Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension

Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related contraindications.With recent advances in precision medicine,precise drug treatment provides better treatment efficacy.Data sources:Literature search was conducted in PubMed,MEDLINE and Web of Science for relevant articles published up to May 2022.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://www.chictr.org.cn/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs.According to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and others.All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.Conclusions:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

Clinical and experimental study of effect of Raondix Salviae Militiorhiza and other blood-activating and stasis-eliminating Chinese herbson hemodynamics of portal hypertension

ＩＮＴＲＯＤＵＣＴＩＯＮＴｈｅｒｅｈａｓｂｅｅｎｎｏｌｏｎｇｌａｓｔｉｎｇａｎｄｓｉｄｅｅｆｆｅｃｔｓｆｒｅｅｄｒｕｇｓｔｏｌｏｗｅｒｔｈｅｐｏｒｔａｌｈｙｐｅｒｔｅｎｓｉｏｎｉｎｐａｔｉｅｎｔｓｗｉｔｈｌｉｖｅｒｃｉｒｒｈｏｓｉｓｓｏｆａｒ．Ｔｈ...

The Principle and Technique of Using Chinese Drugs in the Treatment of Hypertension

There are three principles which need to be grasped in the clinical use of Chinese drugs in the treatment of hypertension: Combination of syndrome differentiation in TCM with disease-differentiation in western medicine; combination of the theory of TCM with the results of modern pharmacological researches; and combination of symptom improving, blood-pressure reducing with complications preventing measures. Use of Chinese Drugs Based on the Western Medical Stages of Hypertension Patients should be classified for clinical stages of hypertension according to western medical criteria before TCM treatment program is made. For instance, in hypertension patients, apart from high blood pressure, there may also be other symptoms such as headache, dizziness, distending sensation in the head, stiff sensation in the neck, dim eyesight, tinnitus, poor memory, inability to concentrate the mind, insomnia, disphoria, general weakness, numbness of the four limbs, and palpitation. In some patients, these symptoms may not always be directly related to hypertension. In these cases, treatment for reducing blood pressure may not be taken into consideration, and the treatment based on general differentiation of the symptoms may serve the purpose. Only after the differential use of Chinese drugs shows no obvious improvement of the symptoms and high blood pressure, the treatment will be aimed at hypertension per se. When Chinese drugs alone can not reduce blood pressure, western medicine is often used in combination to reduce blood pressure, blood lipids and uric acid, correct water-electrolyte metabolism, and improve blood rheology. The combined Chinese and western medical treatment can make up each other's deficiencies so as to give better therapeutic effects.

Short-Term Drug-Drug Interaction between Sildenafil and Bosentan under Long-Term Use in Patients with Pulmonary Arterial Hypertension

Sildenafil and bosentan are often co-administered for pulmonary arterial hypertension (PAH) treatment. The plasma concentration of sildenafil can be decreased by half if co-administered with bosentan. Many patients take these agents simultaneously in the morning and the evening. The aim of this study was to examine the pharmacokinetics of sildenafil which was interfered with bosentan administration to ascertain whether these agents should be given concomitantly or separately. A two-way crossover study was conducted in 6 PAH patients with combination therapy of sildenafil and bosentan. Participants underwent the sequence of treatment phases: phase S (sildenafil administered 3 h before bosen-tan);phase B (bosentan administered 3 h before sildenafil);and phase C (administered concomitantly). Blood samples were collected on the last day of each phase. There was no significant difference in maximum plasma concentration or area under the plasma concentration-time curve (AUC0-8) between phase C and phase S (95.5 ± 24.8 vs. 72.9 ± 40.9 (p = 0.07), 209.7 ± 81.8 vs. 180.2 ± 126.4 (p = 0.24), respectively) or between phases C and B (87.8 ± 42.0 vs. 99.6 ± 33.9 (p = 0.59), 197.2 ± 88.2 vs. 240.7 ± 121.8 (p = 0.19), respectively) (ng/mL, mean ± standard deviation). Large intra-and inter-individual variability in sildenafil concentration was noted. The timing of administration of sildenafil and bosentan does not significantly influence the plasma concentration of sildenafil. Physicians do not need to be overly concerned about the timing of administration of these drugs to maximize the sildenafil concentration.

Analysis of Drug Use in Outpatients with Hypertension Based on Real-World Study

Objective To explore the situation and trend of drug use in the treatment of hypertension in outpatient department of a hospital,and to provide reference for clinical rational drug use.Methods The data of 833 outpatients with hypertension in a hospital from July to December in 2020 were retrospectively analyzed.Results and Conclusion Among the 833 cases,calcium channel blocker(CCB)was the most frequently used drug(38.54%),followed by angiotensin receptor blocker(ARB)(13.81%),β-receptor blockers(β-RB)(10.44%),angiotensin-converting enzyme inhibitor(ACEI)(5.52%),and diuretics(0.72%).The combination rate was 37.09%(including single-pill combination,SPC).The highest rate was the combination of two drugs(28.21%),followed by the combination of three drugs(8.64%)and four drugs(1.20%).The DDDs and DDC of SPC were the highest among the six kinds of drugs.The use of antihypertensive drugs in outpatient department of the hospital is in line with the medication guidelines,but a small number of drugs are used irrationally,which needs further supervision and management.

Vitamin D and hypertension:Is there any significant relation?

Dear Editor,Around a billion individuals worldwide have hypertension.Of these,95%have essential hypertension,a type of undiagnosed hypertension.1 The regulation of blood pressure(BP)involves numerous signaling pathways.Among them,the Renin Angiotensin System is well known.All these pathways are regulated by modulation of renal salt handling and tone of vascular smooth muscle(VSM)tissue.Any of these mechanisms can become faulty and alter the resistance arteries’VSM tone,which can elevate BP.However,since the exact origin of PH and its pathophysiology are unknown,less effective,and generic treatments are used.2 The fact that more than 50%of hypertension patients in the USA do not have their BP under good control serves as an illustration of this.Antihypertensive treatment resistance affects an additional 5 million people and is defined as the inability to regulate BP despite the use of at least three antihypertensive drugs in combination.

PPIs are not associated with a lower incidence of portal-hypertension-related bleeding in cirrhosis

AIM:To determine if proton pump inhibitor use in cirrhotic patients with endoscopic findings of portal hypertension is associated with a lower frequency of gastrointestinal bleeding.METHODS:Patients with cirrhosis and endoscopic findings related to portal hypertension,receiving or not receiving proton pump inhibitor (PPI) therapy,were included retrospectively.We assigned patients to two groups:group 1 patients underwent PPI therapy and group 2 patients did not undergo PPI therapy.RESULTS:One hundred and five patients with a median age of 58 (26-87) years were included,57 (54.3%) of which were women.Esophageal varices were found in 82 (78%) patients,portal hypertensive gastropathy in 72 (68.6%) patients,and gastric varices in 15 (14.3%) patients.PPI therapy was used in 45.5% of patients (n=48).Seventeen (16.1%) patients presented with upper gastrointestinal bleeding;in 14/17 (82.3%) patients,bleeding was secondary to esophageal varices,and in 3/17 patients bleeding was attributed to portal hypertensive gastropathy.Bleeding related to portal hypertension according to PPI therapy occurred in 18.7% (n=9) of group 1 and in 14% (n=8) of group 2 (odds ratio:0.83,95% confidence interval:0.5-1.3,P=0.51).CONCLUSION:Portal hypertension bleeding is not associated with PPI use.These findings do not support the prescription of PPIs in patients with chronic liver disease with no currently accepted indication.

Antihypertensive drugs and glucose metabolism

Hypertension plays a major role in the development and progression of micro-and macrovascular disease.Moreover,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance.As a result the need for a comprehensive management of hypertensive patients is critical.However,the various antihypertensive drug categories have different effects on glucose metabolism.Indeed,angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis.Calcium channel blockers(CCBs)have an overall neutral effect on glucose metabolism.However,some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis.On the other hand,diuretics andβ-blockers have an overall disadvantageous effect on glucose metabolism.Of note,carvedilol as well as nebivolol seem to differentiate themselves from the rest of theβ-blockers class,being more attractive options regarding their effect on glucose homeostasis.The adverse effects of some blood pressure lowering drugs on glucose metabolism may,to an extent,compromise their cardiovascular protective role.As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment,especially in patients which are at high risk for developing diabetes.

Non-interventional management of resistant hypertension

Hypertension is one of the most popular fields of re-search in modern medicine due to its high prevalence and its major impact on cardiovascular risk and con-sequently on global health. Indeed, about one third of individuals worldwide has hypertension and is under increased long-term risk of myocardial infarction, stroke or cardiovascular death. On the other hand, resistant hypertension, the "uncontrollable" part of arterial hy-pertension despite appropriate therapy, comprises a much greater menace since long-standing, high levels of blood pressure along with concomitant debilitating entities such as chronic kidney disease and diabetes mellitus create a prominent high cardiovascular risk milieu. However, despite the alarming consequences, resistant hypertension and its effective management still have not received proper scientific attention. As-pects like the exact prevalence and prognosis are yet tobe clarified. In an effort to manage patients with resis-tant hypertension appropriately, clinical doctors are still racking their brains in order to find the best therapeutic algorithm and surmount the substantial difficulties in controlling this clinical entity. This review aims to shed light on the effective management of resistant hyper-tension and provide practical recommendations for cli-nicians dealing with such patients.

An Analysis of the Effects of Blood Pressure and Antihypertensive Drugs on Heart Disease

Background: The American College of Cardiology (ACC), American Heart Association (AHA) and other organizations announced a new hypertension guideline (2017 ACA/AHA Guideline) in November 2017. However, other organizations such as the European Society of Cardiology and European Society of Hypertension maintained their diagnostic thresholds. It is necessary to evaluate the effects of blood pressure (BP) and antihypertensive drugs on the probability of having heart disease (HD). Data and Methods: The effects of BP, antihypertensive drugs and other factors on the probability of undergoing HD treatment were analyzed. We used a dataset containing 83,287 medical check-up and treatment records obtained from 35,504 individuals in 5 fiscal years. The probit models were used in the study. Considering the possibility of endogeneity problems, different types of models were used. Results: We could not find evidence that a higher systolic BP increased the probability of undergoing HD treatment. However, diastolic BP increased the probability in most of the models. Taking antihypertensive drugs also increased the probability of undergoing HD treatment. Diabetes was another important risk factor. Conclusion: The results of this study did not support the new 2017 ACC/AHA Guideline. It is necessary to choose proper drugs and methods to reduce the risks of side effects. Limitations: The dataset was observatory, the data were obtained from just one medical society, and sample selection bias might exist.

Treatment and exploration of integrated traditional Chinese and Western medicine for hypertension

At present,hypertension has the phenomenon of increasing incidence and advancing age of onset.It can be complicated by various cardiovascular and cerebrovascular diseases and has a poor prognosis.Its pathogenesis is related to vascular endothelial injury and its mediated inflammation,blood flow,changes in mechanical force,and vascular remodeling.Vascular biomechanical changes are the early and critical pathogenic factors of this disease.Mechanosensitive ion channels and their proteins affect the pathological process of hypertension by improving cell membrane tension,regulating vascular tension and contractility,and participating in vascular biomechanical changes such as vascular remodeling.However,the drugs currently used to treat high blood pressure only slow the progression of the disease.Therefore,it is necessary to find and study effective medicines to treat hypertension.At present,modern medical methods do not have targeted treatment measures.Traditional Chinese medicine plays a significant role in treating this disease based on the principle of“treatment according to the syndrome”.Traditional Chinese medicine regulates the mechanical force of blood flow and maintains blood pressure balance in patients with hypertension.There are many kinds of Chinese patent medicines used to treat hypertension with good curative effects.

Management of erectile dysfunction in hypertension:Tips and tricks

Arterial hypertension is a major risk factor for cardiovascular disease and affects approximately one third of the adult population worldwide. The vascular origin of erectile dysfunction is now widely accepted in the vast majority of cases. Erectile dysfunction is frequently encountered in patients with arterial hypertension and greatly affects their quality of life of hypertensive patients and their sexual partners. Therefore, the management of erectile dysfunction in hypertensive patients is of paramount importance. Unfortunately, erectile dysfunction remains under-reported, under-recognized, and under-treated in hypertensive patients, mainly due to the lack of familiarity with this clinical entity by treating physicians. This review aims to discuss the more frequent problems in the management of hypertensive patients with erectile dysfunction and propose ways to overcome these problems in everyday clinical practice.

Screening of Biomarkers for Hypertension Susceptibility in Pregnancy

Objective:To study the differential lncRNA/mRNA expression profiles of placental tissues in patients with gestational hypertension,analyze their possible mechanisms of action,and explore their target genes and small molecule drug-related lncRNAs.Methods:Three patients with gestational hypertension who were treated in our hospital from May 2018 to May 2019 were selected as the research subjects and three healthy pregnant women who underwent a prenatal examination in the same hospital were selected as the control group.The placental tissues were taken from the patients.RNA-sequencing was performed to construct lncRNA/mRNA differential expression profiles;screening differentially expressed lncRNAs were used to predict target genes,and GO and KEGG enrichment analysis predicted the biological functions of target genes and the enriched signal pathways,respectively.Protein-protein interaction network,lncRNA-miRNAmRNA network,and differentially expressed genesmall molecule drug association networks were constructed.Results:RNA-seq analysis revealed 19 differentially expressed lncRNA(4 up-regulated;15 down-regulated)(P<0.05).Moreover,423 differentially expressed genes(DEGs)(84 up-regulated;339 downregulated)(P<0.05).GO and KEGG enrichment analysis found that gestational hypertension is mainly related to endothelial cell damage,inflammatory response,abnormal immune regulation,and abnormal trophoblast invasion.The PPI network and lncRNA-miRNA-mRNA network were constructed.Differentially expressed gene-drug small molecule prediction results found 19 pairs of differentially gene-small drug relationship pairs,mainly including antibody,inhibitor et al.Conclusion:Differently expressed lncRNAs in the placenta of patients with gestational hypertension can participate in the regulation of multiple biological functional levelrelated signal pathways through targeted regulation of their target genes,and play an important role in the occurrence and development of gestational hypertension.The predicted small molecule drug can be used as a reference for clinical treatment.

Long-term outcomes after catheter-based renal artery denervation for resistant hypertension:final follow-up of the randomised SYMPLICITY HTN-3 Trial

Background:The SYMPLICITY HTN-3(Renal Denervation in Patients With Uncontrolled Hypertension)trial showed the safety but not efficacy of the Symplicity system(Medtronic,Santa Rosa,CA,USA)at 6 months follow-up in patients with treatment-resistant hypertension.This final report presents the 36-month follow-up results.Methods:SYMPLICITY HTN-3 was a single-blind,multicentre,sham-controlled,randomised clinical trial,done in 88 centres in the USA.Adults aged 18-80 years,with treatment-resistant hypertension on stable,maximally tolerated doses of three or more drugs including a diuretic,who had a seated office systolic blood pressure of 160 mm Hg or more and 24 h ambulatory systolic blood pressure of 135 mm Hg or more were randomly assigned(2:1)to receive renal artery denervation using the single electrode(Flex)catheter or a sham control.

Effects of anti-hypertensive drugs on esophageal body contraction

AIM:To clarify the effects of anti-hypertensive drugs on esophageal contraction and determine their possi-ble relationship with gastro-esophageal reflux disease.METHODS:Thirteen healthy male volunteers were enrolled. Esophageal body peristaltic contractions and lower esophageal sphincter (LES) pressure were measured using high resolution manometry. All subjects were randomly examined on four separate occasions following administrations of nifedipine,losartan,and atenolol,as well as without any drug administration.RESULTS:Peristaltic contractions by the esophageal body were separated into three segments by two troughs. The peak peristaltic pressures in the mid and lower segments of the esophageal body under atenolol administration were signifi cantly higher than those without medication in a supine position. On the other hand,peristaltic pressures under nifedipine administration were lower than those observed without drug ad-ministration. Losartan did not change esophageal body peristalsis. Atenolol elevated LES pressure and slowed peristaltic wave transition,while the effects of nifedip-ine were the opposite. CONCLUSION:Among the anti-hypertensive drugs tested,atenolol enhanced esophageal motor activity,which was in contrast to nifedipine.

The clinical analysis of secondary hypertension patients

Objective To analyze the situation of secondary hypertension caused by different etiology and its treatment status so as to improve its treatment.Methods Totally 580 patients with secondary hypertension selected with strict criteria were divided into 4 groups in accordance with the etiology.The data were dealt with SPSS 13.0.We analyzed the sex,age,systolic pressure,diastolic pressure and positive incidence of family history of all the secondary hypertension patients in each group,and compared their usage of every unilateral preparation.Results The average age of renal parenchymal disease was more advanced than that of adrenal disease and other diseases.The administration of diuretics and angiotensin-converting enzyme inhibitor(ACEI)in renal parenchymal disease group,αβ receptor blocking agents and calcium antagonists in kidney-artery disease group,α antagonists in adrenal disease and compound antihypertensive agents in other diseases groups all affected advantage of the ratio.Conclusion Diuretics and ACEI are suitable for hypertension caused by renal parenchymal disease.αβ receptor blocking agents and calcium antagonists are suitable for that caused by kidney artery disease,but α receptor blocking agents are suitable for that caused by adrenal disease.

Thermal Decomposition of Some Cardiovascular Drugs (Telmisartane, Cilazapril and Terazosin HCL)

Thermal analysis of some antihypertensive drugs, Telmisartan, Cilazapril and Terazosin HCL was achieved. Thermogravimetry, derivative thermogravimetry and differential thermal analysis were used through the work. Thermogravimetric parameters such as activation energy, frequency factor and reaction order were calculated. The results show the stability value decrease in the order Telmisartan > Cilazapril > Terazosin. This method can be used in the quality control of pharmaceutical compounds because it is simple, fast and cheap.

A Clinical Study on Haunglian Fire-Purging Mixture In Treatment of 46 Cases of Primary Hypertension

In order to observe the therapeutic effects of Huanglian Fire-Purging Mixture (黄连清降合剂) on primary hypertension, 46 cases of primary hypertension in the treatment group were treated with Huanglian Fire-Purging Mixture to clear away heat from the liver, relieve mental stress, purge fire and remove toxin;and the other 26 cases of primary hypertension in the control group were treated with Niuhuang Bolus for Lowering Blood Pressure (牛黄降压丸). The effect in the treatment group was obviously superior to that in the control group (P＜0.05). The Huanglian Fire-Purging Mixture shows noticeable effects 3-6 hours after medication. The mixture can improve the clinical symptoms, the left ventricular diastolic function and myocardial ischemia, correct dyslipoproteinemia and dysglycemia, and reduce blood viscosity. And it is safe and with no obvious adverse reactions.