scholarly journals A Review of the Pharmacokinetics, Pharmacodynamics and Efficacy of Zolmitriptan in the Acute Abortive Treatment of Migraine

2009 ◽  
Vol 1 ◽  
pp. CMT.S2056
Author(s):  
A.A. Kalanuria ◽  
B.L. Peterlin
Keyword(s):  
Nasal Spray ◽  
Plasma Proteins ◽  
Peak Plasma ◽  
Pharmacological Agents ◽  
Orally Disintegrating Tablet ◽  
Central Processing ◽  
Nociceptive Pathways ◽  
Abortive Treatment ◽  
Migraine Pathophysiology

Migraine is a common and often disabling neurovascular disorder. Changes in the metabolism and the central processing of serotonin, as well as abnormalities in the modulation of the central and peripheral trigeminal nociceptive pathways, have been shown to play significant roles in migraine pathophysiology. Recent evidence suggests that a low serotonin state facilitates activation of the trigeminal nociceptive pathways. In addition, several pharmacological agents that modulate serotonin are used in the treatment of migraine. Specifically there are seven FDA approved, 5-hydroxytryptamine (5-HT) 1B/1D receptor agonists, used for the acute abortive therapy of migraine. Zolmitriptan is one such triptan. Zolmitriptan is available as a tablet, orally disintegrating tablet and as a nasal spray. It is rapidly absorbed and detectable within the plasma, within 2 to 5 minutes for the nasal spray and within 15 minutes for the tablet. Zolmitriptan reaches peak plasma levels in 2-4 hours, with good levels maintained for up to 6 hours. Although the metabolism of zolmitriptan is predominantly hepatic, only 25% of zolmitriptan is bound to plasma proteins. Thus it is unlikely for drug interactions involving the displacement of highly protein-bound drugs. Zolmitriptan is very well tolerated with less than half of participants in clinical trials reporting adverse events, most of which were mild and transient. Although rare, serious cardiovascular events have been reported with all triptans. However, when patients are appropriately selected, zolmitriptan is both, a safe and effective acute migraine abortive agent. In this article, we will first briefly review the biological role of serotonin and the literature linking serotonin to migraine pathophysiology. This will be followed by a comprehensive review of the pharmacodynamics, pharmacokinetics and efficacy of zolmitriptan. Finally, the clinical application of the use of zolmitriptan in migraine therapy will be discussed.

Haemostatic Platelet Plug Formation in the Isolated Rabbit Mesenteric Preparation - An Analysis of Red Blood Cell Participation

1980 ◽  
Vol 44 (01) ◽  
pp. 006-008 ◽  
Author(s):  
D Bergqvist ◽  
K-E Arfors
Keyword(s):  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
In Vitro Test ◽  
Pharmacological Agents ◽  
Vitro Test ◽  
Releasing Effect ◽  
Plug Formation

SummaryIn a model using an isolated rabbit mesenteric preparation microvessels were transected and the time until haemostatic plugs formed was registered. Perfusion of platelet rich plasma gave no haemostasis whereas whole blood did. Addition of chlorpromazine or adenosine to the whole blood significantly prolonged the time for haemostasis, and addition of ADP to the platelet rich plasma significantly shortened it. It is concluded that red cells are necessary for a normal haemostasis in this model, probably by a combination of a haemodynamic and ADP releasing effect.The fundamental role of platelets in haemostatic plug formation is unquestionable but there are still problems concerning the stimulus for this process to start. Three platelet aggregating substances have been discussed – thrombin, adenosine diphosphate (ADP) and collagen. Evidence speaking in favour of thrombin is, however, very minimal, and the discussion has to be focused on collagen and ADP. In an in vitro system using polyethylene tubings we have shown that "haemostasis" can be obtained without the presence of collagen but against these results can be argued that it is only another in vitro test for platelet aggregation (1).To be able to induce haemostasis in this model, however, the presence of red blood cells is necessary. To further study this problem we have developed a model where haemostatic plug formation can be studied in the isolated rabbit mesentery and we have briefly reported on this (2).Thus, it is possible to perfuse the vessels with whole blood as well as with platelet rich plasma (PRP) and different pharmacological agents of importance.

Chemo- and Optogenetic Strategies for the Elucidation of Pain Pathways

2019 ◽  
pp. 816-832 ◽  
Author(s):  
Sascha R. A. Alles ◽  
Anne-Marie Malfait ◽  
Richard J. Miller
Keyword(s):  
Chronic Pain ◽  
Pain Response ◽  
Conscious Perception ◽  
Novel Therapies ◽  
The Past ◽  
Nociceptive Pathways ◽  
Pain Pathways ◽  
Technical Advances ◽  
The Brain

Pain is not a simple phenomenon and, beyond its conscious perception, involves circuitry that allows the brain to provide an affective context for nociception, which can influence mood and memory. In the past decade, neurobiological techniques have been developed that allow investigators to elucidate the importance of particular groups of neurons in different aspects of the pain response, something that may have important translational implications for the development of novel therapies. Chemo- and optogenetics represent two of the most important technical advances of recent times for gaining understanding of physiological circuitry underlying complex behaviors. The use of these techniques for teasing out the role of neurons and glia in nociceptive pathways is a rapidly growing area of research. The major findings of studies focused on understanding circuitry involved in different aspects of nociception and pain are highlighted in this article. In addition, attention is drawn to the possibility of modification of chemo- and optogenetic techniques for use as potential therapies for treatment of chronic pain disorders in human patients.

scholarly journals Endothelial Dysfunction in Diabetes Is Aggravated by Glycated Lipoproteins; Novel Molecular Therapies

Biomedicines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 18
Author(s):  
Laura Toma ◽  
Camelia Sorina Stancu ◽  
Anca Volumnia Sima
Keyword(s):  
Plasma Proteins ◽  
Diabetes Complications ◽  
Vascular Complications ◽  
High Density Lipoproteins ◽  
Diabetic Patients ◽  
Inflammatory Stress ◽  
Glycation End Products ◽  
Molecular Therapies ◽  
Specific Receptors

Diabetes and its vascular complications affect an increasing number of people. This disease of epidemic proportion nowadays involves abnormalities of large and small blood vessels, all commencing with alterations of the endothelial cell (EC) functions. Cardiovascular diseases are a major cause of death and disability among diabetic patients. In diabetes, EC dysfunction (ECD) is induced by the pathological increase of glucose and by the appearance of advanced glycation end products (AGE) attached to the plasma proteins, including lipoproteins. AGE proteins interact with their specific receptors on EC plasma membrane promoting activation of signaling pathways, resulting in decreased nitric oxide bioavailability, increased intracellular oxidative and inflammatory stress, causing dysfunction and finally apoptosis of EC. Irreversibly glycated lipoproteins (AGE-Lp) were proven to have an important role in accelerating atherosclerosis in diabetes. The aim of the present review is to present up-to-date information connecting hyperglycemia, ECD and two classes of glycated Lp, glycated low-density lipoproteins and glycated high-density lipoproteins, which contribute to the aggravation of diabetes complications. We will highlight the role of dyslipidemia, oxidative and inflammatory stress and epigenetic risk factors, along with the specific mechanisms connecting them, as well as the new promising therapies to alleviate ECD in diabetes.

scholarly journals The Role of Microbiota in Primary Sclerosing Cholangitis and Related Biliary Malignancies

2021 ◽  
Vol 22 (13) ◽  
pp. 6975
Author(s):  
Burcin Özdirik ◽  
Tobias Müller ◽  
Alexander Wree ◽  
Frank Tacke ◽  
Michael Sigal
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Gut Microbiome ◽  
Sclerosing Cholangitis ◽  
Functional Characterization ◽  
Significant Risk ◽  
Pharmacological Agents ◽  
Experimental Mouse ◽  
Biliary Malignancies ◽  
End Stage

Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy characterized by biliary inflammation, cholestasis, and multifocal bile duct strictures. It is associated with high rates of progression to end-stage liver disease as well as a significant risk of cholangiocarcinoma (CCA), gallbladder cancer, and colorectal carcinoma. Currently, no effective medical treatment with an impact on the overall survival is available, and liver transplantation is the only curative treatment option. Emerging evidence indicates that gut microbiota is associated with disease pathogenesis. Several studies analyzing fecal and mucosal samples demonstrate a distinct gut microbiome in individuals with PSC compared to healthy controls and individuals with inflammatory bowel disease (IBD) without PSC. Experimental mouse and observational human data suggest that a diverse set of microbial functions may be relevant, including microbial metabolites and bacterial processing of pharmacological agents, bile acids, or dietary compounds, altogether driving the intrahepatic inflammation. Despite critical progress in this field over the past years, further functional characterization of the role of the microbiota in PSC and related malignancies is needed. In this review, we discuss the available data on the role of the gut microbiome and elucidate important insights into underlying pathogenic mechanisms and possible microbe-altering interventions.

scholarly journals Anti-neoplastic Potential of Flavonoids and Polysaccharide Phytochemicals in Glioblastoma

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4895
Author(s):  
Ayesha Atiq ◽  
Ishwar Parhar
Keyword(s):  
Cancer Progression ◽  
Therapeutic Option ◽  
Normal Brain ◽  
Current Standard ◽  
Pharmacological Agents ◽  
Initiation Phase ◽  
Therapeutic Outcomes ◽  
Effective Therapeutic Option ◽  
Patient Prognosis

Clinically, gliomas are classified into four grades, with grade IV glioblastoma multiforme being the most malignant and deadly, which accounts for 50% of all gliomas. Characteristically, glioblastoma involves the aggressive proliferation of cells and invasion of normal brain tissue, outcomes as poor patient prognosis. With the current standard therapy of glioblastoma; surgical resection and radiotherapy followed by adjuvant chemotherapy with temozolomide, it remains fatal, because of the development of drug resistance, tumor recurrence, and metastasis. Therefore, the need for the effective therapeutic option for glioblastoma remains elusive. Previous studies have demonstrated the chemopreventive role of naturally occurring pharmacological agents through preventing or reversing the initiation phase of carcinogenesis or arresting the cancer progression phase. In this review, we discuss the role of natural phytochemicals in the amelioration of glioblastoma, with the aim to improve therapeutic outcomes, and minimize the adverse side effects to improve patient’s prognosis and enhancing their quality of life.

The role of plasma proteins and stress in the assessment of hemocompatibility

1999 ◽  
Vol 46 (2) ◽  
pp. 186-192 ◽  
Author(s):  
R. Barbucci ◽  
S. Lamponi ◽  
A. M. Aloisi
Keyword(s):  
Plasma Proteins

The potential role of stress and sex steroids in heritable effects of sevoflurane

2021 ◽  
Author(s):  
Anatoly E Martynyuk ◽  
Ling-Sha Ju ◽  
Timothy E Morey
Keyword(s):  
Sex Steroids ◽  
Age Groups ◽  
Postnatal Period ◽  
Health Concern ◽  
General Anesthetics ◽  
Pharmacological Agents ◽  
Experimental Findings ◽  
Heritable Effects

Abstract Most surgical procedures require general anesthesia, which is a reversible deep sedation state lacking all perception. The induction of this state is possible because of complex molecular and neuronal network actions of general anesthetics (GAs) and other pharmacological agents. Laboratory and clinical studies indicate that the effects of GAs may not be completely reversible upon anesthesia withdrawal. The long-term neurocognitive effects of GAs, especially when administered at the extremes of ages, are an increasingly recognized health concern and the subject of extensive laboratory and clinical research. Initial studies in rodents suggest that the adverse effects of GAs, whose actions involve enhancement of GABA type A receptor activity (GABAergic GAs), can also extend to future unexposed offspring. Importantly, experimental findings show that GABAergic GAs may induce heritable effects when administered from the early postnatal period to at least young adulthood, covering nearly all age groups that may have children after exposure to anesthesia. More studies are needed to understand when and how the clinical use of GAs in a large and growing population of patients can result in lower resilience to diseases in the even larger population of their unexposed offspring. This minireview is focused on the authors’ published results and data in the literature supporting the notion that GABAergic GAs, in particular sevoflurane, may upregulate systemic levels of stress and sex steroids and alter expressions of genes that are essential for the functioning of these steroid systems. The authors hypothesize that stress and sex steroids are involved in the mediation of sex-specific heritable effects of sevoflurane.

scholarly journals Elucidating the Beneficial Role of PPAR Agonists in Cardiac Diseases

2018 ◽  
Vol 19 (11) ◽  
pp. 3464 ◽  
Author(s):  
Zaza Khuchua ◽  
Aleksandr I. Glukhov ◽  
Arnold W. Strauss ◽  
Sabzali Javadov
Keyword(s):  
Animal Models ◽  
Hormone Receptors ◽  
Lipid Lowering ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Pharmacological Agents ◽  
Beneficial Effects ◽  
Ppar Agonists ◽  
Energy Deprivation

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that bind to DNA and regulate transcription of genes involved in lipid and glucose metabolism. A growing number of studies provide strong evidence that PPARs are the promising pharmacological targets for therapeutic intervention in various diseases including cardiovascular disorders caused by compromised energy metabolism. PPAR agonists have been widely used for decades as lipid-lowering and anti-inflammatory drugs. Existing studies are mainly focused on the anti-atherosclerotic effects of PPAR agonists; however, their role in the maintenance of cellular bioenergetics remains unclear. Recent studies on animal models and patients suggest that PPAR agonists can normalize lipid metabolism by stimulating fatty acid oxidation. These studies indicate the importance of elucidation of PPAR agonists as potential pharmacological agents for protection of the heart from energy deprivation. Here, we summarize and provide a comprehensive analysis of previous studies on the role of PPARs in the heart under normal and pathological conditions. In addition, the review discusses the PPARs as a therapeutic target and the beneficial effects of PPAR agonists, particularly bezafibrate, to attenuate cardiomyopathy and heart failure in patients and animal models.

scholarly journals Multimodal analgesia in bariatric surgery

2016 ◽  
Vol 10 (4) ◽  
pp. 254-261
Author(s):  
M. I Neimark ◽  
Roman V. Kiselev
Keyword(s):  
Bariatric Surgery ◽  
Regional Anesthesia ◽  
Traditional Approach ◽  
Multimodal Analgesia ◽  
Pharmacological Agents ◽  
Perioperative Analgesia ◽  
High Degree ◽  
Mandatory Use ◽  
Different Levels

This review is devoted to the treatment of postoperative pain in bariatric surgery. At present, the prevalence of patients with a high degree of obesity is an epidemic that leads steadily growing number of bariatric operations. Showing the risk factors in the traditional approach to the use of opioids in these patients, as well as the consequences of inadequate analgesia in these patients. Details are presented modern pharmacological agents acting on different levels nociceptive system. Substantiates the role of a multi-modal approach to perioperative analgesia, mandatory use of regional anesthesia. The attention to the visualization neuroaxial structures using ultrasound in the context of the implementation of the efficacy and safety of regional anesthesia in patients with morbid obesity. Possible prospects for pain control in bariatric surgery.

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