Lactate infusions in major depression without panic attacks

Sodium lactate infusion provokes panic attacks in panic disorder patients but not in normal controls. We have previously shown that patients who develop panic disorder during a major depressive episode are similar to panic disorder patients in their rate of panic attacks with lactate. In the present pilot study, nine patients with major depression without panic attacks underwent lactate infusions. These patients differed significantly from panic disorder patients but not from controls in their response to lactate. This argues for the specificity of lactate sensitivity for the phenomenon of panic attacks and gives further evidence for biological differences between panic and depression.     

Functional Magnetic Resonance Studies of Brain Activation

Recent advances in functional magnetic resonance imaging (fMRI), have stimulated considerable interest in applying this noninvasive approach to investigate the human brain. From early investigations of the visual and the motor system, applications of fMRI have matured to the demonstration of subtle activations associated with complex neurological tasks involving language, memory, and other higher brain functions. On the other hand, it is clear that current enthusiasm for fMRI must be tempered with the realization that interpretation of findings entails a number of assumptions about image contrast mechanisms which necessitate a more pragmatic assessment of what is actually being measured and how to compare the results to those of more established functional imaging techniques like positron emission tomography. Metabolic changes associated with neuronal activation can now be measured by functional magnetic resonance spectroscopy (fMRS) and functional magnetic resonance spectroscopic imaging (fMRSI). Comination of these approaches with fMRI may help to provide a more complete picture of vascular and metabolic mechanisms associated with brain function.     

Effect of direct thrombin inhibitors, bivalirudin, lepirudin, and argatroban, on prothrombin time and INR values

Direct thrombin inhibitors (DTIs) represent a new class of promising anticoagulation agents. The DTIs frequently are used to provide initial anticoagulation, with long-term therapy requiring eventual transition to coumarins. Unfortunately, DTIs not only prolong the activated partial thromboplastin time but also can affect international normalized ratio (INR) values. We approximated the DTI effect on INRs by each drug to pooled plasma at concentrations between 0.1 and 1.2 microg/mL. We then concurrently tested these samples using 14 prothrombin time (PT) reagents. By using repeated measures analysis of variance, we found significant differences (P < .05) between the median INRs for lepirudin and argatroban for all PT reagents, between lepirudin and bivalirudin for all reagents except PT-Fibrinogen HS Plus (P = .07), and between bivalirudin and argatroban for all reagents except Thromborel S (P = .05). The DTI effect on INRs was dependent on drug, drug concentration, and reagent. Argatroban had the most effect on INRs, while lepirudin had the least effect. Reagents with a lower international sensitivity index were less affected by DTI; ThromboMax HS was the least sensitive PT reagent to any DTI.     

Dabigatran etexilate in clinical practice: confronting challenges to improve safety and effectiveness

A number of novel anticoagulants are moving through various stages of drug development. Recently, the United States Food and Drug Administration approved the oral direct thrombin inhibitor dabigatran etexilate to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Although dabigatran offers a number of advantages over existing oral and parenteral anticoagulants, challenges exist for clinicians who must ensure its safe and effective use. Limited data are available on dabigatran use in patients with renal dysfunction and in obese patients, or in combination with other drugs. Clinical experience is lacking in populations for whom anticoagulants are routinely used, such as patients with a previous stroke, acute coronary syndromes, or pregnancy-associated thrombosis, or those requiring ablation therapy. More important, clinicians will be faced with incorporating dabigatran into hospital guidelines for transitioning between oral and parenteral anticoagulants, measuring anticoagulant intensity, managing anticoagulant-related hemorrhage, ensuring safe use around neuraxial anesthesia, and implementing computer-based alert or warning systems. Since anticoagulants are ubiquitously used in the prevention or treatment of venous and arterial thrombosis, both clinicians and patients must be provided structured education on dabigatran's benefits and limitations. In this article, our goal was to provide practical advice to enhance clinician understanding of dabigatran, identify clinical and operational challenges to its use, and offer system improvements that can ensure safe and effective use of dabigatran.     

Key articles and guidelines in the management of acute coronary syndromes and in percutaneous coronary intervention: 2007 update

Clinical evidence in the management of acute coronary syndromes (ACS) and in percutaneous coronary intervention (PCI) continues to evolve at a rapid pace. For clinicians to provide optimal care for these patients, it is important to keep up with new information as it becomes available. With the existence of numerous pharmacologic agents, abundance of major clinical trials, and several nationally recognized clinical guidelines, compiling the needed reference material to make evidence-based decisions on the care of patients with ACS or those undergoing PCI can be difficult for clinicians. Therefore, we provide an update to the first compiled bibliography of key articles and guidelines relative to patients with ACS published in Pharmacotherapy in 2004. A number of guidelines and practice-changing literature have been published since the initial 2004 document. We hope that this compilation will serve as a resource for pharmacists, physicians, nurses, residents, and students responsible for the care of patients with coronary heart disease.