Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Jul 2013
ReviewTicagrelor: positive, negative and misunderstood properties as a new antiplatelet agent.
Dual antiplatelet therapy is essential for the management of acute coronary syndrome. In particular, combination therapy using aspirin with a platelet ADP (i.e. P2Y12 ) receptor inhibitor, such as clopidogrel, prasugrel or, more recently, ticagrelor, has been recommended for patients with acute coronary syndrome. ⋯ Recent studies into ticagrelor report conflicting data, with certain aspects of its mechanisms of action still not fully understood. Ticagrelor has beneficial effects following its clinical application, such as achieving overall higher reductions in mortality compared with the use of clopidogrel and prasugrel. Harmful effects associated with the use of ticagrelor include a higher incidence of dyspnoea and major bleeding compared with clopidogrel.
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Clin. Exp. Pharmacol. Physiol. · Feb 2013
ReviewHaemodynamic influences on kidney oxygenation: clinical implications of integrative physiology.
Renal blood flow, local tissue perfusion and blood oxygen content are the major determinants of oxygen delivery to kidney tissue. Arterial pressure and segmental vascular resistance influence kidney oxygen consumption through effects on glomerular filtration rate and sodium reabsorption. Diffusive shunting of oxygen from arteries to veins in the cortex and from descending to ascending vasa recta in the medulla limits oxygen delivery to renal tissue. ⋯ This sequence of events appears to cause renal microcirculatory dysfunction, which may then be exacerbated by the inappropriate use of therapies common in peri-operative medicine, such as fluid resuscitation. The development of new ways to prevent and treat AKI requires an integrative approach that considers not just the molecular mechanisms underlying failure of filtration and tissue damage, but also the contribution of haemodynamic factors that determine kidney oxygenation. The development of bedside monitors allowing continuous surveillance of renal haemodynamics, oxygenation and function should facilitate better prevention, detection and treatment of AKI.
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Clin. Exp. Pharmacol. Physiol. · Aug 2012
ReviewNewcastle disease virus: a promising agent for tumour immunotherapy.
Malignant tumours are a major cause of mortality in humans. Currently used therapeutic regimens have not improved survival rates of patients suffering from malignant tumours much because of their limited efficacy and side-effects. A therapeutic approach that uses Newcastle disease virus (NDV) represents an attractive new tool for tumour immunotherapy. ⋯ Apoptosis following NDV infection may contribute to the observed oncolytic effects; however, NDV could also stimulate both innate and adaptive antitumour immune responses. For many years, different approaches have been investigated (or are in the process of being developed) regarding the use of NDV for the treatment of malignancies. Recent advances using reverse genetics have provided a means of generating recombinant NDV strains with improved oncolytic and immune regulatory properties.
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Clin. Exp. Pharmacol. Physiol. · Jun 2012
ReviewContrast-induced nephropathy: protective role of fenoldopam.
1. Contrast-induced nephropathy (CIN) often occurs after contrast media-related procedures and is associated with increased morbidity and mortality. The acute renal failure observed after administration of contrast media is usually transient but, in some cases, it can be severe enough to lead to permanent renal damage with life-long dialysis. 2. ⋯ Initial studies have shown the safety of and favourable results with direct infusion of fenoldopam into the renal arteries using the Benephit renal infusion system (FlowMedica-AngioDynamics, Latham, NY, USA). These results are encouraging and suggest that intrarenal delivery of fenoldopam has an advantage in patients with a high risk of developing CIN. 4. A randomized controlled study comparing intrarenal fenoldopam with placebo is warranted.
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Clin. Exp. Pharmacol. Physiol. · Jun 2012
Reviewβ-lactam pharmacokinetics and pharmacodynamics in critically ill patients and strategies for dose optimization: a structured review.
1. Infections and related sepsis are two of the most prevalent issues in the care of critically ill patients, with mortality as high as 70%. Appropriate antibiotic selection, as well as adequate dosing, is important to improve the clinical outcome for these patients. 2. β-Lactams are the most common antibiotic class used in critically ill sepsis patients because of their broad spectrum of activity and high tolerability. β-Lactams exhibit time-dependent antibacterial activity. ⋯ Critically ill patients experience a myriad of physiological changes that result in changes in the pharmacokinetics (PK) of hydrophilic drugs such as β-lactams. A different approach to dosing with β-lactams may increase the likelihood of positive outcomes considering the pharmacodynamics (PD) of β-lactams, as well as the changes in PK in critically ill patients. 4. The present review describes the strategies for dose optimization of β-lactams in critically ill patients in line with the PK and PD of these drugs.