Short-acting Calcium Channel Blockers Research Articles

Abstract 13555: Effect of Calcium Channel Blockers on Clinical Outcomes in Patients After Percutaneous Coronary Intervention With Left Ventricular Dysfunction

Although calcium channel blockers (CCBs) are effective in hypertension and IHD, short-acting CCBs are not recommended for heart failure due to have negative inotropic effects. On the other hand, long-acting CCBs have been reported to be safe for use in patients with cardiac dysfunction, but details are still unclear. In this study, we investigated the relationship between the effects of CCBs on CAD patients and left LV function. Methods: We enrolled 7173 consecutive CAD patients (Age; 69 [61-76] years and male; 78%) who underwent successful PCI for AP or ACS between April 2008 and March 2020 from prospective, multicenter registry (FUJISUN registry). Of the enrolled patients, 5307 analyzable patients were divided by LVEF <40 or ≥40%. Patients were prospectively followed for a maximum of 8 years or until the occurrence of the cardiac events (CEs): cardiac death, nonfatal MI. Results: During the follow-up period (3.6 [1.4-6.7] years), 230 (4%) CEs occurred (109 Cardiac death, 121 MI). Both patients with LVEF <40% and ≥40% had higher prevalence of HT and lower levels of BNP in CCB group than in non-CCB group. Propensity match analysis was performed to reduced selection bias for CCB use in each group. In patients with LVEF <40%, Kaplan-Meier analysis showed that CCB group had significantly lower probability of CEs than non-CCB group, whereas in those with LVEF ≥40%, the probability of CE was similar in both groups. Multivariate Cox proportional hazards analysis showed that CCB group had significantly lower probabilities of CEs compared with non-CCB group in patients with LVEF<40%, (HR 0.25; 95% CI 0.09-0.71, p <0.01), but not in those with LVEF≥40% (HR 1.13; 95% CI 0.80-1.60, p = 0.50). Conclusions: Long-acting CCBs may improve clinical outcomes in post-PCI CAD patients with LV dysfunction.

The Efficacy and Safety of Etripamil Nasal Spray for Acute Paroxysmal Supraventricular Tachycardia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Paroxysmal supraventricular tachycardia (PSVT) treatment requires medically supervised intervention. Etripamil is a novel short-acting calcium channel blocker. Its intranasal spray formulation has a rapid onset of action and shows promise for the unsupervised treatment of PSVT. We aimed to evaluate the efficacy and safety of etripamil nasal spray for the acute conversion of PSVT. A systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching the PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane databases through to 1 December 2022. RevMan version 5.4 software was used to pool dichotomous outcomes using risk ratio (RR) presented with the corresponding confidence interval (CI). Three RCTs with a total of 496 participants were included in our analysis. Etripamil was effective for PSVT conversion at 15min (RR 1.84, 95% CI 1.37-2.48), 30min (RR 1.86, 95% CI 1.42-2.44), and 60min (RR 1.25, 95% CI 1.05-1.50) after drug administration; decreasing medical intervention-seeking (RR 0.58, 95% CI 0.37-0.90); and decreasing emergency room (ER) visits (RR 0.61, 95% CI 0.38-0.97). However, there was no difference at 300min (RR 1.10, 95% CI 0.97-1.25) and it was associated with higher rates of adverse events (RR 3.17, 95% CI 2.15-4.69). Etripamil nasal spray was effective and well tolerated to induce PSVT termination for up to 60min. Therefore, etripamil nasal spray constitutes a promising strategy for PSVT self-termination without medical supervision; however, further RCTs are required before endorsement in clinical practice.

PO-04-108 THE EFFICACY AND SAFETY OF ETRIPAMIL NASAL SPRAY FOR THE TREATMENT OF ACUTE PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Paroxysmal Supraventricular Tachycardia (PSVT) treatment requires medically supervised intervention. This is derived from the lack of effective and safe self-administrated treatment for PSVT. Etripamil is a novel short-acting calcium channel blocker with a rapid intranasal spray and shows promising potential for the unsupervised treatment of PSVT, especially in the dosage of 70 mg. We aim to evaluate the efficacy and safety of Etripamil for the acute conversion of PSVT. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through December 1st, 2022. RevMan version 5.4 software was used to pool dichotomous outcomes using risk ratio (RR) presented with the corresponding confidence interval (CI) while using the fixed-effects model. Three RCTs with a total of 496 patients (296 in the etripamil group and 200 in the placebo group) were included in our analysis. Etripamil was effective for PSVT conversion at 15 minutes (RR: 1.84 with 95% CI [1.37, 2.48]), 30 minutes (RR: 1.86 with 95% CI [1.42, 2.44]), and at 60 minutes after the drug administration (RR: 1.25 with 95% CI [1.05, 1.50]); decreasing medical intervention seeking (RR: 0.58 with 95% CI [0.37, 0.90]); and decreasing emergency (ER) visits (RR: 0.61 with 95% CI [0.38, 0.97]). However, there was no difference at 300 minutes (RR: 1.10 with 95% CI [0.97, 1.25]). Also, Etripamil was associated with higher rates of the incidence of any adverse events (AEs) (RR: 3.17 with 95% CI [2.15, 4.69]), nasal discomfort (RR: 3.82 with 95% CI [2.01, 7.24]), nasal congestion (RR: 5.89 with 95% CI [1.93, 17.97]), epistaxis (RR: 4.74 with 95% CI [1.21, 18.50]), and rhinorrhea (RR: 3.53 with 95% CI [1.22, 10.26]) with no difference regarding any serious adverse events (SAEs) incidence (RR: 0.30 with 95% CI [0.01, 7.21]). Etripamil was effective in inducing PSVT termination for up to 60 minutes and reduced medical treatment seeking and ER visits. Also, Etripamil was associated with higher rates of AEs, including epistaxis, nasal congestion, and rhinorrhea; however, it was not associated with SAEs. Therefore, Etripamil constitutes a promising strategy for PSVT self-termination without medical supervision; however, further RCTs are required before endorsement in clinical practice.

Update on Etripamil Nasal Spray for the At-home Treatment of Acute Paroxysmal Supraventricular Tachycardia.

The current treatment of sustained paroxysmal supraventricular tachycardia (PSVT) often requires attendance at a medical facility. This burden is driven by the lack of an effective self-administered treatment for PSVT. Etripamil (Milestone Pharmaceuticals, Saint-Laurent, QC, Canada) is a novel intra-nasal preparation of a rapidly effective but short-acting calcium-channel blocker, which shows promise in offering out-of-hospital treatment for patients with PSVT. Studies, to date, have demonstrated good tolerability and potential efficacy, with a safety profile that is acceptable for unsupervised self-administration. This article reviews the current epidemiology and international guidelines for the treatment of acute PSVT, the pharmacology and clinical trial evidence behind the novel agent etripamil, and considers its potential role in the management of patients with PSVT.

The hypertensive emergency situation : Recommendations for initial drug therapy management

The hypertensive emergency situation is characterized by an acute-mostly life-threatening-blood pressure derailment with the risk of acute end organ damage. It is an acute manifestation of arterial hypertension, which manifests in avariety of symptoms. The etiology is in most cases long-term (chronic) hypertension as aresult of low compliance or inadequate antihypertensive therapy. It can also occur as afirst manifestation of arterial hypertension. It requires timely antihypertensive drug therapy, which should be initiated in an intensive or intermediate care unit. The choice of antihypertensive therapy regimen should be based on the underlying end organ damage. Fast-acting, easily controllable and intravenously administered substances should be preferred. The most commonly used substances (groups) are urapidil, nitroglycerin, beta blockers and short-acting calcium channel blockers. With afew exceptions, adeliberate, rapid reduction in blood pressure of no more than 20-25% of the initial value is sufficient for extracerebral causes. Asubsequent systolic blood pressure target of 160/100 mm Hg should be aimed for within the next 2-6 h. Anoverly rapid drop in blood pressure can lead to reduced blood flow to the central nervous system due to changes in autoregulation. Exceptions to this rule are acute aortic dissection and flash pulmonary edema-in these cases, prompt blood pressure normalization should be achieved. The initial acute therapy should be followed by amore detailed investigation of the cause and along-term therapy setting based on this.

Etripamil nasal spray: an investigational agent for the rapid termination of paroxysmal supraventricular tachycardia (SVT)

ABSTRACTIntroduction: Paroxysmal supraventricular tachycardia (SVT) can be very bothersome and may potentially lead to considerable health-care utilization. Non-parenteral medication is currently unavailable for the rapid termination of paroxysmal SVT. However, an intranasal spray formulation of etripamil, a short-acting calcium-channel blocker, is under investigation as a convenient, safe, and rapidly efficacious means to terminate paroxysmal SVT.Areas covered: This review summarizes the clinical rationale, potential benefit, and clinical trials safety and efficacy data for the use of etripamil nasal spray to terminate paroxysmal SVT.Expert opinion: Based on the efficacy and tolerability demonstrated in phase 1 and 2 clinical trials, etripamil nasal spray is a potential convenient, safe, and effective means for patients to terminate paroxysmal SVT. It has the potential to improve quality of life, reduce health-care burden, and alter the current management paradigm for many patients with SVT. Further ongoing evaluation in ambulatory patients will help to determine its real-life practicality, safety, and effectiveness.

Etripamil Nasal Spray for Rapid Conversion of Supraventricular Tachycardia to Sinus Rhythm

BackgroundThere is no nonparenteral medication for the rapid termination of paroxysmal supraventricular tachycardia. ObjectivesThe purpose of this study was to assess the efficacy and safety of etripamil nasal spray, a short-acting calcium-channel blocker, for the rapid termination of paroxysmal supraventricular tachycardia (SVT). MethodsThis phase 2 study was performed during electrophysiological testing in patients with previously documented SVT who were induced into SVT prior to undergoing a catheter ablation. Patients in sustained SVT for 5 min received either placebo or 1 of 4 doses of active compound. The primary endpoint was the SVT conversion rate within 15 min of study drug administration. Secondary endpoints included time to conversion and adverse events. ResultsOne hundred four patients were dosed. Conversion rates from SVT to sinus rhythm were between 65% and 95% in the etripamil nasal spray groups and 35% in the placebo group; the differences were statistically significant (Pearson chi-square test) in the 3 highest active compound dose groups versus placebo. In patients who converted, the median time to conversion with etripamil was <3 min. Adverse events were mostly related to the intranasal route of administration or local irritation. Reductions in blood pressure occurred predominantly in the highest etripamil dose. ConclusionsEtripamil nasal spray rapidly terminated induced SVT with a high conversion rate. The safety and efficacy results of this study provide guidance for etripamil dose selection for future studies involving self-administration of this new intranasal calcium-channel blocker in a real-world setting for the termination of SVT. (Efficacy and Safety of Intranasal MSP-2017 [Etripamil] for the Conversion of PSVT to Sinus Rhythm [NODE-1]; NCT02296190)

Agents with vasodilator properties in acute heart failure.

Millions of patients worldwide are admitted for acute heart failure (AHF) each year and physicians caring for these patients are confronted with the short-term challenges of reducing symptoms while preventing end organ dysfunction without causing additional harm, and the intermediate-term challenges of improving clinical outcomes such as hospital readmission and survival. There are limited data demonstrating the efficacy of any currently available therapies for AHF to meet these goals. After diuretics, vasodilators are the most common intravenous therapy for AHF, but neither nitrates, nitroprusside, nor nesiritide have robust evidence supporting their ability to provide meaningful effects on clinical outcomes, except perhaps early symptom improvement. Recently, a number of novel agents with vasodilating properties have been developed for the treatment of AHF. These agents include serelaxin, natriuretic peptides (ularitide, cenderitide), β-arrestin-biased angiotensin II type 1 receptor ligands (TRV120027), nitroxyl donors (CXL-1020, CXL-1427), soluble guanylate cyclase modulators (cinaciguat, vericiguat), short-acting calcium channel blockers (clevidipine), and potassium channel activators (nicorandil). These development programmes range from the stage of early dose-finding studies (e.g. TRV120027, CXL-1427) to large, multicentre mortality trials (e.g. serelaxin, ularitide). There is an urgent need for agents with vasodilating properties that will improve both in-hospital and post-discharge clinical outcomes, and these novel approaches may provide opportunities to address this need.

DOSING ACCURACY AND STABILITY OF ENTERAL NIFEDIPINE FOR PAEDIATRIC PATIENTS

Administration of nifedipine, a short acting calcium channel blocker used to treat acute and chronic hypertension in paediatric patients, has been associated with large variations in treatment response to individual doses.1 Currently, there is no licensed paediatric nifedipine formulation available in the UK. The aim of this project was to determine the accuracy and precision of methods used in clinical practice to prepare paediatric doses of enteral nifedipine. Method Initially, qualitative data collection and observational studies using questionnaires to identify common preparation techniques used by nursing staff were performed at one children9s hospital. Weight and content uniformity of split and crushed modified release nifedipine tablets (Nifedipressâ MR 10), and an imported 20 mg/mL drop solution (Nifedipin-ratiopharmâ Tropfen), were analysed. The accuracy and precision of three different doses of enteral nifedipine (5 mg, 1 mg and 0.5 mg) prepared using eight techniques identified in clinical practice were determined using High Performance Liquid Chromatography (HPLC). Stability over two hours of nifedipine solutions 5 mg/ml prepared from tablets and the drop solution was determined using HPLC. Results Great variation in dose preparation methods was identified. Analysis of eight preparation techniques showed that doses between 50% and 264% of the intended dose were achieved. For techniques using manipulated tablets only one technique, using split tablets dispersed in an oral syringe, produced an accurate and reproducible dose for 1 mg and 5 mg doses (97.9% [range 96–99.2%] and 94% [range 93.1–95.1%] respectively). For the 0.5 mg dose none of the techniques produced an accurate and reproducible dose. Techniques using dilution of the imported liquid showed significant deviations and variability from the intended dose, particularly when the internal drop dosing device was used. Use of syringes to measure the dose improved accuracy and precision of the dose prepared, although significant carry-over of drug was seen if fresh syringes were not used at each dilution step. Stability studies observed rapid decomposition of nifedipine when exposed to light, forming an unstable preparation within 30 minutes of tablet manipulation and within 60 minutes of liquid manipulation. Conclusion A great variation of preparation techniques is employed by nursing staff to administer fractional doses of nifedipine to infants and children using the modification of either a licensed tablet or an imported drop formulation. Our small study investigating some of these techniques showed significant inaccuracy and imprecision of the doses delivered. Preparation of paediatric doses of nifedipine require specific standardised preparation protocols to ensure accuracy and consistency of doses delivered to the patient. Further studies should be performed to inform the development of these preparation protocols to identify methods which consistently deliver accurate doses across paediatric dosing ranges until more suitable licensed paediatric treatment alternatives become available in the UK.

Prevalence, awareness, treatment and control of hypertension in elderly Chinese

We studied the prevalence, awareness, treatment and control of hypertension in an elderly Chinese population. The study subjects (age ≥60 years) were recruited from a suburban town of Shanghai from 2006 to 2008. We administered a standardized questionnaire to collect information on medical history, the use of medications and lifestyle. We measured blood pressure three times consecutively using a validated Omron 7051 oscillometric device (Kyoto, Japan) after the subjects had rested for at least 5 min in the sitting position. We defined hypertension as a blood pressure of at least 140 mm Hg systolic or 90 mm Hg diastolic or as the use of antihypertensive drugs. The 3949 participants (mean age of 68.3 years) included 2185 (55.3%) women, 182 (4.6%) obese subjects (body mass index ≥30 kg m(-2)) and 366 (9.3%) diabetic patients. The prevalence of hypertension was 59.4%. In the 2345 hypertensive patients, the awareness, treatment and control (<140/90 mm Hg) rates were 72.5%, 65.8% and 24.4%, respectively. In the 1542 treated hypertensive patients, 1196 (77.6%) used fixed-dose combinations of thiazide and reserpine or clonidine (n=1157, 75.0%) or of an angiotensin receptor blocker and hydrochlorothiazide (n=1) or free combinations (n=38, 2.5%), and 346 (22.4%) used a monotherapy of short-acting calcium channel blockers (n=217, 14.1%) or other classes of antihypertensive drugs (n=129, 8.3%). The corresponding control rates were 37.3% and 36.4%, respectively. In a stepwise logistic regression, the risk of uncontrolled hypertension was higher with older age (+10 years, odds ratio (OR) 1.19, P=0.03), female sex (OR 1.40, P=0.01), obesity (OR 2.35, P=0.0002) and heavy drinking (≥300 g per week, OR 2.18, P=0.0007). In conclusion, in elderly Chinese, the prevalence of hypertension is high. In spite of reasonably high awareness and treatment rates, the control rate remains low, most likely due to an unhealthy lifestyle and the underuse and/or underdose of antihypertensive drugs.

Acute Vasoreactivity Testing With Nicardipine in Patients With Pulmonary Arterial Hypertension

Acute vasoreactivity testing for patients with pulmonary arterial hypertension (PAH) has been reported to be useful to identify patients with sustained beneficial response to oral calcium-channel blockers (CCBs), but there is a risk of exacerbation during the testing with oral CCBs. Therefore, we developed a testing method utilizing intravenous nicardipine, a short-acting CCB, and examined the safety and usefulness of acute vasoreactivity testing with nicardipine in PAH patients. Acute vasoreactivity testing with nicardipine was performed in 65 PAH patients. Nicardipine was administered by short-time continuous infusion (1 μg·kg−1·min−1 for 5 min and 2 μg·kg−1·min−1 for 5 min) followed by bolus injection (5 μg/kg). Hemodynamic responses were continuously measured using a right heart catheter. Acute responders were defined as patients who showed a decrease in mean pulmonary artery pressure of at least 10 mmHg to an absolute level below 40 mmHg with preserved or increased cardiac output. Two acute responders and sixty-three non-acute responders were identified. There was no hemodynamic instability requiring additional inotropic agents or death during the testing. Acute responders had good responses to long-term oral CCBs. The acute vasoreactivity testing with nicardipine might be safe and useful for identifying CCB responders in PAH patients.

SCCT guidelines for performance of coronary computed tomographic angiography: A report of the Society of Cardiovascular Computed Tomography Guidelines Committee

The increasing use of coronary computed tomographicangiographic (CTA) requires the establishment of standardsmeant to ensure reliable practice methods and qualityoutcomes. The Society of Cardiovascular ComputedTomography Guidelines Committee was formed to developrecommendations for acquiring, interpreting, and reportingof these studies in a standardized fashion. Indications andcontraindications for specific services or procedures are notincludedinthescopeofthese documents.Theserecommen-dations were produced as an educational tool for practi-tioners to improve the diagnostic care of patients, in theinterest of developing systematic standards of practice forcoronary CTA based on the best available data. Because ofthe highly variable nature of individual medical cases, anapproach to scan performance that differs from these guide-lines may represent an appropriate variation based on alegitimate assessment of an individual patient’s needs.

Long-Acting Calcium Antagonists in Patients with Coronary Artery Disease: A Meta-Analysis

Background The use of calcium channel blockers (CCBs) in patients with coronary artery disease remains controversial, with reports of increased risk of myocardial infarction and all-cause mortality. Short-acting CCBs have an unfavorable hemodynamic profile. The role of long-acting CCBs in patients with coronary artery disease is unknown. Methods MEDLINE/CENTRAL/EMBASE database were searched from 1966 to August 2008 for randomized controlled trials of long-acting CCBs in patients with coronary artery disease with follow-up for at least 1 year. We extracted from the studies the baseline characteristics and 6 outcomes: all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction, stroke, angina pectoris, and heart failure. Results Of the 100 randomized controlled trials of CCBs in patients with coronary artery disease, 15 studies evaluating 47,694 patients fulfilled our inclusion criteria. When compared with the comparison group (including placebo), CCBs were not associated with an increased risk of all-cause mortality (relative risk [RR] 0.99; 95% confidence interval [CI], 0.94-1.05), cardiovascular mortality (RR 1.03; 95% CI, 0.95-1.11), nonfatal myocardial infarction (RR 0.96; 95% CI, 0.87-1.06), or heart failure (RR 0.86; 95% CI, 0.71-1.05), and with a 21% reduction in the risk of stroke (95% CI, 0.70-0.89) and 18% reduction in the risk of angina pectoris (95% CI, 0.72-0.94). When compared with placebo, CCBs resulted in a 28% reduction in the risk of heart failure (95% CI, 0.73-0.92). The results were similar for both dihydropyridines and nondihydropyridine CCBs. Conclusions In patients with coronary artery disease, long-acting CCBs (either dihydropyridines or nondihydropyridines), were associated with a reduction in the risk of stroke, angina pectoris, and heart failure, with similar outcomes for other cardiovascular events as the comparison group.

Calcium channel blocker and cardiac hypertrophy

Calcium channel blockers are commonly treated to the patients with hypertension. Epidemiological studies suggest that cardiac hypertrophy is an independent risk factor for cardiac morbidity and mortality from cardiovascular disease. Long-acting calcium channel blockers, but not short-acting calcium channel blockers had moderately beneficial and statistically indistinguishable effects on regression of LV hypertrophy. Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004) recommended to treat A II receptor blockers, ACE inhibitors or calcium channel blockers against the hypertensive patients with cardiac hypertrophy. Further studies will be necessary to elucidate the detailed molecular mechanism how calcium channel blockers reduce cardiac hypertrophy.

Long-Acting Nifedipine -- Safe, but Not Cardioprotective

Calcium-channel blockers (CCBs) relieve symptoms effectively in patients with stable angina, but short-acting CCBs have been associated with increased coronary and mortality risk in patients with coronary artery disease. Long-acting CCBs can reduce such risk in hypertensive patients, but what are their long-term effects in CAD patients? In a manufacturer-sponsored multinational …

The quality of pharmacologic care for vulnerable older patients.

Although pharmacotherapy is critical to the medical care of older patients, medications can have considerable toxicity in this age group. To date, research has focused on inappropriate prescribing and policy efforts have aimed at access, but no comprehensive measurement of the quality of pharmacologic management using explicit criteria has been performed. To evaluate the broad range of pharmacologic care processes for vulnerable older patients. Observational cohort study. 2 managed care organizations enrolling older persons. Community-dwelling high-risk patients 65 years of age or older continuously enrolled in the managed care organizations from 1 July 1998 to 31 July 1999. Patients' receipt of care as specified in 43 quality indicators covering 4 domains of pharmacologic care: 1) prescribing indicated medications; 2) avoiding inappropriate medications; 3) education, continuity, and documentation; and 4) medication monitoring. Of 475 vulnerable older patients, 372 (78%) consented to participate and had medical records that could be abstracted. The percentage of appropriate pharmacologic management ranged from 10% for documentation of risks of nonsteroidal anti-inflammatory drugs to 100% for avoiding short-acting calcium-channel blockers in patients with heart failure and avoiding beta-blockers in patients with asthma. Pass rates for quality indicators in the "avoiding inappropriate medications" domain (97% [95% CI, 96% to 98%]) were significantly higher than pass rates for "prescribing indicated medications" (50% [CI, 45% to 55%]); "education, continuity, and documentation" (81% [CI, 79% to 84%]); and "medication monitoring" (64% [CI, 60% to 68%]). Fewer than 10 patients were eligible for many of the quality indicators measured, and the generalizability of these findings in 2 managed care organizations to the general geriatric population is uncertain. Failures to prescribe indicated medications, monitor medications appropriately, document necessary information, educate patients, and maintain continuity are more common prescribing problems than use of inappropriate drugs in older patients.

Hypertension and insulin disorders.

Insulin resistance and/or compensatory hyperinsulinemia are associated with hypertension, obesity, dyslipidemia, and glucose intolerance. Insulin resistance and hyperinsulinemia are considered to increase blood pressure through sympathetic nervous system activation, renin-angiotensin system stimulation, and vascular smooth muscle cell proliferation. Leptin, magnesium ions, nitric oxide, endothelin, peroxisome proliferator-activated receptor gamma, and tumor necrosis factor-alpha also modulate blood pressure. Decreasing insulin resistance by lifestyle modification including diet, weight loss, and physical exercise has been shown to reduce blood pressure. Angiotensin-converting enzyme inhibitors have a beneficial effect on insulin resistance. On the other hand, the angiotensin II antagonist, losartan, does not affect insulin sensitivity. The selective alpha1-blockers have a favorable metabolic profile producing increases in insulin sensitivity. A short-acting type calcium channel blocker seems to decrease insulin sensitivity. On the other hand, long-acting type calcium channel blockers improve insulin sensitivity. Thiazide diuretics and most of the beta-blockers decrease insulin sensitivity. Vasodilatory beta-blockers have been reported to improve insulin sensitivity. Use of low-dose diuretics avoids the adverse effects seen with conventional doses.

Evaluation of the safety of short-acting nifedipine in children with hypertension.

Concerns regarding the safety of nifedipine emerged in 1995 with the report of an increased risk of myocardial infarction associated with adult patients receiving short-acting calcium channel blockers. There have been few case reports of adverse events in children. The purpose of this study is to investigate the effect on blood pressure (BP) and the incidence of adverse events associated with nifedipine in our pediatric population. We conducted a retrospective chart review of pediatric patients who received nifedipine. We recorded the dose administered, all BP measurements and all adverse events reported within six hours of a nifedipine dose regardless of the likelihood that those events were related to the nifedipine dose. 1,746 doses of nifedipine in 166 pediatric patients were reviewed. Systolic BP decreased by a mean of 17% and a maximum of 63%. Diastolic BP decreased by a mean of 28% and a maximum of 89%. Adverse events included: a) change in neurologic status, six cases; b) hypotension, two cases; c) oxygen desaturation, 16 cases. Neurologic events occurred in 33% of patients with acute CNS injury and 3.6% of all patients. Short-acting nifedipine is an important and effective oral antihypertensive agent which can be safely used for the treatment of hypertensive emergencies in children. It should be used with caution in children with acute CNS injury.

Short-Acting Nifedipine Is Safe in Most Children

The short-acting calcium-channel blocker nifedipine has been considered a risky antihypertensive agent in adults following reports of myocardial infarctions in some patients. Nifedipine is used frequently in children with hypertension, yet its safety in this population has not been carefully evaluated. These investigators reviewed …

Antihypertensive drug prescription trends at the primary health care centres in Bahrain.

To determine the antihypertensive drug prescribing pattern by primary care physicians in patients with uncomplicated essential hypertension; to identify whether such pattern of prescription is appropriate and in accordance with international guidelines for pharmacotherapy of hypertension; and to estimate the impact of such prescriptions on cost of treatment. A prescription-based survey among patients with uncomplicated essential hypertension was conducted in seven out of a total of 18 health centres in Bahrain. The relevant data for our study was collected using cards, designed for chronically-ill patients. A total of 1019 male and 1395 female (62.9%) out of 3838 of the study population were on monotherapy, whereas 596 male and 828 female (37.1%) were on antihypertensive combination therapy. Among the monotherapy category, the various antihypertensive drugs used were as follows: beta-blockers (58.8%), angiotensin converting enzyme (ACE) inhibitors (14.2%), calcium channel blockers (11.1%), diuretics (8.1%) and alpha-methyldopa (7.0%). With respect to overall utilization pattern, beta-blockers were the most frequently prescribed (65.5%), diuretics ranked second (27.4%), followed by ACE inhibitors (20.6%), calcium channel blockers (19.9%) and alpha-methyldopa (8.5%). Within each class of antihypertensives used, the most frequently used individual agents were as follows: (a) among beta-blockers 97.7% used atenolol; (b) among the diuretics, indapamide (35.4%), hydrochlorothiazide (HCTZ) (32.7%), HCTZ in combination with triamterene (25.7%), and chlorthalidone (4.6%); (c) among the ACE inhibitors, captopril (44.9%), enalapril (29.7%), and lisinopril (19.0%); (d) among the calcium channel blockers, nifedipine (98.2%). Significant age- and gender-related differences in prescribing patterns were seen. Short-acting nifedipine monotherapy was inappropriately prescribed in a significant number of patients above the age of 50 years. ACE inhibitors accounted for approximately two-thirds of the total antihypertensive drug expenditure, although these drugs represent only one-fifth of overall antihypertensives used. There is a trend towards excessive use of expensive thiazide-like diuretics such as indapamide which seems to be unjustifiable practice, particularly in a study population free from diabetic hypertensive patients. The general pattern of antihypertensive utilization appears to be in accordance with the guidelines of WHO and the Joint National Committee issued in the 1990s. The trends of prescribing of antihypertensives were in favour of conventional ones such as the beta blockers and diuretics, and the introduction of newer classes of antihypertensives had a generally minimal impact on the prescribing profile. Almost two-thirds of the patients were treated with monotherapy. A disproportionately large percentage of antihypertensive drug cost was due to overt use of ACE inhibitors, and indapamide, instead of thiazide diuretics. The use of short-acting calcium channel blockers especially in the elderly is unjustifiable.