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Effect of flunitrazepam as an oral hypnotic on 24-hour blood pressure in healthy volunteers

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Abstract

Purpose

The present study was carried out in order to assess the effects of chronic administration of flunitrazepam (as an oral hypnotic) on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults.

Materials and methods

Following a 2-week placebo run-in period, 28 healthy volunteers (13 males and 15 females) between 21 and 30 years were randomized to receive either flunitrazepam 1 mg or placebo (both administered once a day in the evening) for 4 weeks in two cross-over periods; each separated by a 2-week placebo period. At the end of each study period, non-invasive 24-h BP and HR ambulatory monitoring was performed.

Results

Flunitrazepam produced a significant decrease in nighttime systolic blood pressure (SBP) (− 6.4 mmHg) and diastolic blood pressure (DBP) (− 4.1 mmHg) (both P < 0.05 vs placebo) without affecting nocturnal HR. During the morning hours, significantly higher values of SBP (+ 7.4 mmHg, P < 0.01), DBP (+ 3.4 mmHg, P < 0.05) and HR (+ 3.9 beats/min, P < 0.05) were observed in the flunitrazepam group compared to the placebo-treated group. No significant differences were noted between the two groups during afternoon and evening hours.

Conclusions

These results suggest that chronic oral administration of 1 mg flunitrazepam as a hypnotic agent causes a significant nocturnal fall in BP and a transient rebound increase of both BP and HR at awakening in the morning. Mechanisms underlying these cardiovascular effects remain unclear, although the direct vasodilatory effect, which is typical of flunitrazepam (with consequent reflex counter-regulatory responses), and the attenuation of baroreflex sensitivity are likely to play a major role.

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Authors and Affiliations

  1. Interinstitutional Center of Neurological Medicine, IRCCS C. Mondino National Neurological Institute, via Mondino 2, 27100, Pavia, Italy

    Daniele Bosone, Roberto Fogari, Natascia Ghiotto, Giulia Perini, Matteo Cotta Ramusino & Alfredo Costa

  2. Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy

    Giulia Perini, Matteo Cotta Ramusino & Alfredo Costa

  3. Department of Neurosciences and Behaviour, University of Pavia, Pavia, Italy

    Roberto Fogari, Annalisa Zoppi & Angela D’Angelo

Authors
  1. Daniele Bosone
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  2. Roberto Fogari
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  3. Annalisa Zoppi
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  4. Angela D’Angelo
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  5. Natascia Ghiotto
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  6. Giulia Perini
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  7. Matteo Cotta Ramusino
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  8. Alfredo Costa
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Contributions

R. Fogari, A. Costa, and D. Bosone contributed to the conception and design of the study.

M. Cotta Ramusino, N. Ghiotto, and G. Perini performed clinical activity, contacted the subjects involved in the research, and collected the data under the supervision of D. Bosone.

A. Costa, A. Zoppi, and A. D’Angelo performed the analysis and the interpretation of the data.

The paper was drafted by R. Fogari and A. Zoppi.

All the authors approved the final version.

Corresponding author

Correspondence to Roberto Fogari.

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Bosone, D., Fogari, R., Zoppi, A. et al. Effect of flunitrazepam as an oral hypnotic on 24-hour blood pressure in healthy volunteers. Eur J Clin Pharmacol 74, 995–1000 (2018). https://doi.org/10.1007/s00228-018-2466-9

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  • DOI: https://doi.org/10.1007/s00228-018-2466-9

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