Predictable sedation: Safe administration of oral Midazolam and nitrous oxide gas for paediatric patients in the general dental practice

Behaviour management for anxious paediatric dental patients is challenging. Solutions include education and sedation. Various drugs have been used to effectively sedate paediatric patients during treatment. The aim of this study was to review literature on the sedation of paediatric patients. The study specifically looked at those reviews covering the combination of two sedation methods in case of more challenging paediatric patients. The study undertook a literature review focused on studies using nitrous oxide, Midazolam, or a combination of the two substances. An electronic search was done on EBSCOhost to source articles published from 1979 to 2019. A deeper form of sedation can be achieved for paediatric patients when using a combination of nitrous oxide, oxygen and a hypnotic agent such as Midazolam. Dealing with the anxiety levels of paediatric patients is a challenge for dental health providers. Two of the main strategies used to deal with anxious children are behaviour management and sedation. A critical review of journal articles on the use of nitrous oxide and oxygen in combination with Midazolam was therefore undertaken. The findings suggest that, in order to achieve a deeper form of sedation, the combination of nitrous oxide, oxygen and Midazolam works well to reduce discomfort, anxiety and/or pain in paediatric patients.

Syntheses of Analogues of Propofol: A Review

Propofol (2,6-diisopropylphenol) is an intravenous sedative/hypnotic agent that is used extensively for introduction and maintenance of general anaesthesia, sedation of critically ill patients and procedural sedation (e.g., endoscopy). Propofol has a rapid onset and offset of action and shows only minimal accumulation upon prolonged use. Propofol is only sparingly soluble in water and is currently marketed in 10% soybean oil-based lipid emulsion. Propofol’s anaesthetic properties were discovered over forty years ago, and it has been in clinical use for over thirty years. The main use of propofol remains as an anaesthetic but, over the years, analogues have been developed with varying properties from anticancer, anticonvulsant and antioxidant. In addition, large synthetic efforts have been made towards improving propofol’s water-solubility, its activity, and elucidating its structure–activity­ relationship and exact mechanism of action have been made. This review provides an overview of the research pertaining to propofol-like molecules and covers the efforts of synthetic chemists towards propofol analogues over the last 40 years.1 Introduction2 History3 Early Work4 Improving Water Solubility5 The Importance of the Phenol6 Exploring the Structure–Activity Relationship and Attempts to Improve Activity7 Anticancer Activity8 Anticonvulsant Properties9 Antioxidant Activity10 Photoactive Labelling to Elucidate Mechanism of Action11 Photoregulation12 Conclusion

Elaboration and Validation of HPLC/DAD Method for Quality Control of Products Containing Cannabidiol

Background: Cannabidiol (CBD) is the main, physiologically active, but psycho-inactive constituent of the glandular hairs of Cannabis sativa. CBD exhibits diverse pharmacological activities and it is used as anticonvulsant, sedative and hypnotic agent. Other biological properties shown by CBD are antipsychotic, anti-inflammatory and neuroprotective. Objective: The aim of this study is to develop, validate and apply high performance liquid chromatography (HPLC/DAD) method with diode array detection for identification and assay of CBD in food supplements obtained by different types of extraction and purification. Method: HPLC method with isocratic elution using column C18 ODS, 250 x 4.6, 100 A, 5 μm, mobile phase - mixture of acetonitrile and water in ratio 80:20v/v, flow rate of 1.0 ml/min and DAD detection at 220 nm. Results: The method was developed and validated according to European Pharmacopoeia and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). For the purposes analytical parameters repeatability, linearity, accuracy, LOD, LOQ, specificity and system suitability test were studied. The developed method was successfully applied on a series of food supplements containing CBD. Conclusion: The developed method is of practical importance for determination of purity, identification and assay tests of food supplements containing CBD extract in accordance with EU regulation concerning food authorizations because it is useful for analytical tests for identification, purity determination and assay of products containing CBD extract and could serve as part of the testing process in the pharmaceutical industry.

Zolpidem dependence in an adult with bipolar affective disorder and epilepsy: A case report

Zolpidem is a short-acting non-benzodiazepine hypnotic agent, commonly recommended for short-term treatment of insomnia. Zolpidem has less dependence potential than benzodiazepines. Patients with mental illnesses often have disturbed sleep, for which zolpidem is often prescribed. Long-term use and self-medication (in more than recommended doses) are more likely to cause dependence. We report here a case of bipolar affective disorder with epilepsy, who developed dependence to zolpidem and had severe withdrawal symptoms. The management issues are also discussed with review of the literature.

Comparative single-dose bioavailability study of two 10 mg Zolpidem tablet formulations in healthy volunteers

Zolpidem is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, pyrrolopyrazines, pyrazolopyrimidines or other drugs with known hypnotic properties. Zolpidem as conventional tablets is used as a hypnotic agent in the short-term management of insomnia, generally for periods not exceeding 7–10 days in duration. The objective of this study was to evaluate and compare the relative bioavailability, and therefore the bioequivalence of Zolpidem 10 mg test formulation versus a reference Zolpidem 10 mg formulation, following a single dose administration under fasting conditions The study was a single center, open, single dose, randomized, two - way crossover study in healthy male volunteers with a wash - out period of one week between study periods. Twenty-eight male healthy volunteers, aged 20-49 years were included into study. Blood samples for determination of zolpidem plasma concentrations were withdraw at 0 (pre-drug administration), 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-drug. The zolpidem concentrations in plasma were determined with HPLC, using fluorescence detection. The test formulation of zolpidem, dosed at 10 mg is bioequivalent for primary zolpidem parameters (Cmax, AUC0-t and AUC0-∞) to the reference formulation after a single oral administration of 10 mg zolpidem. Both medications are well tolerated with no serious adverse events. Thus, in view of the clinical use, both formulations are exchangeable without restrictions. Keywords: Zolpidem, bioavailability, bioequivalence study, single-dose

Effect of Diazepam on 24-Hour Blood Pressure and Heart Rate in Healthy Young Volunteers

Aim: To assess the effects of evening chronic administration of diazepam on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults. Methods: This randomized double blind, cross-over study evaluated the effects of diazepam 5 mg or placebo, both ingested in the evening, on 24-h ambulatory BP and HR in healthy subjects aged 21–30. Results: A total of 30 subjects were included in the analysis. At the end of 4-week diazepam intake, an increase in 24-h HR mean values was found (+5.2 beats/min, p < 0.05). Analysis of subperiods showed that diazepam produced a 10.1% increase in night-time HR (+6.1 beats/min, p < 0.01) without affecting BP. A significant HR rise (+4.9 beats/min, p < 0.05) and SBP reduction (–3.8 mm Hg, p < 0.05) were observed in the morning hours. The HR increase persisted in day-time hours (+4.6 beats/min, p < 0.05), while BP values resulted unaffected. Conclusions: In healthy subjects, diazepam taken as a hypnotic agent induces a significant HR increase, possibly mediated by a decrease in vagal tone. This effect might be of clinical relevance due to the role that HR plays as an independent cardiovascular risk factor.