Stacy L. Haber

Prasugrel: A novel antiplatelet agent

PURPOSE The pharmacology, pharmacokinetics, safety, and adverse effects of prasugrel, a novel antiplatelet agent, are described. SUMMARY Prasugrel is a third-generation thienopyridine. Like clopidogrel, prasugrel is a prodrug requiring hepatic metabolism to its active form to bind irreversibly to the P2Y(12) adenosine diphosphate receptor and inhibits platelet aggregation for the life of the platelet. Prasugrels pharmacokinetic profile has not been clearly defined. Several preclinical and early-phase clinical trials of prasugrel have been completed. Five trials have assessed the platelet aggregation of prasugrel alone or compared with placebo or clopidogrel. Certain populations with acute coronary syndrome (ACS) may be at higher risk for major bleeding episodes leading to fatal events when using prasugrel with other antithrombotic agents and antiplatelet agents. Information on drug or food interactions with prasugrel is limited. Since prasugrel is still under investigation, an official recommended dosage regimen has yet to be determined. Clinical trials are still being conducted to determine prasugrels exact place in therapy. In early trials, prasugrel has demonstrated a faster onset of action, higher rate of platelet inhibition, and lower rate of response variability compared with clopidogrel. CONCLUSION Prasugrel has demonstrated a greater platelet inhibition and a decreased incidence of ischemic events compared with clopidogrel, but with an increased incidence of bleeding events. Future studies with prasugrel should determine its optimal dosage regimen to minimize bleeding risks and evaluate its outcomes in ACS and safety profile in special patient populations.

Fenugreek use in patients with diabetes mellitus

Fenugreek ( Trigonella foenum-graecum ) is an annual herb belonging to the family Leguminosae.[1][1] Fenugreek is used as a spice, an edible vegetable, a flavoring for imitation maple syrup, and a medicinal plant in countries around the world. The leaves, chemical fractions, and shoots of the

Cranberry and warfarin interaction: a case report and review of the literature.

This case reports on a patient whose International Normalized Ratio (INR) increased after ingestion of cranberry sauce while stabilized on warfarin. It is followed by a review of the published literature on the potential interaction between the two.An 85-year-old woman on chronic warfarin therapy for atrial fibrillation experienced INR elevations of two- to three-fold after two separate ingestions of cranberry sauce. In each case, her INR values decreased after withholding three to four doses and resuming a similar maintenance dose of warfarin. Although the majority of the pharmacokinetic and pharmacodynamic studies did not find a significant interaction between cranberry and warfarin, several case reports indicate that cranberry products may increase INR values in patients on warfarin. Practitioners should consider cranberry usage as a potential contributor in the evaluation of supratherapeutic INR values in patients on warfarin.

Apremilast: A Novel Drug for Treatment of Psoriasis and Psoriatic Arthritis

Objective: To review the pharmacology, efficacy, and safety of apremilast and determine its role relative to other agents in the treatment of psoriasis and psoriatic arthritis. Data Sources: A PubMed search (1946 to December 2015) using the terms apremilast and CC-10004 was conducted to identify relevant articles. Study Selection and Data Extraction: In vitro or in vivo evaluations of apremilast published in the English language were eligible for inclusion. Controlled clinical trials that involved psoriasis or psoriatic arthritis were selected for review. Data Synthesis: Four trials were identified on the treatment of psoriasis. In those that involved doses of 30 mg twice daily, a significantly greater percentage of patients receiving apremilast (28.8% to 40.9%) compared with placebo (5.3% to 5.8%) achieved at least 75% improvement from baseline in Psoriasis Area and Severity Index score at 16 weeks. Two trials were identified on the treatment of psoriatic arthritis. In the one that involved a dose of 30 mg twice daily, a significantly greater percentage of patients receiving apremilast (38.1%) compared with placebo (19.0%) achieved the American College of Rheumatology criteria for 20% improvement at 16 weeks. In all trials, the drug had an acceptable safety profile, with the most common adverse effects of diarrhea, nausea, and headache. Conclusions: Apremilast has a novel mechanism of action and is safe and effective for the management of psoriasis and psoriatic arthritis. At this time, apremilast should be reserved for patients unable to take disease-modifying antirheumatic drugs.OBJECTIVE To review the pharmacology, efficacy, and safety of apremilast and determine its role relative to other agents in the treatment of psoriasis and psoriatic arthritis. DATA SOURCES A PubMed search (1946 to December 2015) using the terms apremilast and CC-10004 was conducted to identify relevant articles. STUDY SELECTION AND DATA EXTRACTION In vitro or in vivo evaluations of apremilast published in the English language were eligible for inclusion. Controlled clinical trials that involved psoriasis or psoriatic arthritis were selected for review. DATA SYNTHESIS Four trials were identified on the treatment of psoriasis. In those that involved doses of 30 mg twice daily, a significantly greater percentage of patients receiving apremilast (28.8% to 40.9%) compared with placebo (5.3% to 5.8%) achieved at least 75% improvement from baseline in Psoriasis Area and Severity Index score at 16 weeks. Two trials were identified on the treatment of psoriatic arthritis. In the one that involved a dose of 30 mg twice daily, a significantly greater percentage of patients receiving apremilast (38.1%) compared with placebo (19.0%) achieved the American College of Rheumatology criteria for 20% improvement at 16 weeks. In all trials, the drug had an acceptable safety profile, with the most common adverse effects of diarrhea, nausea, and headache. CONCLUSIONS Apremilast has a novel mechanism of action and is safe and effective for the management of psoriasis and psoriatic arthritis. At this time, apremilast should be reserved for patients unable to take disease-modifying antirheumatic drugs.

An Evaluation of the Use of Oral Bisphosphonates and Risk of Esophageal Cancer

Objective: To evaluate the use of oral bisphosphonates and risk of esophageal cancer. Data Sources: MEDLINE (1948–October 2011) was searched using the terms esophageal cancer, esophageal carcinoma, bisphosphonate, bisphosphonates, etidronate, Pamidronate, alendronate, tiludronate, risedronate, zoledronic acid, and ibandronate. Citations from relevant publications were reviewed for additional information. Study Selection and Data Extraction: A comprehensive review of the available literature was performed. Data Synthesis: Two summaries of case reports and 3 observational studies were retrieved and reviewed. Oral bisphosphonates can cause esophageal irritation; therefore, it is biologically plausible that they may increase the risk of esophageal cancer. Although many cases were reported, causality was difficult to determine due to their weak methodology, and subsequent evaluations from national registers did not support an increased risk. Of the 3 observational studies (1 in patients with Barretts esophagus and 2 using the same patient database), only 1 found an increased risk with use of daily or weekly regimens, and significant limitations were noted in each. Conclusions: Evidence on the use of bisphosphonates and risk of esophageal cancer is weak and conflicting. Additional studies are needed to further evaluate this issue and formulate stronger conclusions, in the meantime, health care professionals should ensure that patients take oral bisphosphonates properly to minimize esophageal irritation, are prescribed regimens that minimize exposure if adherence is difficult, and are evaluated for discontinuation of the drugs if appropriate. For patients at increased risk of esophageal cancer for other health reasons, nonoral bisphosphonates may be considered.

Antioxidant and antiatherogenic effects of pomegranate

Pomegranate, or Punica granatum , has been used for many years as a food and medicinal agent in Asia and South America.[1][1] In the United States, it is typically made into a juice, or the seeds are consumed as a food. One pomegranate fruit contains about 40% of an adult’s recommended daily

Effects of dark chocolate on blood pressure in patients with hypertension

Cocoa and chocolate are derived from the cacao bean ( Theobroma cacao ), and cocoa products have been considered delicacies for thousands of years.[1][1] Historically, cocoa products have been used as antidiarrheals, antiseptics, diuretics, and parasiticides. In recent years, dark chocolate has been

Elevated International Normalized Ratio Associated with Use of Dronedarone and Warfarin

Objective: To describe a case of elevated International normalized ratio (INR) after addition of dronedarone to warfarin therapy. Case Summary: A 72-year-old white female with a history of tinnitus, gastroesophageal reflux disease, and permanent pacemaker implantation was taking warfarin (target INR 2-3) and Sotalol for chronic atrial fibrillation; atorvastatin for hyperlipidemia; and risedronate for osteopenia. Her warfarin therapy had been managed by a nurse-run anticoagulation clinic for several years. During the prior year, her INR had been stable with a weekly dose of warfarin 25 mg. After persistent episodes of atrial fibrillation, the antiarrhythmic agent was changed from Sotalol to dronedarone 400 mg twice daily. Approximately 10 days after starting dronedarone, the INR was 4.6; she stated that there was no bleeding. The warfarin dose was decreased to 20 mg/wk, and the INR remained stable with that dosage for the next 11 months. Discussion: Postmarketing surveillance has revealed cases of increased INR values with or without bleeding in patients taking warfarin who were started on dronedarone. In this case, the Horn Drug Interaction Probability Scale suggested a probable causality for an interaction between dronedarone and warfarin. Based on current knowledge, this interaction may involve an indirect gastrointestinal mechanism and/or a direct pharmacokinetic mechanism. Conclusions: Clinicians should monitor patients who are taking warfarin and dronedarone for INR changes and bleeding episodes about 1 week after initiation of dronedarone. If a significant interaction Is noted, the warfarin dosage should be decreased and the patient should be monitored within 2 weeks to assess the need for further adjustments.

Safety of Varenicline in Patients With Cardiovascular Disease

Smoking cessation lowers the risk of death substantially in patients with cardiovascular disease. Although varenicline is an effective medication for smoking cessation, its safety in this population has been questioned and evaluated in several studies. In 2 randomized controlled trials of patients with cardiovascular disease, the rates of serious cardiovascular events were up to 2% higher in patients receiving varenicline than placebo, though the differences were not statistically significant. In the first meta-analysis of mostly trials involving patients with a history of cardiovascular disease, varenicline was found to significantly increase the risk of cardiovascular events by 72%; however, a second meta-analysis did not find a significant increased risk. In an observational study, varenicline was not associated with an increased risk of events when compared to bupropion in a subgroup analysis of patients with a history of cardiovascular disease. Because the evidence on the safety of varenicline in this population is limited and conflicting, additional data are needed to formulate stronger conclusions. In the meantime, health care professionals should consider individual smoking patterns, concomitant medical conditions, and cost when recommending smoking cessation pharmacotherapy for patients with cardiovascular disease.

Peppermint oil for treatment of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that affects 5–15% of people worldwide.[1][1] Typically, patients with IBS experience abdominal pain or discomfort and constipation or diarrhea with other gastrointestinal symptoms, such as abdominal distention and bloating;