Basic & Clinical Pharmacology & Toxicology最新文献

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.

Leaves of the Khat plant are widely consumed in the Horn of Africa, Yemen and the Jazan region of Saudi Arabia. I have investigated the mode of cardiovascular and autonomic actions of the stimulant cathine from Khat in terms of direct or indirect adrenergic actions in anaesthetised male and female rats, and in isolated tissues. Male and female rats were anaesthetised with pentobarbitone and changes in diastolic blood pressure and cardioaccelerator responses were examined in vehicle-treated or chemically sympathectomised rats. Cathine produced marked tachycardia and smaller blood pressure responses in vehicle-treated animals, with significant rises in heart rate occurring at cathine (0.1 mg/kg). In sympathectomised rats, cardiac actions were greatly attenuated in both male and female animals, with no differences between male and female rats. Although pressor responses to cathine were relatively small, sympathectomy significantly reduced these responses in female, but not male, rats. In rat aorta and spleen, cathine produced almost no direct contractions. It is concluded that cathine acts predominantly indirectly, presumably by the release of noradrenaline, in both male and female rats to produce cardiovascular actions. This may have implications for adverse cardiovascular actions of consumption of the plant Khat, particularly with dried Khat, in which actions of cathine may predominate over those of cathinone.

Alzheimer's disease is characterized by progressive cognitive decline, and behavioural and psychological symptoms of dementia are common. The APOE ε4 allele, a genetic risk factor, significantly increases susceptibility to the disease. Despite efforts to effectively treat the disease, only seven drugs are approved for its treatment, and only two of these prevent its progression. This highlights the need to identify new pharmacological options. This review focuses on mimetic peptides, small molecule correctors and HAE-4 antibodies that target ApoE. These drugs reduce β-amyloid-induced neurodegeneration in preclinical models. In addition, loop diuretics such as bumetanide and furosemide show the potential to reduce the prevalence of Alzheimer's disease in humans, and antidepressants such as imipramine improve cognitive function in individuals diagnosed with Alzheimer's disease. Consistent with this, both classes of drugs have been shown to exert neuroprotective effects by inhibiting ApoE4-catalysed Aβ aggregation in preclinical models. Moreover, peroxisome proliferator-activated receptor ligands, particularly pioglitazone and rosiglitazone, reduce ApoE4-induced neurodegeneration in animal models. However, they do not prevent the cognitive decline in APOE ε4 allele carriers. Finally, ApoE4 impairs the integrity of the blood–brain barrier and haemostasis. On this basis, ApoE4 modulation is a promising avenue for the treatment of late-onset Alzheimer's disease.

Renewing prescriptions is important for the continuity of pharmacotherapy. However, renewing without the prescriber meeting the patient might lead to insufficient pharmacotherapy monitoring. This study investigated the prevalence of renewed prescriptions, prescriptions renewed without the prescriber meeting the patient and the factors associated with renewals made without meeting the patient. This register-based study employed data on electronic prescriptions and health care contacts from Finnish registers. Prescriptions were classified as renewed if there was a renewal request or a previous prescription for the same ATC code. Prescriptions were considered as being renewed without meeting the patient if there was no patient contact on the renewal date. Descriptive and logistic generalized estimating equation analyses were conducted. The random sample of prescriptions (10%) from the year 2019 amounted to 2 804 048. Of these, 41.9% were original, 35.4% were renewals without meeting the patient and 22.7% were renewed with meeting the patient. Characteristics such as male sex, age 35–54 years, prescription for cardiovascular system preparations and the prescription being renewed during the summer (June–August) were associated with renewals made without meeting the patient. Further research is needed on the implementation of pharmacotherapy monitoring in the case of renewals without the prescriber meeting the patient.

Ramipril is an angiotensin-converting enzyme inhibitor used for hypertension and heart failure management. To date, scarce literature is available on pharmacogenetic associations affecting ramipril. The goal of this study was to investigate the effect of 120 genetic variants in 34 pharmacogenes (i.e., genes encoding for enzymes like CYPs or UGTs and transporters like ABC or SLC) on ramipril pharmacokinetic variability and adverse drug reaction (ADR) incidence. Twenty-nine healthy volunteers who had participated in a single-dose bioequivalence clinical trial of two formulations of ramipril were recruited. A univariate and multivariate analysis searching for associations between genetic variants and ramipril pharmacokinetics was performed. SLCO1B1 and ABCG2 genotype-informed phenotypes strongly predicted ramipril exposure. Volunteers with the SLCO1B1 decreased function (DF) phenotype presented around 1.7-fold higher dose/weight-corrected area under the curve (AUC/DW) than volunteers with the normal function (NF) phenotype (univariate p-value [p_uv] < 0.001, multivariate p-value [p_mv] < 0.001, β = 0.533, R² = 0.648). Similarly, volunteers with ABCG2 DF + poor function (PF) phenotypes presented around 1.6-fold higher AUC/DW than those with the NF phenotype (p_uv = 0.011, p_mv < 0.001, β = 0.259, R² = 0.648). Our results suggest that SLCO1B1 and ABCG2 are important transporters to ramipril pharmacokinetics, and their genetic variation strongly alters its pharmacokinetics. Further studies are required to confirm these associations and their clinical relevance.