A computerized intervention to decrease the use of calcium channel blockers in hypertension

Objective

To determine whether a computer-assisted reminder would alter prescribing habits for the treatment of hypertension in accordance with current clinical guidelines in a general internal medicine clinic.

Design

A randomized trial.

Setting

The General Internal Medicine Clinic of the Veterans Affairs Puget Sound Health Care System, Seattle Division.

Patients/Participants

Clinic providers were randomized to a control group (n=35) or intervention group (n=36). We targeted the providers of patients being treated for hypertension with calcium channel blockers, a class of drug not recommended for initial therapy.

Intervention

An automated computer query identified eligible patients and their providers. A guideline reminder was placed in the charts of patients of intervention providers; the charts of patients of control providers received no reminder.

Measurements and main results

During the 5-month study period, 346 patients were seen by the 36 primary care providers (staff physicians, nurse practitioners, residents, and fellows) in the intervention group, and 373 patients were seen by the 35 providers in the control group. Intervention providers changed 39 patients (11.3%) to other medications during the study period, compared with 1 patient (<1.0%) of control providers (p<.0001). For patients whose therapy was unchanged, providers noted angina in 23.1%, indications other than those for hypertension in 9.5%, intolerable adverse effects with first-line therapy in 13.9%, and inadequte control with first-line therapy in 13.9%. Of those patients without provider-indicated contraindications, 23.6% were switched from calcium channel blockers to first-line agents during the intervention period.

Conclusions

The use of a computerized, clinic-based intervention increased compliance with guidelines in the treatment of primary hypertension in general, and decreased the use of calcium channel blockers for the treatment of hypertension in particular.     

不同药物致神经阻滞剂恶性综合征的护理

目的:探讨不同抗精神病药物致神经阻滞剂恶性综合征的护理方法。方法:采用Levenson的恶性综合征诊断标准,对44例精神病患者的临床特征进行回顾性分析,在早期识别和及时停药后进行支持性护理。结果:44例患者在使用高效价抗精神病药物时出现以发热、肌张力增高、意识障碍、血清肌酸磷酸激酶升高以及植物神经功能紊乱等明显的临床表现,在治疗1~4周内,临床症状逐渐消失,病情得到有效控制和缓解。结论:要求护理人员了解患者用药情况,尤其在医师换药、调药的过程中应重点监护,加强患者服药后的观察。早期发现异常情况及时停药并给予支持性护理,避免造成严重不良反应的发生。     

Antiplatelet Effect of Clopidogrel Can Be Reduced by Calcium-Channel Blockers

Purpose

Clopidogrel is metabolized by the hepatic cytochrome P450 (CYP) system into its active thiol metabolite. CYP3A4 is involved in the metabolism of both clopidogrel and dihydropyridine calcium channel blockers (CCBs). A few reports have suggested an inhibitory interaction between CCBs and clopidogrel. Accordingly, the aim of this study was to determine the effect of CCBs on the antiplatelet activity of clopidogrel by serial P2Y12 reaction unit (PRU) measurements.

Materials and Methods

We assessed changes in antiplatelet activity in patients receiving both clopidogrel and CCBs for at least 2 months prior to enrollment in the study. The antiplatelet activity of clopidogrel was measured by VerifyNow P2Y12 assay in the same patient while medicated with CCBs and at 8 weeks after discontinuation of CCBs. After discontinuation of the CCBs, angiotensin receptor blockers were newly administered to the patients or dosed up for control of blood pressure.

Results

Thirty patients finished this study. PRU significantly decreased after discontinuation of CCBs (238.1±74.1 vs. 215.0±69.3; p=0.001). Of the 11 patients with high post-treatment platelet reactivity to clopidogrel (PRU≥275), PRU decreased in nine patients, decreasing below the cut-off value in seven of these nine patients after 8 weeks. Decrease in PRU was not related to CYP2C19 genotype.

Conclusion

CCBs inhibit the antiplatelet activity of clopidogrel.     

Role of antispasmodics in the treatment of irritable bowel syndrome

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_1A 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.     

Influence of autoantibodies against AT1 receptor and AGTR1 polymorphisms on candesartan-based antihypertensive regimen: Results from the Study of Optimal Treatment in Hypertensive Patients with Anti-AT1-Receptor Autoantibodies trial

The autoantibodies against angiotensin AT₁ receptors (AT₁-AAs) in patients with essential hypertension exhibited an agonistic action like angiotensin II and maintained high blood pressure (BP). Angiotensin II receptor gene (AGTR1) polymorphisms were associated with BP response to RAS inhibition in the hypertensive population. Furthermore, the BP response to AT₁ receptor blockers varied significantly among individuals with hypertension. We hypothesized that the polymorphisms of the AGTR1 and AT₁-AAs might affect antihypertensive response to AT₁ receptor blockers based in patients with primary hypertension. Patients who received a candesartan-based regimen came from the SOT-AT₁ study (Study of Optimal Treatment in Hypertensive Patients with Anti-AT₁-Receptor Autoantibodies). The established enzyme-labeled immunosorbent assay was used to detect AT₁-AAs in the sera of the patients. Genotype 3 single nucleotide polymorphisms in AGTR1 gene was used by DNA sequencing. The correlations among AT₁-AAs, AGTR1 gene polymorphisms or haplotypes, and the antihypertensive effect candesartan-based were analyzed using SPSS. The percentage of systolic BP reduction that was candesartan-based was greater in AT₁-AA positive groups than in AT₁-AA negative ones (21 ± 8 vs. 18 ± 9; P = .001). Meanwhile, systolic BP reduction that was candesartan-based was more significant in the group of rs5186 AC genotypes than AA homozygotes after adjusting for other confounding factors (37.55 ± 13.7 vs. 32.47 ± 17.27 mm Hg; adjusted P = .028). Furthermore, haplotypes (GCC) and (AAC) had impacts on the antihypertensive effect of candesartan therapy. The AT₁-AAs, AGTR1 gene polymorphisms and haplotypes solely or jointly have influences on candesartan-based antihypertensive response in patients with primary hypertension.     

全国多中心564 711例高血压患者RAS抑制剂药物利用分析

目的：分析2017年全国8个城市口服RAS抑制剂的高血压患者特征和药品使用特征,为临床合理用药提供参考。方法：基于2017年《医院处方分析项目》随机抽取的处方数据,采用WHO推荐的药物利用分析方法,对ACEI和ARBs使用情况进行分析。结果：共抽得8个城市101家医院的564 711例的口服ACEI和ARBs类降血压药高血压患者。北京地区患者最多,占26.20%。男女比例为1.17。中位年龄64岁。老年患者占比49.90%。患者主要于门诊购药,占89.10%。处方科室以内科为主,占89.40%。303例患者存在潜在超适应证用药风险。ARBs处方数量占78.71%,处方金额占83.05%。处方数量和处方金额最大的3种药品依次为：缬沙坦、厄贝沙坦和氯沙坦;其PDD/DDD值均大于1：缬沙坦（1.32±0.53）、厄贝沙坦（1.33±0.87）和氯沙坦（1.70±0.65）;合并肾病、肝病及同时合并肾病和肝病患者的PDD/DDD值高于患者平均水平。结论：ARBs是临床更常用的RAS抑制剂,特别是缬沙坦、厄贝沙坦和氯沙坦;仍须规范ARBs和ACEIs类药物的适应证,且重视高血压合并肾病、肝病患者的药物剂量管理。     

Recent progress in the treatment of cardiovascular disease using olmesartan

Angiotensin II (Ang II) evokes inflammatory responses and plays a central role in atherosclerosis mediated by Ang II type 1 (AT₁) receptor. AT₁ receptor blockers (ARBs) prevent the diverse effects of Ang II. Unique molecule-specific, or off-target effects of ARBs are due to their slightly different structures, although all ARBs have common, or class, effects. In nonsignificant coronary stenotic lesions, it is important that we use aggressive medical treatments using ARBs in addition to statins and oral hypoglycemic agents, to induce the regression and stabilization of coronary plaque. This review focuses on current evidence regarding the molecule-specific effects of ARB olmesartan to prevent the increase in coronary atheroma volume.