Administration Of Calcium Channel Antagonists Research Articles

The impact of fixed combination of amlodipine and perindopril (drug Prestance)on the mechanisms of heat adaptation in patients with arterial hypertension

Relevance. The impact of the drugs on adaptation to the heat wave of abnormal temperature has been one of the most important practical medicine questions, concerning heat waves, recent years. One of the points at issue is safety administration of calcium channel antagonists and ACE inhibitors during abnormal heat.Aim of the study is to assess the efficacy and safety of the fixed combination of perindopril arginine (drug Prestance, Servier Industries, Ltd.)/amlodipine in patients with arterial hypertension (AH) during the summer heat and the summer heat influence on the mechanisms of heat adaptation to abnormally high temperature.Material and methods: The study enrolled 165 patients with stages 1-2 AH: 69 patients with average risk and 91 patients with high/very high risk of cardiovascular complications. There were 69 men and 96 women in the study, living in Moscow city, in the Moscow and in the Ivanovo Regions. All patients were measuring office BP, undergoing biochemical analysis of blood, running questionnaire survey: visual analogue scale (VAS), questionnaire for the patients who were exposed to heat, the level of products reacting with the 2-thiobarbituric acid (malonyldialdehyde, MDA) and activity of superoxide dismutase (SOD) using standard test-kits and the pulse ware velocity (PWV) was measured in 30 patients. The first visit was in the first half of June 2013, the second visit - during the heat (July 2013) and the third one in September 2013.Results: In the course of the study SBP (systolic BP) and DBP (diastolic BP) were reduced (р

Влияние фиксированной комбинации амлодипина и периндоприла (препарат Престанс) на механизмы тепловой адаптации у больных артериальной гипертонией

Relevance. The impact of the drugs on adaptation to the heat wave of abnormal temperature has been one of the most important practical medicine questions, concerning heat waves, recent years. One of the points at issue is safety administration of calcium channel antagonists and ACE inhibitors during abnormal heat.Aim of the study is to assess the efficacy and safety of the fixed combination of perindopril arginine (drug Prestance, Servier Industries, Ltd.)/amlodipine in patients with arterial hypertension (AH) during the summer heat and the summer heat influence on the mechanisms of heat adaptation to abnormally high temperature.Material and methods: The study enrolled 165 patients with stages 1-2 AH: 69 patients with average risk and 91 patients with high/very high risk of cardiovascular complications. There were 69 men and 96 women in the study, living in Moscow city, in the Moscow and in the Ivanovo Regions. All patients were measuring office BP, undergoing biochemical analysis of blood, running questionnaire survey: visual analogue scale (VAS), questionnaire for the patients who were exposed to heat, the level of products reacting with the 2-thiobarbituric acid (malonyldialdehyde, MDA) and activity of superoxide dismutase (SOD) using standard test-kits and the pulse ware velocity (PWV) was measured in 30 patients. The first visit was in the first half of June 2013, the second visit - during the heat (July 2013) and the third one in September 2013.Results: In the course of the study SBP (systolic BP) and DBP (diastolic BP) were reduced (р<0,00001), target level of SBP and DBP reached 73,9% (41,9% - the second visit).We observed the increase of VAS scores, hyperkalemia (р=0,0056), hyponatremia (р=0,00042), hypocreatinemia (р=0,018), hypocholesterolemia (р<0,00001), hypotrigliceridemia (р=0,027), hypoglucosemia (р=0,0035). We were observing the reduction of PWV and of the characteristics of oxidative stress (MDA, р<0,0001 and MDA/ SOD, р<0.001) during the peak of the heat, during the 3ed visit. Conclusion: Prestance therapy during the summer heat showed efficacy and safety and was well tolerated by AH patients without any signs of hypotension and electrolyte imbalance which were attributed to body heat. The improvement of adaptive human body response was associated with effective arterial elastance and reduction of oxidative stress.

Update on endovascular therapies for cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage

Cerebral vasospasm remains a major source of morbidity and death in patients with aneurysmal subarachnoid hemorrhage (SAH). When vasospasm becomes refractory to maximal medical management consisting of induced hypertension and hypervolemia and administration of calcium channel antagonists, endovascular therapies should be considered. The primary goal of endovascular treatment is to increase cerebral blood flow to prevent cerebral infarction. Two of the more frequently studied endovascular treatments are transluminal balloon angioplasty and intraarterial papaverine infusion. These two have been used either alone or in combination for the treatment of vasospasm. Other pharmacological vasodilating agents currently being investigated are intraarterial nimodipine, nicardipine, verapamil, and milrinone. Newer intraarterial agents, such as fasudil and colforsin daropate, have also been investigated. In this article the authors review the current options in terms of endovascular therapies for treatment of cerebral vasospasm. The mechanism of action, technique of administration, clinical effect and outcomes, and complications of each modality are discussed.

Drug therapy of primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is a rare but life-threatening disease. Median survival, from the time of diagnosis, is considered to be 2.8 years. However, therapeutic medical advances over the past 2 decades have resulted in significant improvements in quality of life and survival in patients with PPH. Because pulmonary vasoconstriction, endothelial cell proliferation, smooth muscle cell proliferation, and in situ thrombosis contribute to the development of this disease, treatment with vasodilators, anti-proliferative agents, and anticoagulants is recommended.Currently, oral administration of calcium channel antagonists and intravenous infusion of epoprostenol (prostacyclin) are established as treatment of PPH. Epoprostenol has vasoprotective effects including vasodilation, anti-platelet aggregation, and inhibition of smooth muscle cell proliferation. Interestingly, prostacyclin synthase deficiency in the lungs, and impaired prostacyclin production, have been linked to the development of pulmonary hypertension in this disease. As a result, continuous intravenous infusion of epoprostenol has become recognized as a therapeutic breakthrough that can improve hemodynamics and survival in patients with PPH. The dramatic success of long-term intravenous prostacyclin is now leading to the development of epoprostenol analogs using newer drug delivery systems (oral beraprost, aerosolized iloprost, and subcutaneous treprostinil). In addition, promising drugs including endothelin antagonists and type V phosphodiesterase inhibitors have recently been developed. Furthermore, gene therapy with endothelial nitric oxide synthase gene or prostacyclin synthase gene may hold great promise in the treatment of PPH. Finally, accurate evaluation of disease severity and the efficacy of vasodilator therapy are important in the management of patients with PPH. In addition to invasive assessment by cardiac catheterization, we recommend repeated measurements of plasma brain natriuretic peptide, serum uric acid, and the distance walked in 6 minutes. These noninvasive parameters may be helpful as part of the evaluation of treatment in patients with PPH and, in particular, as a guide to the selection and timing for alternative therapies.

Effects of Intrathecal Calcium Channel Blockers on the MAC of Isoflurane in Rats

Background: Much evidence suggests that the spinal cord may be an important anesthetic action site. Volatile anesthetics have been shown to inhibit neurotransmitter release by inhibition of intracellular calcium entry. Many types of calcium channels (L, N, P, Q, T) were demonstrated in the dorsal horn of the spinal cord. Therefore, the aim of this study was to determine whether intrathecal calcium channel antagonists may change the minimum alveolar concentration (MAC) of isoflurane in rats and examine the role of spinal calcium channels for anesthetic action of isoflurane. Methods: In Sprague-Dawley rats, the MAC of isoflurane was determined by the tail-clamp technique. First, control MAC was determined and then changes of control MAC were observed after intrathecal administration of calcium channel antagonists. Change of mean arterial pressure (MAP) and general behavior were also examined following intrathecal delivery of calcium channel antagonists. Results: Neither abnormal behavior nor change of MAP occured after intrathecal injection of all types of calcium channel antagonists. All drugs decreased the MAC of isoflurane. Conclusions: These results suggested that L, N, P, Q and T types of the calcium channel might play an important role in determining the MAC of isoflurane in the spinal cord.

Diffuse spasm of a free gastroepiploic artery graft during percutaneous balloon angioplasty

Percutaneous transluminal balloon dilation of an 8-month-old free graft of the gastroepiploic artery was followed by diffuse and profound graft spasm. Because free arterial grafts are more prone to spasm, suitable precautions, such as administration of calcium channel antagonists, should be taken before attempting any interventions on these vessels.

The effects of chronic treatment with the dihydropyridine, Bay K 8644, on hyperexcitability due to ethanol withdrawal, in vivo and in vitro.

1. The effects of chronic treatment with the dihydropyridine, Bay K 8644, were studied on the ethanol withdrawal syndrome, in vivo and in vitro. 2. Addition of racemic Bay K 8644 to the drinking mixture, throughout the chronic ethanol treatment, decreased the behavioural excitability seen during ethanol withdrawal in vivo. 3. All the signs of hyperexcitability in field potentials in the isolated hippocampal slice, caused by ethanol withdrawal, were decreased by the chronic administration of Bay K 8644. 4. These effects resembled those previously reported for chronic administration of calcium channel antagonists; racemic Bay K 8644 has both calcium channel activating and antagonist properties. 5. Measurement of brain levels of Bay K 8644 at the end of the chronic treatment showed that the compound reached micromolar concentrations during the treatment, but none could be detected in the tissues at the time of the above measurements. 6. It is possible that the results might be explained by predominance of the calcium channel antagonist properties of this compound, owing to the high central concentrations achieved during the treatment. Tolerance to the calcium channel activating properties of Bay K 8644 may also have occurred during the chronic treatment.

Some behavioral effects of repeated administration of calcium channel antagonists

The effect of the calcium channel antagonists nifedipine, nimodipine, and diltiazem (10 mg/kg PO) was studied after single and repeated administration to rats. All the compounds administered repeatedly reduced significantly the duration of immobility in the forced swimming test. At the same time the locomotor activity of rats was reduced (nifedipine, nimodipine) or unchanged (diltiazem). All the calcium channel antagonists studied did not modify the behavior of normal or phenylephrine-stimulated rats in the open field test. Only nimodipine, given repeatedly, was able to antagonize the clonidine-induced behavioral inhibition in the latter test. The results indicate that, like antidepressants, calcium channel antagonists given repeatedly to rats reduce the immobility time in the forced swimming test, but do not change the responsiveness of α 1- and α 2-adrenoceptors to their agonists.

The neurochemistry of mania: The effect of lithium on catecholamines, indoleamines and calcium mobilization

In an attempt to elucidate the chemical pathology of mania one has to consider the pharmacology of the two most effective treatments for this illness: lithium and the neuroleptics. Some of the possible mechanisms of action of these drugs on catecholamine and indoleamine mechanisms are discussed. The majority of this article is based on my and my colleagues' work which has been carried out in this MRC Laboratory on the effect of lithium on biological variates in bipolar patients and the effects of the administration of antidepressant treatments in these patients. It is concluded that lithium has a similar action on these mechanisms in both unipolar and bipolar patients which might suggest a common pathology in both unipolar and bipolar illness. It is suggested that in order to maintain an euthymic state in a bipolar patient one should maintain a certain degree of sensitivity of 5-HT 2 receptors. This sensitivity may be related to the activity of calcium channels and to the polyphosphoinositide system. The former system can be regulated by the administration of calcium channel antagonists which have been shown to be effective in the treatment of mania. The polyphosphoinositide system is one that can be regulated by therapeutic concentrations of lithium. It is concluded that co-administration of a calcium channel antagonist and lithium may be a very effective treatment for mania.