EFFICACY AND SAFETY OF AZILSARTAN IN PATIENTS OF HYPERTENSION WITH DIABETES IN GWALIOR DISTRICT.

Background: Angiotensin receptor blockers are well established drugs for the treatment of hypertension with or without renal disease. Azilsartan is a new angiotensin receptor blocker being used in the treatment of hypertension. Present study is done to evaluate efficacy and safety of azilsartan in patients of hypertension with diabetes mellitus in Gwalior district. Methods: The study was conducted in department of pharmacology, Gajra raja medical college, Gwalior Madhya Pradesh during February 2018 to march 2019. It is a longitudinal, prospective, randomized study and total 90 patients of hypertension with diabetes were enrolled out of which 83 patients completed study with a follow up of 1 year period and were divided equally into two groups. Group I received Azilsartan 40- 80 mg once daily and group II received another drug once daily for 12 weeks. Baseline Systolic blood Pressure and diastolic blood pressure were recorded at the start and then at 4th, 8thand 12th weeks after therapy. Fasting and post prandial blood sugar, HDL, LDL-C , total cholesterol values were recorded at start and after 12 weeks of therapy. All the patients were screened for any adverse drug reactions on each visit. Result: Azilsartan effectively lowered the levels of systolic and diastolic blood pressure from baseline (p=0.00001) confirming the antihypertensive efficacy also there was overall significant improvement in HDL values from baseline (p=0.000) and also significant improvement was shown in LDL Total cholesterol levels from baseline (p =0.005). There was significant improvement in FBS and PPBS from baseline (p value 0.00). Conclusion: Azilsartan effectively lowered the levels of systolic and diastolic blood pressure in patients of hypertension with diabetes and the difference was significant. Azilsartan showed overall improvement in HDL, LDL, TC values with significant difference in hypertensive with diabetes patients.

An observational comparative study of different doses of azilsartan and with chlorthalidone combination in moderate hypertension

Background: High blood pressure (BP) is one of the significant non-communicable diseases that are of high prevalence in our country. Hypertension (HTN) is responsible cause of 57% of stroke and 24% of coronary heart disease deaths in India. Eight classes of medications are currently used in the treatment of hypertension. Azilsartan medoxomil is a newly added FDA approved drug to the ARB class of antihypertensive agents. azilsartan and chlorthalidone combination is also got the FDA approval. There is limited study in between these two groups regarding efficacy especially in rural Bengal.Methods: A prospective observational study was done in medicine OPD of Bankura Sammilani Medical College for twelve weeks with two groups that are azilsartan (80mg) and fixed dose combination of azilsartan (40mg) plus chlorthalidone (12.5mg) in the age group of 18 to 55years of moderate hypertensive patients. Change of heart rate was assessed as safety parameter.Results: It was found that both the group of drugs are very much effective in lowering blood pressure constantly in respect of both systolic and diastolic BP but azilsartan monotherapy in high dose reduce systolic blood pressure slightly high. Significant change of heart rate was not seen with both the groups.Conclusions: Both the group was effective as well as safe in hypertensive patients.

Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of azilsartan

Tremendous efforts have been devoted to the enhancement of drug solubility using nanotechnologies, but few of them are capable to produce drug particles with sizes less than a few nanometers. This challenge has been addressed here by using biocompatible versatile -cyclodextrin (-CD) metal-organic framework (CD-MOF) large molecular cages in which azilsartan (AZL) was successfully confined producing clusters in the nanometer range. This strategy allowed to improve the bioavailability of AZL in Sprague-Dawley rats by 9.7-fold after loading into CD-MOF. The apparent solubility of AZL/CD-MOF was enhanced by 340-fold when compared to the pure drug. Based on molecular modeling, a dual molecular mechanism of nanoclusterization and complexation of AZL inside the CD-MOF cages was proposed, which was confirmed by small angle X-ray scattering (SAXS) and synchrotron radiation-Fourier transform infrared spectroscopy (SR-FTIR) techniques. In a typical cage-like unit of CD-MOF, three molecules of AZL were included by the -CD pairs, whilst other three AZL molecules formed a nanocluster inside the 1.7 nm sized cavity surrounded by six -CDs. This research demonstrates a dual molecular mechanism of complexation and nanoclusterization in CD-MOF leading to significant improvement in the bioavailability of insoluble drugs.

Salt sensitivity and its implication in clinical practice

Hypertension (HTN) is a complex multi-factorial disease and is considered one of the foremost modifiable risk factors for stroke, heart failure, ischemic heart disease and renal dysfunction. Over the past century, salt and its linkage to HTN and cardiovascular (CV) mortality has been the subject of intense scientific scrutiny. There is now consensus that different individuals have different susceptibilities to blood pressure (BP)-raising effects of salt and this susceptiveness is called as salt sensitivity. Several renal and extra-renal mechanisms are believed to play a role. Blunted activity of the renin–angiotensin–aldosterone system (RAAS), adrenal Rac1-MR-Sgk1-NCC/ENaC pathway, renal SNS-GR-WNK4-NCC pathway, defect of membrane ion transportation, inflammation and abnormalities of Na+/Ca2+ exchange have all been implicated as pathophysiological basis for salt sensitive HTN. While salt restriction is definitely beneficial recent observation suggests that treatment with Azilsartan may improve salt sensitivity by selectively reducing renal proximal tubule Na+/H+ exchange. This encourages the future potential benefits of recognizing and therapeutically addressing the salt sensitive phenotype in humans.

Comparative study to evaluate efficacy and safety of azilsartan and telmisartan in patients with grade I-II essential hypertension

Background: Objectives of the study was to study the effect of Azilsartan 40mg once daily versus Telmisartan 40mg once daily in patients with Grade I-II essential hypertension.Methods: A prospective study was conducted at MGM Medical college and Hospital which included 80 patients in each group with Grade I–II essential hypertension. The sex, age, presenting illness, and family history of the patients were recorded. Investigations such as blood sugar, urine analysis, kidney function test, lipid profile, and ECG were performed before starting the treatment. Any adverse effects during the treatment were noted. Blood pressure was recorded at baseline and during follow-up. One group received Azilsartan 40mg once daily and another group Telmisartan 40mg once daily. Patients were followed-up every week for 5 weeks.Results: Patients receiving Azilsartan 40mg and Telmisartan 40mg showed a significant fall (P <0.05) in systolic (SBP) at the end of fifth week, when compared to baseline and diastolic blood pressure (DBP) significant fall at fourth and fifth week. The difference in fall in SBP and DBP was insignificant between the groups, after first, second and third week (P >0.05). Adverse effects such as Nasopharyngitis, Upper respiratory tract inflammation, Gastroenteritis, headache, dizziness, and fatigue were reported with both drugs.Conclusions: Reduction of blood pressure with Azilsartan and Telmisartan was similar, but fall in blood pressure from baseline was highly significant in both groups.

AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits

BACKGROUND AND OBJECTIVES: Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats. MATERIALS AND METHODS: HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff's perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts. RESULTS: Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N⁵-(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS). CONCLUSION: Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC.

Inhibitory Effect and Mechanism of Azilsartan Medoxomil on Carotid Artery Intimal Hyperplasia in Balloon-Injured Rats / 医学研究杂志

Objective To investigate the inhibitory effect of a new antihypertensive drug on carotid artery intimal hyperplasia in balloon-injured rats and its possible mechanism.Methods A total of 48 SD rats were randomly divided as follows:sham operation group,model group,low-dose Azilsartan medoxomil group and high-dose Azilsartan medoxomil group(n =12).The rats in sham operateion group and model group were treated by by gavage with 3ml normal saline every day,and rats in low-dose Azilsartan medoxomil group and high-dose Azilsartan medoxomil group were treated by by gavage at adose of 2mg/kg and 4mg/kg Azilsartan medoxomil(3ml) every day.14 and 28 days after operation,we can observe the morphological changes of the injured arteries by HE staining and measure intimal area (IA),medial area(MA),the intimal/medial area ratio (IA/MA).The expression of PCNA,TLR4,NF-κB p65 in each group were detected by immunohistochemistry and the plasma level of TNF-α,IL-6 were detected by enzyme-linked immunosorbent assay (ELISA).Results Compared with the model group,the intimal area and the intimal / medial area ratio were significantly reduced in the low-dose group and hige-dose group (P ＜ 0.05).The expression of PCNA,TLR4 and NF-κB p65 in carotid artery were significantly lower (P ＜ 0.05).The plasma level of TNF-α、IL-6 were significantly lower (P ＜ 0.05).Compared with the sham operation group,the intimal area and the intimal/medial area ratio were significantly increased in the operation group (P ＜ 0.05) and the expression of PCNA,TLR4 and NF-κB p65 in carotid artery were significantly increased (P ＜0.05).The plasma level of TNF-α、IL-6 were significantly increased (P ＜ 0.05).Conclusion Azilsartan medoxomil can alleviate the incidence of vascular restenosis.The mechanism of action possibly was related to reducing the expression of inflammatory factors such as TNF-α,IL-6 by TLR4/NF-κB pathway and inhibiting the carotid artery intimal hyperplasia.

Azilsartan medoxomil: Angiotensin receptor blocker in the treatment of hypertension.

Hypertension is an important risk factor for cardiovascular and renal disease. It’s early detection and control is critically important as it is an important attributable cause of stroke, coronary artery disease, heart failure, atrial fibrillation and ESRD. Recent data indicates increasing prevalence of hypertension amongst various populations. This reflects the importance of having a variety of treatment options for the management of this condition. Angiotensin receptor blockers are highly effective at reducing blood pressure, have excellent tolerability and renoprotective properties, hence they remain a useful choice in the management of hypertension. Azilsartan medoxomil has recently been approved by the FDA for the oral treatment of hypertension making it the eighth Angiotensin receptor blocker to be approved for this indication.