Factors influencing the relationship between the dose of amlodipine required for blood pressure control and change in blood pressure in hypertensive cats

BACKGROUND: Hypertension is a common problem in elderly cats. In most cats, systolic blood pressure (SBP) of <160 mmHg is achieved in response to amlodipine besylate at either 0.625 or 1.25 mg q24h. The individual cat factors determining dose requirement dose have not been explored. AIMS: To determine whether individual cat factors influence the dose of amlodipine required to achieve adequate blood pressure control and to determine whether factors other than the prescribed dose of drug alter the achieved plasma amlodipine concentrations. METHODS: Fifty‐nine hypertensive cats that required 0.625 mg (A) and 41 cats that required 1.25 mg (B) amlodipine to reach a target SBP of <160 mmHg were identified, and plasma amlodipine concentrations were determined. Comparisons were made between groups, and multivariable linear regression models were performed to investigate predictors of antihypertensive response. RESULTS: Cats that required a greater dose of amlodipine had significantly higher SBP at diagnosis of hypertension (A: (median [25th, 75th percentile]) 182 [175,192] mmHg; B: 207 [194,217] mmHg, P < .001), but comparable blood pressure was achieved after treatment. Plasma amlodipine concentrations were directly related to the dose of amlodipine administered. At diagnosis, cats in group B had significantly lower plasma potassium concentration (A: 4.1 [3.8,4.5]; B: 3.8 [3.6,4.2] mEq/L, P < .01). Weight did not differ between groups. The decrease in SBP was directly and independently associated with the SBP at diagnosis and the plasma amlodipine concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with higher blood pressure at diagnosis might require a greater dose of amlodipine to control their blood pressure adequately. Differences in amlodipine pharmacokinetics between cats do not seem to play a role in the antihypertensive response

Antidepressive and anxiolytic effects of ostruthin, a TREK-1 channel activator

We screened a library of botanical compounds purified from plants of Vietnam for modulators of the activity of a two-pore domain K+ channel, TREK-1, and we identified a hydroxycoumarin-related compound, ostruthin, as an activator of this channel. Ostruthin increased whole-cell TREK-1 channel currents in 293T cells at a low concentration (EC50 = 5.3 μM), and also activity of the TREK-2 channel (EC50 = 3.7 mM). In contrast, ostruthin inhibited other K+ channels, e.g. human ether-à-go-go-related gene (HERG1), inward-rectifier (Kir2.1), voltage-gated (Kv1.4), and two-pore domain (TASK-1) at higher concentrations, without affecting voltage-gated potassium channel (KCNQ1 and 3). We tested the effect of this compound on mouse anxiety- and depression-like behaviors and found anxiolytic activity in the open-field, elevated plus maze, and light/dark box tests. Of note, ostruthin also showed antidepressive effects in the forced swim and tail suspension tests, although previous studies reported that inhibition of TREK-1 channels resulted in an antidepressive effect. The anxiolytic and antidepressive effect was diminished by co-administration of a TREK-1 blocker, amlodipine, indicating the involvement of TREK-1 channels. Administration of ostruthin suppressed the stress-induced increase in anti-c-Fos immunoreactivity in the lateral septum, without affecting immunoreactivity in other mood disorder-related nuclei, e.g. the amygdala, paraventricular nuclei, and dorsal raphe nucleus. Ostruthin may exert its anxiolytic and antidepressive effects through a different mechanism from current drugs

Hypertension

Hypertension is a rapidly moving clinical field with frequent developments in new pharmacologic agents and management strategies. Perhaps more importantly, there have been substantial improvements in our understanding of how best to use the drugs available to us. In this article, I will review some of the more important advances in our understanding of hypertension over the past two years, specifically by reviewing six important trials, one survey and two sets of guidelines, all published between January 2002 and June 2004.peer-reviewe

A survey of Top 200 Drugs—Inconsistent Practice of Drug Strength Expression for Drugs Containing Salt Forms

Many ionizable drugs are developed and marketed as salt forms. However, there are no clear US regulatory guidelines on drug strength labeling for salts. The strengths of some drugs are expressed as salts and some as free acids/bases. This study surveyed the top 200 US drugs to assess the common practice in industry. The top 200 drugs prescribed in the United States were included in this survey. The drugs containing active pharmaceutical ingredient (API) salts were selected for analysis. Generic or combination products with redundant API salts were excluded. The package insert of each selected drug was reviewed, and the information on drug strength expression was extracted and categorized. Out of the top 200 drugs, 59 unique API salts were identified. The drug strengths were expressed as salts for 32 drugs (54%) and as free acids/bases for 27 drugs (46%). The survey results revealed the inconsistent practice among the industries regarding the drug strength expression for salts. Non-harmonized labeling practice can lead to confusions, potential calculation/dosing errors, and complications in labeling new products. The authors recommend the US Food and Drug Administration to standardize the labeling format for salts and preferably express the drug strengths based on the free acid/base forms. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association

Economic evaluation of ASCOT-BPLA: Antihypertensive treatment with an amlodipine-based regimen is cost-effective compared to an atenolol-based regimen

Copyright © 2010 BMJ Publishing Group Ltd & British Cardiovascular Society. Internal or personal use of this material is permitted. However, permission to reprint/republish this material must be obtained from the Publisher.Objective: To compare the cost effectiveness of an amlodipine-based strategy and an atenolol-based strategy in the treatment of hypertension in the UK and Sweden. Design: A prospective, randomised trial complemented with a Markov model to assess long-term costs and health effects. Setting: Primary care. Patients: Patients with moderate hypertension and three or more additional risk factors. Interventions: Amlodipine 5–10 mg with perindopril 4–8 mg added as needed or atenolol 50–100 mg with bendroflumethiazide 1.25–2.5 mg and potassium added as needed Main outcome measures: Cost per cardiovascular event and procedure avoided, and cost per quality-adjusted life-year gained. Results: In the UK, the cost to avoid one cardiovascular event or procedure would be €18 965, and the cost to gain one quality-adjusted life-year would be €21 875. The corresponding figures for Sweden were €13 210 and €16 856. Conclusions: Compared with the thresholds applied by NICE and in the Swedish National Board of Health and Welfare’s Guidelines for Cardiac Care, an amlodipine-based regimen is cost effective for the treatment of hypertension compared with an atenolol-based regimen in the population studied.The study was supported by the principal funding source, Pfizer, New York, USA

Is early and fast blood pressure control important in hypertension management?

Control of blood pressure (BP) in hypertension is recognized as a key measure in the management of cardiovascular (CV) risk and is a cornerstone of preventive strategies. It is not defined, however, whether an initiation of the antihypertensive treatment in the early stages of hypertension (such as prehypertension or high-normal BP), may bring benefits for the long-term prevention of CV events. In addition, it has not been thoroughly addressed the issue whether achievement of a prompt BP reduction in hypertensive patients may contribute to reduce CV damage and events. The aim of this article is to critically examine data from studies exploring these important questions. Our conclusion is that the available evidence, though not very extensive, supports the prevailing benefits associated with early BP control. We also discuss the therapeutic strategies to achieve early control of BP. Finally, we believe that this aspect deserves to be more thoroughly addressed in upcoming international guidelines

Olmesartan-based monotherapy vs combination therapy in hypertension: A meta-analysis based on age and chronic kidney disease status.

Antihypertensive monotherapy is often insufficient to control blood pressure (BP). Several recent guidelines advocate for initial combination drug therapy in many patients. This meta-analysis of seven randomized, double-blind studies (N = 5888) evaluated 8 weeks of olmesartan medoxomil (OM)-based single-pill dual-combination therapy (OM+amlodipine/azelnidipine or hydrochlorothiazide) vs OM monotherapy in adults with hypertension. BP-lowering efficacy, goal achievement, and adverse events were assessed in the full cohort and subgroups (elderly/nonelderly and patients with and without chronic kidney disease). In the full cohort at week 8, for dual therapy vs monotherapy, seated BP was lower (137.5/86.1 mm Hg vs 144.4/89.9 mm Hg), and the mean change from baseline in BP and BP goal achievement (&lt;140/90 mm Hg) were greater (-22.7/-15.0 mm Hg vs -16.0/-11.3 mm Hg and 51.2% vs 34.7%, respectively). Adverse events were similar between groups. BP-lowering efficacy among subgroups mirrored the findings in the full cohort whereby changes were significantly greater following OM dual-combination therapy vs OM monotherapy

The Method of Forecasting of the Indicators for Drug Reimbursement to Patients with Cardiovascular Diseases in Ukraine

The aim of the study is to develop a method for forecasting the indicators for drug reimbursement to patients with cardiovascular diseases (CVD) in Ukraine within the framework of the government program “Available medicines”.Materials and methods: materials of the State Statistics Service of Ukraine and medical records of patients with CVD, who were prescribed with medicines according to the government program, were used in the study.Results: according to the method proposed for forecasting the volume of drug reimbursement to patients with CVD under the government program it has been found that Enalapril has the highest indicator – 10916.4 USD thousand in 2019 and 10736.8 USD thousand in 2020. Clopidogrel takes the second position – 12108.13 USD thousand and 11908.24 USD thousand, while Amlodipine occupies the third position – 9105.60 USD thousand and 8955.28 USD thousand.Among the medicines not included in the government program, but prescribed rather frequently the largest forecasting amount required for reimbursement (in case of inclusion in the program) is 18910.55 USD thousand in 2019 and 18598.36 USD thousand in 2020 for Magnicor, and the least amount is 444.55 USD thousand and 437.22 USD thousand for Acetylsalicylic acid, respectively.Conclusions. The government program to provide patients with effective and affordable medicines has a significant impact on reforming the healthcare system of Ukraine. The study conducted can be used to expand the government program in the process of formation and distribution of budget funds