Losartan and Eprosartan Induce a Similar Effect on the Acute Rise in Serum Uric Acid Concentration after an Oral Fructose Load in Patients with Metabolic Syndrome

Introduction. Excessive intake of fructose increases serum uric acid concentration. Hyperuricemia induces a negative effect on atherosclerosis and inflammation. Hyperuricemia is common in patients with arterial hypertension. Several antihypertensive drugs including diuretics increase serum uric acid concentration. In contrast, the angiotensin II receptor antagonist (ARB) losartan was found to lower serum uric acid though it may increase renal excretion while other ARBs showed mostly a neutral effect. In this study, effects of two AT1 receptor antagonists losartan and eprosartan on serum uric acid changes induced by oral fructose load were directly compared. Methods. The randomized, crossover, head-to-head comparative study comprised 16 ambulatory patients (mean age 64.5 ± 9.8 years). The patients fulfilled AHA/NHLBI 2005 criteria of metabolic syndrome. A daily single morning dose of each study drug (50 mg of losartan or 600 mg of eprosartan) was given during two 3-month periods in a random order separated by 2-week washout time. The oral fructose tolerance test (OFTT) was performed at baseline and after each two 3-onth treatment periods. Before and during OFTT, urine excretion of uric acid and creatinine was assessed in the first morning portion of urine. Blood samples for the measurement of serum uric acid and lipids were taken at baseline and 30, 60, and 120 minutes after oral intake of 75 g of fructose. Results. After 3-month treatment with eprosartan and losartan, both systolic and diastolic blood pressure decreased significantly and to a similar extent. After the treatment, serum uric acid and its baseline and postfructose urine excretion were unchanged. No significant changes of plasma lipids before and after OFTT were observed throughout the study. Conclusions. The study showed that in patients with hypertension and metabolic syndrome, both losartan and eprosartan have a neutral effect on fasting and postfructose load serum uric acid concentration and its urinary excretion. This trial is registered with NCT04954560.

Evaluation of anticonvulsant activity of angiotensin receptor antagonists in an animal model

Background: Epilepsy is common chronic disorder in clinical practice and there was some studies which shows brain renin angiotensin system may be involved in upregulation of seizures hence present study was planned to investigate whether angiotensin II AT1 receptor antagonists possess anticonvulsant activity in experimental animals.Methods: The anticonvulsant activity of angiotensin receptor antagonists, losartan (50 mg/kg), telmisartan (30 mg/kg) and candesartan (20 mg/kg), were administered intraperitoneally to the mice and evaluated by using maximum electroshock (MES) and pentylenetetrazol induced seizures (PTZ) seizure methods. The standard was taken as phenytoin for MES and diazepam for PTZ method. Motor impairment of performance was assessed by the inverted screen test and spontaneous motor activity with digital actophotometer.Results: Losartan demonstrated the anticonvulsant efficacy in MES and PTZ models. Telmisartan and candesartan have anticonvulsant activity in MES induced seizures, but did not show protection against pentylenetetrazol induced seizures. Losartan at dose 50 mg/kg prolonged the mean latency to convulsion (p<0.01) and mean number of convulsions also significantly reduced (p<0.05) convulsions in the mice. Telmisartan and candesartan at dose 30 mg/kg and 20 mg/kg respectively showed significant prolongation in mean latency to convulsion (p<0.05). None of the test drugs i.e. angiotensin receptor antagonists showed significant motor impairment.Conclusions: Angiotensin receptor antagonists: losartan, telmisartan and candesartan had showed anticonvulsant activity in PTZ and MES seizure methods. The exact mechanism of action of their anticonvulsant action not precisely known and hence there is more studies need to test it in various other animal anticonvulsant models.

Renin-Angiotensin-Aldosterone System and Migraine: A Systematic Review of Human Studies

Migraine is a common neurologic condition marked by recurrent episodes of headache. Its pathophysiology is highly complex involving neuronal, inflammatory and vascular mechanisms. The Renin-Angiotensin System (RAS) can modulate all these mechanism, being a potential pharmacological target for migraine treatment. We carried out a systematic review of the studies evaluating the involvement of RAS in patients with migraine. There is evidence from genetic studies exploring the relation between migraine and RAS-related genes and from clinical trials evaluating the efficacy of Angiotensin II Type 1 (AT1) receptor antagonists and angiotensin converting enzyme inhibitors in migraine prophylaxis. RAS seems to play a role in the pathophysiology of migraine, but more direct evidence is still missing.

Angiotensin ii and its role in regulation of heart tolerance to ischemia/reperfusion inhibitors and angiotensin ii at1-receptor antagonists

Цель обзора - анализ данных о роли ангиотензина II в регуляции толерантности сердца к действию ишемии/реперфузии, а также анализ данных о кардиопротекторных свойствах ингибиторов ангиотензинпревращающего фермента (АПФ) и антагонистов АТ1-рецептора ангиотензина II. Установлено, что ангиотензин II оказывает инфаркт-лимитирующий эффект, который, по одним данным, связан с активацией АТ1-рецептора, по другим - является следствием стимуляции АТ2-рецептора. Кроме того, ангиотензин способствовал улучшению сократимости сердца в реперфузионном периоде, эффект был связан с активацией AT1-рецептора. Установлено, что ангиотензин II и АТ1-рецептор участвуют в инфаркт-лимитирующем эффекте ишемического прекондиционирования. Экспериментальные данные о способности антагонистов AT1-рецептора влиять на размер инфаркта носят противоречивый характер: есть сообщения о способности этих антагонистов оказывать инфаркт-лимитирующий эффект, есть данные об отсутствии у них подобного эффекта. Экспериментальные данные свидетельствуют, что ингибиторы АПФ оказывают инфаркт-лимитирующий эффект, который связан с увеличением уровня брадикинина и усилением продукции NO. Нет убедительных данных о том, ингибиторы АПФ и антагонисты АТ1-рецептора оказывают инфаркт-лимитирующий эффект у пациентов с острым инфарктом миокарда. Однако ингибиторы АПФ и антагонисты АТ1-рецептора препятствуют постинфарктному ремоделированию сердца. The review analyzes reports on the role of angiotensin II in regulation of heart tolerance to ischemia/reperfusion and cardioprotective properties of angiotensin converting enzyme (ACE) inhibitors and angiotensin II AT1-receptor antagonists. Angiotensin II is known to have an infarct-limiting effect, which according to some reports is associated with activation of the AT1 receptor and according to other reports results from stimulation of the AT2 receptor. In addition, angiotensin improves heart contractility during reperfusion, which is associated with activation of the AT1 receptor. Angiotensin II and AT1 receptor are also involved in the infarct-reducing effect of ischemic preconditioning. Experimental data on the ability of AT1 receptor antagonists to influence the infarct size are inconsistent; one study showed that these antagonists can exert an infarct-limiting effect whereas there is some evidence against such effect. Experimental studies have suggested that ACE inhibitors can restrict the infarct size, which is associated with increased bradykinin level and NO production. There is no convincing evidence that ACE inhibitors and AT1 receptor antagonists can restrict the infarct size in patients with acute myocardial infarction. However, ACE inhibitors and AT1 receptor antagonists prevent post-infarction heart remodeling.

CHALLENGES FOR GENERIC DRUG PRODUCERS

In the fiercely competitive global market for generic drugs, the complexities and interconnectivities come to the fore when a drug is recalled. In recent months, as you may be aware, the sartans (also known as AT1 receptor antagonists, angiotensin II receptor blockers/antagonists) have come into the limelight due to the recall of some of them from the regulated markets of USA and Europe.