The benzodiazepines.

The benzodiazepines are remarkably effective anxiolytic drugs. However, they are prone to misuse by both physicians and patients. They should be used in clearly defined clinical situations for short periods, at the lowest possible dosages. Although rare, toxicity can be severe. These agents should be used with caution in persons likely to abuse medication, in the elderly, in patients with glaucoma and in patiens with known hepatic impairment. Sudden cessation may be followed by a withdrawal state.     

Influence of Abuse History on Concurrent Benzodiazepine and Opioid Use in Chronic Pain Patients

An important predictor of opioid overdose is co-use of benzodiazepines, which are often prescribed for anxiety. Coping with anxiety may be particularly difficult among individuals with a history of abuse, as it is often linked to higher pain severity and poorer coping skills. We explored whether abuse history moderated the association between anxiety and benzodiazepine use among current opioid users. New patients at a tertiary care, outpatient pain clinic completed self-report measures of medication use, anxiety, and physical and sexual abuse history (child abuse only, adult abuse only, or cumulative abuse). The present study included adult patients reporting current opioid use (n?=?1,785). Approximately 16% reported co-use of benzodiazepines, and 17% reported a history of abuse. Patients reporting child abuse only and cumulative abuse reported co-use of benzodiazepines and opioids more often than those denying abuse and patients reporting adult abuse only (P < .001). Multivariate logistic regression analyses showed that the probability of benzodiazepine use among patients reporting cumulative abuse increased sharply at high levels of anxiety (P?=?.003). Cumulative abuse may increase sensitivity to psychological distress and put patients at risk for co-use. Providers should be aware of life history factors, including abuse, that may drive the need for medication.Perspective: This article examines the association between history of abuse victimization and co-use of benzodiazepines among chronic pain patients reporting current opioid use. The findings suggest that cumulative victimization across the lifespan may contribute to co-use by increasing sensitivity to psychological or physical distress or by negatively impacting coping skills.     

Benzodiazepines: selective use to avoid addiction

When judiciously used, benzodiazepines are therapeutically effective and remarkably safe. Long-term use may result in addiction and physical dependence in some patients. The physician's awareness of this risk helps in the prevention of dependence. Four variables play a part in the development of dependence, ie, dose, duration of treatment, the history, and the patient's personality. A dosage higher than the usual therapeutic dose not only is not needed in most patients but produces more side effects. Short term therapy carries a low risk of dependence and is preferred. It is advisable not to use benzodiazepines in patients with a history of alcohol or drug abuse, as dependent personalities pose a higher risk than other personality types.     

Pharmacologic considerations in the treatment of substance abuse.

Drug and alcohol abuse continue to be commonly encountered problems in most patient populations. To deal effectively with these problems, the primary care physician must have a thorough knowledge of the pharmacology of commonly abused drugs and the adjunctive agents used in treatment. Management of alcoholism may involve a range of medical interventions, including the treatment of alcohol intoxication, the use of benzodiazepines for alcohol withdrawal, and possibly the short-term administration of disulfiram to maintain sobriety. Successful management of cocaine or amphetamine abuse requires an understanding of the powerful reinforcing properties of these drugs and the unique problems that arise in the recovery period. Barbiturate intoxication and withdrawal are potentially life-threatening events requiring skilled in-patient treatment. Prolonged use of benzodiazepines can lead to drug dependence; successful withdrawal involves gradual dosage reduction. Acute intoxication from marijuana or hallucinogenic drugs may occasionally result in adverse reactions requiring medical intervention, but significant withdrawal reactions are rare. Management of opioid overdose, whether illicit or iatrogenic, requires the prompt and skillful use of opioid overdose, whether illicit or iatrogenic, requires the prompt and skillful use of opioid antagonists. Promising new pharmacologic approaches are now being successfully applied to the management of opioid dependence. An acceptance of nicotine as the addictive component of tobacco smoke has led to the development of nicotine gum as substitution therapy for cigarette smoking. Successful pharmacologic management of overdose or withdrawal is often the prerequisite for effective long-term treatment and recovery.     

Psychotropics in dermatology

In dermatology, psychotropics are sometimes useful. But it is not still popular in clinical dermatology. It is recommended to use them for the patients who have psychosomatic aspect, anxiety and depression due to skin disease. Psychotropics are also useful to alleviate the sensation of itch. Trichotillomania and excess scratch are treated with antidepressants, anticonvulsants or antipsychotics. Cutaneous dysesthesia and delusional parasitosis are treated with antipsychotics. In prescribing benzodiazepines and hypnotics, we have to check abuse and dependency. Decrease of dosage should be made gradually. Antidepressants, anticonvulsants (except barbiturates) and antipsychotics have no dependency. They are much easily used than benzodiazepines. Drowsy and thirsty are main side effects that antihistamines also have. It should be noticed to use both simultaneously.     

Acute phenobarbital intoxication.

Phenobarbital is a long-acting barbiturate often prescribed for seizure disorders. It has a high abuse potential and was commonly used in suicide attempts in the past. Although benzodiazepines are now more frequently used in suicide attempts, barbiturate intoxications are still occasionally seen and constitute a medical emergency. The management of phenobarbital overdose includes cardiac and respiratory support, cathartics, activated charcoal, and alkaline diuresis. In severely compromised patients, hemodialysis and hemoperfusion can be used to enhance drug clearance.     

Analgesic and sedative pharmacology in the intensive care unit

Sedation and analgesia are central elements in the care of critically ill, mechanically-ventilated patients. The goal of analgesic therapy is to provide relief from pain and physical discomfort which may lead to poor sleep, agitation, or a stress response. Opioids, such as morphine, fentanyl, and hydromorphone, are considered first-line agents for treating pain. All of these agents are equally effective at equipotent doses and the choice of an agent depends on both drug and patient characteristics. Sedatives with amnestic properties are desirable to prevent or relieve anxiety and agitation. The benzodiazepines and propofol are the primary sedative agents used in the intensive care unit (ICU). Agents such as clonidine and haloperidol may have a role in the ICU when used concomitantly with sedatives and analgesics. An understanding of the pharmacotherapy of sedation and analgesia in the ICU will help support appropriate usage of these agents and improve patient care.     

Severe Carisoprodol Withdrawal After a 14-Year Addiction and Acute Overdose

Background

Carisoprodol, a centrally acting muscle relaxant with a high abuse potential, has barbiturate-like properties at the GABA-A receptor, leading to central nervous system depression and desired effects. Its tolerance and dependence has been previously demonstrated in an animal model, and withdrawal has been described in several recent case reports. Many cases can be effectively managed with a short course of benzodiazepines or antipsychotic agents. However, abrupt cessation in a patient with a history of long-term and high-dose carisoprodol abuse may result in symptoms that are more difficult for providers to treat.

Benzodiazepines and the risk of urinary incontinence in frail older persons living in the community

OBJECTIVE: Urinary incontinence is a common problem among older persons living in different community settings. The multifactorial origin of urinary incontinence has been largely addressed, and many previous studies have identified several reversible factors associated with incontinence. The aim of this study was to estimate the risk of urinary incontinence associated with the use of oxidative or nonoxidative benzodiazepines. METHODS: We analyzed data from a large collaborative observational study group, the Italian Silver Network Home Care project, which collected data on patients admitted to home care programs (N = 4583). A total of 22 home health agencies participated in the project, which evaluated the implementation of the Minimum Data Set for Home Care instrument. The main outcomes measure was the prevalence of urinary incontinence and the association with benzodiazepine use. RESULTS: A total of 1475 individuals (21% of patients aged 60-74 years and 38% aged >or=75 years) reported urinary incontinence. Users of benzodiazepines had an increased risk of urinary incontinence of nearly 45% (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.12-1.83). The risk seemed to be of greater magnitude for exposure to oxidative agents (adjusted OR, 1.47; 95% CI, 1.09-1.99) than to nonoxidative benzodiazepines (adjusted OR, 1.35; 95% CI, 0.93-1.96). Among the oxidative benzodiazepines, the effect mainly resulted from agents with a long elimination half-life (adjusted OR, 1.75; 95% CI, 1.13-2.72). CONCLUSIONS: The metabolic pathway of the benzodiazepines is a good predictor of urinary incontinence. In frail elderly patients, oxidative benzodiazepines are potentially more harmful than nonoxidative agents. Among oxidative benzodiazepines, the best ones seem to be those with a short elimination half-life.     

Chemically induced seizures

Drug- and toxin-associated seizures (DTS) may result from exposure to a wide variety of agents. Most DTS can be managed with supportive care. First-line anticonvulsant therapy should include benzodiazepines, unless agents require a specific antidote. Phenytoin is generally not expected to be useful for DTS and in some instances may be harmful. In this article the authors discuss the pathophysiology of DTS, the potential differential diagnosis, and the clinical presentation. They also review selected agents that cause DTS and provide an overview of how the clinician should approach the management of patients who have DTS.     

Comparison of patient questionnaires, medical records, and plasma assays in assessing exposure to benzodiazepines in elderly subjects.

OBJECTIVE: Exposure in pharmacoepidemiologic studies can rely on various sources such as medical records, patient questionnaires, or plasma samples, which do not always concur. This study endeavored to compare sources of information on current exposure to benzodiazepines in elderly subjects. METHODS: In a study in a hospital admissions department, 1136 elderly subjects included in a case-control study each completed a structured questionnaire. In addition, an inspection of the medical records of each subject was performed, as well as screening of a plasma sample (high-pressure liquid chromatography--diode array detector) for current exposure to benzodiazepines. RESULTS: Benzodiazepines were found in the plasma of 33% of 1013 patients, in the records of 31% of patients, and in the questionnaires of 36% of 797 respondents. With use of the plasma results as a standard, questionnaires had 11% false positives and 28% false negatives; medical records had 14% false positives and 23% false negatives. The kappa for concordance between questionnaires and records was 0.63. Most of the errors were related to the unexpected presence in plasma of clorazepate, commonly used as a hypnotic agent. CONCLUSIONS: Patient recall and medical records are not reliable measures of current exposure to benzodiazepines in elderly persons, although this unreliability may be more marked with certain drugs used as hypnotic agents.     

Treatment of insomnia in hospitalized patients.

OBJECTIVE: To provide recommendations for the short-term management of insomnia in hospitalized patients and review patient assessment, nonpharmacologic treatment modalities, and selection of hypnotic medications. DATA SOURCES: Review articles and primary literature representative of current knowledge regarding the treatment of insomnia were identified by MEDLINE search (1966-January 2001). Search terms included insomnia (sleep initiation and maintenance disorders), benzodiazepines, zaleplon, zolpidem, and trazodone. DATA SYNTHESIS: Literature regarding the management of insomnia in hospitalized patients is limited; therefore, data pertinent to the treatment of ambulatory patients must be extrapolated to the inpatient setting. When evaluating insomnia in hospitalized patients, it seems reasonable to obtain a thorough history and physical examination to identify potential underlying etiologies. Treatment of these underlying etiologies should be considered. When the use of a sedative-hypnotic agent is necessary, medication and dose selection should be based on the pharmacokinetic and adverse effect profiles of each agent. Patent-specific characteristics should also be considered to provide effective treatment while minimizing adverse effects. CONCLUSIONS: Nonpharmacologic approaches to the treatment of insomnia should be considered for hospitalized patients. When sedative-hypnotic medications must be administered, the pharmacokinetic profile of intermediate-acting benzodiazepines (e.g., lorazepam, temazepam) makes them good first-line agents. Zaleplon and zolpidem are also attractive hypnotic agents; however, they are typically reserved for second-line therapy due to cost. Trazodone may be an alternative for patients unable to take benzodiazepines.     

Sedation of the mechanically ventilated patient

Goals in the care of the mechanically ventilated patient are sedation, analgesia, anxiolysis, and muscle relaxation. Causes of distress in these patients include: pain, sleep deprivation, anxiety, psychosis, agitation, and delirium. Drugs used to alleviate these stressors are opiates, benzodiazepines, neuromuscular blocking agents, anesthetic induction agents, and inhalational agents. When caring for the agitated patient on the mechanical ventilator, physiologic, mechanical, and emotional causes must all be investigated. Finally, nonpharmacologic therapy is of utmost importance in the care of these patients.     

The use of intramuscular benzodiazepines and antipsychotic agents in the treatment of acute agitation or violence in the emergency department

The management of an agitated, abusive or violent patient is a common and challenging problem in Emergency Medicine. Priorities include measures to ensure the safety of the patient and the emergency staff, including provision of physical restraint of the patient and evaluation for correctable medical causes of such behavior. Medications used in the treatment of such patients include benzodiazepines and antipsychotic agents. The newer atypical antipsychotic agents seem to provide a safe and effective treatment for such patients. The atypical antipsychotic agents may have fewer short-term side effects than older typical antipsychotic agents, such as haloperidol and droperidol. Currently available atypical antipsychotic medications for the treatment of acute agitation include ziprasidone and olanzapine, which can be administered in an intramuscular formulation, and risperidone, which is available in a rapidly dissolvable tablet and liquid formulation.     

Benzodiazepines for acute pain in children

When pediatric pain is refractory and unresponsive to appropriate use of analgesic agents, there might be additional physical or psychologic dimensions of the pain that are not addressed by the analgesics. In addition to appropriate analgesic therapy, the psychologic needs of the child should be directly addressed and appropriate adjunctive physical modalities employed. Although benzodiazepines lack direct analgesic effects, they can reduce the distress associated with acute pain states by decreasing anxiety, insomnia, and muscle spasms that can be associated with acute pain. Intermediate or long-acting benzodiazepines in modest doses can be useful adjunctive agents when used short term for the treatment of selected acute pain complaints. In the highly distressed school-age child or adolescent with pain complaints relatively unresponsive to appropriate care, judicious use of benzodiazepines is worthy of consideration.     

Benzodiazepines for panic disorder. Are they safe?

The incidence of benzodiazepine dependence in properly selected patients with panic disorder appears to be very low. Patients with a history of drug abuse should not be given benzodiazepines. Physical dependence manifested by withdrawal symptoms occurs in 5% to 45% of patients who discontinue benzodiazepine therapy. Withdrawal symptoms are usually mild and attenuated by use of a tapering schedule of several weeks' duration. Physical dependence should not be confused with substance dependence, a disorder characterized by multiple problems in daily life caused by use of a particular substance.     

Dexmedetomidine: a novel analgesic with palliative medicine potential

Dexmedetomidine has gained popularity in anesthesia and critical care for use in deep sedation and analgesia due to a combination of its efficacy and safety compared with other available agents (e.g., opioids, benzodiazepines, propofol) conventionally used in these settings. This brief review is meant to introduce this unique agent to the palliative care field, as dexmedetomidine may hold promise for patients in hospice and palliative care settings whose symptoms are refractory to usual therapies. [Be sure to be clear in the abstract that more studies are warranted and its role is not well defined and is complicated by significant drug interactions, invasive i.v. route and has a significant side effect profile.]