Current pharmaceutical biotechnology
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Curr Pharm Biotechnol · Dec 2011
ReviewDosing of antibiotics in critically ill patients undergoing renal replacement therapy.
On September 11, 1945 Maria Schafstaat was the first patient who successfully underwent a dialysis treatment for acute kidney injury (AKI), formerly known as acute renal failure. Since then, the number of patients with AKI is increasing worldwide. Today AKI is generally one feature of a multiple organ dysfunction syndrome (MODS), which develops in response to major surgery, cardiogenic shock or sepsis. ⋯ We reflect on failure of several large prospective controlled studies to show a survival benefit of higher doses of renal replacement therapy, a finding that might be caused by the fact that we still adhere to dosing guidelines for antibiotics which are at best ineffectual but might also lead to potentially dangerous underdosing of these life saving drugs. Lastly we address possible strategies to overcome the lack of knowledge, the lack of data and the lack of interest in this important area of critical care medicine. Improvement of clinical outcomes and reduction of antibiotic resistance in this patient population will require nephrologist, intensivists and pharmacists to work together.
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Curr Pharm Biotechnol · Dec 2011
ReviewUsing PK/PD to optimize antibiotic dosing for critically ill patients.
Antibiotic prescription for critically ill patients is a complicated process because of the pharmacokinetic differences of this patient population with non-critically ill patients and the lack of robust informative studies. This article seeks to review the available literature describing dosing requirements for optimized treatment of critically ill patients and to discuss a framework to rationally address complex cases by outlining the suggested processes for optimal achievement of pharmacokinetic/ pharmacodynamic targets. A variety of papers exist describing the effect of pathophysiology on antibiotic kinetics. ⋯ Dysfunction of the cardiovascular and renal systems in particular is problematic and can lead to potentially sub-therapeutic antibiotic concentrations in blood and in interstitial fluid. In response to altered pharmacokinetics, dose regimens that adhere to the pharmacodynamics of the antibiotic are essential. In the absence of validated dosing algorithms, therapeutic drug monitoring data and susceptibility data of the infecting pathogen should be inputted into a Bayesian software program that include population pharmacokinetic models to calculate dosing regimens that are personalized for the critically ill patient.
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Curr Pharm Biotechnol · Dec 2011
ReviewThe relevance of drug clearance to antibiotic dosing in critically ill patients.
To maximise the effect of an antibiotic it is necessary to pay careful attention to dosing. The maintenance dose is determined by antibiotic clearance which is usually determined in young healthy adults with normal physiology. Antibiotic clearance in critically ill patients may increase or decrease due to altered physiology and the treatments that are administered. ⋯ If blood sampling is carefully planned it may be possible to directly measure antibiotic clearance for dose adjustment. The purpose of this article is to review the concept of clearance and to highlight circumstances where antibiotic clearance may be altered in patients with critical illness. Strategies for dose modification of antibiotics in critically ill patients will be discussed.
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Curr Pharm Biotechnol · Nov 2011
ReviewMetastasis: recent discoveries and novel perioperative treatment strategies with particular interest in the hemostatic compound desmopressin.
Metastatic disease is responsible for most of cancer lethality. A main obstacle for therapy of advanced cancers is that the outcome of metastasis depends on a complex interplay between malignant and host cells. The perioperative period represents an underutilized window of opportunity for cancer treatment where tumor-host interactions can be modulated, reducing the risk of local recurrences and distant metastases. ⋯ Desmopressin (DDAVP) is a safe and convenient hemostatic peptide with proved antimetastastic properties in experimental models and veterinary clinical trials. The compound seems to induce a dual angiostatic and antimetastatic effect, breaking the cooperative function of cancer cells and endothelial cells during residual tumor progression. DDAVP is therefore an interesting lead compound to develop novel synthetic peptide analogs with enhanced antitumor properties.
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Curr Pharm Biotechnol · Oct 2011
ReviewFibromyalgia: mechanisms, current treatment and animal models.
Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by diffuse musculoskeletal pain. In quantitative sensory testing studies, FMS patients display alterations in heat, cold, and mechanical sensitivity. Genetic studies support a key role for the biogenic amine system, and single nucleotide polymorphisms have been identified in serotonin and dopamine transporter and receptor genes of FMS patients. ⋯ One hurdle in the development of drugs specifically for FMS is the availability of preclinical animal models of the disease. Recently, several rodent models have been described with potential for translation to the human pain syndrome. In this review, we discuss recent developments toward understanding the pathophysiology of FMS, currently available pharmacologic therapy, ongoing clinical trials, and potential animal models of FMS.