Basic & Clinical Pharmacology & Toxicology最新文献

Phenibut is a gamma aminobutyric acid derivative with activity at γ-aminobutyric acid (GABA)_B, _A and β-phenethylamine receptors. It was developed as a drug in the former Soviet Union to overcome anxiety and improve cognitive function in military personnel. In the last decade, it has made inroads into the European and U.S. markets, being marketed for purported nootropic properties. Here, we summarize the current knowledge on phenibut, its toxicology, pharmacology, adverse health effects, and patterns of use. Publications in peer-reviewed journals were searched in PubMed, Web of Science, and Google Scholar databases. Available literature points to adverse side effects associated with intoxication, withdrawal, and addiction to phenibut. Some of these effects can be life-threatening, requiring hospitalization and therapeutic interventions. Supportive efforts are often complicated by a lack of knowledge regarding phenibut's toxicology and pharmacology. Ingestion of phenibut was often associated with concomitant use of other substances of abuse. As control over its online marketing seems unrealistic, current efforts need to be focused on the addition of phenibut to current drug screening tests and the development of generally accepted treatment strategies for phenibut-associated toxicities.

Multiple myeloma (MM) is an incurable cancer in the bone marrow. The treatment of MM has developed significantly during the last 20 years, which has resulted in increased survival. Daratumumab is the first CD38 antibody approved for the treatment of MM. It has improved the treatment of MM even further. This is an evaluation of the modes of action of daratumumab and a description of the development of resistance with a focus on inhibitory checkpoint receptors on CD8⁺ T-cells, complement activation and extracellular vesicles.

Tramadol is a weak opioid used to treat moderate pain. Stronger opioids inhibit gastrointestinal function, but little is known about the gastrointestinal effects of tramadol. Our aim was to investigate if tramadol causes opioid-induced bowel dysfunction (OIBD). Twenty healthy male participants (mean age 24 [range 20–31] years) were included. Tramadol (extended-release formulation, 200 mg/day) or placebo was administered for 10 days in two study periods separated by 3 weeks. Gastrointestinal transit times and segmental volume, motility and water content were investigated with the 3D-transit system and magnetic resonance imaging. Bowel movements and gastrointestinal symptoms were recorded daily. Tramadol prolonged colonic transit time (34 h vs. 25 h, p < 0.001) and increased small bowel motility (p < 0.01) and water content (p = 0.002) compared to placebo. Across all days of treatment, tramadol reduced the number of mean daily bowel movements (p = 0.001) and increased mean stool consistency (p = 0.006). Gastrointestinal symptom scores increased with tramadol (indigestion: +358%, p = 0.01; constipation: +475%, p = 0.01). Additionally, more participants fulfilled the diagnostic criteria for constipation after tramadol treatment compared to placebo (40% vs. 0%, p < 0.001). This study showed that tramadol treatment is associated with OIBD, and management of constipation and other bowel symptoms should, therefore, be prioritised when treating pain patients with tramadol.

Pharmacogenetic variants of the steroid hormone-metabolizing enzyme cytochrome P450 2B6 (CYP2B6) were reported to be associated with breast cancer (BC) risk and prognosis. CYP2B6 expression is inducible by estradiol (E2) but induction was demonstrated only under steroid hormone-deprived medium conditions. Physiological conditions, however, even under endocrinological BC treatment, do not correspond to complete steroid hormone depletion. The aim of this study was to investigate the E2-mediated CYP2B6 and CYP1B1 regulation under various steroid hormone conditions, including physiological concentrations, in human oestrogen receptor positive (T47D, MCF-7) and negative (MDA-MB-231) BC cell lines. We confirm that steroid-deprived pre-cultivation led to CYP2B6 upregulation in T47D, but not in MCF-7. However, when pre-cultivated with steroid-containing medium CYP2B6 was downregulated in T47D and MCF-7, while the addition of physiological E2 concentrations to steroid-deprived medium resulted in a downregulation in T47D. In contrast, CYP1B1 was never downregulated in any culture condition. Thus, we show that E2-mediated CYP2B6 regulation in BC cells depends on steroid hormone exposure in a cell line-specific manner. Our data indicates the importance of being careful with conclusions drawn from CYP2B6 induction findings in vitro, as we demonstrate potential influences of hormonal changes on CYP2B6 expression, which could impact steroid hormone homeostasis and, consequently, BC risk.

Due to changes in pharmacokinetics and pharmacodynamics, patients with impaired renal function suffer an increased risk of suboptimal and potentially harmful medication treatment. This necessitates careful consideration of medications affected by impaired renal function when performing medication reviews. The aim of this study was to develop a quick guide (a list of recommendations) for assessing renal risk medications in medication reviews led by hospital pharmacists. The list was based on the 100 most frequently used medications in Danish hospitals and primary care. After combining the 200 records, 29 duplicates were excluded resulting in a pool of 171 medications. Assessment by two clinical pharmacists led to the exclusion of 121 medications. Of the remaining 50 medications, seven were discussed among the two pharmacists, and two of these were also in the research group to reach a consensus. The renal risk quick guide comprised 50 medications. The most prevalent medications on the list were from Anatomical Therapeutic Chemical Classification System (ATC)-group N, C and L. Recommendations from two databases were included in the quick guide in order to provide clinical pharmacists with existing, updated evidence on medication use in impaired renal function. The next step is to test the feasibility of the quick guide in daily practice when performing medication reviews.

The healthcare sector is a major contributor of greenhouse gas emissions, and reduction and proper sorting of healthcare waste is essential to achieve sustainable healthcare. This study aimed to characterize the quantity and composition of pharmaceutical waste from a major Danish hospital. Pharmaceutical waste was collected from Odense University Hospital, including departments located in both Odense and Svendborg. The average daily production of pharmaceutical waste was 1150 g/day in Odense and 5967 g/day in Svendborg, with the operating rooms in Svendborg contributing 3143 g/day. The amount and composition of pharmaceutical waste varied greatly between departments, but some common patterns were identified. Propofol accounted for about one third of the pharmaceutical waste obtained from operating rooms. Antibiotics for systemic use constituted a significant proportion of the pharmaceutical waste from several departments and were the therapeutic group from which most different drugs were identified. Paracetamol accounted for 33.5% of the discarded tablets/capsules in Odense and 12.6% in Svendborg. Medications dispensed by automated dose dispensing accounted for a significant proportion of the discarded tablets/capsules in departments using this service. This study highlights some key areas for reduction and management of pharmaceutical waste and contributes to the currently limited evidence within this area.

We aimed to map tasks related to medication management and time consumption in Danish home health care. Nursing staff (n = 30) from five municipalities were followed during a 10-week period and tasks related to medication management, time consumption and information on citizens' medication were registered. A total of 269 courses were registered, including 163 (61%) home visits, 76 (28%) in-office courses, 29 (11%) in-clinic courses and 1 (0.4%) acute visit. Of defined categories related to medication management, ‘record-keeping and communication’ (62%, n = 167), ‘dispensing’ (48%, n = 129) and ‘identification’ (30%, n = 81) were most often performed. During half of courses (55%, n = 147), the nursing staff was interrupted at least one time. The median time spent on medication management was less than the time allocated in most of allocated time slots (82%), with a median excess time of 5.1 min (range 0.02–24 min). Citizens (n = 32) used a median of 11 (interquartile range [IQR] 9–13) regular medications and 2 (IQR 1–4) as-needed, and 69% (n = 22) used high-risk situation medications. In conclusion, employees in Danish home health care perform diverse medication-related tasks and are frequently interrupted in their work. Employees spend less time than allocated but do not fully solve all tasks according to best practice guidance.

Tea is a recommended way of administration of prescribed cannabis plant products in Denmark. We aimed to investigate the cannabinoid and terpene doses contained in different teas. We analysed tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), cannabidiolic acid (CBDA), and terpene concentrations in three repeated preparations of each type of tea, and in plant material.

In standard tea, concentrations of THC were [median (min-max)] 9.5 (2.3–15), 19 (13–34), and 36 (26–57) μg/mL for products with a labelled content of 6.3%, 14%, and 22% total THC (THC + THCA), respectively. The CBD concentration in tea from a product labelled with 8% total CBD (CBD + CBDA) was 7.5 (1.9–10) μg/mL. Based on this, the recommended starting amount of 0.2 L of the different teas would contain between 0.46 and 11.3 mg THC, and 0.38 to 2.0 mg CBD. Adding creamer before, but not after boiling, increased the THC and CBD concentration 2.3–4.4 and 2.1-fold, respectively. Terpenes were detected in plant material, but not in tea.

The study elucidates THC and CBD doses in different teas, which may assist the clinician's choice of cannabis product. Moreover, it underscores the need for caution as administration as tea can result in exposure to different doses, even when the same cannabis product is used.