Biomedical subjects

Nancy L Shapiro

Publications and source records attributed to Nancy L Shapiro.

9 recordsLinked to original sources

PubMed2006

New anticoagulant agents: direct thrombin inhibitors.

Decades of research have been devoted to developing effective, safe, and convenient anticoagulant agents. In recent years, much emphasis has been placed on the development of direct thrombin inhibitors (DTIs) that offer benefits over agents like heparin and warfarin including the inhibition of both circulating and clot-bound thrombin; a more predictable anticoagulant response, because they do not bind to plasma proteins and are not neutralized by platelet factor 4; lack of required cofactors, such as antithrombin or heparin cofactor II; inhibiting thrombin-induced platelet aggregation; and absence of induction of immune-mediated thrombocytopenia. Various injectable DTIs are currently available and used for many indications. In addition, research is now focusing on oral DTIs that seem promising and offer various advantages, such as oral administration, predictable pharmacokinetics and pharmacodynamics, a broad therapeutic window, no routine monitoring, no significant drug interactions, and fixed-dose administration.

Administration, Oral↗

PubMed2006

Warfarin and its interactions with foods, herbs and other dietary supplements.

Despite its complex pharmacokinetic and pharmacodynamic profile, warfarin is still one of the most widely used oral anticoagulant agents. Attaining optimal anticoagulation with this agent is clinically challenging in view of its many food and drug interactions. Inappropriate anticoagulation control can expose patients to an increased risk of bleeding or thromboembolic complications, due to over and underanticoagulation, respectively. Fluctuations in dietary vitamin K intake can have a significant effect on the degree of anticoagulation in patients treated with warfarin. In addition, the explosion in use of various dietary supplements and herbal products can lead to undesired outcomes on anticoagulant levels. The aim of this review is to discuss the scope and the potential clinical impact of the most commonly reported food, dietary supplement and herbal interactions with warfarin therapy. Practical steps for patients and providers to minimise these interactions are highlighted.

Administration, Oral↗

PubMed2006

Prolonged anticoagulation after discontinuation of argatroban and warfarin therapy in an obese patient with heparin-induced thrombocytopenia.

A 32-year-old, morbidly obese African-American woman developed bilateral pulmonary emboli 12 days after undergoing Roux-en-Y gastric bypass surgery. Three days later, after receiving heparin and warfarin, she developed heparin-induced thrombocytopenia type II (HIT-II). An argatroban 1.5-microg/kg/minute infusion was administered for approximately 2.5 days. The patient also received four doses of warfarin, totaling 37.5 mg. The argatroban infusion was discontinued early on hospital day 6, at which time the patient's international normalized ratio (INR) was 4.36 and activated partial thromboplastin time (aPTT) 85.9 seconds. Her INR and aPTT values continued to rise after the argatroban was discontinued and peaked 3 days later at 5.28 and 123.6 seconds, respectively. At this time her platelet count had improved from 139 x 10(3)/mm(3) to 543 x 10(3)/mm(3). No additional warfarin was administered before discharge. On hospital day 11, the patient was discharged home with an INR of 4.12 and an aPTT of 67.1 seconds. Her aPTT and INR values remained elevated for 19 days after receiving her last dose of warfarin and for 20 days after argatroban discontinuation. She experienced no bleeding complications from these supratherapeutic coagulation parameters. She resumed treatment with warfarin as an outpatient and completed a 6-month course of anticoagulation without further incident. Clinicians should be aware that coagulation parameters may remain elevated longer than expected after argatroban discontinuation in certain patients taking concomitant warfarin. Patients with liver dysfunction and obesity appear most likely to be affected.

Adult↗

PubMed2006

Interaction between warfarin and cranberry juice.

Warfarin is extensively used for anticoagulation to a target international normalized ratio of 2.0-3.0 for most indications or 2.5-3.5 for high-risk indications; however, many drugs and dietary supplements induce fluctuations in the international normalized ratio. Such fluctuations may lead to therapeutic failure or bleeding complications. Cranberry juice is increasingly used for the prevention and adjunctive treatment of urinary tract infections. The United Kingdom's Committee on Safety of Medicines has alerted clinicians to a potential interaction between warfarin and cranberry juice and has advised that patients avoid their concurrent use. Review and analysis of the literature revealed that ingestion of large volumes of cranberry juice destabilize warfarin therapy. Small amounts of juice are not expected to cause such an interaction. Clinicians should be aware of this potential interaction and monitor and counsel patients accordingly.

Anticoagulants↗

PubMed2005

The development and performance validation of a tool to assess patient anticoagulation knowledge.

BACKGROUND: The complexity of anticoagulation therapy requires a patient's command of anticoagulation-related knowledge to assist in maintaining optimal therapy and reducing adverse events. Verbal evaluations may overestimate the patient's comprehension of anticoagulation knowledge. OBJECTIVES: This first phase study developed and pilot tested the Anticoagulation Knowledge Assessment (AKA) instrument, and provided validity evidence to support the use of the AKA. The AKA is an assessment instrument that (1) pharmacists can use to obtain objective evidence of patient anticoagulation knowledge, (2) can provide pharmacists with direction for patient-specific medication management education, and (3) functions as a tool for continuous quality improvement in anticoagulation education. METHODS: Using objective measurement methods, a convenience sample of 60 English-speaking patients receiving services from an inner-city and suburban pharmacist managed anticoagulation clinics was used in conjunction with objective measurement methods. RESULTS: Rasch analysis of 32 multiple-choice items representing 10 anticoagulation educational content areas demonstrated misfit statistics of less than 1.2. All 60 patients demonstrated person misfit statistics of less than 1.3. The educational content area was well represented and distributed. CONCLUSIONS: Because the AKA performed well, the data support that information gained from the AKA will provide pharmacists with direction for anticoagulation management education that is targeted to each patient's specific needs. Additionally, responses demonstrated objective data about those components of practice that are being taught effectively.

Aged↗

PubMed2005

A pharmacologic overview of current and emerging anticoagulants.

For over 50 years, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to traditional agents such as unfractionated heparin and oral vitamin K antagonists such as warfarin. These traditional agents are fraught with limitations that complicate their clinical use. A variety of novel anticoagulants with improved pharmacologic and clinical profiles have recently been introduced or are in development, offering benefits over traditional therapies. Specifically, progress has been made in the development of low-molecular-weight heparins, factor Xa inhibitors, and direct thrombin inhibitors. Because of their convenience and ease of use, some of these novel compounds are competing with the traditional anticoagulants and are needed additions to the antithrombotic arsenal.

Anticoagulants↗

PubMed2004

Initiating warfarin therapy: 5 mg versus 10 mg.

OBJECTIVE: To review the literature investigating initial dosing of warfarin at 5 or 10 mg for treatment of acute venous thromboembolism. DATA SOURCES: Articles were identified through searches of MEDLINE (1966-December 2003) using the key words warfarin, oral anticoagulation, warfarin dose, warfarin initiation, venous thromboembolism, and anticoagulation. Additional references were located through review of the bibliographies of the articles cited. STUDY SELECTION AND DATA EXTRACTION: Studies of the initial dosing of warfarin at 5 or 10 mg were evaluated and relevant information was included, as were those that identified known factors that influence the maintenance dose of warfarin. DATA SYNTHESIS: For the treatment of acute venous thromboembolism, warfarin dosing is often provider dependent. Until recently, studies suggested that 5 mg initiation was as effective as 10 mg, without increasing the risk of bleeding. However, the most recent study comparing a 5- versus 10-mg initial dosing nomogram supports an initial dose of 10 mg. These results should be interpreted with caution, however, since patients at high risk for bleeding were excluded from the study. Several patient-specific factors will affect the maintenance dose, guiding clinicians to start with lower (<5 mg) or higher (>5 mg) doses. CONCLUSIONS: Although recent evidence supports a 10-mg initiation nomogram, clinicians should consider patient-specific factors prior to deciding an initial warfarin dose. If a 10-mg loading dose is utilized, strict compliance with the protocol is necessary.

Acute Disease↗

PubMed2003

Tinzaparin: considerations for use in clinical practice.

OBJECTIVE: To evaluate the safety and effectiveness of tinzaparin for the prevention and treatment of venous thromboembolism (VTE). DATA SOURCES: A MEDLINE and PubMed database search (1980-December 2002) was conducted. Only articles written in English were reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles reporting the safety, efficacy, and cost-effectiveness of tinzaparin in humans were evaluated. Emphasis was placed on randomized, controlled trials. DATA SYNTHESIS: Tinzaparin sodium is a low-molecular-weight heparin (LMWH) that exerts its anticoagulant effect through inhibition of factors Xa and IIa and release of tissue factor pathway inhibitor from the vascular epithelium. Tinzaparin is indicated for treatment of acute symptomatic deep-vein thrombosis (DVT), with or without pulmonary embolism. Clinical studies suggest that tinzaparin is also effective for VTE prophylaxis, as well as other indications. Once-daily subcutaneous tinzaparin is equally or more effective than intravenous unfractionated heparin (UFH) for prevention and treatment of VTE, at least as safe as UFH for bleeding complications, and requires little or no monitoring. No dose "cap" is required for obese patients, and no initial dosing adjustments are necessary in elderly and/or renally impaired patients, although some monitoring is recommended. The few comparative data available suggest that tinzaparin efficacy may be comparable to that of other LMWHs; more comparative studies are needed. Pharmacoeconomic studies indicate a favorable cost-benefit ratio. CONCLUSIONS: Tinzaparin is safe and effective for prevention and treatment of DVT. Consistent once-daily dosing may facilitate self-administration of tinzaparin in the outpatient setting.

Animals↗

PubMed2003

Ezetimibe: a selective cholesterol absorption inhibitor.

Ezetimibe is the first agent of a novel class of selective cholesterol absorption inhibitors recently approved by the Food and Drug Administration for treatment in the United States. Ezetimibe inhibits the absorption of biliary and dietary cholesterol from the small intestine without affecting the absorption of fat-soluble vitamins, triglycerides, or bile acids. Ezetimibe localizes at the brush border of the small intestine and decreases cholesterol uptake into the enterocytes. Preclinical studies demonstrated lipid-lowering properties of ezetimibe as monotherapy and showed a synergistic effect in combination with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). The efficacy and safety of ezetimibe 10 mg/day have been established in phase III clinical trials. In these trials, ezetimibe was investigated as monotherapy, as an add-on to ongoing statin therapy, and as combination therapy with statins in patients with primary hypercholesterolemia. In addition, ezetimibe has been evaluated in patients with homozygous and heterozygous familial hypercholesterolemia and in those with sitosterolemia. When given as monotherapy or in combination with statins or fenofibrate, ezetimibe reduces low-density lipoprotein cholesterol (LDL) by 15-20% while increasing high-density lipoprotein cholesterol by 2.5-5%. Unlike other intestinally acting lipid-lowering agents, ezetimibe does not adversely affect triglyceride levels and, due to its minimal systemic absorption, drug interactions are few. Ezetimibe's side-effect profile resembles that of placebo when given as monotherapy or in combination with statins. In clinical practice, ezetimibe has a role as monotherapy for patients who require modest LDL reductions or cannot tolerate other lipid-lowering agents. In combination therapy with a statin, ezetimibe is used in patients who cannot tolerate high statin doses or in those who need additional LDL reductions despite maximum statin doses.

Animals↗