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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 -
Kidney International Oct 2020Hyponatremia is a common electrolyte disorder observed in a wide variety of malignancies and is associated with substantial morbidity and mortality. Newer cancer... (Review)
Review
Hyponatremia is a common electrolyte disorder observed in a wide variety of malignancies and is associated with substantial morbidity and mortality. Newer cancer therapies have improved patient outcomes while contributing to new cases of hyponatremia. Patients should be monitored closely for the development of vasopressin- and non-vasopressin-mediated hyponatremia. Acute and symptomatic forms of hyponatremia require urgent intervention, and recent findings support the correction of chronic "asymptomatic" hyponatremia. Optimizing hyponatremia may reduce medical costs, and improve cancer survival likelihood and quality of life. In this article, we review the epidemiology, pathophysiology, etiology, diagnosis, and treatment of hyponatremia in the cancer patient.
Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Humans; Hyponatremia; Inappropriate ADH Syndrome; Neoplasms; Quality of Life; Tolvaptan
PubMed: 32497528
DOI: 10.1016/j.kint.2020.05.015 -
Current Opinion in Anaesthesiology Aug 2020Anaesthesia and sedation are ubiquitous in contemporary medical practice. Developments in anaesthetic pharmacology are targeted on reducing physiological disturbance... (Review)
Review
PURPOSE OF REVIEW
Anaesthesia and sedation are ubiquitous in contemporary medical practice. Developments in anaesthetic pharmacology are targeted on reducing physiological disturbance whilst maintaining or improving titrateability, recovery profile and patient experience. Remimazolam is a new short-acting benzodiazepine in the final stages of clinical development.
RECENT FINDINGS
Clinical experience with remimazolam comprises volunteer studies and a limited number of clinical investigations. In addition, laboratory investigations explore the implications of its 'soft drug' pharmacology.
SUMMARY
Remimazolam provides effective procedural sedation with superior success rates and recovery profile when compared to midazolam. Comparisons with propofol are required. Preliminary studies suggest potential for using remimazolam as the hypnotic component of general anaesthesia. Definitive studies are awaited. As a benzodiazepine, remimazolam could be evaluated as an anticonvulsant and for intensive care sedation.
Topics: Benzodiazepines; Conscious Sedation; Humans; Hypnotics and Sedatives; Midazolam; Propofol
PubMed: 32530890
DOI: 10.1097/ACO.0000000000000877 -
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 -
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 -
CNS & Neurological Disorders Drug... 2023Insomnia, defined as a difficulty in initiating or maintaining sleep, is a relevant medical issue. Benzodiazepines (BZDs) are commonly prescribed to treat insomnia. Two...
BACKGROUND
Insomnia, defined as a difficulty in initiating or maintaining sleep, is a relevant medical issue. Benzodiazepines (BZDs) are commonly prescribed to treat insomnia. Two phases characterize human sleep structure: sleep with Non-Rapid Eye Movement (NREM) and sleep with Rapid Eye Movement (REM). Physiological sleep includes NREM and REM phases in a continuous cycle known as "Sleep Architecture."
OBJECTIVE
This systematic review summarizes the studies that have investigated effects of BZDs on Sleep Architecture.
METHODS
The articles selection included human clinical trials (in English, Portuguese, or Spanish) only, specifically focused on BZDs effects on sleep architecture. PubMed, BVS, and Google Scholar databases were searched.
RESULTS
Findings on BZDs effects on sleep architecture confirm an increase in stage 2 of NREM sleep and a decrease in time of stages 3 and 4 of NREM sleep with a reduction in time of REM sleep during the nocturnal sleep.
CONCLUSION
Variations in NREM and REM sleep may lead to deficits in concentration and working memory and weight gain. The increase in stage 2 of NREM sleep may lead to a subjective improvement of sleep quality with no awakenings. BZDz should be prescribed with zeal and professional judgment. These patients should be closely monitored for possible long-term side effects.
Topics: Humans; Benzodiazepines; Sleep
PubMed: 34145997
DOI: 10.2174/1871527320666210618103344 -
Drug and Alcohol Dependence Oct 2023Cytisine is a smoking cessation medication. This systematic review incorporates recently published randomized controlled trials (RCTs) to provide an updated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cytisine is a smoking cessation medication. This systematic review incorporates recently published randomized controlled trials (RCTs) to provide an updated evidence-based assessment of cytisine's efficacy and safety.
METHODS
We searched Cochrane Library, MEDLINE, and EMBASE, for RCTs comparing cytisine to other smoking cessation treatments in adults who smoke.
PRIMARY OUTCOME
6-month biochemically verified continuous abstinence. Other outcomes: abstinence at longest follow-up, adverse events, mortality, and health-related quality of life (HRQOL). We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess evidence certainty.
RESULTS
We included 14 RCTs involving 9953 adults. Cytisine was superior to placebo (risk ratio [RR] 2.25, 95% confidence interval [CI] 1.13-4.47; 5 RCTs, 4325 participants), but not varenicline (RR 1.13, 95% CI 0.65-1.95; 2 RCTs, 2131 participants) for the primary outcome. Cytisine was superior to placebo (RR 2.78, 95% CI 1.64-4.70; 8 RCTs, 5762 participants) and nicotine replacement therapy [NRT] (RR 1.39, 95% CI 1.12-1.73; 2 RCTs, 1511 participants), but not varenicline (RR 1.02, 95% CI 0.72-1.44; 4 RCTs, 2708 participants) for abstinence at longest follow-up. Cytisine increased mostly gastrointestinal adverse events compared to placebo (RR 1.15; 95% CI 1.06-1.25; 8 RCTs, 5520 participants) and NRT (RR 1.52, 95% CI 1.26-1.84; 1 RCT, 1310 participants) but less adverse events compared to varenicline (RR 0.67; 95% CI 0.48-0.95; 3 RCTs, 2484 participants).
CONCLUSION
Cytisine shows greater efficacy than placebo and NRT, but more adverse events. It is comparable to varenicline, with fewer adverse events. This can inform clinicians and guidelines on cytisine for smoking cessation.
Topics: Adult; Humans; Varenicline; Smoking Cessation; Nicotinic Agonists; Nicotine; Bupropion; Benzazepines; Alkaloids; Azocines; Quinolizines
PubMed: 37678096
DOI: 10.1016/j.drugalcdep.2023.110936 -
Clinical Journal of the American... Jan 2023Tolvaptan slows expansion of kidney volume and kidney function decline in adults with autosomal dominant polycystic kidney disease (ADPKD). Progression during childhood... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tolvaptan slows expansion of kidney volume and kidney function decline in adults with autosomal dominant polycystic kidney disease (ADPKD). Progression during childhood could be treated before irreversible kidney damage occurs, but trial data are lacking. We evaluated the safety and efficacy of tolvaptan in children/adolescents with ADPKD.
METHODS
This was the 1-year, randomized, double-blind, portion of a phase 3b, two-part trial being conducted at 20 academic pediatric nephrology centers. Key eligibility criteria were ADPKD and eGFR ≥60 ml/min per 1.73 m2. Participants aged 12-17 years were the target group (group 1, enrollment goal n≥60); participants aged 4-11 years could additionally enroll (group 2, anticipated enrollment approximately 40). Treatments were tolvaptan or placebo titrated by body weight and tolerability. Coprimary end points, change from baseline in spot urine osmolality and specific gravity at week 1, assessed inhibition of antidiuretic hormone activity. The key secondary end point was change in height-adjusted total kidney volume (htTKV) to month 12 in group 1. Additional end points were safety/tolerability and quality of life. Statistical comparisons were exploratory and post hoc.
RESULTS
Among the 91 randomized (group 1, n=66; group 2, n=25), least squares (LS) mean reduction (±SEM) in spot urine osmolality at week 1 was greater with tolvaptan (-390 [28] mOsm/kg) than placebo (-90 [29] mOsm/kg; P<0.001), as was LS mean reduction in specific gravity (-0.009 [0.001] versus -0.002 [0.001]; P<0.001). In group 1, the 12-month htTKV increase was 2.6% with tolvaptan and 5.8% with placebo (P>0.05). For tolvaptan and placebo, respectively, 65% and 16% of subjects experienced aquaretic adverse events, and 2% and 0% experienced hypernatremia. There were no elevated transaminases or drug-induced liver injuries. Four participants discontinued tolvaptan, and three discontinued placebo. Quality-of-life assessments remained stable.
CONCLUSIONS
Tolvaptan exhibited pharmacodynamic activity in pediatric ADPKD. Aquaretic effects were manageable, with few discontinuations.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease) NCT02964273.
Topics: Adult; Humans; Adolescent; Child; Tolvaptan; Polycystic Kidney, Autosomal Dominant; Antidiuretic Hormone Receptor Antagonists; Quality of Life; Benzazepines; Kidney
PubMed: 36719158
DOI: 10.2215/CJN.0000000000000022 -
Blood Nov 2019B-cell maturation antigen (BCMA) is a validated target for chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma (MM). Despite promising objective response...
B-cell maturation antigen (BCMA) is a validated target for chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma (MM). Despite promising objective response rates, most patients relapse, and low levels of BCMA on a subset of tumor cells has been suggested as a probable escape mechanism. BCMA is actively cleaved from the tumor cell surface by the ubiquitous multisubunit γ-secretase (GS) complex, which reduces ligand density on tumor cells for CAR T-cell recognition and releases a soluble BCMA (sBCMA) fragment capable of inhibiting CAR T-cell function. Sufficient sBCMA can accumulate in the bone marrow of MM patients to inhibit CAR T-cell recognition of tumor cells, and potentially limit efficacy of BCMA-directed adoptive T-cell therapy. We investigated whether blocking BCMA cleavage by small-molecule GS inhibitors (GSIs) could augment BCMA-targeted CAR T-cell therapy. We found that exposure of myeloma cell lines and patient tumor samples to GSIs markedly increased surface BCMA levels in a dose-dependent fashion, concurrently decreased sBCMA concentrations, and improved tumor recognition by CAR T cells in vitro. GSI treatment of MM tumor-bearing NOD/SCID/γc-/- mice increased BCMA expression on tumor cells, decreased sBCMA in peripheral blood, and improved antitumor efficacy of BCMA-targeted CAR T-cell therapy. Importantly, short-term GSI administration to MM patients markedly increases the percentage of BCMA+ tumor cells, and the levels of BCMA surface expression in vivo. Based on these data, a US Food and Drug Administration (FDA)-approved clinical trial has been initiated, combining GSI with concurrent BCMA CAR T-cell therapy. This trial was registered at www.clinicaltrials.gov as #NCT03502577.
Topics: Amyloid Precursor Protein Secretases; Animals; B-Cell Maturation Antigen; Benzazepines; Clinical Trials as Topic; Humans; Immunotherapy, Adoptive; Mice; Mice, Inbred NOD; Mice, SCID; Multiple Myeloma; Receptors, Chimeric Antigen; Xenograft Model Antitumor Assays
PubMed: 31558469
DOI: 10.1182/blood.2019000050