Vasorelaxant effects of benzodiazepines, non-benzodiazepine sedative-hypnotics, and tandospirone on isolated rat arteries

Kagota, Satomi; Morikawa, Kana; Ishida, Hirotake; Chimoto, Junko; Maruyama‐Fumoto, Kana; Yamada, Shizuo; Shinozuka, Kazumasa

doi:10.1016/j.ejphar.2020.173744

Cited by 14 publications

(12 citation statements)

References 23 publications

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“…The strength of these clinical effects is product specific. In general practice, BZRA are often used to treat insomnia, anxiety, and muscle tension, but also addiction, agitation and neurological disorders (3)(4)(5)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

Evolution of benzodiazepine receptor agonist prescriptions in general practice: A registry-based study

Coteur

Mamouris

Vaes

et al. 2022

Front. Public Health

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BackgroundContrary to most European guidelines, benzodiazepine receptor agonists (BZRA) are often used continuously at a low dosage, being the most common form of long-term use. In Belgium, BZRA use is monitored by analyzing self-report data about medication use in the last 24 h. This method provides insufficient insight into the terms of use of these psychoactive drugs.AimTo describe trends in BZRA prescribing in Flanders, Belgium, between 2000 and 2019.Design and settingPopulation-based trend analysis and a case-control study for the year 2019 were done with data from a morbidity registry in general practice.MethodsRepeated cross-sectional and joinpoint regression analyses revealed trends in sex- and age-standardized prescription rates among adult patients (18+).ResultsOverall, BZRA prescriptions increased. The highest overall increase was found among male patients 18–44 years old, with an average annual percentage change of 2.5 (95% CI: 0.9, 4.3). Among 65+ female patients, a decrease was found since 2006, with an annual percentage change of −0.7 (95% CI: −1.3, −0.1). In 2019, 12% of registered patients received minimally one prescription, long-term use was observed in 5%, back pain was the most common morbidity significantly associated with a rise in BZRA prescriptions, and zolpidem was the most prescribed BZRA (22%).ConclusionDespite some statistically significant decreasing trends, an overall increase in BZRA prescriptions was observed throughout the 19-year study period, especially among long-term users of 18–44 years and 65-plus. Zolpidem became the most prescribed BZRA and warrants more attention.

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Section: Introductionmentioning

confidence: 99%

Evolution of benzodiazepine receptor agonist prescriptions in general practice: A registry-based study

Coteur

Mamouris

Vaes

et al. 2022

Front. Public Health

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“…One of the potential reasons for these varying results could be that in the short-term management (which is a recommended practice) patients are mostly prescribed one type of BZD and a smaller dose. However, in the long-term management, patients could be prescribed different types of BZD, and longer use of these medications may also increase tolerance leading to higher dose, which could have an accumulative effect on vasodilation and vasorelaxation, eventually on BP (Crestani et al, 2001;Kagota et al, 2021) Apart from the increasing tolerance due to long-term management with BZD, the hypotensive effect of long-term BZD prescriptions observed only among older patients could also be due to alteration in the pharmacokinetics of these drugs with increasing age, leading to impaired clearance, and higher plasma concentration of BZD and its metabolites (Madhusoodanan & Bogunovic, 2004). Indeed, the elimination half-life of BZD, particularly diazepam, increases with age and is almost double among older than younger people (Herman & Wilkinson, 1996).…”

Section: Comparison With Other Studiesmentioning

confidence: 99%

“…The increased risk of falls among BZD users is attributed to the BZD sedative effect that compromises gait and balance, as well as cognitive and psychomotor functioning impairment related to the use of these drugs (de Groot et al., 2013; Ng et al., 2018). Moreover, apart from the hypnotic‐sedative and muscle‐relaxant effects, BZDs have vasodilator, vasorelaxant and myorelaxant properties that may reduce blood pressure (BP) levels (Colussi et al., 2017; Kagota et al., 2021), making older people more vulnerable to falls and accidents. In fact, hypotension is a well‐known risk factor for falls and accidents in old age (Klein et al., 2013; Sagawa et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

Impact of long‐term management with sleep medications on blood pressure: An Australian national study

et al. 2023

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Background: There is mixed evidence about the impact of long-term management with hypnotic medications on blood pressure (BP).Aim: To estimate the effect of short-and long-term management with benzodiazepine and z-drugs (BZD) on BP.Method: Open cohort study using deidentified electronic health records of 523,486 adult regular patients (42.3% males; mean age 59.0 ± 17.0 years) annually attending 402 Australian general practices between 2016 to 2018 (MedicineInsight database).Average treatment effects (ATE) of recorded incident BZD prescriptions in 2017 on systolic (SBP) and diastolic (DBP) BP after starting these prescriptions were computed using augmented inverse probability weighting (AIPW). Results:In 2017, 16,623 new cases of short-term management with BZD and 2532 cases of long-term management with BZD were identified (incidence 3.2% and 0.5%, respectively). The mean BP among those not treated with BZD (reference group) was 130.9/77.3 mmHg. Patients prescribed short-term BZD showed a slightly higher SBP (ATE 0.4; 95% CI 0.1, 0.7) and DBP (ATE 0.5; 95% CI 0.3, 0.7), while those on long-term BZD prescriptions showed lower SBP (ATE -1.1; 95% CI −2.0, −0.2), but no effect on DBP (ATE −0.1; 95% CI −0.8, 0.5). However, long-term BZD prescriptions showed a stronger BP-lowering effect among patients aged 65+ years (SBP ATE −2.5 [95% CI −3.8, −1.3]; DBP ATE −1.0 [95% CI −1.7, −0.2]), but almost no effect was observed among younger patients. Conclusion:Long-term management with BZD had a BP-lowering effect among older patients. These findings add new evidence to current recommendations on limiting long-term BZD management in the elderly.

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“…In hypoxia/reoxygenation-mediated H9C2 cells, midazolam was found to retard the I/R-induced cardiomyocyte apoptosis by inhibiting the JNK/p38 MAPK-signaling pathway [ 6 ]. The endothelium-independent vasorelaxation in response to most of the BDZs and two non-BDZs (zaleplon and zolpidem) was determined by myograph methods, using isolated thoracic aortas in the Wistar rat [ 7 ]; however, the direct vasodilatory effects of these drugs may be involved in the mechanisms underlying their adverse effects, such as a potential decrease in blood pressure. The above-mentioned laboratory studies may have underlain the pharmacological basis of the potential association of hypnotic drugs with cardiovascular risk.…”

Section: Introductionmentioning

confidence: 99%

Hypnotics Use Is Associated with Elevated Incident Atrial Fibrillation: A Propensity-Score Matched Analysis of Cohort Study

Jong

Wang

et al. 2022

JPM

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We aimed to investigate the association between either or both of benzodiazepines (BZDs) and non-BZDs and the incidence of atrial fibrillation (AF) in the Taiwan National Health Insurance Database. The participants with at least two prescriptions of BZDs and/or non-BZDs were identified as hypnotics users, whereas those without any prescription of hypnotics were non-hypnotics users. The hypnotics and non-hypnotics cohorts were 1:1 matched on their propensity scores. A total of 109,704 AF-free individuals were included; 610 AF cases occurred in the 54,852 hypnotics users and 166 in the 54,852 non-hypnotics users during the 602,470 person-years of follow-up, with a higher risk of new-onset AF in the users than the non-users (hazard ratio (HR): 3.61, 95% confidence interval [CI]: 3.04–4.28). The users at the highest tertiles of the estimated defined daily doses per one year (DDD) had a greater risk for AF than the non-users, with the risk increasing by 7.13-fold (95% CI: 5.86–8.67) for >0.74-DDD BZDs, 10.68-fold (95% CI: 6.13–18.62) for >4.72-DDD non-BZDs, and 3.26-fold (95% CI: 2.38–4.47) for > 1.65-DDD combinations of BZDs with non-BZDs, respectively. In conclusion, hypnotics use was associated with elevated incidence of AF in the Taiwanese population, which highlighted that the high-dose usage of hypnotics needs more caution in clinical cardiological practice.

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Vasorelaxant effects of benzodiazepines, non-benzodiazepine sedative-hypnotics, and tandospirone on isolated rat arteries

Cited by 14 publications

References 23 publications

Evolution of benzodiazepine receptor agonist prescriptions in general practice: A registry-based study

Evolution of benzodiazepine receptor agonist prescriptions in general practice: A registry-based study

Impact of long‐term management with sleep medications on blood pressure: An Australian national study

Hypnotics Use Is Associated with Elevated Incident Atrial Fibrillation: A Propensity-Score Matched Analysis of Cohort Study

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