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Overactive bladder (OAB) is a frequent chronic disorder which impairs quality of life by frequent, uncontrollable urination. Newly developed selectiveβ 3-adrenoceptor agonists (sβ 3-agonists) have the same efficacy in treating OAB but significantly fewer side effects than the traditionally used anti-muscarinics. However, safety data on these compounds are scarce. In this study, we analysed the occurrence of adverse effects in patients taking sβ 3-agonists and their characteristics using the JADER database. The most frequently reported adverse effect associated with the use of sβ 3-agonists was urinary retention [mirabegron; crude reporting odds ratios (ROR): 62.1, 95% confidence interval (CI): 52.0-73.6, P<0.001, vibegron; crude ROR: 250, 95% CI : 134-483, P<0.001]. Data from patients with urinary retention were stratified by sex. In both men and women, the rate of urinary retention was higher when using the mirabegron/anti-muscarinic drug when compared to mirabegron monotherapy; its occurrence was higher in men with a history of benign prostatic hypertrophy than in those without. Weibull analysis showed that approximately 50% of sβ 3 agonist-induced urinary retention occurred within 15 days after initiation of treatment, and then gradually decreased. Although sβ 3-agonists are useful against OAB, they may induce several side effects, especially urinary retention, which can further evolve into more severe conditions. Urinary retention occurs more frequently in patients concomitantly taking medication that either increases urethral resistance or has organic factors that block the urethra. When using sβ 3-agonists, the concomitantly used medications and underlying diseases should be thoroughly reviewed, and safety monitoring should be instituted early during the treatment.

Adverse drug events (ADEs) rates associated with anti-dementia acetylcholinesterase inhibitors are estimated to be 5%-20% and show a wide range of symptoms. No report has examined whether there is a difference in the anti-dementia drugs' ADEs profile. This study aimed to establish whether anti-dementia drugs' ADEs profile differed. Data was based on the Japanese Adverse Drug Event Report (JADER) database. The reporting odds ratios (RORs) was used to analyze data for ADEs from April 2004-October 2021. The target drugs were donepezil, rivastigmine, galantamine, and memantine. The top ten most frequently occurring adverse events were selected. The association between the RORs and antidementia drug ADEs was evaluated, and compared the distribution rate of expression age related to ADEs and each ADEs' timing of onset due to anti-dementia drugs. The primary outcome was RORs. Secondary outcome were expression age and time-to-onset of ADE associated with anti-dementia drugs. A total of 705,294 reports were analyzed. The adverse events incidence differed. Bradycardia, loss of consciousness, falls, and syncope incidence were significantly diverse. The Kaplan-Meier curve results for the cumulative ADEs incidence showed that donepezil had the slowest onset, while galantamine, rivastigmine, and memantine had approximately the same timing of onset.

Cyclosporine (CyA) and atorvastatin (AT) are often administered concomitantly to treat dyslipidemia in renal transplant recipients. However, CyA greatly increases the plasma concentration of AT; therefore, concomitant use might increase the frequency of statin-induced adverse effects. The aim of this study was to investigate whether concomitant use of CyA and AT increases intolerance of the latter agent in Japanese renal transplantation recipients. We performed a retrospective cohort analysis of renal transplant recipients aged 18 years and older who had concomitantly received AT and CyA, or tacrolimus (Tac) therapy. We defined statin intolerance as a decrease in dose or discontinuation of AT due to adverse effects. We evaluated the incidence of statin intolerance in concomitant therapy with CyA for 100 days after the initial administration of AT in comparison with Tac. A total of 144 renal transplant recipients who received AT and CyA, or Tac between January 2013 and December 2019 were included. There was no statistical difference in the incidence of statin intolerance in both the CyA (1.8%; 1/57 patients) and Tac (3.4%; 3/87 patients) groups. Concomitant use of CyA and AT might not increase the incidence of statin intolerance in Japanese renal transplant recipients.

This study aimed to investigate the possible drug-drug interactions (DDIs) of 5-FU with antihypertensives metabolised by CYP3A4 and 2C9, using blood pressure (BP) as a pharmacodynamic (PD) parameter. Patients who received 5-FU in combination with antihypertensives metabolised by CYP3A4 or 2C9, specifically, a) amlodipine, nifedipine, or amlodipine + nifedipine, b) candesartan or valsartan, or c) amlodipine + candesartan, amlodipine + losartan, or nifedipine + valsartan, (Group A, n = 20) were identified. Patients who received 5-FU with WF and antihypertensives, specifically, a) amlodipine or b) amlodipine + telmisartan, amlodipine + candesartan, or amlodipine + valsartan, (Group B, n = 5) or 5-FU alone (Group C, n = 25) were also identified and analysed as a comparator and control group, respectively. Regarding the peak BP levels during chemotherapy, there was a significant increase in both SBP (P < 0.0002 and 0.0013) and DBP (P = 0.0243 and 0.0032) in Groups A and C, respectively (Tukey-Kramer test). In contrast, although SBP also increased in Group B during chemotherapy, the change was not statistically significant and there was a decrease in DBP. The significant increase in SBP can be attributed to chemotherapy-induced hypertension by 5-FU or other drugs in the chemotherapeutic regimens. However, when comparing the lowest BP levels during chemotherapy, there was a decrease in SBP and DBP in all groups from the baseline values. The median time to peak and lowest BP was at least 2 weeks and 3 weeks, respectively, for all groups, suggesting that a BP lowering effect was observed following the offset of the initial chemotherapy-induced hypertension. At least 1 month after 5-FU chemotherapy, the SBP and DBP returned to baseline values in all groups. Since Group B also showed a significant increase in PT-INR, possibly demonstrating 5-FU inhibition of CYP activity and, consequently, of WF metabolism, it is likely that 5-FU also inhibited the metabolism of the antihypertensive drugs. The findings suggest possible DDIs between 5-FU and antihypertensives metabolised by CYP3A4.

A specialized drug information service can assist professionals in collating relevant information and hereby help to increase medication safety. It is only helpful if the information provided can also be put into practice, though. The aim of this study was to evaluate the benefits of a specialized palliative care drug information service AMInfoPall and its users' experience. A web-based survey among health care professionals subsequent to inquiry between 07/2017 and 06/2018 was conducted. Twenty questions related to the use and transfer of received information into clinical practice and the result of the consecutive treatment. Invitations to participate/ reminders were sent out 8 and 11 days after receiving the requested information. The survey's response rate was 119/176 (68%). Most participants were physicians (54%), followed by pharmacists (34%) and nurses (10%), 33/119 (28%) worked in palliative home care teams, 29 (24%) on palliative care units, and 27 (23%) in retail pharmacies. 86/99 respondents had conducted an unsatisfiable literature search before contacting AMInfoPall. 113/119 (95%) were satisfied with the provided answer. Information was transferred into clinical practice as recommended in 65/119 (55%) cases and led to a change in patient status in 33%, mostly improvement. No change was reported in 31% and in 36% it was unclear. AMInfoPall was well accepted and mostly used by physicians and palliative home care services. It provided helpful support for decision-making. The obtained information was mostly well transferable into practice.

In a compatibility study of parenteral drugs commonly used in paediatric cardiological intensive care units, an unknown reaction product was found in a mixture of etacrynic acid and theophylline. The conditions in terms of the concentration of etacrynic acid and theophylline as well as the materials used corresponded to the conditions in the intensive care unit. Initially, the reaction product appeared as a significant and increasing peak in the chromatograms when determining the content of etacrynic acid and theophylline via HPLC. At the same time, the concentrations of both drugs decreased. A literature search in the chemical databases Reaxys® and Scifinder ® revealed a patent from 1967 describing an aza-Michael addition between etacrynic acid and theophylline to either N-7 or N-9. Using LC-MS/MS experiments, we were able to confirm that Michael-like reaction between etacrynic acid and theophylline occurs. To elucidate the exact structure of the reaction product we performed NMR experiments (COSY, HSQC and HMBC). With the acquired data we were finally able to identify the unknown compound as the N-7 substituted adduct [2-(2,3-dichloro-4-{2-[(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)methyl]butanoyl}phenoxy)acetic acid]. Our findings show that etacrynic acid and theophylline should not be mixed and should be administered through separate venous lines when infused.

The current conflict between Russia and Ukraine increased concerns in the German population of a release of radioactive substances, e.g.radioactive iodine. A high dose of potassium iodide (PI) may prevent accumulation of radioactive iodine in the thyroid gland. Therefore, the German government keeps a sufficient quantity of PI in stock for public supply in case of an emergency. We investigated ambulatory drug dispensing rates of PI and found that the total dispensing of PI (statutory health insurance (SHI), private health insurance (PHI), and overthe-counter (OTC)) increased by 106% from February to March 2022. Changes in PI dispensing were mainly due to an increase in OTC sales, where PI as an antidote showed a sevenfold increase from around 930 packages (February 2022) to 6,500 packages (March 2022), while SHI and PHI dispensing remained relatively low. Furthermore, we investigated whether these changes in dispensing raised the number of suspected adverse drug reactions (ADR). We found no increase of ADR reports related to the use of PI-containing medicinal products between February and September 2022, neither in our national pharmacovigilance nor in the European EudraVigilance database. The data suggest that the mere possibility of a nuclear disaster in Ukraine raised the demand of PI in Germany. Thus, timely and proactive information and reassurance of the public of supply reliability by the Government in a case of a nuclear emergency could be helpful in preventing potential drug shortages and unfounded concern.

The Town Hall Pharmacy (Raeapteek) in the Town Hall Square of Tallinn, Estonia (N59°26'16.001'' E24°44'45.412'') was first mentioned in historical records on 8 April 1422. To our best knowledge, the Raeapteek is the oldest community pharmacy in Europe which has operated on the same premises since the beginning. There are several hypotheses about the actual opening time of Raeapteek: it is possible that the pharmacy was operating on the square of the Tallinn Town Hall as early as in 1415, 1420, 1392 or even in 1248. In the territory of present-day Estonia, two pharmacies (in Tartu first mentioned in 1430) were already in business in less than 200 kilometres from each other before community pharmacies were opened in Russia, Sweden, Finland, Norway, Denmark, Lithuania, and other cities. The Raeapteek played an essential role in the establishment of the current Estonian History Museum, the Estonian Pharmaceutical Factory, K. C. Fick's faience manufactory and other dignified institutions had their beginning at the pharmacy. Now, the pharmacy functions hand-in-hand with the museum which is supported by the city of Tallinn.

To explore potential indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors, we designed a series of compounds incorporating urea and 1,2,3-triazole structures. IDO1 enzymatic activity experiments with the synthesized compounds were used to verify their molecular-level activity; for instance, the half maximal inhibitory concentration value of compound 3c was 0.07 μM. Our research has yielded a series of novel IDO1 inhibitors which may be beneficial in the development of drugs targeting IDO1 for cancer treatment.