Current pharmaceutical design
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Levosimendan is a new calcium sensitizer developed for the treatment of congestive heart failure. Experimental studies indicate that levosimendan increases myocardial contractility and dilates both the peripheral and coronary vessels. Its positive inotropic effect is based on calcium-dependent binding of the drug to cardiac troponin C. ⋯ The most common adverse events associated with levosimendan treatment are headache and hypotension, as a likely consequence of the vasodilating properties of the compound. In conclusion, levosimendan offers a new effective option for the treatment of acutely decompensated heart failure. Unlike traditional inotropes, levosimendan seems also to be safe in terms of morbidity and mortality.
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NMDA (N-methyl-D-aspartate) receptors are one class of ionotropic receptor for the ubiquitous excitatory neurotransmitter L-glutamate. The receptor is made up of four protein subunits combined from a larger library of proteins, which gives this receptor a great deal of variability. This explains the large number of modulatory sites, a variety of sites at which antagonists can interact, and therefore a number of potential drug targets. ⋯ This review summarises the preclinical rationale, based on animal models, and the clinical evidence on the use of NMDA antagonists in pain states. It also summarises the details of the receptor so as to explain the rationale for targeting either specific sites on the receptor, or exploiting anatomical differences in subtype expression, so as to provide the beneficial effects of NMDA receptor block with an improved side effect profile. In particular, agents that are selective for receptors that include the NR2B subunit preclinically have a substantially better profile for treating neuropathic pain than do current NMDA antagonists; some emerging clinical evidence supports this view.
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Editorial Comment
Coping with neuropathic pain: do we need more selective analgesic drugs?
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Spinal cord injuries (SCI) result in a devastating loss of function below the level of the lesion in which there are variable motor recoveries and, in the majority of cases, central neuropathic pain syndromes (CNP) develop several months to years following injury. Unfortunately, the study of chronic pain after SCI has been neglected in the past due in part to the lack of good animal models but largely due to the clinically held dogma that CNP is not a real phenomenon and is psychogenic in nature rather than based on described pathophysiological mechanisms. The purpose of this article is to offer standardized terminology of pain, insight into animal modeling issues of CNP, descriptions of current clinical therapies and to discuss the pathophysiological mechanisms that provide the substrate for CNP that will lead to innovative new therapies. It is hoped that this information will give insight for research strategies as well as better care not only of SCI individuals, but is generalizable to many other CNP syndromes.
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Early postpartum hemorrhage remains a significant cause of maternal morbidity and mortality. Postpartum hemorrhage is most commonly due to uterine atony and often responds to medical treatments such as administration of uterotonic drugs, alone or in combination with uterine massage or bimanual compression. As the incidence of cesarean section continues to rise, the problem of placenta previa and accreta is likely to become more common. ⋯ In recent years new therapeutic measures to control the bleeding have gained attention. Although, these newer therapies focus on avoiding the need for emergency hysterectomy and preservation of reproductive function, reports of subsequent pregnancies are still scarce. Established management options are shortly reviewed and novel medical and surgical treatments are more extensively discussed.