugs at 4 weeks of follow-up was higher in patients who commenced treatment in autumn/winter ( n = 302) than those who commenced treatment in spring/summer ( n = 199, 24.5 vs. 12.0%, P < 0.001). The control rate of clinic blood pressure, however, was lower in autumn/winter than in spring/summer at 4 (56.7 vs. 70.7%, P = 0.003) and 8 weeks of follow-up (52.5 vs. 74.9%, P < 0.001). At 8 weeks, patients who commenced treatment in autumn/winter, compared with those who commenced treatment in spring/summer, had a significantly ( P ≤0.03) smaller daytime (mean between-season difference -3.2/-2.8 mmHg) but greater nighttime SBP/DBP reduction (3.6/1.6 mmHg). Accordingly, at 8 weeks, the prevalence of nondippers was significantly ( P < 0.001) higher in spring/summer than in autumn/winter for both SBP (54.8 vs. 30.0%) and DBP (53.4 vs. 28.8%). Clinic blood pressure-guided antihypertensive treatment requires a higher dosage of medication in cold than warm seasons, which may have led to over- and under-treatment of nighttime blood pressure, respectively.

Calcium Channel Blocker Overdose.

Emergency medicine residents and medical students on emergency medicine rotation. Calcium channel blocker (CCB) overdoses can be severe with potentially serious adverse outcomes. CCBs work by blocking the calcium channels on smooth and cardiac muscle tissue. At low dose ranges, dihydropyridine CCBs (such as nifedipine, amlodipine, and nicardipine) block the L-type calcium receptors in the peripheral vasculature, whereas non-dihydropyridine CCBs (such as: verapamil and diltiazem) affect the L-type calcium receptors in the myocardium.1 Because of this distinction, dihydropyridine CCB toxicity manifests as arterial vasodilation and non-dihydropyridine CCB toxicity is associated with cardiac manifestations such as bradycardia and negative inotropy.2 It is important to note that in high concentrations (such as in overdoses), CCBs lose specificity for their specific receptors and can show all the manifestations of toxicity such as bradycardia, peripheral vasodilation, and hypotension. Patients can develop both vasoplegic shock from peripheral vasodilation and cardiogenic shock. This is a high acuity low occurrence case with infrequently used but specific treatments, and thus this case provides educational value. At the end of this oral board session, examinees will: (1) demonstrate ability to evaluate a patient with undifferentiated shock with bradycardia and discuss the differential diagnosis, (2) recognize the signs and symptoms of calcium channel blocker overdose, (3) demonstrate ability to manage treatment of a patient with calcium channel overdose. This oral board case followed the standard American Board of Emergency Medicine-style case in a tertiary care hospital with access to all specialists and resources needed. This case was tested using 12 resident volunteers ranging from PGY 1-2 in an ACGME (Accreditation Council for Graduate Medical Education) accredited emergency medicine residency program. Immediate feedback was solicited both from the learners and from the evaluators following the debriefing session. Residents were asked to evaluate the educational value of the case using a 1-5 Likert scale (5 being excellent). Evaluators were asked to score the residents using the ACGME core competencies with a scale of 1-8, 1-4 being unacceptable and 5-8 being acceptable. Seven PGY1 residents and five PGY2 residents, thus twelve residents in total, completed the case. The average score was 5.10/8. Three residents missed zero critical actions. The most common critical action missed was consulting cardiology or cardiothoracic surgery for circulatory support options. Many residents failed to recognize that the patient did not have a perfusing blood pressure at the beginning of the case and did not start CPR. Although most residents recognized the patient's hemodynamic collapse was from a calcium channel blocker overdose, most did not know the treatment for this beyond atropine and intravenous fluids.The learners rated the educational value of the case as 4.9/5. Seven residents reported that the case definitely increased their medical knowledge; five residents reported that it somewhat increased their medical knowledge. All residents rated the case as helpful in preparing to manage this medical condition. The educational content from this case was effective. This is a high acuity low occurrence case that has unique treatments that are not commonly used. This makes this case excellent for practice and discussion. We learned during implementation that this case has a high degree of difficulty compared to other cases, and junior learners will need more prompting. It is also important for the proctor to keep the case moving because there is a lot to cover in the allotted amount of time. Calcium channel blocker overdose, toxicology.

Management of initial and surgical management of amlodipine-induced gingival enlargement with multifactorial etiology: a case report with 6 months follow-up

Drug-induced gingival enlargement can be seen as a side effect of systemically used drugs such as calcium channel blockers, anticonvulsants, and immunosuppressants. One of these drugs is amlodipine, a dihydropyridine derivative calcium channel blocker used in the treatment of high blood pressure and coronary artery disease. Amlodipine-induced gingival overgrowth is rarely seen compared to other calcium channel blockers. The aim of this case is to present the diagnosis of gingival overgrowth due to amlodipine use and the identification of other etiologic factors such as labial frenulum, phase 1 initial, and phase 2 surgical treatment approaches. A 56-year-old female patient presented to our clinic with severe gingival overgrowth, intense bleeding, difficulty feeding, and pain. The anamnesis revealed that she had hypertension and had been taking amlodipine derivative Norvasc 10 mg once a day for 8 years. A look inside the mouth showed that there was a lot of gum tissue growing over the crowns from the labial and palatal sides, mainly in the front of the maxilla. Phase 1 treatment was initiated. As a result of the consultation with the patient's cardiologist, the hypertension medication Norvasc 10 mg was replaced with Candexil 16 mg by the medical physician. The preoperative tension and blanch test was positive, and the labial frenulum was seen to mobilize the free gingival margin of the central teeth. After the same session of gingivoplasty, the labial frenulum was removed by a frenectomy operation. After the operation, antibiotics, analgesics, and mouthwash were prescribed. The patient stated that he did not have any problems after the operation. 6-month follow-up showed uneventful healing. No recurrence of gingival growth was found in the 1st, 3rd, and 6th month follow-ups. In conclusion, this case report shows that non-surgical periodontal treatment alone isn't always enough to treat drug-induced gingival overgrowths. The gingival shape should be changed so that the patient can properly clean their teeth, and drug-induced gingival overgrowths, like the one in this case, may have more than one cause and may need additional surgery like a labial frenectomy.

Combined use of beta-blockers and non-dihydropyridine calcium channel blockers: possible or contraindicated?

One of the most effective medications used for various cardiac diseases and syndromes to improve symptoms and, in some cases, prognosis, are betablockers (BBs) and calcium channel blockers (CCBs). The combination of BBs and dihydropyridine CCBs has a synergistic clinical effect and is well tolerated. The clinical effects of a combination of beta blockers and non-dihydropyridine CCBs (verapamil, diltiazem) are also synergistic. However, this combination increases the incidence of side effects and complications of drug therapy.The article discusses the controversial issues of such a combination and substantiates the main conclusion that the discussed combination is not applicable in routine practice. This position should be clearly reflected in all Russian cardiology guidelines. However, the article discusses the possible combined use of BBs with nondihydropyridine CCBs in isolated cases, excluding contraindications, taking into account almost daily monitoring of tolerability, individual characteristics of the patient and by decision of a medical team.

Central ECMO cannulation for severe dihydropyridine calcium channel blocker overdose

Calcium channel blocker (CCB) toxicity carries a high mortality and is the sixth most fatal drug class reported to US poison centers. Amlodipine overdose is characterized by a life-threatening arterial vasodilation that compromises organ perfusion. The management of CCB intoxication is focused on maintaining adequate organ perfusion. In cases refractory to medical therapies, hemodynamic support with extracorporeal membrane oxygenation (ECMO) is warranted necessitating higher flows than usual to compensate for the vasodilation and requiring central cannulation. We present a case of a 12-year-old with severe dihydropyridine CCB ingestion, refractory to medical management and successfully treated with central ECMO cannulation. The patient was discharged home with no significant disability. Central ECMO cannulation may be helpful to facilitate adequate flows in vasodilatory shock such as CCB overdose.

Characterization of the calcineurin inhibitor pain syndrome in patients undergoing allogeneic hematopoietic cell transplantation

Calcineurin inhibitor pain syndrome (CIPS) is a rare complication of graft-vs-host disease prophylaxis following allogeneic hematopoietic cell transplant (alloHCT). CIPS presents as severe bilateral lower extremity pain, and the incidence, risk factors, and management of CIPS are poorly characterized. This is a single center retrospective study of patients who received tacrolimus (TAC) following alloHCT to describe the characteristics and management of CIPS and compare to a cohort who did not develop CIPS. Fifteen of 585 alloHCT patients (2.6%) developed CIPS at a median of 5 days following TAC initiation and a median level of 10.5 ng/mL. Severe bilateral foot, ankle, or leg pain were the primary symptoms. Patients with CIPS were younger and more frequently received myeloablative conditioning and total body irradiation compared to patients without CIPS. Analgesic regimens included dihydropyridine calcium channel blockers, gabapentinoids, topical diclofenac, and opioids. Clinicians should be aware of this uncommon but severe adverse effect.

Mebudipine as an Overlooked Cardioprotective Drug: A Review Study

Context: Calcium channel blockers (CCBs) play a crucial role in the treatment of cardiovascular diseases. Mebudipine, a dihydropyridine derivative CCB, was first synthesized in 1997. This study explores the potential benefits of mebudipine in managing cardiovascular disease, particularly as a derivative of nifedipine. Evidence Acquisition: The article succinctly presents the advancements in mebudipine research, which were uncovered through extensive searches in reputable scientific databases such as ScienceDirect, Google Scholar, Scopus, and PubMed, conducted by 2 blinded researchers. The search focused on studies relevant to mebudipine, using specific keywords. Results: Mebudipine exhibits cardioprotective effects, reducing the occurrence of arrhythmias and minimizing heart tissue damage. Additionally, it has been found to enhance the levels of nitric oxide metabolites. Due to its limited solubility in water, mebudipine is typically administered using a nanoemulsion. Importantly, it has been deemed a safe drug without mutagenic effects. Conclusions: Our review study underscores that mebudipine not only has a cardioprotective effect but also offers protection to other organs against various forms of injury induction. The mechanisms responsible for these protective effects may be linked to its ability to counteract oxidative stress, prevent apoptosis, and mitigate inflammation. Nevertheless, further research is needed to fully elucidate its potential.

Practical recommendations for antihypertensive therapy during the primary aldosteronism screening test.

The aldosterone-to-renin activity ratio (ARR) is recommended as a screening test for primary aldosteronism (PA). The use of antihypertensive medication is one of the most important factors to take into account when interpreting the ARR. The goal of this study was to compare the effect of various antihypertensive drug classes on biochemical testing and provide practical recommendations for antihypertensive medication regimens in patients suspected of having PA. We retrospectively investigated 4218 hypertensive patients who underwent PA detection between January 2020 and February 2023. Finally, 25 patients with essential hypertension (EH) and 39 with PA were involved. The enrolled EH patients were selected from EH patients with at least two screening tests with interfering medication changes for at least 4 weeks. A total of 2/18 (11.1%) EH patients had opposite screening results after angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), dihydropyridine-calcium channel blockers (DHP-CCBs) and diuretics were withdrawn. A total of 3/3 (100%) of the patients were initially screened as positive but had results that tested negative after β-blockers withdrawal. A total of 3/39 (7.7%) PA patients were misdiagnosed with EH with drug effects. Only plasma renin activity was markedly reduced after antihypertensive medication washout (P = 0.0173). Not every patient receiving β-blockers, ACEIs, ARBs and DHP-CCBs with negative reports needed withdrawal or switching antihypertensive drugs. We recommend that patients be left on a regimen that includes β-blockers, ACEIs, ARBs, DHP-CCBs and spironolactone when determining the ARR during the initial test.

Factors affecting the preparation of Cilnidipine nanoparticles

Cilnidipine is a dihydropyridine calcium channel blocker used to improve the neurological outcome following subarachnoid hemorrhage. It belongs to BCS class II drugs that have a low oral bioavailability of 13%, thus preparation as nanoparticles would be expected to improve bioavailability.&#x0D; The aim of the study is to prepare Cilnidipine as nanoparticles using different carriers and co-carriers, concentrations, and types.&#x0D; Cilnidipine nanoparticles were prepared by a solvent anti-solvent method using different carriers (Soloplus®, Poloxamer 188, PVA cold) with co-stabilizers (PEG200, glycerol) at different ratios.&#x0D; Based on the obtained results, formula N4, which included Soloplus in a 1:1:1 weight ratio of drug to the polymer to co-stabilizer, exhibited a particle size of 88.89 nm when stirred at 1000 rpm with an injection speed of 1 ml/min. The polydispersity index (PDI) for this formula was measured at 0.2413. Furthermore, formula N4 demonstrated an impressive 92.2% drug content and an entrapment efficiency (EE) of 95.8%, giving 100% release in 30 min.&#x0D;

Advanced Progress of the Relationship Between Antihypertensive Drugs and Bone Metabolism.

Hypertension and osteoporosis are common comorbidities among elderly individuals. Drug therapy has been widely used in clinical practice as the preferred antihypertensive treatment. Therefore, antihypertensive drugs have become some of the most commonly prescribed drugs in healthcare settings. However, antihypertensive drugs have different effects on bone metabolism. The results of animal and clinical studies on the effects of antihypertensive drugs on osteoporosis or fracture risk are controversial and have aroused widespread concern among clinicians. Recent studies found that angiotensin receptor blockers, selective β-adrenergic receptor blockers, and thiazide diuretics might improve bone trabecular number and bone mineral density by stimulating osteoblast differentiation, reducing osteoclast generation, and other mechanism. Furthermore, nonselective β-adrenergic receptor blockers and dihydropyridine calcium channel blockers were found to have no significant relationship with bone mineral density or bone strength, and α-adrenergic receptor blockers and loop diuretics might increase fracture risk by decreasing bone mineral density. This article aimed to review previous animal experiments, clinical studies, and meta-analyses focusing on the effects of different antihypertensive drugs on bone metabolism, and to provide a new approach for the prevention and treatment of osteoporosis.