Therapeutic Considerations in the Management of Agitated or Delirious Critically 111 Patients

Agitation and delirium in the critical care unit are common problems that at times are difficult to treat. The difficulty stems from few placebo-controlled or even blinded trials evaluating various therapies. In addition, the literature in these areas is scattered through various journals in a variety of disciplines. Pharmacologic and nonpharmacologic techniques may achieve the therapeutic objective for these patients. Since no one drug will achieve the goals in every patient, therapy must be tailored to the characteristics and needs of each individual.     

Pharmacotherapy of Methamphetamine Addiction: An Update

ABSTRACT

Methamphetamine dependence is a serious public health problem worldwide for which there are no approved pharmacological treatments. Psychotherapy is still the mainstay of treatment; however, relapse rates are high. The search for effective pharmacological treatment has intensified in the last decade. This review will highlight progress in pharmacological interventions to treat methamphetamine dependence as well as explore new pharmacological targets. Published data from clinical trials for stimulant addiction were searched using PubMed and summarized, as well as highlights from a recent symposium on methamphetamine pharmacotherapy presented at the ISAM 2006 meeting, including interim analysis data from an ongoing D-amphetamine study in Australia. Early pilot data are encouraging for administering D-amphetamine and methylphenidate as treatment for heavy amphetamine users. Abilify at 15 mg/day dose increased amphetamine use in an outpatient pilot study. Sertraline, ondansetron, baclofen, tyrosine, and imipramine were ineffective in proof-of-concept studies. Development of pharmacotherapy for methamphetamine dependence is still in an early stage. Data suggesting D-amphetamine and methylphenidate as effective pharmacotherapy for methamphetamine addiction will need to be confirmed by larger trials. Preclinical data suggest that use of GVG, CB1 antagonist, and lobeline are also promising therapeutic strategies.     

Cardiovascular Pharmacotherapy in Patients with Marfan Syndrome

The cardiovascular complications of Marfan syndrome (MFS) remain the primary source of morbidity and mortality in affected patients. Over the last decade, the underlying pathogenesis of these cardiovascular abnormalities has been the focus of much research. Such research has shed light on the potential role of several novel medical therapies and their ability to prevent cardiovascular disease progression. This paper summarizes the research underlying new medical therapies and provides a review of the scientific foundation underlying all current medical therapies used for prevention of cardiovascular disease in patients with MFS, including beta-adrenoceptor antagonists, calcium channel antagonists, ACE inhibitors, and angiotensin receptor antagonists.     

Pharmacologic Considerations in the Management of Patients Receiving Left Ventricular Percutaneous Mechanical Circulatory Support

Percutaneous mechanical circulatory support (MCS) devices, including the intraaortic balloon pump, Impella, and TandemHeart, are often used for hemodynamic support in the setting of refractory cardiogenic shock. The thrombotic and bleeding complications associated with these devices is well recognized, and the Impella and TandemHeart devices have unique anticoagulation considerations that may influence patient outcomes. Both devices typically require use of a heparinized purge solution in combination with intravenous unfractionated heparin, thereby providing multiple sources of heparin exposure. Each device also has specific monitoring requirements and goal ranges. This review provides an overview of percutaneous MCS devices commonly used in the acute management of left ventricular failure, with an emphasis on pharmacologic considerations. We review recent evidence and guidelines and provide recommendations for appropriate use of anticoagulation during device support. Approaches to managing heparinized purge solutions, monitoring, and the utility of nonheparin anticoagulants are also provided because high‐quality evidence in the literature is limited.     

药物治疗对首发精神分裂症患者认知功能的影响

目的:探讨药物治疗对首发精神分裂症认知功能的影响.方法:78例精神分裂症患者, 随机分为氯丙嗪组38例、氯氮平组40例,双盲给药,初始剂量均为25 mg,第28天增至氯氮平400 mg•d 1,氯丙嗪 600 mg•d 1,以后维持该剂量8周,共观察12周,于治疗前及治疗12 周末各作1次Wisconsin卡片分类测验(WCST)、韦氏成人智力量表(WAIS R)、韦氏记忆量表(WMS)、语言流利性测验等.结果:首发精神分裂症确实存在广泛的认知功能损害,在治疗末氯氮平组WCST表现,WAIS R的言语分,WMS的图片、理解分以及语言流利性得分显著优于氯丙嗪组,且WCST表现与阴性症状(SANS)分、迟发性运动障碍(TD)分、总体社会功能(GAF)分有显著相关性,而与脑电图(EEG)是否异常无关.结论:氯氮平对认知功能有显著的改善作用,而氯丙嗪作用不明显,认知功能改善与精神症状好转无平行关系.     

Management of Self-injurious Behaviors in Children with Neurodevelopmental Disorders: A Pharmacotherapy Overview

Neurodevelopmental disorders (NDDs), a group of disorders affecting ~1–2% of the general population, are caused by changes in brain development that result in behavioral and cognitive alterations, sensory and motor changes, and speech and language deficits. Neurodevelopmental disorders encompass a heterogeneous group of disorders including, but not limited to, Smith-Magenis syndrome, Lesch-Nyhan disease, cri du chat syndrome, Prader-Willi syndrome, pervasive developmental disorders, fragile X syndrome, Rett syndrome, Cornelia de Lange syndrome, and Down syndrome. Self-injurious behaviors (SIBs) are common in children with NDDs; depending on the specific NDD, the incidence of SIBs is nearly 100%. The management of SIBs in this population is complex, and little high-quality data exist to guide a consistent approach to therapy. However, managing SIBs is of the utmost importance for the child as well as the family and caregivers. Behavior therapies must be implemented as first-line therapy. If behavioral interventions alone fail, pharmacotherapy becomes an essential part of management plans. The limited available evidence for the use of common pharmacologic agents, such as second-generation antipsychotics, and less common agents, such as clonidine, n-acetylcysteine, riluzole, naltrexone, and topical anesthetics, is reviewed. Additional data from well-designed studies in children with NDDs are needed to gain a better understanding of this common and troublesome problem including efficacy and safety implications associated with pharmacotherapy. Until then, clinicians must rely on the limited available data, clinical expertise, and ongoing systematic monitoring when managing SIBs in children with NDDs.     

Caveolae: An Alternative Membrane Transport Compartment

Caveolae are omega-shaped invaginations of the plasma membrane with a diameter of 50-100 nm. Caveolae invaginations can detach from the plasma membrane to form discrete functional caveolae vesicles within the cell cytoplasm. Caveolae are most prominent in adipocytes, fibroblasts, muscle cells (skeletal, smooth and cardiac), capillary endothelium and type I pneumocytes, although other cell types also display these structures but at a lower numerical density. The key structural and functional protein for caveolae is caveolin. At the plasma membrane caveolae serve to compartmentalise and integrate a wide range of signal transduction processes. Caveolae also serve transport functions including that of the vesicular internalisation of small molecules by the process of potocytosis, and the endocytic and transcytotic movements of macromolecules. Opportunities exist for basic and applied investigators working within the pharmaceutical sciences to exploit caveolae membrane interactions with the aim to develop novel cellular or transcellular drug delivery strategies.