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Journal of Hospital Medicine Jul 2022Opioid and benzodiazepine prescribing after COVID-19 hospitalization is not well understood. We aimed to characterize opioid and benzodiazepine prescribing among naïve...
Opioid and benzodiazepine prescribing after COVID-19 hospitalization is not well understood. We aimed to characterize opioid and benzodiazepine prescribing among naïve patients hospitalized for COVID and to identify the risk factors associated with a new prescription at discharge. In this retrospective study of patients across 39 Michigan hospitals from March to November 2020, we identified 857 opioid- and benzodiazepine-naïve patients admitted with COVID-19 not requiring mechanical ventilation. Of these, 22% received opioids, 13% received benzodiazepines, and 6% received both during the hospitalization. At discharge, 8% received an opioid prescription, and 3% received a benzodiazepine prescription. After multivariable adjustment, receipt of an opioid or benzodiazepine prescription at discharge was associated with the length of inpatient opioid or benzodiazepine exposure. These findings suggest that hospitalization represents a risk of opioid or benzodiazepine initiation among naïve patients, and judicious prescribing should be considered to prevent opioid-related harms.
Topics: Analgesics, Opioid; Benzodiazepines; Hospitalization; Humans; Retrospective Studies; COVID-19 Drug Treatment
PubMed: 35621024
DOI: 10.1002/jhm.12842 -
Drug Testing and Analysis Jan 2018The market for new psychoactive substances has increased markedly in recent years and there is now a steady stream of compounds appearing every year. Benzodiazepines... (Review)
Review
The market for new psychoactive substances has increased markedly in recent years and there is now a steady stream of compounds appearing every year. Benzodiazepines consist of only a fraction of the total number of these compounds but their use and misuse has rapidly increased. Some of these benzodiazepines have only been patented, some of them have not been previously synthesised, and the majority have never undergone clinical trials or tests. Despite their structural and chemical similarity, large differences exist between the benzodiazepines in their pharmacokinetic parameters and metabolic pathways and so they are not easily comparable. As benzodiazepines have been clinically used since the 1960s, many analytical methods exist to quantify them in a variety of biological matrices and it is expected that these methods would also be suitable for the detection of benzodiazepines that are novel psychoactive substances. Illicitly obtained benzodiazepines have been found to contain a wide range of compounds such as opiates which presents a problem since the use of them in conjunction with each other can lead to respiratory depression and death. This review collates the available information on these benzodiazepines and provides a starting point for the further investigation of their pharmacokinetics which is clearly required.
Topics: Analgesics, Opioid; Animals; Benzodiazepines; Humans; Illicit Drugs; Psychotropic Drugs; Substance-Related Disorders
PubMed: 28471096
DOI: 10.1002/dta.2211 -
Psychopharmacology Mar 1995This article deals with some of the recent evidence bearing on the issues of the liability of benzodiazepines to lead to abuse, dependence, and adverse behavioral... (Review)
Review
This article deals with some of the recent evidence bearing on the issues of the liability of benzodiazepines to lead to abuse, dependence, and adverse behavioral effects. Reviews of epidemiological, clinical and experimental literature indicated that the previous conclusion about abuse of these drugs still holds: the vast majority of the use of benzodiazepines is appropriate. Problems of nonmedical use arise nearly exclusively among people who abuse other drugs. Nevertheless, there are reasons for concern about patients who take benzodiazepines regularly for long periods of time. These drugs can produce physiological dependence when taken chronically, and although this does not appear to result in dose escalation or other evidence of "psychological dependence," physiological dependence can result in patient discomfort if drug use is abruptly discontinued. Also, physicians are currently prescribing shorter-acting benzodiazepines in preference to longer-acting benzodiazepines. The shorter-acting drugs can produce a more intense withdrawal syndrome following chronic administration. Furthermore, rates of use of benzodiazepines increase with age, and elderly patients are more likely than younger ones to take the drug chronically. The clearest adverse effect of benzodiazepines is impairment of memory. This, too, may be particular concern in older patients whose recall in the absence of drug is typically impaired relative to younger individuals, and who are more compromised following drug administration.
Topics: Age Factors; Benzodiazepines; Humans; Memory Disorders; Risk Factors; Substance Withdrawal Syndrome; Substance-Related Disorders; Triazolam
PubMed: 7617794
DOI: 10.1007/BF02245824 -
Revista Da Associacao Medica Brasileira... Jul 2020OBJECTIVE To discuss the role of the benzodiazepine class in delirium patient management. METHODS Using the PubMed database, articles were reviewed after the year 2000... (Review)
Review
OBJECTIVE To discuss the role of the benzodiazepine class in delirium patient management. METHODS Using the PubMed database, articles were reviewed after the year 2000 containing in their title the words 'delirium' and 'benzodiazepines'. DISCUSSION Delirium is an acute confusional state that leads to altered attention, awareness, and cognition. It presents with some well-established risk factors, especially older individuals with cognitive decline. There is currently no definite consensus regarding its pathophysiology, nor regarding pharmacological measures, especially concerning the benzodiazepine class. CONCLUSION Evidence suggests that there may be a role for the use of pharmacological class in the treatment of this condition, indicating a change in the previously paradigmatic pattern of treatment.
Topics: Benzodiazepines; Cognition; Delirium; Humans; Risk Factors
PubMed: 32844935
DOI: 10.1590/1806-9282.66.7.998 -
Psychiatria Danubina Mar 2010The use of benzodiazepine anxiolytics and hypnotics continues to excite controversy. Views differ from expert to expert and from country to country as to the extent of... (Review)
Review
BACKGROUND
The use of benzodiazepine anxiolytics and hypnotics continues to excite controversy. Views differ from expert to expert and from country to country as to the extent of the problem, or even whether long-term benzodiazepine use actually constitutes a problem. Although as a class benzodiazepines act rapidly and are well tolerated, their use presents clinical issues such as dependence, rebound anxiety, memory impairment, and discontinuation syndrome. The aim of this article is to review literature regarding different side effects associated with treatment with benzodiazepines - effects on cognition, treatment with benzodiazepines during pregnancy, dependence on benzodiazepines and risk of falling.
CONTENT ANALYSIS OF LITERATURE
Literature research included structured searches of Medline and other publications on the subject of treatment with benzodiazepines, particularly effects on cognition, risk of falls, benzodiazepine dependence and treatment with benzodiazepines during pregnancy.
CONCLUSION
Results of investigations have revealed different side effects associated with treatment with benzodiazepines. Previous investigations showed that treatment with benzodiazepines may induce anterograde amnesia. Also, previous studies confirmed occurrence of physical dependence in high percentage of patients in long term treatment with benzodiazepines at therapeutic dosages. Some investigation suggested higher risk of oral cleft, the floppy infant syndrome, or marked neonatal withdrawal symptoms when using benzodiazepines during pregnany. Investigations have shown increased risk of falling in elderly persons taking benzodiazepines.
Topics: Abnormalities, Drug-Induced; Accidental Falls; Anti-Anxiety Agents; Benzodiazepines; Breast Feeding; Cognition Disorders; Female; Humans; Hypnotics and Sedatives; Infant, Newborn; Long-Term Care; Mental Disorders; Pregnancy; Risk Factors; Substance-Related Disorders
PubMed: 20305598
DOI: No ID Found -
Deutsches Arzteblatt International Jan 2015Benzodiazepine abuse and dependence have been recognized and widely discussed for more than 40 years. With more than 230 million daily doses prescribed in Germany per... (Review)
Review
BACKGROUND
Benzodiazepine abuse and dependence have been recognized and widely discussed for more than 40 years. With more than 230 million daily doses prescribed in Germany per year, the burden of reimbursement on the statutory health insurance carriers is high, albeit with a slight decline from year to year. At present, about 50% of all prescriptions in Germany are issued privately, even for patients who have statutory health insurance.
METHODS
We selectively review the literature on the epidemiology and treatment of benzodiazepine dependence and abuse in Germany.
RESULTS
Estimates of the number of benzodiazepine-dependent persons in Germany range from 128 000 to 1.6 million. Most estimates take no account of the large number of private prescriptions (i.e., those that are not reimbursed by the statutory health insurance scheme), while many exclude prescriptions for elderly persons, for whom these drugs are frequently prescribed. For the outpatient treatment of benzodiazepine withdrawal, it is recommended that the drug should first be switched to an equivalent dose of another benzodiazepine with an intermediate or long-acting effect; the dose should then, in general, be reduced weekly. In case of consumption of a high dose (≥ 20 mg diazepam equivalent), hospitalization and the additional administration of carbamazepine or valproic acid are recommended. Flumazenil treatment can improve with - drawal symptoms and leads to higher abstinence rates. Antidepressants should be given only if the patient is depressed. The dependence potential of nonbenzodiazepine drugs such as zolpidem and zopiclon must also be borne in mind.
CONCLUSION
Benzodiazepines are generally highly effective when first given, but they should generally be given only for strict indications and for a limited time. If these drugs still need to be given beyond the short term, timely referral to a specialist is indicated, and possibly also contact with the addiction aid system.
Topics: Benzodiazepines; Carbamazepine; Flumazenil; Germany; Humans; Prevalence; Risk Factors; Substance Withdrawal Syndrome; Substance-Related Disorders; Valproic Acid
PubMed: 25613443
DOI: 10.3238/arztebl.2015.0001 -
Journal of Enzyme Inhibition and... Dec 2022The poly (ADP-ribose) polymerase (PARP) inhibitors play a crucial role in cancer therapy. However, most approved PARP inhibitors cannot cross the blood-brain barrier,...
The poly (ADP-ribose) polymerase (PARP) inhibitors play a crucial role in cancer therapy. However, most approved PARP inhibitors cannot cross the blood-brain barrier, thus limiting their application in the central nervous system. Here, 55 benzodiazepines were designed and synthesised to screen brain penetrating PARP-1 inhibitors. All target compounds were evaluated for their PARP-1 inhibition activity, and compounds with better activity were selected for further assays . Among them, compounds , , , and displayed acceptable inhibition effects on breast cancer cells. Also, computational prediction together with the permeability assays and proved that the benzodiazepine PARP-1 inhibitors we synthesised were brain permeable. Compound exhibited a B/P ratio of 40 times higher than that of Rucaparib and would be selected to develop its potential use in neurodegenerative diseases. Our study provided potential lead compounds and design strategies for the development of brain penetrating PARP-1 inhibitors.HIGHLIGHTSStructural fusion was used to screen brain penetrating PARP-1 inhibitors.55 benzodiazepines were evaluated for their PARP-1 inhibition activity.Four compounds displayed acceptable inhibition effects on breast cancer cells.The benzodiazepine PARP-1 inhibitors were proved to be brain permeable.
Topics: Benzodiazepines; Dose-Response Relationship, Drug; Drug Design; Humans; Molecular Structure; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Structure-Activity Relationship
PubMed: 35317687
DOI: 10.1080/14756366.2022.2053524 -
Ugeskrift For Laeger Jun 2022In this case report we describe a life-threatening episode of delirium in a 51-year-old man. The condition was triggered by an abrupt withdrawal of benzodiazepines. The...
In this case report we describe a life-threatening episode of delirium in a 51-year-old man. The condition was triggered by an abrupt withdrawal of benzodiazepines. The patient had been taking multiple sedatives for several years but a large proportion of the drugs were not available in Denmark. His general practitioner substituted and prescribed oxazepam and zolpidem for ten days. Afterwards the patient did not have access to benzodiazepines and developed a severe benzodiazepine withdrawal delirium. He was treated with diazepam and olanzapine with gradual dose reduction.
Topics: Alcohol Withdrawal Delirium; Benzodiazepines; Delirium; Diazepam; Humans; Male; Middle Aged; Oxazepam; Substance Withdrawal Syndrome
PubMed: 35703059
DOI: No ID Found -
Anesthesia Progress 1986The benzodiazepines are among the most widely used drugs in the world. When first introduced, little was known about their mechanism of action. However, in the last 20... (Review)
Review
The benzodiazepines are among the most widely used drugs in the world. When first introduced, little was known about their mechanism of action. However, in the last 20 years, our understanding of the chemistry and function of the central nervous system (CNS) has increased substantially. This knowledge has shed some light on the mechanism of action of the benzodiazepines and other centrally acting drugs. It is well established that the benzodiazepines act by combining with specific receptors in the central nervous system. These receptors are anatomically in close association with gamma amino butyric acid (GABA) receptors and appear to reside on the neuronal membrane in the same supramolecular protein complex. GABA is the major inhibitory neurotransmitter of the CNS. The benzodiazepines act by increasing the affinity of the GABA receptor for its ligand, thereby augmenting the inhibitory effect of a given concentration of GABA. Two hypotheses of benzodiazepine ligand-receptor interactions in this supramolecular protein complex have been proposed: (1) multiple receptor subtypes analogous to the opioid receptors; (2) single receptor with multiple conformations. The multiple receptor hypothesis suggests that each pharmacologic effect of the benzodiazepines (i.e., anxiolysis) is mediated by interaction with a specific receptor subtype. On the other hand, the alternative hypothesis suggests that only one receptor exists which has a dynamic conformation. Experimental evidence in support of each hypothesis is presented and critically evaluated.
Topics: Benzodiazepines; Humans; Receptors, GABA-A; gamma-Aminobutyric Acid
PubMed: 3022619
DOI: No ID Found -
Angewandte Chemie (International Ed. in... Jan 2017The pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are a family of sequence-selective DNA minor-groove binding agents that form a covalent aminal bond between their... (Review)
Review
The pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are a family of sequence-selective DNA minor-groove binding agents that form a covalent aminal bond between their C11-position and the C2-NH groups of guanine bases. The first example of a PBD monomer, the natural product anthramycin, was discovered in the 1960s, and the best known PBD dimer, SJG-136 (also known as SG2000, NSC 694501 or BN2629), was synthesized in the 1990s and has recently completed Phase II clinical trials in patients with leukaemia and ovarian cancer. More recently, PBD dimer analogues are being attached to tumor-targeting antibodies to create antibody-drug conjugates (ADCs), a number of which are now in clinical trials, with many others in pre-clinical development. This Review maps the development from anthramycin to the first PBD dimers, and then to PBD-containing ADCs, and explores both structure-activity relationships (SARs) and the biology of PBDs, and the strategies for their use as payloads for ADCs.
Topics: Anthramycin; Antibiotics, Antineoplastic; Antibodies; Benzodiazepines; Cell Proliferation; Female; Humans; Leukemia; Molecular Structure; Ovarian Neoplasms; Pyrroles
PubMed: 27862776
DOI: 10.1002/anie.201510610