Benzodiazepines: a major component in unintentional prescription drug overdoses with opioid analgesics.

The misuse and abuse of prescription medications in the United States continues to increase despite interventions by health care professionals, regulatory, and law enforcement agencies. Opioid analgesics are the leading class of prescription drugs that have caused unintentional overdose deaths. Benzodiazepines when taken alone are relatively safe agents in overdose. However, a 5-fold increase in deaths attributed to benzodiazepines occurred from 1999 to 2009. Emergency department visits related to opioid analgesics increased by 111% followed by benzodiazepines 89%. During 2003 to 2009, the 2 prescriptions drugs with the highest increase in death rates were oxycodone 264.6% and alprazolam 233.8%. Therefore, benzodiazepines have a significant impact on prescription drug unintentional overdoses second only to the opioid analgesics. The combination prescribing of benzodiazepines and opioid analgesics commonly takes place. The pharmacokinetic drug interactions between benzodiazepines and opioid analgesics are complex. The pharmacodynamic actions of these agents differ as their combined effects produce significant respiratory depression. Physician and pharmacy shopping by patients occurs, and prescription drug-monitoring programs can provide important information on benzodiazepine and opioid analgesic prescribing patterns and patient usage. Health care professionals need to inform patients and work closely with regulatory agencies and legislatures to stem the increasing fatalities from prescription drug unintentional overdoses.

Clinically significant drug interactions with atypical antipsychotics.

Atypical antipsychotics [also known as second-generation antipsychotics (SGAs)] have become a mainstay therapeutic treatment intervention for patients with schizophrenia, bipolar disorders and other psychotic conditions. These agents are commonly used with other medications--most notably, antidepressants and antiepileptic drugs. Drug interactions can take place by various pharmacokinetic, pharmacodynamic and pharmaceutical mechanisms. The pharmacokinetic profile of each SGA, especially with phase I and phase II metabolism, can allow for potentially significant drug interactions. Pharmacodynamic interactions arise when agents have comparable receptor site activity, which can lead to additive or competitive effects without alterations in measured plasma drug concentrations. Additionally, the role of drug transporters in drug interactions continues to evolve and may effect both pharmacokinetic and pharmacodynamic interactions. Pharmaceutical interactions occur when physical incompatibilities take place between agents prior to drug absorption. Approximate therapeutic plasma concentration ranges have been suggested for a number of SGAs. Drug interactions that markedly increase or decrease the concentrations of these agents beyond their ranges can lead to adverse events or diminished clinical efficacy. Most clinically significant drug interactions with SGAs occur via the cytochrome P450 (CYP) system. Many but not all drug interactions with SGAs are identified during drug discovery and pre-clinical development by employing a series of standardized in vitro and in vivo studies with known CYP inducers and inhibitors. Later therapeutic drug monitoring programmes, clinical studies and case reports offer methods to identify additional clinically significant drug interactions. Some commonly co-administered drugs with a significant potential for drug-drug interactions with selected SGAs include some SSRIs. Antiepileptic mood stabilizers such as carbamazepine and valproate, as well as other antiepileptic drugs such as phenobarbital and phenytoin, may decrease plasma SGA concentrations. Some anti-infective agents such as protease inhibitors and fluoroquinolones are of concern as well. Two additional important factors that influence drug interactions with SGAs are dose and time dependence. Smoking is very common among psychiatric patients and can induce CYP1A2 enzymes, thereby lowering expected plasma levels of certain SGAs. It is recommended that ziprasidone and lurasidone are taken with food to promote drug absorption, otherwise their bioavailability can be reduced. Clinicians must be aware of the variety of factors that can increase the likelihood of clinically significant drug interactions with SGAs, and must carefully monitor patients to maximize treatment efficacy while minimizing adverse events.

Computerized prescriber order entry and opportunities for medication errors: comparison to tradition paper-based order entry.

PURPOSE: Predefined error opportunity categories were used as a surrogate for medication errors to assess the impact of computerized prescriber order entry (CPOE) on the potential for error in the prescribing and order entry phases of the medication-use process. METHODS: This study was performed in a neonatal intensive care unit at a 535-bed tertiary care center. Pre- and post-CPOE implementation incidence of error opportunity was compared by evaluating 500 orders before and after implementation using 18 predefined criteria. RESULTS: A total of 14 913 opportunities for error (OE) existed in our sample of 1000 medication orders. The number of orders with zero OE improved from 42% (n = 209) to 98% (n = 480; P < .0001), in the pre- and postgroups, respectively. The odds ratio with 95% confidence interval was 0.058 (0.036-0.094) in favor of CPOE. CONCLUSIONS: The implementation of CPOE was associated with a reduction in OEs in the prescribing phase or order entry phase of the medication-use process.

Acamprosate.

IMPORTANCE OF THE FIELD: Alcohol abuse and dependence are major causes of morbidity and mortality and come with a high societal cost. The illness is notoriously difficult to treat and relapse is a common occurrence. Acamprosate represents an effective addition to the treatment options available for alcohol dependence with a novel mechanism of action. AREAS COVERED IN THIS REVIEW: We review the published acamprosate literature focusing on major and recent comparative clinical trials and meta-analyses. We included all studies found in National Library of Medicine's PubMed database searching on Mesh term: acamprosate excluded animal studies excluding non-English publications, and focusing on efficacy/effectiveness studies. Additionally, we discuss background information on alcohol dependence and acamprosate's putative mechanism of action. Safety and tolerability data are also presented. WHAT THE READER WILL GAIN: The reader will gain a better understanding of the role of acamprosate in the treatment of alcohol dependence and find a useful synopsis of the more recently published literature evaluating acamprosate's effectiveness based on what are not always identically defined primary study outcomes. TAKE HOME MESSAGE: Acamprosate is safe and effective in the maintenance of abstinence from alcohol use/abuse and is most commonly used in combination with nonpharmacologic therapeutic modalities. The effect size ranged from 1.3 to 2 for most of the studies included in this review.