Tenecteplase: a review.

BACKGROUND: Certain shortcomings of the available thrombolytic agents have prompted the search for a more fibrin specific fibrinolytic agent with a longer half-life. Such properties would allow bolus administration, possibly leading to faster reperfusion of occluded arteries. OBJECTIVE: This article focuses on the new thrombolytic agent tenecteplase, reviewing its mechanism of action, pharmacokinetic characteristics, clinical efficacy, tolerability, and potential for drug interactions in the management of acute myocardial infarction. METHODS: English-language articles for inclusion in this review were identified through searches of MEDLINE, EMBASE, and International Pharmaceutical Abstracts from 1966 to April 2001. The search terms used included tenecteplase, myocardial infarction, TNK, and TNK-tPA. Abstracts from recent conferences and symposia were also consulted. RESULTS: Tenecteplase is a variant of the native tissue-type plasminogen activator (tPA) molecule that has 14-fold greater fibrin specificity than alteplase, a longer half-life, slower plasma clearance, and 80-fold greater resistance to inhibition by plasminogen activator inhibitor type 1. Its half-life of approximately 18 minutes allows single-bolus administration. In comparative clinical trials, tenecteplase was found to have equivalent efficacy to recombinant tPA (alteplase). The rate of intracranial hemorrhage with tenecteplase was similar to that with alteplase, and tenecteplase was associated with fewer noncerebral complications and less need for blood transfusions. CONCLUSIONS: Tenecteplase appears to be as effective and well tolerated as alteplase in the management of acute myocardial infarction and offers the convenience of single-bolus administration.

Olanzapine-induced diabetes mellitus.

OBJECTIVE: To report two cases of new-onset diabetes mellitus resulting after the initiation of olanzapine treatment. CASE SUMMARY: A 31-year-old African American man and a 44-year-old white man, both with schizoaffective disorder, developed diabetes mellitus within weeks or months of olanzapine initiation. DISCUSSION: Our reports of new-onset diabetes due to olanzapine are consistent with those in the literature. Although the mechanism is not yet known, it has been hypothesized that perhaps damage to the pancreatic islet cells, weight gain, dysregulation of the sympathetic system, and insulin resistance are contributing factors. CONCLUSIONS: Diabetes mellitus secondary to olanzapine use seems to be a rare occurrence. However, certain risk factors such as obesity, family history, and concomitant medications may predispose an individual to development of diabetes mellitus while taking olanzapine. An increased awareness of this reaction is essential in the treatment of patients at risk. Periodic serum glucose monitoring in these individuals may be warranted.

The association of infection and coronary artery disease: an update.

Numerous studies have reported an association of coronary atherosclerosis and restenosis with certain bacterial and viral infections. This article reviews the pathophysiology of atherosclerosis, the role of infectious agents (cytomegalovirus, Chlamydia pneumoniae and Helicobacter pylori) in atherogenesis and studies supporting the potential beneficial effects of antibiotics or antiviral agents in the management of atherosclerotic disease. The interactions of cytomegalovirus and the arterial wall have been extensively studied. However, despite the successful preliminary therapeutic trials with the use of macrolides in augmenting possible C. pneumoniae-induced cardiovascular events, the exact mechanisms of how C. pneumoniae enters the arterial wall remains unknown at this point. For H. pylori, regardless of the large number of studies performed to assess the association between H. pylori and coronary artery disease, no definitive conclusion could be made at this time, due to contradictory results. Before one can widely adopt the use of antibiotics or antiviral agents as treatment for atherosclerosis, further studies must be designed to address some important issues. In vivo animal models need to be established to further examine the various hypotheses regarding the interaction of infectious agents and atherosclerosis and restenosis. Large-scale prospective cohort studies should be designed to relate evidence of infection to future risk of cardiovascular diseases. Confounding variables, such as other cardiovascular risk factors and socio-economic status, should be controlled in order to strengthen the association. Further interventional studies are also required to establish the best antibiotic or antiviral regimen to maximise efficacy and minimise side effects.

Outcomes of weight-based heparin dosing based on literature guidelines and institution individualization.

STUDY OBJECTIVE: To determine whether unfractionated heparin is optimally dosed using published weight-based guidelines. DESIGN: Six-month, prospective study. SETTING: University hospital. PATIENTS: Ninety-six patients in the weight-based unfractionated heparin-dosing group 1 (WBHD1; 37 men; mean age 66.9 +/- 15.1 years; mean weight 80.1 +/- 20.6 kg) and 68 patients in the WBHD2 (25 men; mean age 68.2 +/- 15.6 years; mean weight 82.0 +/- 19.6 kg). INTERVENTIONS: The WBHD1 received a 100-U/kg intravenous bolus followed by an 18-U/kg/hour continuous intravenous infusion. After 3 months, the protocol was modified, and the WBHD2 received a 90-U/kg bolus followed by a 16-U/kg/hour continuous infusion for 3 months. MEASUREMENTS AND MAIN RESULTS: Activated partial thromboplastin times (aPTTs), frequency of bleeding episodes that required blood transfusions, and the number of recurrent thromboembolic events were collected from both groups after 3 months on the study. In the WBHD1, 24 hours after starting heparin, 38.5% of patients had therapeutic aPTTs, and at 48 hours, 54.3% were therapeutic. In the WBHD2, 42.6% and 51.4% of patients had therapeutic aPTTs at 24 and 48 hours, respectively. There was no statistical difference between the WBHD1 and WBHD2 in the percentage of patients with therapeutic aPTTs. CONCLUSIONS: Weight-based heparin dosing resulted in low percentages of patients with therapeutic aPTTs. The use of weight alone to dose heparin may not be adequate to optimize therapy.

Clozapine-induced hypersalivation.

OBJECTIVE: To review underlying pathophysiology and possible treatments for clozapine-induced hypersalivation. DATA SOURCES: Primary literature was accessed through MEDLINE (1966-May 1999). Key search terms included clozapine, hypersalivation, sialorrhea, and treatment. DATA SYNTHESIS: Hypersalivation occurs in up to 54% of patients receiving clozapine. An evaluation of studies and case reports focusing on management of clozapine-induced hypersalivation was conducted. CONCLUSIONS: It is unclear whether clozapine increases salivation through its muscarinic M4 receptor activation and/or blockade of alpha2-adrenoceptors, or by causing a distortion in swallowing reflex. Treatment options include chewing gum, reducing the dosage of clozapine, or prescribing pharmacologic agents such as anticholinergics or alpha2-adrenoceptor agonists.