Jose A. Rey

Sibutramine: A Serotonin–Norepinephrine Reuptake-Inhibitor for the Treatment of Obesity:

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy data, adverse effects, and drug interactions of sibutramine as a treatment for obesity. DATA SOURCES: English-language clinical studies, abstracts, and review articles were identified using MEDLINE, EMBASE, and a manual search from January 1980 through December 1998. References were also obtained from the reference section of published articles. STUDY SELECTION AND DATA EXTRACTION: All articles identified were evaluated for possible inclusion in this review. Evaluative and comparative data from prospective, open-label, double-blind, and controlled studies were reviewed. DATA SYNTHESIS: Sibutramine is a serotonin–norepinephrine reuptake-inhibitor effective in the treatment of obesity. It does not act as a releasing agent of these neurotransmitters. Sibutramine undergoes extensive metabolism in the liver via CYP3A4, forming two pharmacologically active metabolites. This agent has demonstrated efficacy superior to placebo in reducing weight when used as part of an integrated regimen involving behavior modification, physical activity, and a reduced-calorie intake. The most frequently reported adverse effects include dry mouth, anorexia, headache, insomnia, and constipation. Sibutramine has also been shown to substantially increase blood pressure and heart rate in some patients. CONCLUSIONS: Based on anorectic efficacy data, sibutramine, a serotonin–norepinephrine reuptake-inhibitor, is a viable therapeutic option for the treatment of obesity. Recommended candidates for this medication are patients with a body mass index (BMI) ≥30 kg/m2 without concomitant risk factors or patients with a BMI ≥27 kg/m2 with concomitant risk factors. Sibutramine should be used with caution in patients with a history of hypertension and should not be used in those with uncontrolled hypertension and concomitant cardiovascular disease. Further studies need to be conducted in order to identify long-term outcomes beyond one year.

The discovery and status of sibutramine as an anti-obesity drug.

Sibutramine is a serotonin-norepinephrine reuptake inhibitor indicated for the management of obesity in conjunction with a reduced calorie diet. Though sibutramine was originally evaluated for possible use as an antidepressant, its research development was eventually redirected to evaluate it as an anorexiant. The pharmacological mechanisms by which sibutramine exerts its weight loss effect are likely due to a combination of reduced appetite, feelings of satiety, and possibly the induction of thermogenesis. Its efficacy for inducing an initial weight-loss and the subsequent maintenance of the weight-loss is well proven in short- and long-term clinical trials of up to 2 years duration. In general, sibutramine has been well tolerated. Increases in blood pressure and heart rate are possible adverse effects that require regular monitoring. Sibutramine is one of the few established and well-proven agents for obesity available for use today and should be considered effective in the management of patients requiring pharmacotherapy as part of the multi-modal approach to weight-loss.

Atypical Antipsychotics in Children with Pervasive Developmental Disorders

The treatment of pervasive developmental disorders (PDDs) is a challenging task, which should include behavioral therapy modifications as well as pharmacologic therapy. There has been a lack of data on using medications in children with PDDs until recent years. Within the last 10 years, an increase in clinical research has attempted to provide efficacy and safety data to support the use of medications in children with PDDs. Double-blinded and open-label research of atypical antipsychotics has been of particular focus.Evidence shows that atypical antipsychotics (AAs) may be useful in treating certain symptoms associated with PDDs, such as aggression, irritability, and self-injurious behavior. This article reviews the literature regarding the use of AAs in children with PDDs. Of the AAs, risperidone has the largest amount of evidence with five published double-blinded, placebo-controlled trials and nine open-label trials. These risperidone trials have consistently shown improvements in aggression, irritability, self-injurious behavior, temper tantrums, and quickly changing moods associated with autistic disorder and other PDDs. Data for the other AAs are limited, but ziprasidone and aripiprazole appear to be promising treatment options. Based on clinical trials, olanzapine and quetiapine have shown minimal clinical benefit and a high incidence of weight gain and sedation. It should be noted that all AAs do have a risk of metabolic syndrome, and patients should be monitored appropriately while receiving these medications.Overall, AAs can be beneficial in alleviating behavioral symptoms, and should be considered an appropriate therapeutic option, as part of a comprehensive treatment strategy, for children with PDD.

Role of Risperidone in Children with Autism Spectrum Disorder

Objective: To review the clinical trials investigating the efficacy and safety of risperidone in the treatment of children with autism spectrum disorder (ASD). Data Sources: Searches of MEDLINE/PubMed (1992–February 2006) were conducted, as well as an extensive manual review of journals, using the key words autism and risperidone. Study Selection and Data Extraction: Only double-blind, placebo-controlled trials were included for review. Data Synthesis: ASD is the most common of the pervasive developmental disorders. The main characteristics (core symptoms) of autism are impairment in social skills, problems communicating, and stereotypical movements. Behavioral manifestations or maladaptive behaviors include aggression, irritability, hyperactivity, inattention, impulsivity, tantrums, and self-injurious behavior. Conclusions: Based on the data examined, risperidone appears efficacious and safe for treating certain behavioral aspects of autism including irritability, aggression, hyperactivity, and stereotypy. It does not appear to be as effective for the treatment of the core symptoms of autism.

Prevalence of hazardous alcohol use among pharmacy students at nine U.S. schools of pharmacy

Hazardous use of alcohol continues to be recognized as a problem at the university level. Knowledge regarding alcohol consumption in healthcare professional students is limited, especially in regards to pharmacy students. Much of the information available focuses on pharmacy student drinking patterns in specific geographic regions or is simply outdated. Objective This study was designed to assess levels of alcohol consumption and estimate the level of hazardous drinking among pharmacy students in a larger sample size that is representative of US pharmacy schools. Methods An anonymous survey regarding alcohol usage was offered to students at nine schools of pharmacy across the United States. The survey consisted of demographic questions, the World Health Organization Alcohol Use Disorders Identification Test (AUDIT), and questions that assess particular alcohol-induced behaviors. Results More than 25% of 1161 respondents had a total AUDIT score ≥ 8, which indicates a risk of alcohol-related problems. Students that were male, in their first or second professional year of school, not married, and without children were statistically more likely to have AUDIT scores in the hazardous drinking range. Grade point average and student housing did not statistically affect student’s AUDIT scores. Conclusions These results indicate that over one-fourth of pharmacy students surveyed have indicators of harmful alcohol use. Pharmacy schools should continue to address and confront hazardous alcohol use on campuses in order to curtail heavy alcohol consumption and reduce the risk of alcohol-related problems in pharmacy students.

Clinically Significant Interactions with Benzodiazepines

Benzodiazepines are a class of lipophilic compounds used for a variety of indications including anxiety disorders, insomnia, epilepsy, musculoskeletal disorders, and as sedatives during surgery. The chemical nucleus of each benzodiazepine as well as their pharmacodynamic activity is identical. However, alterations to this basic structure lead to numerous benzodiazepines with different pharmacokinetic properties and lipid solubility resulting in agents with differing rates of elimination, concentrations, volumes of distribution, and potencies. In this chapter we will review the varied kinetics of available benzodiazepines and discuss the metabolic pathways leading to excretion of these medications. This review includes the enzymes (Phase I and Phase II) responsible for metabolism of the parent compound and their intermediates. We also review the pharmacologic and pharmacokinetic activity of the intermediate metabolites. Furthermore we will identify pharmacokinetic interactions of benzodiazepines including: drug-drug interactions, P-gylcoprotein interactions, protein-binding interactions, and food/herbal interactions. Other factors that may require alterations in benzodiazepine dosing such as weight, sex, age, smoking status, genetic polymorphisms, and pharmacokinetic interactions will similarly be discussed. Finally we will identify the clinical monitoring that is required for individuals being prescribed benzodiazepines including respiratory depression, sedation, and withdrawal. The goal of this chapter is to give the reader a background of the factors that should be considered when choosing or monitoring the available benzodiazepines in clinical practice.