Thomas L. Lenz

Supplemental products used for weight loss.

OBJECTIVE To review the scientific literature on several dietary supplements and herbal products commonly promoted for weight loss. DATA SOURCES Recently published articles and abstracts identified through PubMed (May 1987-May 2003), MEDLINE (January 1966-May 2003), International Pharmaceutical Abstracts (January 1970-May 2003), and Natural Medicines Comprehensive Database (January 1995-May 2003) using the search terms supplement, herbal, weight loss, obesity, overweight, conjugated linoleic acid, ephedra, ephedrine, chromium, Garcinia cambogia, hydroxycitric acid, chitosan, and pyruvate. STUDY SELECTION Performed manually by the authors. DATA EXTRACTION Performed manually by the authors. Only single-agent, randomized, blinded, controlled studies with sufficient scientific rigor in overweight or obese subjects were included. DATA SYNTHESIS Approximately 50 individual supplemental products and hundreds of combination products are promoted for weight loss. As a result, much confusion exists among health care professionals regarding the efficacy and safety of these products. Results for conjugated linoleic acid were positive in three clinical studies, with few adverse effects. Ephedra has been shown to be effective in promoting weight loss, especially when combined with caffeine, but it has a high adverse effect risk profile. The data regarding ephedra and ephedra combinations are conflicting, and many of the studies were poorly designed. Garcinia and chitosan have not shown much promise for weight loss, but little research has been done. Pyruvate has consistently shown positive weight loss effects. CONCLUSION Overall, herbal products and dietary supplements promoted for weight loss lack sufficient supporting efficacy and safety data. More research is needed to draw definitive conclusions. Conjugated linoleic acid and pyruvate have the best supporting evidence, but larger and better-controlled trials are needed before pharmacists should recommend these agents to patients seeking to lose weight.

Potential interactions between exercise and drug therapy

Certain physiological changes caused by aerobic exercise can alter the pharmacokinetics of some drugs. A systematic review of the pharmacokinetic changes that can affect drugs as a result of aerobic exercise is provided. Eleven commonly used drugs are reviewed for their potential interaction with exercising patients. Serum concentrations of two β-blocking agents, atenolol and propranolol, and one antibiotic, doxycycline, have shown to increase as a result of exercise. No pharmacokinetic changes have been found in exercising patients taking Carvedilol or verapamil. Patients who exercise after taking digoxin experience a decreased digoxin serum concentration with an increased skeletal muscle concentration. The clearance of theophylline has been shown to decrease resulting in an increase in plasma half-life during exercise. The risk of hypoglycaemia may increase when patients with diabetes mellitus inject insulin into a muscle just prior to exercising that muscle. Increasing physical activity in patients taking warfarin has been shown to decrease the international normalised ratio. Much is still unknown regarding the interactions that exist between exercise and drug therapy. More studies need to be completed in this area before definite conclusions are made and clinical relevance can be established. Clinicians should be aware that the potential for such interactions exists, especially for drugs with a narrow therapeutic range and in patients who participate in extreme sporting activities.

An evidence-based review of fat modifying supplemental weight loss products.

Objective. To review the literature on fat modifying dietary supplements commonly used for weight loss. Methods. Recently published randomized, placebo-controlled trials were identified in PubMed, MEDLINE, International Pharmaceutical Abstracts, Cochrane Database, and Google Scholar using the search terms dietary supplement, herbal, weight loss, obesity, and individual supplement names. Discussion. Data for conjugated linoleic acid (CLA), Garcinia cambogia, chitosan, pyruvate, Irvingia gabonensis, and chia seed for weight loss were identified. CLA, chitosan, pyruvate, and Irvingia gabonensis appeared to be effective in weight loss via fat modifying mechanisms. However, the data on the use of these products is limited. Conclusion. Many obese people use dietary supplements for weight loss. To date, there is little clinical evidence to support their use. More data is necessary to determine the efficacy and safety of these supplements. Healthcare providers should assist patients in weighing the risks and benefits of dietary supplement use for weight loss.

Dofetilide, a New Class III Antiarrhythmic Agent

Dofetilide is a new antiarrhythmic agent recently approved for conversion and maintenance of sinus rhythm in patients with atrial fibrillation (AF) and atrial flutter (AFl). It is a class III antiarrhythmic that works by selectively blocking the rapid component of the delayed rectifier outward potassium current. Dofetilide prolongs the effective refractory period in accessory pathways, both anterograde and retrograde. This can be seen on the electrocardiogram through a dose‐dependent prolongation of the QT and QTc intervals, with parallel increases in ventricular refractoriness. Approximately 80% of drug is excreted in urine, so dosing must be based on creatinine clearance. The elimination half‐life is approximately 10 hours. In clinical trials dofetilide was superior to flecainide in converting patients with AFl to normal sinus rhythm (NSR; 70% vs 9%, p<0.01). It also was more effective than sotalol in converting patients with both AF and AFl to NSR (29% vs 6%, p<0.05) and maintaining them in NSR for up to 1 year. Most patients converted within 24–36 hours. Dofetilide has a favorable risk:benefit profile. Torsades de pointes is the most serious side effect; it occurs in 0.3–10.5% of patients and is dose related. To minimize the risk of induced arrhythmia, patients who start or restart the drug should be hospitalized a minimum of 3 days for creatinine clearance measurements, continuous electrocardiographic monitoring, and cardiac resuscitation, if necessary.

Clinical pharmacokinetics of antiplatelet agents used in the secondary prevention of stroke

Stroke is one of the leading causes of death and debilitation. Several million stroke survivors are alive throughout the world today. Prevention of recurrent stroke is of major importance to stroke survivors. Several pharmacological agents are currently available for use in secondary stroke prevention.Clopidogrel, the combination of immediate-release aspirin and extendedrelease dipyridamole and aspirin alone are the most widely recommended agents for use in the secondary prevention of strokes. Clopidogrel has shown superiority over aspirin in the combined endpoints of stroke, death and myocardial infarction. The immediate-release aspirin/extended-release dipyridamole combination has shown superiority to aspirin alone in the secondary prevention of stroke.Dipyridamole has been studied as an antiplatelet agent for several decades. Early trials to prove its efficacy compared with aspirin were not favourable, and patients often experienced many adverse effects. Researchers began developing an extended-release formulation in an effort to maintain therapeutic blood concentrations with less frequent daily administration and better adverse effect profile. Pharmacokinetic analysis of this new product showed it to have a more consistent and reproducible absorption compared with immediate-release dipyridamole. The rate of absorption of extended-release dipyridamole is considerably slower than that of immediate-release dipyridamole, while similar plasma concentrations are maintained to optimise antiplatelet efficacy. This allows extended-release dipyridamole to be administered twice daily rather than four times daily.A large-scale randomised trial was conducted with extended-release dipyridamole 200mg in combination with immediate-release aspirin 25mg given twice daily. The combination product showed a greater efficacy at preventing a recurring stroke then either agent administered alone. Indirect comparisons with clopidogrel show that the combination of immediate-release aspirin/extendedrelease dipyridamole may be more effective than clopidogrel at preventing a recurring stroke.

Therapeutic change of HMG-CoA reductase inhibitors in patients with coronary artery disease.

Study Objective. To evaluate short‐term outcomes when atorvastatin was substituted for pravastatin or simvastatin in patients with coronary artery disease.

Comparison of gemfibrozil and Fenofibrate in patients with dyslipidemic coronary heart disease

Study Objective. To compare the lipid‐lowering effects of gemfibrozil and fenofibrate in patients with dyslipidemic coronary heart disease.

The effects of high physical activity on pharmacokinetic drug interactions

Introduction: With the development of new drugs, it is common practice for drug manufacturers to measure their pharmacokinetic parameters. This testing involves the discovery of the absorption, distribution, metabolic, excretory and toxicological properties of drugs. The testing is usually done in non-stressful conditions at rest, however, this does not necessarily tell the entire picture as there is increasing knowledge about the effects that high levels of physical activity can have on the pharmacokinetics of some medications. Areas covered: This review discusses the alterations that physical activity can have on the absorption, distribution, metabolism and elimination parameters of commonly used medications, and clinical outcomes data are reported when known, demonstrating that an interaction exists between exercise and certain medications. This drug–exercise pharmacokinetic interaction alters the performance of medications especially under conditions where exercise is performed for a long period of time. Particular medications that may be affected are those with a narrow therapeutic dosing range, such as digoxin, theophylline and warfarin. Other important medications include insulin and those administered via a transdermal patch drug delivery system. For this review, a literature search was performed between 1966 and 2010. Expert opinion: Patients and healthcare providers should be aware that exercise can adversely affect the way some medications are intended to work. Patients taking certain medications should be closely monitored when performing high amounts of physical activity.

Impact of nesiritide on health care resource utilization and complications in patients with decompensated heart failure.

Study Objective. To determine the impact of nesiritide on health care resource utilization and complications in patients hospitalized with decompensated heart failure.

Reducing the Risk of Obesity: Defining the Role of Weight Loss Drugs

The prevalence of obesity has increased dramatically in the past 20 years. As a public health concern, obesity is associated with a health care resource burden that is quickly approaching that associated with tobacco use. Although lifestyle intervention (diet and exercise) remains the mainstay of treatment of obesity, its effectiveness is limited by poor long‐term adherence. Drug therapy has historically been unsuccessful in producing sustained weight loss. Many older weight loss drugs have adverse benefit‐to‐risk profiles. This review provides an overview of nonpharmacologic interventions for weight loss. The safety and efficacy of older weight loss drugs, as well as current data related to lorcaserin, phentermine/topiramate, and naltrexone‐bupropion, are evaluated. Although associated with modest weight loss and some improvement in adverse obesity‐related metabolic effects, none of these drugs has been demonstrated to reduce mortality. In addition, the long‐term safety of these drugs remains largely unknown. Bariatric surgery is an option for patients with morbid obesity who have failed conventional treatment.