Antihypertensive Drugs

Hypertension, known as a "silent killer" is widely prevalent and a major risk factor for cardiovascular diseases. It afflicts more than one billion population worldwide and is a leading cause of morbidity and mortality. The authors of the chapters look from different angles to hypertension, sharing their new knowledge and experience in the direction of deep understanding and more clarification of the disease providing an invaluable resource not only for clinicians, but also for all medical sciences students and health providers.

Penyakit hipertensi merupakan peningkatan tekanan darah diatas 140/90 mmHg yang disebabkan oleh aterosklerosis (penebalan dinding arteri yang menyebabkan hilangnya elastisitas pembuluh darah) dan pengerasan dinding pembuluh darah karena endapan kolesterol dan kapur. Hipertensi dapat terjadi karena beberapa faktor yaitu kadar natrium dalam darah, merokok dan stress. Jika didalam arteri terdapat tekanan darah yang tinggi maka akan meningkatkan resiko terhadap stroke, gagal jantung, serangan jantung dan gagal ginjal.

En el embarazo, de forma precoz y antes de la placentación completa (semanas 20-22), se produ-ce una disminución del nivel de presión arterial (PA) media y de las resistencias periféricas en relación con la instauración del flujo sanguíneo útero-placentario y del aumento de síntesis de ciertas sustancias vasodilatadoras (prostaciclinas, óxido nítrico) 1 . En respuesta a la vasodilatación renal y la activación del eje renina-angiotensina-aldosterona, aumentan el gasto cardíaco, el volumen plasmático, el flujo plasmático renal y la tasa de filtración glomerular generando un descenso sostenido del nivel de PA hasta la segunda mitad de la gestación 2 . A partir de entonces la PA alcanza progresivamente sus niveles habituales a finales

The increasing discovery of more medicinal plants have triggered increased scientific screening of their bioactivity in order to provide data that will help physicians and patients make wise decision before using them. This study was designed to elucidate comparative phytochemical and antioxidant properties of crude seed powder, aqueous and methanolic seed extracts of Buchholzia coriacea. The results showed that crude seed powder had the highest alkaloid and phenol content of 3.98 ± 0.00% and 0.92 ± 0.00%, while aqueous extract had the least alkaloid and phenol content of 1.00 ± 0.00% and 0.12 ± 0.00% respectively. Methanolic extracts had the highest phytochemical components among the three extracts with flavonoids (12.03 ± 0.0), saponins (1.99 ± 0.01), terpenoids (2.00 ± 0.00), tannin (0.10 ± 0.00) and phytate (2.02 ± 0.01) compositions, while aqueous extracts had the highest hydrogen cyanide (0.30 ± 0.00) and glycoside (0.35 ± 0.00). Antioxidant (DPPH) activities of B. coriacea showed that aqueous extract and crude seed powder had inhibition concentration (IC50) of 4.65 mg/ml while methanolic extract had IC50 of 5.85 mg/ml. The result of the LD50 of the extracts showed the each extracts was well tolerated at a dose of 5000 mg/kg, an indication of high safety profile. The study therefore clearly demonstrated that methanolic extracts of B. coriacea have antioxidant, antihypertensive, hypocholesterolmic and anticarcinogenic properties owing to the presence of high levels of phytochemical components than the aqueous and crude seed powder.

OBJECTIVE: Whether all antihypertensive drugs are equally effective in patients with metabolic syndrome is still unclear. The goal of the Zofenopril in Advanced MEtabolic Syndrome (ZAMES) study was to investigate whether treatment with the fixed-dose combination of sulphydril-containing angiotensin-converting enzyme inhibitor zofenopril plus hydrochlorothiazide is at least as effective as that with the angiotensin receptor blocker irbesartan plus hydrochlorothiazide in
patients with metabolic syndrome and essential hypertension, uncontrolled by a previous monotherapy.
METHODS: We enrolled 721 patients in a multicenter, international (Italy and Romania), randomized, double-blind, parallel group, phase III study. Following a 1-week screening withdrawal period, 482 patients (mean age 59 ± 10 years, 53% men) bearing a SBP at least 140 mmHg and/or DBP at least 90 mmHg plus metabolic syndrome (ATP-III criteria) were randomly allocated to a fixed-dose combination of zofenopril 30 mg plus hydrochlorothiazide 12.5 mg or irbesartan 150 mg plus hydrochlorothiazide 12.5 mg once daily for a cumulative period of 24 weeks. After 8 and 16 weeks, zofenopril and irbesartan doses were doubled in nonnormalized study participants. The study endpoint was the office DBP reduction at study end. In 20% of patients, an ambulatory blood pressure monitoring was performed. RESULTS: The prevalence of diabetes at baseline was significantly (P < 0.05) greater in the zofenopril plus hydrochlorothiazide group (82%) than in the irbesartan plus hydrochlorothiazide (73%) group. Baseline-adjusted DBP reductions
were superimposable (P = 0.370) with zofenopril plus hydrochlorothiazide
[n = 231; 9.8 (95% confidence interval: 11.1, 8.4) mmHg] and irbesartan plus hydrochlorothiazide [n = 235; 10.4 (11.8, 9.0) mmHg]. The same was for SBP [17.0 (19.2, 14.8) mmHg zofenopril plus hydrochlorothiazide vs. 18.8 (21.0, 16.6) mmHg irbesartan plus hydrochlorothiazide, P = 0.113]. Rate of normalized and responder patients (SBP/DBP < 140/90 mmHg or SBP reduction more than 20 mmHg or DBP reduction more than 10 mmHg) did not differ at study end (65.8% and 77.5% zofenopril plus hydrochlorothiazide vs. 67.7% and 81.5% irbesartan plus hydrochlorothiazide; P = 0.695, P = 0.301). These results were confirmed in the 69 study participants undergoing ambulatory blood pressure monitoring (35 zofenopril plus hydrochlorothiazide; 34 irbesartan plus hydrochlorothiazide), with a comparable 24-h average BP reduction [BP difference between-treatment: SBP: 0.1 (-5.7, 5.9) mmHg, P = 0.975; DBP: -0.9 (-3.8, 2.0) mmHg, P = 0.541]. Both drugs attained similar BP reductions also in the last 6 h of the dosing interval [between-treatment difference SBP: 0.1 (-7.4, 7.5) mmHg P = 0.990; DBP: -0.9 (-4.4, 2.6) mmHg, P = 0.602]. Metabolic and renal indexes were not altered.
Few patients were withdrawn for moderate adverse events (5% zofenopril plus hydrochlorothiazide; 5% irbesartan plus hydrochlorothiazide). CONCLUSION: This is the first study supporting the comparable antihypertensive and metabolic response to fixed-dose combinations of sulphydril-containing angiotensin-converting enzyme inhibitors (zofenopril) or angiotensin receptor blockers (Irbesartan) with a diuretic in patients with advanced metabolic syndrome and nonresponders to monotherapy. The results of this study can further
improve the clinical management of high cardiovascular risk patients with hypertension and metabolic syndrome, because these two drug combinations increase the number of available combinations, which may significantly improve patients' adherence in this special clinical condition that is frequently found in everyday practice.

Drug discovery and development is a high-risk enterprise that requires significant investments in capital, time and scientific expertise. The studies of xenobiotic metabolism remain as one of the main topics in the research and development of drugs, cosmetics and nutritional supplements.
Antihypertensive drugs are used for the treatment of high blood pressure, which is one the most frequent symptoms of the patients that undergo cardiovascular diseases such as myocardial infraction and strokes. In current cardiovascular disease pharmacology, four drug clusters - Angiotensin Converting Enzyme Inhibitors, Beta-Blockers, Calcium Channel Blockers and Diuretics - cover the major therapeutic characteristics of the most antihypertensive drugs. The pharmacokinetic and specifically the metabolic profile of the antihypertensive agents are intensively studied because of the broad inter-individual variability on plasma concentrations and the diversity on the efficacy response especially due to the P450 dependent metabolic status they present.

Several computational methods have been developed with the aim to: (i) model and better understand the human drug metabolism; and (ii) enhance the experimental investigation of the metabolism of small xenobiotic molecules. The main predictive tools these methods employ are rule-based approaches, quantitative structure metabolism/activity relationships and docking approaches.

This review paper provides detailed metabolic profiles of the major clusters of antihypertensive agents, including their metabolites and their metabolizing enzymes, and it also provides specific information concerning the computational approaches that have been used to predict the metabolic profile of several antihypertensive drugs.

Hypertension is a chronic cardiovascular disease affecting the adult population. Clinical pharmacy is a health science discipline in which pharmacists provide patient care and optimizes medication therapy management and promotes health and disease prevention. Clinical pharmacist meets multiple health care practioners during the practice and promotes beneficial services to them. Blood pressure is the force of blood pushing against the walls of arteries. Hypertension causes many health complications that results in increased morbidity and mortality. Blood pressure is the combination of cardiac output and systemic vascular resistance.The regulation of blood pressure depends on baro receptor and chemo receptor mechanisms may plays vital role in regulating the blood pressure changes with in the body. The higher elevated blood pressure may impact the functions of vital organs leads to damage the organs. The clinical pharmacist should Provide awareness and implementation of effective life style interventions in the practice it includes both pharmacological and non pharmacological methods will maintain the blood pressure in controlled levels. The life style modifications includes increasing physical activity, reduced salt intake, increase potassium intake, decrease the use of alcohol,proper use of antihypertensive medications and promoting effective suggestions towards public health strategies can ultimately support to reduce the blood pressure in the community.

Combinations between an angiotensin converting enzyme (ACE) inhibitor or an angio-tensin II receptor blocker (ARB) and hydrochlorothiazide (HCTZ) are among the recommended treatments for hypertensive patients uncontrolled by monotherapy. Four randomized, double-blind, parallel group studies with a similar design, including 1469 hypertensive patients uncontrolled by a previous monotherapy and with C1 cardiovascular risk factor, compared the efficacy of a combination of a sulfhydryl ACE inhibitor (zofenopril at 30 or 60 mg) or an ARB (irbesartan at 150 or 300 mg) plus HCTZ 12.5 mg. The extent of blood pressure (BP)-lowering was assessed in the office and over 24 h. Pleiotropic features of the treatments were evaluated by studying their effect on systemic inflammation, organ damage, arterial stiffness, and metabolic biochemical parameters. Both treatments similarly reduced Enhanced content To view enhanced content for this article go to

The dislipidemias are a risk factor well recognized of the cardiovascular diseases and constitute a problem of public health. A descriptive study in 150 patient elders of 30 years with diagnosis of Izquemic Cardiopathyes accomplished itself for the sake of identifying dislipidemias in patients of high cardiovascular risk that they helped the high-technology General Medical Center state James Mariño Aragua, at the Republic Bolivariana of Venezuela, that you constituted the sign of study from October 2011 to October 2012. They used quantitative and qualitative variables like weight, age, sex, pathological personal background, risk factors cardiovascular associates, seric levels of total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol VLDL cholesterol. 63 percent of patients with dislipidemias were detected, being hypercholesterolemia the more alteration frequently found. The ages understood between 41 and 60 years evidenced the bigger frequency.

On the other side, despite the availability of a wide range of antihypertensive drugs (Van Bortel and others 2011), blood pressure has remained poorly controlled in a majority of health Antihypertensive Drugs 132 care settings, particularly in low resource settings. The access to medicines is highly driven by the availability and the cost of these drugs and strongly influences the prescription and usage patterns which in the end affect control of blood pressure(Twagirumukiza and others 2010). The rational use of available resources and the integration of the management strategies at primary health care level (De Maeseneer J 2009) have been advocated as key point of improving hypertension treatment (Twagirumukiza and Van Bortel 2011).

Short half life of propranolol hydrochloride (PPN), an antihypertensive drug is a prime requirement to develop a formulation which could sustain the release of PPN in the human body and also eliminate daily multiple dosage of propranolol. In this study organoclay Pluronic F68 modified montmorillonite (Mt) has been explored as a sustained release carrier for oral delivery of PPN. The developed organoclay PF68-Mt was compared for adsorption capacity of PPN with pristine Mt. A detailed and systematic study to evaluate the effect of pH, time and initial PPN concentration on drug loading capacity of organoclay PF68-Mt and pristine Mt has been evaluated. The synthesized PF68-Mt-PPN composites were characterized by XRD, FTIR, TGA techniques. XRD studies suggested the intercalation of PPN within the pristine Mt and organoclay PF68 -Mt. In vitro drug release profile of PPN from organoclay PF68-Mt composites is compared with that of pristine Mt and the pure PPN, in simulated gastric and intestinal fluids. The release profile of loaded PPN in organoclay PF68-Mt shows pH dependent release in simulated gastrointestinal fluid. The release behaviour of PPN from PF68-Mt-PPN composites was appeared to be in more sustained manner than prisine Mt and pure PPN over a period of 24 hours. This study suggests that the modification of Mt with a non ionic tri block co polymer Pluronic F68 provides better controlled on the release of PPN as compared to pristine Mt and pure drug. The obtained PF68-Mt-PPN composites with high drug loading capacity and sustained drug release characteristics supposed to be a better oral drug delivery system, for a highly hydrophilic low molecular weight antihypertensive drug PPN. The PF68-Mt-PPN composites developed have the potential to minimize the drug dosing frequency and hence improving the patient compliance. Thus, proposing a new promising formulation for oral sustained release drug delivery.

AIM: Gaining an insight into the utilization of antihypertensive medicines against a background of evolving hypertension treatment guidelines that might not be relevant to the oldest old is important. The aim of the present study was to characterize the overall trends in the utilization of antihypertensive medicines in the oldest old by therapeutic class and chemical type, stratified by age and sex over a decade. METHODS: Antihypertensive medicines utilization was examined using the therapeutic and chemical groups based on the World Health Organization Collaborating Center for Drug Statistics Mythology&#39;s Anatomical Therapeutic Chemical classification system for all individuals aged ≥80 years. Regression and repeated cross-sectional analyses was carried out, and defined daily dose was used to describe the utilization per thousand older people per day. RESULTS: Utilization of antihypertensive medicines increased over the decade from 187.28 in 2005 to 205.01 defined daily dose per ...

A sensitive, rapid and reproducible LC-MS/MS method for the determination of olmesartan (OLM), amlodipine (ALM) and hydrochlorothiazide (HCZ) in rat plasma and urine has been developed and validated. Irbesartan (IRB) was used as an internal standard. The analytes were separated on a Waters XTerra-C 18 column using gradient elution with acetonitrile and 10 mM ammonium acetate buffer (pH 3.5, adjusted with acetic acid) at a flow rate of 1.0 mL min −1. The three analytes were ionized by positive ion electrospray using multiple-reaction monitoring (MRM) mode to monitor precursor → product ion transitions m/z 447.31 → 234.97 for OLM, 408.87 → 238.18 for AML and 290.1 → 204.85 for HCZ. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision, and stabilities were all validated over the concentration range 0.4-100 ng mL −1 for AML, 0.2-100 ng mL −1 for OLM, 0.1-100 ng mL −1 for HCZ. The mean concentrations (C max) are 10.32, 587, and 3.4 for OLM, ALM, and HCZ, respectively, by the oral administration of 15 mg kg −1 of each analyte.

Background. Hypertension in blacks imposes a greater left ventricular hypertrophy, and accelerated heart failure onset. We evaluated and compared the echocardiographically determined systolic and left ventricular diastolic functional indices in Nigerian hypertensive patients, associated with the chronic use of ACE inhibitors, Calcium channel blockers (CCB) or their combinations. Methods. Ejection fraction -EF, intraventricular relaxation time (IVRT), E/A peak velocity ratio, E wave deceleration time] as well as the left ventricular mass index (LVMI) was undertaken among 41 Nigerian patients with essential hypertension only, on treatment for 4-6 months prior. The 41 patients (aged 59 Ϯ 10 years, 40% females) were divided into three groups; those receiving (i) ACE inhibitors; or (ii) CCB or (iii) combination of ACEI and CCB. All the three groups had a background of diuretic treatment for optimal blood pressure control. Results. There were no statistically significant differences in the mean LVMI or sitting blood pressure between treatment groups. E/A ratio for ACEI treatment was 1.06 Ϯ 0.44, CCB 0.74 Ϯ 0.19, and for ACEI + CCB 0.87 Ϯ 0.26 (F = 3.29, P = 0.048 anova). The 95% confidence interval for the E/A ratio on ACEI was 0.8 to 1.33. The A wave duration time integral (AVVTi) were all abnormally large, but showed a significant between treatment group difference (P = 0.037, anova). The values were 21.9 Ϯ 4.7 for ACEI, 25.3 Ϯ 6.3 for CCB, and least at 20.1 Ϯ 3.6 cm for the ACE + CCB combination. Similarly, the IVRT was lowest and <100 ms with ACEI + CCB being 93 Ϯ 18 ms, ACEI 115 Ϯ 23 ms, and CCB being 117 Ϯ 22 ms (F = 4.92, P = 0.01, anova). The 95% CI for IVRT on ACEI + CCB was 82 to 104 ms. There were no between treatment group differences in systolic contractility, (fractional shortening or EF).

The efficacy and safety of the novel calcium antagonist Amlodipine (Pfizer Laboratories, New York, New York) and hydrochlorothiazide were evaluated and compared in a randomized, single-blind, parallel group study in black Africans with essential hypertension. Twenty Nigerians with newly diagnosed mild to moderate essential hypertension were randomized to receive ascending doses of Amlodipine (5 mg and 10 mg) or hydrochlorothiazide (25 mg or 50 mg), and blood pressure and heart rate were measured at baseline and at 2, 4, and 6 weeks of therapy. Both Amlodipine and hydrochlorothiazide significantly reduced supine and erect blood pressure. Supine blood pressure on Amlodipine fell from a mean of 190/104 mm Hg to 150/79 mm Hg, and on thiazide from 180/103 mm Hg to 141/84 mm Hg. There was, however, no significant difference between both drugs in antihypertensive efficacy. Neither drug induced a reflex increase in heart rate. The fall in blood pressure on both agents was associated with an increase in plasma urea. Amlodipine induced no change in plasma

Hypertension in pregnancy is associated with increased maternal and fetal mortality and morbidity. About 8 % of all pregnancies are complicated with hypertensive disorders. There is concordance that severe hypertension should be treated without delay to reduce maternal risks of acute cerebrovascular complications. Intravenous labetalol and oral nifedipine are as effective as intravenous hydralazine in control of severe hypertension, with less adverse effects. Still, there is no consensus as to whether mild-to-moderate hypertension in pregnancy should be treated, considering that there are no definitive conclusions which can be made about the relative maternal or perinatal benefits/risks of antihypertensive treatment. Considering their safe usage during pregnancy, methyldopa, labetalol and nifedipine are commonly used blood-pressure lowering drugs for pregnant women with hypertension. The cardio-selective β- blocker atenolol should be avoided in pregnancy, because it has been associa...

Aim: In the present study, the alkaloid, flavonoid and saponin-rich extracts of the leaves and seeds of Moringa oleifera were partially-purified and the ACE inhibitory activities and patterns of inhibition determined. Methodology: Alkaloids, flavonoids and saponins were extracted from the leaves and seeds of Moringa oleifera. They were then partially-purified via thin layer chromatography and column chromatography. The Angiotensin Converting Enzyme (ACE) inhibitory activities of each fraction was determined using Cushman and Cheung method with some modifications on the assay conditions, while the mechanisms of inhibition investigated using Lineweaver-Burk plots. Results: The alkaloid-rich extracts of the leaves (6.27±0.12 mg/ml) and seeds (2.04±0.95 mg/ml) as well as flavonoid-rich extracts of the leaves (1.20±0.31 mg/ml) and seeds (2.16±0.56 mg/ml) of Original Research Article Abdulazeez et al.; JABB, 5(2): 1-11, 2016; Article no.JABB.21974 2 M. oleifera inhibited ACE at concentrations significantly (P <.05) lower than the saponin-rich extracts (26.01±1.02 and 24.32±2.31 mg/ml for the leaves and seeds, respectively). Thus, both alkaloid and flavonoid-rich extracts were further purified via thin layer chromatography and column chromatography. Of the four fractions obtained from the alkaloid-rich leaf extract, the ACE inhibitory activity of fraction 2 (0.46±0.01 mg/ml) was significantly higher (P <.05), while fraction 1 (0.07±0.01 mg/ml) of the alkaloid-rich seed extract significantly (P <.05) inhibited ACE compared to other fractions. For the flavonoid-rich extracts, fractions 3 (0.03±0.01 mg/ml) and 4 (0.42±0.03 mg/ml) obtained from the leaves and seeds, respectively, significantly (P <.05) inhibited ACE than other fractions. From the kinetic studies, fractions 1 and 2 exhibited uncompetitive types of inhibition with a decrease in V max and corresponding decrease in K m at 0.5 mg and 1.0 mg of inhibitor, respectively. Fractions 3 and 4 were competitive inhibitors of ACE, as the K m increased with increasing concentration of inhibitor, while V max remain unchanged. In conclusion, this study has demonstrated the ACE inhibitory activity of alkaloids and flavonoids from the seeds and leaves of Moringa oleifera and their potential as source of ACE inhibitors that may be beneficial for the management of hypertension.

Background: Hypertension is a prominent public health problem, with considerable health consequences. Recommended guidelines encourage use of antihypertensive medications with the best evidence of reducing cardiovascular risk. Data on antihypertensive medications use among older Nigerians is limited. Objective: This study evaluated the antihypertensive medication use among older persons with hypertension in compliance with the Eighth Joint National Committee guidelines (JNC 8). Method: A retrospective cross-sectional study, of older patients diagnosed with hypertension between the 1 st January 2017 and 31 st December 2017 at the geriatric center, University College Hospital, Ibadan. Results: The mean age was 70.2 ± 7.2 years and 62% were female. The mean number of medications used by the patient was 4.5 ± 1.4. Of the patients, 56% were receiving combination therapy, 42% two drugs and 14% three drugs. Most patients were receiving calcium channel blockers (33.8%), followed by diuretics (29.6%), angiotensin receptor blockers (23.4%) and angiotensin-converting enzyme inhibitors (10.8%). Commonest combination therapy was calcium channel blockers and thiazide diuretics (28.3%), while the commonest multi-morbidities were osteoarthritis (32.7%), diabetes (17.3%) and dyslipidemia (8.7%). Conclusion: This study showed that more than half of older persons with hypertension were on combination therapy, and the most frequently used class of antihypertensive drugs were calcium channel blockers, followed by diuretics. The guidelines and data for black ≥60 years indicate that lower doses of combination therapy are more effective in achieving blood pressure target. Despite the numerous advantages of ACEIs, they remain underutilized.

High Performance Liquid Chromatographic method was developed and applied for the simultaneous determination of diltiazem and fluoroquinolones in bulk, pharmaceutical formulations and human serum in presence of caffeine as internal standard. A Hiber®, RP-18 column was used with mobile phase consisting of acetonitrile:methanol:water (30:20:50 v/v, pH 3.6) and quantitative evaluation was performed at 230 nm. Suitability of this method for the quantitative determination of the drugs was proved by validation in accordance with the requirements laid down by International Conference on Harmonization (ICH) guidelines.The method was selective, precise, accurate and can be used for routine analysis of pharmaceutical preparations, quality control and clinical laboratories.

Gaining an insight into the utilization of antihypertensive medicines against a background of evolving hypertension treatment guidelines that might not be relevant to the oldest old is important. The aim of the present study was to characterize the overall trends in the utilization of antihypertensive medicines in the oldest old by therapeutic class and chemical type, stratified by age and sex over a decade. Methods: Antihypertensive medicines utilization was examined using the therapeutic and chemical groups based on the World Health Organization Collaborating Center for Drug Statistics Mythology's Anatomical Therapeutic Chemical classification system for all individuals aged ≥80 years. Regression and repeated cross-sectional analyses was carried out, and defined daily dose was used to describe the utilization per thousand older people per day. Results: Utilization of antihypertensive medicines increased over the decade from 187.28 in 2005 to 205.01 defined daily dose per thousand older people per day in 2014, and shifted from mainly diuretics to angiotensin-converting enzyme inhibitors. Interestingly, with the exception of diuretics, utilization of all medicines decreased gradually with increasing age. Single products use increased by 1.48-fold in 2014 compared with 2005, and for fixed-dose combinations the increase was 1.41-fold for the same period. The increased utilization of angiotensin-converting enzyme inhibitors is consistent with recommendations from cardiovascular guidelines formulated from large randomized control trials that often exclude the oldest old. Interestingly, the utilization of beta-blockers decreased and diuretics increased in centenarians. The utilization of calcium channel blockers and angiotensin-converting enzyme inhibitors across the study period increased in all age categories. Geriatr Gerontol Int 2016; ••: ••-••.

Gaining an insight into the utilization of antihypertensive medicines against a background of evolving hypertension treatment guidelines that might not be relevant to the oldest old is important. The aim of the present study was to characterize the overall trends in the utilization of antihypertensive medicines in the oldest old by therapeutic class and chemical type, stratified by age and sex over a decade. Methods: Antihypertensive medicines utilization was examined using the therapeutic and chemical groups based on the World Health Organization Collaborating Center for Drug Statistics Mythology's Anatomical Therapeutic Chemical classification system for all individuals aged ≥80 years. Regression and repeated cross-sectional analyses was carried out, and defined daily dose was used to describe the utilization per thousand older people per day. Results: Utilization of antihypertensive medicines increased over the decade from 187.28 in 2005 to 205.01 defined daily dose per thousand older people per day in 2014, and shifted from mainly diuretics to angiotensin-converting enzyme inhibitors. Interestingly, with the exception of diuretics, utilization of all medicines decreased gradually with increasing age. Single products use increased by 1.48-fold in 2014 compared with 2005, and for fixed-dose combinations the increase was 1.41-fold for the same period. Conclusions: The increased utilization of angiotensin-converting enzyme inhibitors is consistent with recommendations from cardiovascular guidelines formulated from large randomized control trials that often exclude the oldest old. Interestingly, the utilization of beta-blockers decreased and diuretics increased in centenarians. The utilization of calcium channel blockers and angiotensin-converting enzyme inhibitors across the study period increased in all age categories.

Melilotus officinalis (L.) Pallas., is used traditionally to treat hypertension and chronic venous insufficiency. The high prevalence of hypertension and the side effects of antihypertensive drugs potentiate us to evaluate Melilotus officinalis. The hypotensive effect of Melilotus officinalis butanolic fraction (MOBF) was investigated in anaesthetized normotensive rats. The doses of 60, 80 and 100 mg/kg, i.v., produced a significant (P&lt; 0.05) decrease in blood pressure. The statistically non significant reduction in blood pressure was showed by 20 and 40 mg/kg, i.v. These results suggest that Melilotus officinalis exhibited hypotensive effect in normotensive rats. However further evaluation of compound related activity is required.

Objective: The purpose of present research work is to develop the sustained release formulation for Olmesartan medoxomil using 32  factorial design. Olmesartan an Antihypertensive agent, angiotensin‒II receptor (type AT1) blocker and BCS class‒II
agent.
Methods: Sustained Release tablets of Olmesartan medoxomil were prepared using different quantities of HPMCK4M and Xanthan Gum in combinations by direct
compression technique. The concentration of Polymers, HPMCK4M and Xanthan gum required to achieve the drug release was selected as independent variables, X1 and X2 respectively whereas, time required for 10% of drug release (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables.
Results: Nine formulations were prepared and are evaluated for various pharmacopoeial tests. The results reveals that all formulations were found to be with
in the pharmacopoeial limits and In vitro drug release profiles of all formulations were fitted in to various Kinetic models. The statistical parameters like intercept, slope & correlation coefficient were calculated. Polynomial equations were developed for dependent variables. Validity of developed polynomial equations were checked by designing 2 check point formulations (C1 , C2 ).
Conclusion: According to SUPAC guidelines formulation (F5 ) containing combination of 15% HPMCK4M and 15% Xanthan gum, is the most identical formulation (similarity factor f2 = 91.979, dissimilarity factor f1 = 1.546 & No significant difference, t=0.0338) to marketed product (BENICAR). Best Formulation F5 follows First order, Higuchi’s kinetics, and the mechanism of drug release was found to be Non‒Fickian Diffusion Anomalous Transport. (n=0.828).

Objective: Hypertension is a leading contributor to the global burden of cardiovascular morbidity and mortality. The main objective of the present study was to assess the prescribing patterns for antihypertensives in geriatric patients. Materials and Methods: A Prospective observational study was carried out for the period of six months in an out-patient department. Elderly patients who have been diagnosed with hypertension as per JNC-7 guidelines and patients receiving or prescribed with antihypertensive drugs were included. Results: A total of 100 prescriptions were analyzed during the six-month study period. 72% of the patients were in the age group of 65-67 years and this was found to be higher in men 69%. During the study period 80% of the patients were Pre-Hypertensive systolic (80-89 mmHg) and Diastolic (120-139 mmHg) followed by Stage-I Hypertension and Stage-II Hypertension. The most common drug classes involved in the study was Calcium Channel Blockers 37% followed by Angiotensin II receptor antagonists 21% and the most commonly prescribed drugs in the study population were Amlodipine 37%, Losartan 11% and Telmisartan 10%. The most common anti-hypertensive fixed dose combination therapy involved in the study was Telmisartan + Hydrochlorothiazide 15% and most common two drug combination therapy involved in the study was Amlodipine + Atenolol 7% followed by Metoprolol + Amlodipine 1%. Conclusion: Our study shows that the most commonly prescribed drug classes involved were Calcium Channel Blockers followed by Angiotensin II receptor antagonists and the anti-hypertensive drug combinations among hypertensive patients were considerable and this practice positively impacted on the overall blood pressure control.

A simple reverse phase HPLC method has been developed and validated for the simultaneous determination of prazosin hydrochloride and three calcium channel blockers; diltiazem hydrochloride, verapamil and amlodipine besylate in bulk material, their finished product and human serum. The separation was carried out using a mobile phase consisting of acetonitrile:methanol:water: (10:55:35 v/v, pH 2.65±0.02), on a Nuclosil 100-10 C-18 (250×4.6mm), 10 micron particle size column. Studies were performed on a HPLC system equipped with a UV/visible detector at 240 nm. The flow rate employed for analysis was 1mL min-1 in isocratic mode. All drugs were eluted within 6 minutes and give sharp peak with high theoretical plate count and low tailing factor. The retention time of prazosin, verapamil, diltiazem and amlodipine were 3.02, 3.84, 3.94 and 4.92 minutes respectively. The validation study was carried out according to ICH guide lines. The described method was linear over a concentration range of 5–100 μg mL-1, 10–200 μg mL-1, 15–300 μg mL-1 and 30–600 μg mL-1 for the
assay of prazosin, diltiazem, amlodipine and verapamil respectively. The limit of quantitation and the limit of detection were found to be 0.0994, 0.0926, 0.1642, 0.0905 μg mL-1 and 0.0328, 0.0306, 0.0542 and 0.0299 μg mL-1 for prazosin, amlodipine, diltiazem and verapamil respectively. Therefore, the study showed that the proposed RP-HPLC method is rapid, simple, specific, precise and accurate, which is useful for the routine determination of prazosin, amlodipine, diltiazem and verapamil in bulk materials, dosage formulations and serum.

Background. Hypertension in blacks imposes a greater left ventricular hypertrophy, and accelerated heart failure onset. We evaluated and compared the echocardiographically determined systolic and left ventricular diastolic functional indices in Nigerian hypertensive patients, associated with the chronic use of ACE inhibitors, Calcium channel blockers (CCB) or their combinations. Methods. Ejection fraction-EF, intraventricular relaxation time (IVRT), E/A peak velocity ratio, E wave deceleration time] as well as the left ventricular mass index (LVMI) was undertaken among 41 Nigerian patients with essential hypertension only, on treatment for 4-6 months prior. The 41 patients (aged 59 Ϯ 10 years, 40% females) were divided into three groups; those receiving (i) ACE inhibitors; or (ii) CCB or (iii) combination of ACEI and CCB. All the three groups had a background of diuretic treatment for optimal blood pressure control. Results. There were no statistically significant differences in the mean LVMI or sitting blood pressure between treatment groups. E/A ratio for ACEI treatment was 1.06 Ϯ 0.44, CCB 0.74 Ϯ 0.19, and for ACEI + CCB 0.87 Ϯ 0.26 (F = 3.29, P = 0.048 anova). The 95% confidence interval for the E/A ratio on ACEI was 0.8 to 1.33. The A wave duration time integral (AVVTi) were all abnormally large, but showed a significant between treatment group difference (P = 0.037, anova). The values were 21.9 Ϯ 4.7 for ACEI, 25.3 Ϯ 6.3 for CCB, and least at 20.1 Ϯ 3.6 cm for the ACE + CCB combination. Similarly, the IVRT was lowest and <100 ms with ACEI + CCB being 93 Ϯ 18 ms, ACEI 115 Ϯ 23 ms, and CCB being 117 Ϯ 22 ms (F = 4.92, P = 0.01, anova). The 95% CI for IVRT on ACEI + CCB was 82 to 104 ms. There were no between treatment group differences in systolic contractility, (fractional shortening or EF). Conclusions. The results indicate that use of an antihypertensive drug regime inclusive of an ACE inhibitor (ϮCCB) may be associated with greater salutary effect on indices of diastolic function, (E/A > 1, lower AVVTi, IVRT < 100 ms) even in the presence of an equivalent effect on systolic function and blood pressure.

Background. Hypertension in blacks imposes a greater left ventricular hypertrophy, and accelerated heart failure onset. We evaluated and compared the echocardiographically determined systolic and left ventricular diastolic functional indices in Nigerian hypertensive patients, associated with the chronic use of ACE inhibitors, Calcium channel blockers (CCB) or their combinations. Methods. Ejection fraction-EF, intraventricular relaxation time (IVRT), E/A peak velocity ratio, E wave deceleration time] as well as the left ventricular mass index (LVMI) was undertaken among 41 Nigerian patients with essential hypertension only, on treatment for 4-6 months prior. The 41 patients (aged 59 Ϯ 10 years, 40% females) were divided into three groups; those receiving (i) ACE inhibitors; or (ii) CCB or (iii) combination of ACEI and CCB. All the three groups had a background of diuretic treatment for optimal blood pressure control. Results. There were no statistically significant differences in the mean LVMI or sitting blood pressure between treatment groups. E/A ratio for ACEI treatment was 1.06 Ϯ 0.44, CCB 0.74 Ϯ 0.19, and for ACEI + CCB 0.87 Ϯ 0.26 (F = 3.29, P = 0.048 anova). The 95% confidence interval for the E/A ratio on ACEI was 0.8 to 1.33. The A wave duration time integral (AVVTi) were all abnormally large, but showed a significant between treatment group difference (P = 0.037, anova). The values were 21.9 Ϯ 4.7 for ACEI, 25.3 Ϯ 6.3 for CCB, and least at 20.1 Ϯ 3.6 cm for the ACE + CCB combination. Similarly, the IVRT was lowest and <100 ms with ACEI + CCB being 93 Ϯ 18 ms, ACEI 115 Ϯ 23 ms, and CCB being 117 Ϯ 22 ms (F = 4.92, P = 0.01, anova). The 95% CI for IVRT on ACEI + CCB was 82 to 104 ms. There were no between treatment group differences in systolic contractility, (fractional shortening or EF). Conclusions. The results indicate that use of an antihypertensive drug regime inclusive of an ACE inhibitor (ϮCCB) may be associated with greater salutary effect on indices of diastolic function, (E/A > 1, lower AVVTi, IVRT < 100 ms) even in the presence of an equivalent effect on systolic function and blood pressure.

Melilotus officinalis (L.) Pallas., is used traditionally to treat hypertension and chronic venous insufficiency. The high prevalence of hypertension and the side effects of antihypertensive drugs potentiate us to evaluate Melilotus officinalis. The hypotensive effect of Melilotus officinalis butanolic fraction (MOBF) was investigated in anaesthetized normotensive rats. The doses of 60, 80 and 100 mg/kg, i.v., produced a significant (P&lt;0.05) decrease in blood pressure. The statistically non significant reduction in blood pressure was showed by 20 and 40 mg/kg, i.v. These results suggest that Melilotus officinalis exhibited hypotensive effect in normotensive rats. However further evaluation of compound related activity is required.

INTRODUCTION Essential hypertension is a common cardiovascular disorder with sustained increase in blood pressure ≥140/90 mmHg. The elevated arterial pressure causes pathological changes in the vasculature and hypertrophy of the left ventricle. Hypertension is the principle cause of stroke that is a major risk factor for coronary artery disease (CAD) and its attendant complications like myocardial infarction and sudden cardiac death. It is also a major contributor to cardiac failure, renal insufficiency and dissecting aneurysm of aorta. 1 Hypertension is an increasingly prevalent chronic condition that is associated with serious morbidity and mortality. It is an important risk factor for the development and progression of cardiovascular disease (CVD), which is predicted to become the leading cause of death and disability worldwide by 2020. 2 As per the Registrar General of India and Million Death Study investigators (2001-2003), CVD was the largest cause of deaths in males (20.3%) as well as females (16.9%) and led to about 2 million deaths annually. In India, 23.10% men and 22.60% women over the age of 25 years suffer from hypertension. 3 Treating systolic blood pressure (SBP) and diastolic blood pressure (DBP) to targets that are <140/90 mmHg is ABSTRACT 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.

Introduction: Hypertension is significantly contributing to global mortality and morbidity and has been identified as the most important modifiable risk factor for early development of cardio-vascular diseases (CVD). Aim: The aim of this study was to investigate the efficacy of different combinations of antihypertensive therapy on blood pressure, arterial stiffness and peripheral resistance in patients with essential hypertension using the brachial oscillometric ambulatory blood pressure monitor. Methods: This study was designed as an observational, prospective, multi centric study conducted in eight primary care centers of the Health Center of Canton Sarajevo during the period of six months. The study included 655 participants, both genders, aged between 30 and 75, who were diagnosed with hypertension according to the ESC/ESH guidelines. Participants were divided into six treatment groups based on the hypertensive drug therapy they were using; lisinopril, losartan or valsartan alone or in combination with hydrochlorothiazide (A, B and C group respectively) or combination of lisinopril, losartan or valsartan with/without hydrochlorothiazide together with amlodipine (D, E and F respectively). The participants were monitored at baseline, after 3 and 6 months (1 st and 2 nd follow-up). Brachial oscillometric ambulatory blood pressure monitor was used for measuring systolic (SBP), diastolic (DBP), pulse pressure (PP), pulse wave velocity (PWV) and peripheral resistance (PR). Results: SBP, DPB, PP, and PWV significantly decreased from baseline to 2 nd follow-up in all treatment groups. The mean reductions in SBP were from-11.7 (95%CI; 9.3-14.1) to-23.2 (95%CI; 18.3-28.1) mmHg and DBP reductions varied from-5.5 (95%CI; 3.9-7.1) to-13.4 (95%CI; 7.7-19.1) mmHg. PWV decreased in all treatment groups (from-3.3% to-8.2%). Treatment regiment was not associated with significant differences in SBP, DBP, PP or PWV reductions or their values measured at 2 nd follow-up. Peripheral resistance significantly decreased only in group C (p=0.011), group D (p=0.009) and group F (p=0.027). Conclusion: These data suggest that lisinopril/lisinopril + hydrochlorothiazide, losartan/losartan + hydrochlorothiazide and valsartan/valsartan + hydrochlorothiazide alone or in combination with amlodipine are equally effective and well tolerated for the reduction of both systolic and diastolic blood pressure and improve arterial stiffness in patients with essential hypertension.

Hen egg white lysozyme (HEWL) was hydrolysed with trypsin, papain and a combination of the two. The prepared hydrolysates exhibited ACE inhibitory activity. The hydrolysates were fractionated using ultrafiltration and reverse phase-high performance liquid chromatography (RP-HPLC). Three fractions, which showed the highest ACE inhibitory activities, were purified by RP-HPLC. They were the F7 (from papain–trypsin hydrolysate), F8 (from papain hydrolysate) and F3 (from trypsin hydrolysate) fractions. The IC50 values were 0.03, 0.155 and 0.23 mg/ml for F7, F8 and F3, respectively. The F7 fraction was the most potent ACE inhibitor peptide, and was composed of 12 amino acids, Phe-Glu-Ser-Asn-Phe-Asn-Thr-Gln-Ala-ThrAsn-Arg (MW: 1428.6 Da). Lineweaver–Burk plots suggest that the F7 peptide acts as an uncompetitive inhibitor against ACE. The kinetic parameters (Km, Vmax, and Ki) for the F7 peptide were measured and compared to the control.

BACKGROUND:
Elevated blood pressure (BP), a heritable risk factor for many age-related disorders, is commonly investigated in population and genetic studies, but antihypertensive use can confound study results. Routine methods to adjust for antihypertensives may not sufficiently account for newer treatment protocols (i.e., combination or multiple drug therapy) found in contemporary cohorts.
METHODS:
We refined an existing method to impute unmedicated BP in individuals on antihypertensives by incorporating new treatment trends. We assessed BP and antihypertensive use in male twins (n = 1,237) from the Vietnam Era Twin Study of Aging: 36% reported antihypertensive use; 52% of those treated were on multiple drugs.
RESULTS:
Estimated heritability was 0.43 (95% confidence interval (CI) = 0.20-0.50) and 0.44 (95% CI = 0.22-0.61) for measured systolic BP (SBP) and diastolic BP (DBP), respectively. We imputed BP for antihypertensives by 3 approaches: (i) addition of a fixed value of 10/5mm Hg to measured SBP/DBP; (ii) incremented addition of mm Hg to BP based on number of medications; and (iii) a refined approach adding mm Hg based on antihypertensive drug class and ethnicity. The imputations did not significantly affect estimated heritability of BP. However, use of our most refined imputation method and other methods resulted in significantly increased phenotypic correlations between BP and body mass index, a trait known to be correlated with BP.
CONCLUSIONS:
This study highlights the potential usefulness of applying a representative adjustment for medication use, such as by considering drug class, ethnicity, and the combination of drugs when assessing the relationship between BP and risk factors.

Melilotus officinalis (L.) Pallas., is used traditionally to treat hypertension and chronic venous insufficiency. The high prevalence of hypertension and the side effects of antihypertensive drugs potentiate us to evaluate Melilotus officinalis. The hypotensive effect of Melilotus officinalis butanolic fraction (MOBF) was investigated in anaesthetized normotensive rats. The doses of 60, 80 and 100 mg/kg, i.v., produced a significant (P<0.05) decrease in blood pressure. The statistically non significant reduction in blood pressure was showed by 20 and 40 mg/kg, i.v. These results suggest that Melilotus officinalis exhibited hypotensive effect in normotensive rats. However further evaluation of compound related activity is required.