There is a lack of data on how to treat hypertensive patients with diabetes when treatment with medium doses of calcium channel blocker and angiotensin II type 1 receptor blocker (ARB) is insufficient to achieve the target blood pressure (BP). A total of 121 participants with type 2 diabetes and uncontrolled essential hypertension, who were receiving medium doses of amlodipine (5 mg/day) and ARB, were enrolled. Participants were randomized to receive either a high dose of amlodipine (10 mg/day) plus a medium dose of ARB (high-AML) or a medium dose of amlodipine (5 mg/day) plus a high dose of ARB (high-ARB). The depressor effects of these two regimens were monitored using a telemonitoring home BP-measuring system. Fifty-four patients were excluded after an observation period, and the remaining 67 eligible participants were randomized into the two groups; 42 which had a record of their home BP for analysis. The change in morning home systolic and diastolic BP was greater in the high-AML than in the high-ARB (systolic BP; - 7.9 mmHg vs. + 2.7 mmHg; p = 0.0002, diastolic BP; - 3.9 mmHg vs. + 0.6 mmHg; p = 0.0007). In addition, the home systolic and diastolic BP before going to bed and office systolic BP were significantly reduced from week 0 only in the high-AML. An increased dose of amlodipine, but not ARB, reduced home morning BP in hypertensive patients with type 2 diabetes who were already receiving combination therapy with medium doses of amlodipine and ARB.

Osteoarthritis constitutes one of the leading causes of pain and disability worldwide with a significant impact on health-care costs. Patients with osteoarthritis are often affected by a number of cardiovascular comorbidities, including hypertension, which is present in about 40% of cases. Just recently, a single tablet combination of amlodipine besylate, a calcium channel blocker, and celecoxib, a nonsteroidal anti-inflammatory drug, indicated for patients for whom treatment with amlodipine for hypertension and celecoxib for osteoarthritis are appropriate, has been recently approved. Areas covered: We reviewed data from clinical studies that investigated safety and efficacy of the combination of amlodipine and celecoxib in hypertensive patients with osteoarthritis published before 31 August 2018. The literature search was conducted using research Methodology Filters. Expert commentary: The advantages of this single formulation over sequential administration include increased compliance, possibly reduced cost, and less likelihood of dosage-related issues. Moreover, this single tablet formulation combines the anti-inflammatory activity of the celecoxib with the systemic vasodilatation induced by the amlodipine. It is a promising treatment for patients with osteoarthritis and hypertension. Nevertheless, celecoxib may cause a variable degree of blood pressure increase and only a small clinical trial has been conducted before approval to assess interactions related to blood pressure effect between these two molecules.

We for the first time report the primitive origins of eukaryotic voltage-gated calcium channels [Cav] in the eukaryotic time-line. The evolution of Cav in eukaryotes is an area of interest for biologists worldwide. The CLAN CL0030 and its family Ion_Trans 2 PF 07885 has been known to be present in prokaryotes, but the origin of these channels in Acanthamoeba are yet to be determined. We inferred the origin of primitive forms of two pore channels [TPC] like proteins, human-like Cav 1.1 of L type and Cav subunit alpha-2/delta in Acanthamoeba spp early during evolution. By in-depth investigation into genomics, transcriptomics, use of bioinformatics tools and experimentations done with drugs like amlodipine and gabapentin on Acanthamoeba spp, we show the evidence of these channels in this protist pathogen. Genomics and transcriptomics of proteins ACA1_167020, 092610 and 270170 reflected their cellular expression in Acanthamoeba spp. We performed amino acid sequence homology, 3D structural modelling, ligand binding predictions and dockings. Bioinformatics and 3D structural models show similarities between ACA1_167020, 092610, 270170 and different types of human Cav. We show the amoebicidal effects of amlodipine and gabapentin on Acanthamoeba which can help design their structural analogs to target Acanthamoeba in diseases like Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis (GAE). This article is protected by copyright. All rights reserved.

The article describes the definition of dementia, its diagnostic criteria, classification. Differences in the pathogenesis and clinical manifestations of different types of dementia are considered. The issues of interrelation of arterial hypertension and the risk of development of cognitive disorders and dementia in old and very old people are discussed in detail. Data on the effect of antihypertensive drugs of different groups on the risk of dementia and the state of cognitive functions are presented. The evidence base of dihydropyridine calcium antagonist amlodipine and thiazide-like diuretic indapamide-retard is discussed with respect to the prevention of dementia and cognitive decline and their beneficial effect on cognitive function in patients with arterial hypertension.

Although orthostatic hypotension (OH) is often considered a contraindication to blood pressure (BP) treatment, evidence is lacking. We examined the effect of BP goal or initial medication choice on OH in AASK (African American Study of Kidney Disease and Hypertension), a 2×3 factorial trial. Blacks with chronic kidney disease attributed to hypertension were randomly assigned 1 of 2 BP goals: intensive (mean arterial pressure, ≤92 mm Hg) or standard (mean arterial pressure, 102-107 mm Hg) and 1 of 3 initial medications (ramipril, metoprolol, and amlodipine). Postural changes in systolic BP, diastolic BP, or heart rate (HR) were determined after 2 minutes and 45 seconds of standing. OH was assessed each visit and defined using the consensus definition (drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg). Median follow-up was 4 years. Outcomes were congestive heart failure, stroke, nonfatal cardiovascular disease (CVD), fatal CVD, any CVD (composite of preceding events), and all-cause mortality. There were 1094 participants (mean age, 54.5±10.7 years; 38.8% female; OH was assessed at 52 864 visits). Mean seated systolic BP, diastolic BP, and HR were 150.3±23.9 mm Hg, 95.5±14.2 mm Hg, and 72.0±12.6 bpm, respectively. A more intensive BP goal did not alter the distributions of standing BP and was not associated with OH, but metoprolol was associated with systolic OH compared with ramipril (odds ratio, 1.68; 95% CI, 1.15-2.46) and amlodipine (odds ratio, 1.94; 95% CI, 1.09-3.44). Although consensus OH was associated with stroke (HR, 5.01; 95% CI, 1.80-13.92), nonfatal CVD (HR, 2.28; 95% CI, 1.21-4.30), and any CVD event (HR, 2.12; 95% CI, 1.12-3.98), neither BP goal or medication altered this risk. Concerns about causing OH or its CVD consequences should not deter a lower BP goal among adults with chronic kidney disease attributed to hypertension.

Amlodipine is a classical drug with varied properties extending from control of blood pressure to as an antianginal and anti atherosclerotic agent. Amlodipine is a longer acting dihydropyridine calcium channel blocker, effective for 24 hours BP control and cause no BP variability. It is a powerful, well-tolerated, and safe antihypertensive agents that is widely used either alone or as a key component of combination therapy for hypertension. Its effective BP reduction has shown proven benefits in cardiovascular event reduction that is supported with strong evidences from large randomised controlled trials. Combination therapies of amlodipine with other agents eliciting renin-angiotensin-aldosterone system blockade (angiotensin II receptor blockers or renin inhibitors) have shown effective blood pressure-lowering strategies in CV risk reduction and progression of renal disease. Novel type of calcium channel blockers have been developed which have additional properties of blocking T and N subtypes of calcium channels and apart from their class effects they exerts specific action on heart rate and renin aldosterone system. They are considered to be more renoprotective due to this additional properties. Amlodipine is most potent and longer acting agent compared to the newer CCBs, its effectiveness in BP lowering still makes it the agent of choice among all the CCBs.