Lendormin (brotizolam) / Boehringer Ingelheim - LARVOL DELTA

An Unusual Case of High-Renin Hypertension (KIDNEY WEEK 2024) - "Introduction: We present an unusual case in which negative sodium balance was the etiology of high renin hypertensionCase Description: A 75-year-old woman consulted us due to high blood pressure.PMH: LBP, history of excessive NSAIDS use, s/p partial colectomyMeds : amlodipine, zolpidem, bisacodyl, pregabalin, , acetaminophen tramadol, brotizolam, atorvastatin, ezetimibe, esomeprazoleBP- 150/84mmHgLabs - 24 hour urine collection – 240 mg protein (0 albumin), intermittent leukocytuiaRenal US – echogenic diminished parenchymaOn addition of low dose ARB ( 25mg losartan) her creatinine rose from 1.28 to 1.87 mg/dL, blood pressure dropped to 101/64 mmHg, and renin was found to be elevated to >500 microunits/ml. Aldosterone was also extremely elevated to 64.7ng/dlRenal artery doppler showed no evidence of renal artery stenosis.She reported keeping to a low salt diet as well self-prescribing 10 tabs of bisacodyl every evening (!) We suspected sodium malabsorption, and,..."

Clinical • Cardiovascular • Endocrine Disorders • Hypertension • Hypotension

Exploring the Metabolism of Flubrotizolam, a Potent Thieno-Triazolo Diazepine, Using Human Hepatocytes and High-Resolution Mass Spectrometry. (PubMed, Metabolites) - "We suggest detecting flubrotizolam and its hydroxylated metabolites as markers of consumption after the glucuronide hydrolysis of biological samples. The results are consistent with the in vivo metabolism of brotizolam, a medically used benzodiazepine and a chloro-phenyl analog of flubrotizolam."

Journal

Remimazolam anaphylaxis in a patient not allergic to brotizolam: a case report and literature review. (PubMed, BMC Anesthesiol) - "Remimazolam is an ultrashort-acting sedative; however, it can cause life-threatening anaphylaxis. In addition, its cross-reactivity with other benzodiazepines is not fully understood. To increase the safety of this drug, further research and more experience in its use are needed."

Journal • Review • Allergy • Anesthesia • Cardiovascular • Immunology

Treatment of sleep-related eating disorder with suvorexant: A case report on the potential benefits of replacing benzodiazepines with orexin receptor antagonists. (PubMed, PCN Rep) - "She had a diagnosis of major depressive disorder at age 20 and was on paroxetine and brotizolam for depression and insomnia. This case highlights the importance of discontinuing benzodiazepines in the treatment of SRED, but also suggests the potential benefit of orexin receptor antagonists in the treatment of SRED. The efficacy of orexin receptor antagonists in idiopathic SRED should be tested in future studies."

Journal • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

Inhibitory Actions of Antidepressants, Hypnotics, and Anxiolytics on Recombinant Human Acetylcholinesterase Activity. (PubMed, Biol Pharm Bull) - "At a concentration of 10 M, 22 antidepressants, 19 hypnotics, and 11 anxiolytics inhibited rhAChE activity by <20%, whereas nine antidepressants (clomipramine, amoxapine, setiptiline, nefazodone, paroxetine, sertraline, citalopram, escitalopram, and mirtazapine), two hypnotics (triazolam and brotizolam), and one anxiolytic (buspirone) inhibited rhAChE activity by ≥20%. Among these drugs, only nefazodone inhibited rhAChE activity within the blood concentration range achievable at clinical doses. Therefore, nefazodone may not only improve the depressive symptoms of BPSD through its antidepressant actions but also slow the progression of cognitive symptoms of AD through its AChE inhibitory actions."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Pain

A Pharmacovigilance Study of Drug-Induced Glaucoma Utilizing the Japanese Adverse Event Reporting System. (PubMed, Clin Ophthalmol) - "Among 609 reports of adverse events corresponding to glaucoma (46%, women), the most frequently implicated drug were steroids (prednisolone, betamethasone sodium phosphate, triamcinolone acetonide, and fluorometholone), pregabalin, ranibizumab, crizotinib, tacrolimus hydrate, darbepoetin alfa, and foscarnet sodium hydrate...Signals were also detected in bromazepam (ROR, 69.7; 95% CI, 30.9-157.5), oral brotizolam (ROR, 16.6; 95% CI, 6.18-44.8), and oral milnacipran hydrochloride (ROR, 22.8; 95% CI, 8.46-61.4) for angle-closure glaucoma. A national pharmacovigilance database enabled us to identify the drugs that frequently induce glaucoma. The likelihood of the reporting of glaucoma varied among the drugs, which should be used carefully in clinical practice to avoid it."

Adverse events • Journal • Glaucoma • Ophthalmology

Trends in the multiple prescriptions of hypnotic drugs in a university outpatient in Japan. (PubMed, Neuropsychopharmacol Rep) - "The characteristics and success factors in relation to drug reduction in patients with multiple prescriptions of hypnotic drugs identified in this study may contribute to solving the problem of multiple prescriptions of hypnotic drugs."

Journal • CNS Disorders • Insomnia • Psychiatry • Sleep Disorder

Effects of Blindness on Sleep/Wakefulness States in Mice. (PubMed, Biol Pharm Bull) - "To examine the effects of blindness on sleep/wakefulness states, we compared locomotor activity and delayed recovery from isoflurane anesthesia induced by hypnotics during light and dark periods in sighted CBA/N and blind CBA/J mice...Delayed recovery induced by brotizolam was attenuated in both periods in CBA/J mice. In addition, the period specificity of delayed recovery caused by suvorexant or diphenhydramine in CBA/N mice was abolished in CBA/J mice. These results suggest that blindness impairs sleep quality."

Journal • Preclinical • Anesthesia • Ophthalmology

Effects of brotizolam as a co-agent with ketamine for induction of anaesthesia in calves. (PubMed, Vet J) - "The aim of this study was to investigate the effects of brotizolam as a co-agent with ketamine on the quality of induction, intubation, muscle relaxation and recovery from isoflurane anaesthesia. Brotizolam had a negative effect on the quality of induction, intubation, and muscle relaxation compared to ketamine alone. We do not recommend using brotizolam under these circumstances."

Journal • Anesthesia

Eleven-Year Trend of Drug and Chemical Substance Overdose at a Local Emergency Hospital in Japan. (PubMed, Cureus) - "There was a decreasing trend in overdose, and OTC medicines, sedatives, and anxiolytics were the primary medications causing overdose. OTC antipyretic analgesics and cold medicines were the most common suspected overdose drugs, with an increasing trend in the later years."

Journal • Pain • Psychiatry

Talking to nobody (EUSEM 2022) - "Usual treatment: Chlorthalidone, omeprazole, manidipine.He came to our emergency department referred by his spouse due to the presence of marked temporal-spatial disorientation not previously evidenced, with slow and partial recovery, starting when he woke up; Added to this picture, he refers visual hallucinations (inanimate objects and people), with a tendency to talk with them, disorientation and subsequent amnesia of the episode...The wife reports having started Brotizolam 3 days before the onset of symptoms, at a dose of 0.25mg per day...Sleep disturbances are very frequent in this pathology (40-60%), and special care must be taken both in the choice of the active ingredient and its dosage to avoid undesirable adverse effects or overdosing, and individualize its prescription. In patients with these characteristics, the drug of choice is clonazepam."

Anesthesia • Ataxia • CNS Disorders • Immunology • Movement Disorders • Multiple System Atrophy • Ophthalmology • Otorhinolaryngology • Parkinson's Disease • Retinal Disorders • Sleep Disorder

Talking to nobody (EUSEM 2022) - "Usual treatment: Chlorthalidone, omeprazole, manidipine.He came to our emergency department referred by his spouse due to the presence of marked temporal-spatial disorientation not previously evidenced, with slow and partial recovery, starting when he woke up; Added to this picture, he refers visual hallucinations (inanimate objects and people), with a tendency to talk with them, disorientation and subsequent amnesia of the episode...The wife reports having started Brotizolam 3 days before the onset of symptoms, at a dose of 0.25mg per day...Sleep disturbances are very frequent in this pathology (40-60%), and special care must be taken both in the choice of the active ingredient and its dosage to avoid undesirable adverse effects or overdosing, and individualize its prescription. In patients with these characteristics, the drug of choice is clonazepam."

Anesthesia • Ataxia • CNS Disorders • Immunology • Movement Disorders • Multiple System Atrophy • Ophthalmology • Otorhinolaryngology • Parkinson's Disease • Retinal Disorders • Sleep Disorder

Talking to nobody (EUSEM 2022) - "Usual treatment: Chlorthalidone, omeprazole, manidipine.He came to our emergency department referred by his spouse due to the presence of marked temporal-spatial disorientation not previously evidenced, with slow and partial recovery, starting when he woke up; Added to this picture, he refers visual hallucinations (inanimate objects and people), with a tendency to talk with them, disorientation and subsequent amnesia of the episode...The wife reports having started Brotizolam 3 days before the onset of symptoms, at a dose of 0.25mg per day...Sleep disturbances are very frequent in this pathology (40-60%), and special care must be taken both in the choice of the active ingredient and its dosage to avoid undesirable adverse effects or overdosing, and individualize its prescription. In patients with these characteristics, the drug of choice is clonazepam."

Anesthesia • Ataxia • CNS Disorders • Immunology • Movement Disorders • Multiple System Atrophy • Ophthalmology • Otorhinolaryngology • Parkinson's Disease • Retinal Disorders • Sleep Disorder

Talking to nobody (EUSEM 2022) - "Usual treatment: Chlorthalidone, omeprazole, manidipine.He came to our emergency department referred by his spouse due to the presence of marked temporal-spatial disorientation not previously evidenced, with slow and partial recovery, starting when he woke up; Added to this picture, he refers visual hallucinations (inanimate objects and people), with a tendency to talk with them, disorientation and subsequent amnesia of the episode...The wife reports having started Brotizolam 3 days before the onset of symptoms, at a dose of 0.25mg per day...Sleep disturbances are very frequent in this pathology (40-60%), and special care must be taken both in the choice of the active ingredient and its dosage to avoid undesirable adverse effects or overdosing, and individualize its prescription. In patients with these characteristics, the drug of choice is clonazepam."

Anesthesia • Ataxia • CNS Disorders • Immunology • Movement Disorders • Multiple System Atrophy • Ophthalmology • Otorhinolaryngology • Parkinson's Disease • Retinal Disorders • Sleep Disorder

Pharmacotherapeutic management of insomnia and effects on sleep processes, neural plasticity, and brain systems modulating stress: A narrative review. (PubMed, Front Neurosci) - "Several combinations of terms were used such as "hypnotic benzodiazepines" or "brotizolam," or "lormetazepam" or "temazepam" or "triazolam" or "zolpidem" or "zopiclone" or "zaleplon" or "eszopiclone" and "insomnia" and "effects on sleep" and "effect on brain plasticity" and "effect on stress system". In this framework, among the short/medium acting hypnotic benzodiazepines, triazolam has been the most studied compound while among the Z-drugs eszopiclone has demonstrated interesting effects. Both offer potential new insight for treating insomnia."

Journal • Review • CNS Disorders • Insomnia • Sleep Disorder

In silico studies on recreational drugs: 3D-QSAR prediction of classified and de novo designer benzodiazepines. (PubMed, Chem Biol Drug Des) - "The DBZDs predicted to be the most active were flubrotizolam, clonazolam, pynazolam and flucotizolam, consistently with what reported in literature and/or drug discussion fora. The scaffold hopping studies strongly suggests that replacement of the pendant phenyl moiety with a five-membered ring could increase biological activity and highlight the existence of a still unexplored chemical space for DBZDs. QSAR could be of use as a preliminary risk assessment model for (newly) identified DBZDs, as well as scaffold hopping for the creation of computational libraries that could be used by regulatory bodies as support tools for scheduling procedures."

Journal

Transfer of brotizolam, periciazine, and sulpiride in cord blood and breast milk, and alprazolam in breast milk: a case report. (PubMed, J Pharm Health Care Sci) - "Use of brotizolam, propericiazine, and sulpiride during pregnancy and lactation, and use of alprazolam during lactation were acceptable in this case."

Journal • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Psychiatry

Relationship between use of sleep medication and accidental falls during hospitalization. (PubMed, Nagoya J Med Sci) - "Zolpidem (25%, n=63), a non-benzodiazepine, was the most frequently used sleep medication, followed by brotizolam (16%, n=41) and etizolam (13%, n=32), which are both benzodiazepines...Taking multiple sleeping pills makes it easier to fall, and even drugs with a short half-life, which are considered to be safe, can cause falls at night in elderly patients. The results of this study show that careful selection of sleep medications is required to prevent fall in elderly patients."

Clinical • Journal • CNS Disorders • Gastroenterology • Ophthalmology • Orthopedics • Sleep Disorder

The prevalence and prescribing patterns of benzodiazepines and Z-drugs in older nursing home residents in different European countries and Israel: retrospective results from the EU SHELTER study. (PubMed, BMC Geriatr) - "Despite global recommendations and warnings, the preference for and extent of use of individual BZDs and Z-drugs in vulnerable NH residents differ significantly across countries. The strong association with country of residence compared to clinical and functional factors denotes that prescribing habits, social, cultural, behavioural, and regulatory factors still play an important role in the current diverse use of these medications."

Journal • Retrospective data • Alzheimer's Disease • Anesthesia • CNS Disorders • Dementia

"Benzodiazepine: Alprazolam, Bromazepam, Brotizolam, Clobazam, Clonazepam, Clorazepat, Diazepam, Flunitrazepam, Flurazepam, Lorazepam, Lormetazepam, Medazepam, Midazolam, Nitrazepam, Oxazepam, Prazepam, Temazepam und Triazolam" (@RuisingerR)

Influence of light-dark cycle on delayed recovery from isoflurane anesthesia induced by hypnotics in mice. (PubMed, J Pharmacol Sci) - "In blind mice, delayed recovery induced by brotizolam was identical in both periods, while suvorexant did not influence recovery from isoflurane anesthesia. These results suggest that the effects of hypnotics on isoflurane anesthesia are altered by the circadian rhythm and that daily light-dark stimuli may be required for the chronopharmacological effects of hypnotics."

Journal • Anesthesia

Brotizolam During Pregnancy and Lactation: Brotizolam Levels in Maternal Serum, Cord Blood, Breast Milk, and Neonatal Serum. (PubMed, Breastfeed Med) - "Brotizolam is a sedative-hypnotic thienotriazolodiazepine that is a benzodiazepine analog used for debilitating insomnia...A 28-year-old woman diagnosed with bipolar II disorder received brotizolam during pregnancy (28-40 weeks' gestational age) and lactation, along with sertraline, alprazolam, and trazodone...Brotizolam transfer into placenta and breast milk was negligible. Further studies should assess the safety of brotizolam in fetuses and breastfed infants."

Journal • Bipolar Disorder • CNS Disorders • Depression • Insomnia • Mood Disorders • Movement Disorders • Psychiatry • Respiratory Diseases • Sleep Disorder

Taking Sleeping Pills and the Risk of Chronic Kidney Disease: A Nationwide Population-Based Retrospective Cohort Study. (PubMed, Front Pharmacol) - "After the subgroup analysis for sleeping pill use, brotizolam (p = 0.046), chlordiazepoxide (p < 0.001), clonazepam (p < 0.001), diazepam (p < 0.001), dormicum (p < 0.001), estazolam (p < 0.001), fludiazepam (p < 0.001), flunitrazepam (p < 0.001), nitrazepam (p < 0.001), trazodone (p < 0.001), zolpidem (p < 0.001), and zopiclone (p < 0.001) were found to have significant correlation with increased CKD risk. Sleeping pill use was related to an increased risk of CKD and ESRD. Further studies are necessary to corroborate these findings."

Journal • Retrospective data • Chronic Kidney Disease • Dyslipidemia • Nephrology • Renal Disease • Sleep Disorder

Benzodiazepine Concentrations in the Breast milk and Plasma of Nursing Mothers: Estimation of Relative Infant Dose. (PubMed, Breastfeed Med) - "The target benzodiazepines were alprazolam, brotizolam, clonazepam, clotiazepam, etizolam, ethyl loflazepate, flunitrazepam, and lorazepam. The RID results of this study suggest that drug exposure through breast milk is small; thus, maternal drug treatment and breastfeeding are compatible."

Journal • CNS Disorders • Insomnia • Obstetrics • Sleep Disorder

Vasorelaxant effects of benzodiazepines, non-benzodiazepine sedative-hypnotics, and tandospirone on isolated rat arteries. (PubMed, Eur J Pharmacol) - "Zolpidem and tandospirone caused over 80% relaxation at a concentration of 10 μM; diazepam, estazolam, etizolam, and tofisopam caused 60-70% relaxation; whereas 18 other BDZs (alprazolam, bromazepam, brotizolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, ethyl loflazepate, flunitrazepam, flurazepam, lorazepam, lormetazepam, midazolam, nimetazepam, nitrazepam, oxazepam, temazepam, and triazolam) and zaleplon caused less than 50% relaxation. In conclusion, the direct vasodilatory effects of these drugs may be involved in the mechanisms underlying their adverse effects. Additionally, the decreased BP observed in persons who take BDZs or non-BDZs may be partly due to direct vasodilation."

Journal • CNS Disorders • Insomnia • Pain • Sleep Disorder