Ezogabine: a novel antiepileptic for adjunctive treatment of partial-onset seizures.

Epilepsy is defined as a tendency toward recurrent seizures unprovoked by any systemic or acute neurologic insults. It is a disruption of the electrical conductivity or activity in the brain, resulting in a seizure. In the United States, approximately 120 of every 100,000 people seek medical attention due to new seizure activity. Ezogabine, known as retigabine in Europe, is an ethyl N-(2-amino-4-[{fluorophenyl}methlamino]phenylcarbamate). The drug has been approved by the United States Food and Drug Administration (FDA) and European Medicines Agency for adjunctive treatment of partial-onset seizures in adults. Ezogabine exerts its therapeutic effect by enhancing transmembrane potassium channels (KCNQ ion channels), which is a novel mechanism in comparison with other antiepileptics. There are no specific documented contraindications to ezogabine. Warnings target patients that have benign prostatic hyperplasia or are receiving concomitant anticholinergic drugs due to a risk of urinary retention (2%). The FDA has required that ezogabine be part of a risk evaluation and mitigation strategy program in order to inform health care professionals of the risk of urinary retention. Prescribers should inform patients that ezogabine can cause urinary retention, including urinary hesitation, and instruct them to seek immediate medical attention if these symptoms occur. A medication guide has been developed for distribution to patients.

Antidepressant-induced liver injury.

OBJECTIVE: To review principles of drug-induced liver injury (DILI), summarize characteristics of antidepressant-mediated liver injury, and provide recommendations for monitoring and management. DATA SOURCES: A search relating to antidepressant-induced liver injury was performed using MEDLINE (1966-March 2007). Search terms included antidepressant, cholestasis, hepatotoxicity, jaundice, liver injury, toxic hepatitis, and transaminases. Reference citations not identified in the initial database search were also utilized. STUDY SELECTION AND DATA EXTRACTION: All English-language case reports, letters, and review articles identified from the data sources were used. Case reports and letters relating to hepatotoxicity from antidepressant overdose were excluded. DATA SYNTHESIS: Antidepressant-induced liver injury described in published cases were of the idiopathic type and, by definition, cannot be predicted based on dose or specific risk factors. Paroxetine had the largest number of cases within the selective serotonin-reuptake inhibitor class. Nefazodone, a serotonin-norepinephrine reuptake inhibitor, appeared to have the most serious cases and is the only antidepressant agent that carries a Food and Drug Administration Black Box Warning regarding hepatotoxicity. The tricyclic antidepressants and monoamine oxidase inhibitors are capable of producing hepatotoxicity, but fewer cases with these agents have been reported in the past 15 years, possibly due to a decline in their use. Causality has not been well established in all reports due to the concurrent use of other drugs and/or underlying liver disease. CONCLUSIONS: Most antidepressant agents have the potential to produce idiopathic liver injury. There is no way to prevent idiopathic DILI, but the severity of the reaction may be minimized with prompt recognition and early withdrawal of the agent. The clinician must be careful to provide ongoing therapy of the underlying depressive disorder and be aware of possible drug discontinuation syndromes should potential hepatotoxicity be suspected.

Overview of oral modified-release opioid products for the management of chronic pain.

OBJECTIVE: To evaluate pharmaceutical and pharmacotherapeutic differences in oral opioid modified-release products used in the management of chronic pain. DATA SOURCES: Searches of MEDLINE (1966-May 2006) and an extensive review of peer reviewed journals were conducted using the key search terms opioid, morphine, hydromorphone, and oxycodone. Supplemental information was gathered through the American Pain Society, and limited but relevant information was obtained from manufacturers' labeling. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated. Information deemed relevant was included for this review if it introduced new or well supported concepts or clarified clinical practice issues. DATA SYNTHESIS: The recognition and treatment of pain has become a major focus of healthcare professionals. The Joint Commission on Accreditation of Healthcare Organizations mandates compliance with recommended standards, outcome measures, and other initiatives. A general review of pain management and pharmacokinetic parameters are included. CONCLUSIONS: Oral modified-release products have enabled patients to better maintain pain control due to convenient dosing intervals and sustained blood concentrations. The differences between available oral modified-release products are half-life, cost, and formulation (excipients and drug-release properties).

Parecoxib for parenteral analgesia in postsurgical patients.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy and safety studies, adverse effects, drug interactions, and dosage and administration of parecoxib sodium, a selective cyclooxygenase-2 (COX-2) inhibitor. DATA SOURCES: Information was obtained from MEDLINE searches of the English-language literature (1996-May 2003). Search terms included parecoxib, parecoxib sodium, SC-69124A, and selective cyclooxygenase-2 inhibitor. STUDY SELECTION AND DATA EXTRACTION: We reviewed available literature, which included abstracts, clinical trials, and data on file with the manufacturer. DATA SYNTHESIS: Parecoxib sodium is a novel selective COX-2 inhibitor under development for parenteral administration. It has produced efficacious analgesia following dental, gynecologic, and orthopedic surgery. The adverse effect profile has been compared with that of ketorolac; no statistically significant differences were identified. There are no documented drug interactions when parecoxib is coadministered with midazolam, propofol, or unfractionated heparin. CONCLUSIONS: Parecoxib sodium is in the final stages of Phase III trials and has a favorable safety and efficacy profile. Its place in moderate to severe postsurgical pain management will be further defined when more pharmacoeconomic and postmarketing safety data are available. Theoretical benefits are its lower potential for gastrointestinal adverse effects compared with ketorolac and lower opioid requirements after surgery.

Impact of an alcohol withdrawal syndrome practice guideline on surgical patient outcomes.

STUDY OBJECTIVE: To standardize treatment of alcohol withdrawal syndrome (AWS) in surgical patients using an AWS practice guideline with a symptom-triggered approach. DESIGN: Prospective interventional (pilot group) and retrospective (comparison group). SETTING: University teaching hospital. PATIENTS: Thirty-eight trauma, orthopedic, and general surgery patients identified at risk for AWS in the pilot group, and 34 patients who were managed using nonstandardized approaches. INTERVENTIONS: At-risk patients in the pilot group were assessed using the AWS Type Indicator. They received lorazepam, clonidine, or haloperidol, based on AWS Type Indicator assessment and AWS practice guideline criteria. MEASUREMENTS AND MAIN RESULTS: A standardized symptom-triggered approach to managing AWS was expected to decrease the use of benzodiazepines, avoid undertreatment of adrenergic hyperactivity and delirium, decrease the need for sitters and physical restraints, and reduce hospital length of stay. Pilot patients received a mean of 23 mg less benzodiazepine (p=0.01), 0.1 mg more clonidine (p=0.01), and 20 mg less haloperidol (p=0.06) than comparison patients. Pilot patients also required significantly fewer sitter hours (p=0.04) and hours of restraint use (p=0.09) than comparison patients. No significant differences were found between groups for length of stay (p=0.77). CONCLUSIONS: This pilot project suggests that trauma, orthopedic, and general surgery patients at risk for AWS can be safely and effectively managed with a standardized, symptom-triggered approach. Moreover, this approach decreased the amounts of benzodiazepines and haloperidol administered to patients at risk for AWS.