Abstract：
:For many years, warfarin was the only effective oral anticoagulant to prevent and treat thromboembolism. Nevertheless, its clinical use is limited by a narrow therapeutic window, extensive drug interactions, need of strict dietary control and frequent monitoring. The pharmacological response is also unpredictable and highly variable among patients. Suboptimal anticoagulation can lead to detrimental thromboembolic events or life-threatening bleeding. Direct thrombin inhibitor (DTI) activity represents a new class of anticoagulant activity that was intended to replace warfarin. Ximelagatran was the first DTI shown to have similar efficacy to warfarin, but failed to replace it because of a high incidence of liver toxicity. Dabigatran etexilate is another novel DTI with a more predictable pharmacokinetic profile and fewer drug interactions compared with warfarin. Recent large-scaled, randomized studies have shown that it does not share ximelagatran's hepatotoxicity, and is as effective as conventional anticoagulants for venous thromboembolism (VTE) and prophylaxis in atrial fibrillation (AF). These findings led to the approval of dabigatran etexilate for thromboprophylaxis following hip or knee replacement surgery in Europe, Canada and the United Kingdom. Here we summarize the latest evidence concerning the use of dabigatran etexilate in VTE (BISTRO, RE-MODEL, RE-NOVATE, RE-MOBILIZE and RECOVER) and AF (PETRO and RELY). Potential problems related to dabigatran use are also discussed to examine whether it can truly replace warfarin as the gold standard.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Ma TK,Yan BP,Lam YYdoi
10.1016/j.pharmthera.2010.09.005subject
Has Abstractpub_date
2011-02-01 00:00:00pages
185-94issue
2eissn
0163-7258issn
1879-016Xpii
S0163-7258(10)00189-0journal_volume
129pub_type
杂志文章,评审abstract：:Conditional gene knockout represents an extremely powerful approach to study the function of single genes in the nervous system. The Cre-LoxP system is the most advanced technology for spatial and temporal control of genetic inactivation, and there is rapid progress using this methodology in neuroscience research. In ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2006.12.003
更新日期：2007-03-01 00:00:00
abstract：:Progress in methods of investigating endothelial function in humans has led to the demonstration that endothelial dysfunction is an early process involved in the pathophysiology of cardiovascular diseases, and represents a new independent therapeutic target that may help to improve patient health. The administration o...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.03.015
更新日期：2011-07-01 00:00:00
abstract：:Since its commercial advent in 1985, transcranial magnetic stimulation (TMS), a technique for stimulating neurons in the cerebral cortex through the scalp, safely and with minimal discomfort, has captured the imaginations of scientists, clinicians and lay observers. Initially a laboratory tool for neurophysiologists s...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.09.003
更新日期：2012-01-01 00:00:00
abstract：:Venoms from stonefish (genus Synanceja) have marked effects on the cardiovascular and neuromuscular systems and on vascular permeability; the venoms also exhibit haemolytic and hyaluronidase activity. Recently, a toxic protein, stonustoxin (SNTX), was purified from the venom of S. horrida: the primary lethal action of...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(94)90022-1
更新日期：1994-01-01 00:00:00
abstract：:Drug therapy directed toward the fetus would be intended for either treating a fetal disorder or improving the capacity for later intrauterine or postnatal adaptation. Most reported trials involve single cases or small numbers of fetuses receiving the drug transplacentally after the first trimester, but before attaini...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(93)90051-e
更新日期：1993-01-01 00:00:00
abstract：:In the 1980s, Bowery and colleagues discovered the presence of a novel, bicuculline-resistant and baclofen-sensitive type of GABA receptor on peripheral nerve terminals, the GABA(B) receptor. Since this pioneering work, GABA(B) receptors have been identified in the Central Nervous System (CNS), where they provide an i...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.06.004
更新日期：2011-11-01 00:00:00
abstract：:Cyclooxygenase (COX) enzymes, or prostaglandin-endoperoxide synthases (PTGS), are heme-containing bis-oxygenases that catalyze the first committed reaction in metabolism of arachidonic acid (AA) to the potent lipid mediators, prostanoids and thromboxanes. Two isozymes of COX enzymes (COX-1 and COX-2) have been identif...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.04.011
更新日期：2006-11-01 00:00:00
abstract：:The cardiac ryanodine receptor-Ca2+ release channel (RyR2) is an essential sarcoplasmic reticulum (SR) transmembrane protein that plays a central role in excitation-contraction coupling (ECC) in cardiomyocytes. Aberrant spontaneous, diastolic Ca2+ leak from the SR due to dysfunctional RyR2 contributes to the formation...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.03.006
更新日期：2009-08-01 00:00:00
abstract：:S-Adenosylhomocysteine (AdoHcy), formed after the donation of the methyl group of S-adenosylmethionine to a methyl acceptor, is hydrolyzed to adenosine and homocysteine by AdoHcy hydrolase physiologically. The administration of the inhibitors of AdoHcy hydrolase to cells or animals normally results in an accumulation ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)00089-2
更新日期：1998-02-01 00:00:00
abstract：:Extracellular vesicles (EVs) are a heterogenous population of vesicles originate from cells. EVs are found in different biofluids and carry different macromolecules, including proteins, lipids, and nucleic acids, providing a snap shot of the parental cells at the time of release. EVs have the ability to transfer molec...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.08.002
更新日期：2018-12-01 00:00:00
abstract：:P2Y12 receptor inhibition in addition to aspirin is the cornerstone of treatment in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI). Despite advances in contemporary antithrombotic therapy, periprocedural thrombotic complications such as myocardial infarction ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.01.004
更新日期：2016-03-01 00:00:00
abstract：:Hypertension is an epidemic health concern and a major risk factor for the development of cardiovascular disease. Although there are available treatment strategies for hypertension, numerous hypertensive patients do not have their clinical symptoms under control and it is imperative that new avenues to treat or preven...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.02.005
更新日期：2013-06-01 00:00:00
abstract：:Cardiovascular diseases cause more mortality and morbidity worldwide than any other diseases. Although many intracellular signaling pathways influence cardiac physiology and pathology, the mitogen-activated protein kinase (MAPK) family has garnered significant attention because of its vast implications in signaling an...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.05.013
更新日期：2014-11-01 00:00:00
abstract：:Hypertension is associated with immune cells activation and their migration into the kidney, vasculature, heart and brain. These inflammatory mechanisms are critical for blood pressure regulation and mediate target organ damage, creating unique novel targets for pharmacological modulation. In response to angiotensin I...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107799
更新日期：2020-12-24 00:00:00
abstract：:In the heart, Ca(2+) released from the intracellular Ca(2+) storage site, the sarcoplasmic reticulum (SR), is the principal determinant of cardiac contractility. SR Ca(2+) release is controlled by dedicated molecular machinery, composed of the cardiac ryanodine receptor (RyR2) and a number of accessory proteins, inclu...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.06.002
更新日期：2008-09-01 00:00:00
abstract：:Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed the therapeutic management of solid tumors, particularly ovarian cancer. Initially studied in BRCA deficient tumors, the Food and Drug Administration (FDA) indications have expanded to include other homologous recombination deficient tumors as well as bio...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107588
更新日期：2020-09-01 00:00:00
abstract：:Protein tyrosine kinases (PTKs) play a key role in normal cell and tissue development. Enhanced PTK activity is intimately correlated with proliferative diseases, such as cancers, leukemias, psoriasis, and restenosis. This realization prompted us to systematically synthesize tyrosine phosphorylation inhibitors (tyrpho...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(98)00066-7
更新日期：1999-05-01 00:00:00
abstract：:Organic anion transporters (OATs), which belong to the superfamily SLC22A, are key determinants in the absorption, distribution, and excretion of a diverse array of environmental toxins, and clinically important drugs, and, therefore, are critical for the survival of mammalian species. Alteration in the function of th...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.08.002
更新日期：2010-01-01 00:00:00
abstract：:Severe and prolonged impairment of mitochondrial beta-oxidation leads to microvesicular steatosis, and, in severe forms, to liver failure, coma and death. Impairment of mitochondrial beta-oxidation may be either genetic or acquired, and different causes may add their effects to inhibit beta-oxidation severely and trig...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(95)00012-6
更新日期：1995-01-01 00:00:00
abstract：:In spite of a lack of compounds acting selectively at the 5-hydroxytryptamine (5-HT)1B and 5-HT1D receptor subtypes, by cross-relating the available data, this review attempts to tentatively assign behavioural and other in vivo correlates of these receptor subtypes. In addition, a summary of data from microdialysis st...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(94)90051-5
更新日期：1994-01-01 00:00:00
abstract：:The precise mechanism(s) of the progression of advanced heart failure (HF) should be determined to establish strategies for its treatment or prevention. Based on pathological, molecular, and physiological findings in 3 animal models and human cases, we propose a novel scheme that a vicious cycle formed by increased sa...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2004.12.006
更新日期：2005-07-01 00:00:00
abstract：:As our ability to provide in-depth, patient-specific characterisation of the molecular alterations within tumours rapidly improves, it is becoming apparent that new approaches will be required to leverage the power of this data and derive the full benefit for each individual patient. Systems biology approaches are beg...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107555
更新日期：2020-08-01 00:00:00
abstract：:Ion channels play key roles in determining smooth muscle tone by setting the membrane potential and allowing Ca2+ influx. Perhaps not surprisingly, therefore, they also provide targets for neurotransmitters and other messengers that act on smooth muscle. Application of patch-clamp and molecular biology techniques and ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)87271-3
更新日期：1997-01-01 00:00:00
abstract：:The leukotrienes are synthesized from essential fatty acids via a 5-lipoxygenase enzyme. Most is known about the four-series leukotrienes derived from arachidonic acid. Leukotriene B4 is a potent chemotactic agent for leukocytes and it induces neutrophil-dependent increased microvascular permeability. Leukotrienes C4,...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(90)90035-z
更新日期：1990-01-01 00:00:00
abstract：:Dysregulation of inflammation is central to the pathogenesis of innumerable human diseases. Understanding and tracking the critical events in inflammation are crucial for disease monitoring and pharmacological drug discovery and development. Recent progress in molecular imaging has provided novel insights into spatial...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.05.006
更新日期：2012-08-01 00:00:00
abstract：:Glucocorticoids (GC) in all its various forms and formulations are likely one of the most commonly used pharmacologic agents in medicine. Their use can be profoundly therapeutic but are also associated with a myriad of acute and chronic side effects. It is fairly well-accepted in the medical community that GC can be l...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2019.107428
更新日期：2020-02-01 00:00:00
abstract：:KIT is a receptor tyrosine kinase that after binding to its ligand stem cell factor activates signaling cascades linked to biological processes such as proliferation, differentiation, migration and cell survival. Based on studies performed on SCF and/or KIT mutant animals that presented anemia, sterility, and/or pigme...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.12.008
更新日期：2019-05-01 00:00:00
abstract：:Progranulin (PGRN) is abundantly expressed in epithelial cells, immune cells, neurons, and chondrocytes, and reportedly contributes to tumorigenesis. PGRN is a crucial mediator of wound healing and tissue repair. PGRN also functions as a neurotrophic factor and mutations in the PGRN gene resulting in partial loss of t...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.10.003
更新日期：2012-01-01 00:00:00
abstract：:Matricellular proteins (MCPs) are the non-structural extracellular matrix (ECM) proteins with various regulatory functions. MCPs are critical regulators of ECM homeostasis and are often found dysregulated in various malignancies. They interact with various proteins like ECM structural proteins, integrins, growth facto...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.09.002
更新日期：2016-12-01 00:00:00
abstract：:The developing lung is highly susceptible to damage from exposure to environmental toxicants particularly due to the protracted maturation of the respiratory system, extending from the embryonic phase of development in utero through to adolescence. The functional organization of the lungs requires a coordinated ontoge...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.01.011
更新日期：2007-05-01 00:00:00
