Central effects of combined bendrofluazide and atenolol administration. A single dose study in normal subjects.
Twelve normal male subjects received single oral doses of atenolol 100 mg (AT), bendrofluazide 5 mg (BFZ), combined atenolol 100 mg and bendrofluazide 5 mg (AT/BFZ), diazepam 5 mg (Dz), or one of two matching placebos, on each of 6 study days. Tests of psychomotor performance [digit symbol substitution (DSST), letter cancellation (LCT), continuous attention, choice reaction time (CRT), finger tapping, short-term memory, body sway], physiological measurements [critical flicker fusion (CFF), two-flash fusion (2FF)] and subjective assessments using visual analogue scales (VAS), were performed at 2 and 4 hours post-ingestion. Dz (active control) significantly worsened VAS scores at 2 h (+0.68) and reduced DSST scores at both 2 h (-15.0) and 4 h (-11.0). AT and BFZ given alone, each produced significant worsening of VAS at 2 h [AT +1.0; BFZ +1.38], but had no significant effects on performance. In combination however, AT/BFZ at 4 h produced significant impairment of DSST scores (-10.4), reduced finger tapping (-16.5) and increased involuntary rest pauses (+16.5). Despite these effects, no change in VAS scores occurred. In summary, we have demonstrated significant impairment of psychomotor performance in normal subjects with the AT/BFZ combination, which was not evident with the single agents and which occurred in the absence of a change in subjective awareness. These central effects may have important clinical implications for patients taking combined antihypertensive medication.
Gerrard
L
L
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland, UK.
Wheeldon
N M
NM
McDevitt
D G
DG
D000328:Adult; D001262:Atenolol / Q000009:adverse effects / Q000494:pharmacology*; D001288:Attention / Q000187:drug effects; D001539:Bendroflumethiazide / Q000009:adverse effects / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D004311:Double-Blind Method; D005425:Flicker Fusion / Q000187:drug effects; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects
D001262:Atenolol; D001539:Bendroflumethiazide; D003975:Diazepam