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Current Obesity Reports Mar 2021As a chronic and relapsing disease, obesity impairs metabolism and causes cardiovascular diseases. Although behavioral modification is important for the treatment of... (Review)
Review
PURPOSE OF REVIEW
As a chronic and relapsing disease, obesity impairs metabolism and causes cardiovascular diseases. Although behavioral modification is important for the treatment of obesity, it is difficult to achieve an ideal weight or sustain the process of long-term weight loss. Therefore, the obesity control guidelines strongly recommend lifestyle interventions along with medical treatment for patients who are overweight. There is sufficient evidence supporting that pharmacotherapy in combination with behavior-based interventions can result in significant weight loss and improved cardiometabolism.
RECENT FINDINGS
Recent meta-analyses of new anti-obesity drugs and their weight-loss efficacy have shown that the overall placebo-subtracted weight reduction (%) for at least 12 months ranged from 2.9 to 6.8% for the following drugs: phentermine/topiramate (6.8%), liraglutide (5.4%), naltrexone/bupropion (4.0%), orlistat (2.9%), and lorcaserin (3.1%). However, very recently, on February 13, 2020, the US Food and Drug Administration (FDA) ordered the withdrawal of lorcaserin from markets, as a clinical trial to assess drug safety showed an increased risk of cancer. Currently, the anti-obesity medications that have been approved by the FDA for chronic weight management are orlistat, phentermine/topiramate, naltrexone/bupropion, and liraglutide. However, they are costly and may have adverse effects in some individuals. Therefore, drug therapy should be initiated in obese individuals after weighing its benefits and risks. One of the strategies for long-term obesity control is that anti-obesity medications should be tailored for specific patients depending on their chronic conditions, comorbidities, and preferences.
Topics: Animals; Anti-Obesity Agents; Benzazepines; Bupropion; Humans; Liraglutide; Naltrexone; Obesity; Orlistat; Overweight; Phentermine; Topiramate; United States; United States Food and Drug Administration; Weight Loss
PubMed: 33410104
DOI: 10.1007/s13679-020-00422-w -
Diabetes & Metabolism Journal Dec 2020Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and... (Review)
Review
Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and heterogeneous disease influenced by genetic, developmental, biological, and environmental factors, it is necessary to approach obesity with an integrated and comprehensive treatment strategy. As it is difficult to achieve and sustain successful long-term weight loss in most patients with obesity through lifestyle modifications (e.g., diet, exercise, and behavioral therapy), pharmacological approaches to the treatment of obesity should be considered as an adjunct therapy. Currently, four drugs (orlistat, naltrexone extended-release [ER]/bupropion ER, phentermine/topiramate controlled-release, and liraglutide) can be used long-term (>12 weeks) to promote weight loss by suppressing appetite or decreasing fat absorption. Pharmacotherapy for obesity should be conducted according to a proper assessment of the clinical evidence and customized to individual patients considering the characteristics of each drug and comorbidities associated with obesity. In this review, we discuss the mechanisms of action, efficacy, and safety of these available long-term anti-obesity drugs and introduce other potential agents under investigation. Furthermore, we discuss the need for research on personalized obesity medicine.
Topics: Anti-Obesity Agents; Benzazepines; Humans; Orlistat; Phentermine; Weight Loss
PubMed: 33389955
DOI: 10.4093/dmj.2020.0258 -
Drug Design, Development and Therapy 2022Remimazolam (CNS7056) is a novel benzodiazepine for intravenous sedation; it has an ultra-short duration of action and was recently approved for use in procedural... (Review)
Review
Remimazolam (CNS7056) is a novel benzodiazepine for intravenous sedation; it has an ultra-short duration of action and was recently approved for use in procedural sedation and general anaesthesia. It acts on γ-aminobutyric acid type A receptors and is rapidly converted into an inactive metabolite by tissue esterase enzymes. Remimazolam has been successfully used in endoscopic inspection or surgery and general anaesthesia induction and maintenance with fast and predictable onset and recovery times, high procedure success rates, and minor respiratory and hemodynamic fluctuations and without serious drug-related adverse reactions. If needed, the effects of remimazolam can be reversed by flumazenil, which allows prompt termination of sedation. Although remimazolam has great potential for sedation in patients admitted to intensive care units, future studies are needed to evaluate its efficacy and safety in patients requiring sedation for a long period, and numerous studies are warranted to explore the optimal dose in different application scenarios. The review aimed to provide an introduction to the process of remimazolam synthesis and its current clinical uses and future clinical developments.
Topics: Humans; Hypnotics and Sedatives; Midazolam; Double-Blind Method; Benzodiazepines; Anesthetics; Anesthesia, General
PubMed: 36411859
DOI: 10.2147/DDDT.S384155 -
CNS Drugs Sep 2022Status epilepticus (SE) is an acute, life-threatening medical condition that requires immediate, effective therapy. Therefore, the acute care of prolonged seizures and... (Review)
Review
Status epilepticus (SE) is an acute, life-threatening medical condition that requires immediate, effective therapy. Therefore, the acute care of prolonged seizures and SE is a constant challenge for healthcare professionals, in both the pre-hospital and the in-hospital settings. Benzodiazepines (BZDs) are the first-line treatment for SE worldwide due to their efficacy, tolerability, and rapid onset of action. Although all BZDs act as allosteric modulators at the inhibitory gamma-aminobutyric acid (GABA) receptor, the individual agents have different efficacy profiles and pharmacokinetic and pharmacodynamic properties, some of which differ significantly. The conventional BZDs clonazepam, diazepam, lorazepam and midazolam differ mainly in their durations of action and available routes of administration. In addition to the common intravenous, intramuscular and rectal administrations that have long been established in the acute treatment of SE, other administration routes for BZDs-such as intranasal administration-have been developed in recent years, with some preparations already commercially available. Most recently, the intrapulmonary administration of BZDs via an inhaler has been investigated. This narrative review provides an overview of the current knowledge on the efficacy and tolerability of different BZDs, with a focus on different routes of administration and therapeutic specificities for different patient groups, and offers an outlook on potential future drug developments for the treatment of prolonged seizures and SE.
Topics: Anticonvulsants; Benzodiazepines; Clonazepam; Diazepam; Humans; Lorazepam; Midazolam; Seizures; Status Epilepticus; gamma-Aminobutyric Acid
PubMed: 35971024
DOI: 10.1007/s40263-022-00940-2 -
Journal of Oral Science Jun 2021Remimazolam is a new ultrashort-acting benzodiazepine with fast onset, quick recovery, and few side effects, such as hypotension and respiratory depression. It is... (Review)
Review
Remimazolam is a new ultrashort-acting benzodiazepine with fast onset, quick recovery, and few side effects, such as hypotension and respiratory depression. It is expected to be safe and effective for a wide range of patients undergoing intravenous sedation for dental procedures. The aim of this literature review was to evaluate clinical and sedation outcomes for remimazolam, including method of administration, level of sedation at the dose required, and clinical adverse events. An electronic literature search of databases was conducted, and eight articles were selected for inclusion in this review. Onset time from drug administration to optimal sedation level was faster for remimazolam (around 1.5-6.4 min) than for midazolam. Recovery time was significantly shorter for remimazolam than for midazolam and propofol. A study comparing various doses of remimazolam with midazolam found no significant difference in safety. Comparison of a remimazolam group with a propofol group showed that incidences of hypotension (13.0% vs 42.9%, respectively) and respiratory depression (1.1% vs 6.9%, respectively) were significantly lower for remimazolam. Remimazolam appears to be an ideal sedative.
Topics: Benzodiazepines; Humans; Hypnotics and Sedatives; Midazolam
PubMed: 34092775
DOI: 10.2334/josnusd.21-0051 -
Cell Feb 2021The D1- and D2-dopamine receptors (D1R and D2R), which signal through G and G, respectively, represent the principal stimulatory and inhibitory dopamine receptors in the...
The D1- and D2-dopamine receptors (D1R and D2R), which signal through G and G, respectively, represent the principal stimulatory and inhibitory dopamine receptors in the central nervous system. D1R and D2R also represent the main therapeutic targets for Parkinson's disease, schizophrenia, and many other neuropsychiatric disorders, and insight into their signaling is essential for understanding both therapeutic and side effects of dopaminergic drugs. Here, we report four cryoelectron microscopy (cryo-EM) structures of D1R-G and D2R-G signaling complexes with selective and non-selective dopamine agonists, including two currently used anti-Parkinson's disease drugs, apomorphine and bromocriptine. These structures, together with mutagenesis studies, reveal the conserved binding mode of dopamine agonists, the unique pocket topology underlying ligand selectivity, the conformational changes in receptor activation, and potential structural determinants for G protein-coupling selectivity. These results provide both a molecular understanding of dopamine signaling and multiple structural templates for drug design targeting the dopaminergic system.
Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Amino Acid Sequence; Conserved Sequence; Cryoelectron Microscopy; Cyclic AMP; GTP-Binding Proteins; HEK293 Cells; Humans; Ligands; Models, Molecular; Mutant Proteins; Receptors, Adrenergic, beta-2; Receptors, Dopamine D1; Receptors, Dopamine D2; Signal Transduction; Structural Homology, Protein
PubMed: 33571431
DOI: 10.1016/j.cell.2021.01.027 -
Korean Journal of Anesthesiology Aug 2022Intravenous anesthetic agents such as midazolam, propofol, and ketamine are routinely used to provide anesthesia and sedation. They have been shown to effectively induce... (Review)
Review
Intravenous anesthetic agents such as midazolam, propofol, and ketamine are routinely used to provide anesthesia and sedation. They have been shown to effectively induce and maintain amnesia, sedation, and hypnosis in various patient groups and clinical settings. However, all anesthetic agents have the potential to cause unwanted side effects such as hemodynamic instability, respiratory depression, or slow recovery due to prolonged post-procedural sedation. Remimazolam, a recently approved benzodiazepine for general anesthesia and procedural sedation in Korea, has been successfully used for these purposes. To date, inconclusive knowledge has been obtained regarding the use of remimazolam in different patient populations and under various surgical conditions. With respect to the specific pharmacokinetic and pharmacodynamic characteristics of remimazolam, the use of remimazolam is expected to increase providing safe general anesthesia and sedation. This review aims to provide an overview of the basic and clinical pharmacology of remimazolam and to compare it with midazolam and propofol.
Topics: Anesthesia, General; Anesthetics, Intravenous; Benzodiazepines; Double-Blind Method; Humans; Hypnotics and Sedatives; Midazolam; Propofol
PubMed: 35585830
DOI: 10.4097/kja.22297 -
Minerva Anestesiologica Oct 2021Remimazolam is a new ultrashort acting benzodiazepine anesthetic which has predictable sedative duration and rapid recovery in gastrointestinal endoscopy. Propofol is a... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Remimazolam is a new ultrashort acting benzodiazepine anesthetic which has predictable sedative duration and rapid recovery in gastrointestinal endoscopy. Propofol is a commonly used intravenous anesthetic in clinical work which also has rapid action, short action time and rapid recovery. To date, there have been relatively few articles comparing the two for general anesthesia induction. So, we conducted a randomized trial to evaluate whether remimazolam is superior to propofol during anesthesia induction in terms of efficacy and safety.
METHODS
One hundred and eighty nine ASA I or II patients scheduled for elective surgery were divided into four groups: remimazolam 0.2 mg/kg (R1 group), 0.3 mg/kg (R2 group), 0.4 mg/kg (R3 group), and propofol group (P group). All patients were anesthetized with single shots of experimental drugs during induction period. Efficacy was measured by completing the induction of anesthesia without rescue sedation; and safety was defined as no severe adverse events.
RESULTS
Success induction rates in remimazolam groups were 89% (R1 group), 94% (R2 group) and 100% (R3 group) while success induction rate in P group was 100%. Hypotension rates during induction were lower in R1 group (13%) and R2 group (24%) compared with P group (44%). Hypotension rate in R3 group (34%) was similar to propofol (44%). Injection site pain in group P was 27% while no pain was observed in remimazolam groups.
CONCLUSIONS
Remimazolam is a safe and effective sedative drug during induction with less adverse effects for general anesthesia in ASA I or II patients.
Topics: Anesthesia, General; Benzodiazepines; Humans; Hypnotics and Sedatives; Midazolam; Propofol
PubMed: 34263581
DOI: 10.23736/S0375-9393.21.15517-8 -
Journal of Pain and Symptom Management Nov 2022Subcutaneous drug administration is an interesting approach for symptom control in hospice and palliative care. However, most drugs have no marketing authorization for... (Review)
Review
BACKGROUND
Subcutaneous drug administration is an interesting approach for symptom control in hospice and palliative care. However, most drugs have no marketing authorization for subcutaneous administration and are therefore used off-label. In order to meet the requirements of a safe and effective drug therapy, especially in highly vulnerable patients, it is essential to investigate the scope of evidence of these common practices.
OBJECTIVES
The purpose of this scoping review was to provide an overview of available data on the tolerability and/or effectiveness of subcutaneously administered and off-label used drugs.
METHOD
We performed a scoping review according to the PRISMA extension to identify data available on the tolerability and/or effectiveness of 17 predefined drugs that are commonly administered subcutaneously in Swiss hospices and hospice-like institutions and that have no marketing authorization (off-label use).
RESULTS
The scoping review identified 57 studies with most data available on their tolerability (68% local, 54% systemic), clinical effects (82%), details on dosage (96%) and routes of application (100%). Information on pharmacokinetic properties was mostly missing and only available for fentanyl, levetiracetam, midazolam, and ondansetron. For seven drugs, less than five articles were identified and no studies on codeine or clonazepam were available.
CONCLUSION
This work provides an overview of current evidence on subcutaneous and off-label used drugs in hospice and palliative care. Although both are common practices, evidence on tolerability and effectiveness, particularly pharmacokinetic data, is limited and the identified information gaps need to be closed. This work establishes a basis for further research in this area.
Topics: Clonazepam; Codeine; Fentanyl; Hospice Care; Hospices; Humans; Levetiracetam; Midazolam; Off-Label Use; Ondansetron; Palliative Care; Pharmaceutical Preparations
PubMed: 35870656
DOI: 10.1016/j.jpainsymman.2022.07.006 -
Brain and Behavior Feb 2022Anorexia nervosa (AN) is a severe psychiatric disorder characterized by starvation and malnutrition, a high incidence of coexisting psychiatric conditions, and treatment... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Anorexia nervosa (AN) is a severe psychiatric disorder characterized by starvation and malnutrition, a high incidence of coexisting psychiatric conditions, and treatment resistance. The effect of pharmacotherapy has been controversial.
METHOD
A systematic review was conducted for evidence of an effect of olanzapine versus placebo in adults or its effect as adjuvant treatment of AN in adolescents.
RESULTS
A total of seven articles (304 patients with AN) were identified. There were four double-blind, randomized studies examining the effect of olanzapine in the treatment of AN. The mean difference in body mass index (BMI) at the end of treatment between olanzapine and placebo was 0.67 kg/m (95% confidence interval (CI) 0.15-1.18 kg/m ; p = 0.01; I = 0%, p for heterogeneity < 0.79). The olanzapine groups showed a significant increase in BMI of 0.68 kg/m (95% CI 0.22-1.13 kg/m ; p < 0.001; I = 0%, p for heterogeneity = 0.74) compared to the placebo groups. Only two studies examined the effect of olanzapine as adjuvant treatment in adolescents and showed an increase in BMI of 0.66 kg/m (95% CI -0.36 to 1.67 kg/m ; p = 0.21; I = 11%, p for heterogeneity = 0.32).
DISCUSSION
Olanzapine showed efficacy in the treatment of AN with an increased BMI at the end of treatment in adults. The effect of olanzapine as adjuvant treatment in adolescents remains unclear.
Topics: Adolescent; Adult; Anorexia Nervosa; Benzodiazepines; Body Mass Index; Double-Blind Method; Humans; Olanzapine; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35020271
DOI: 10.1002/brb3.2498