Central effects of combined bendrofluazide and atenolol administration : a single dose study in normal subjects

• Published in: European journal of clinical pharmacology 1993-12, Vol.45 (6), p.539-543
• Main Authors: GERRARD, L, WHEELDON, N. M, MCDEVITT, D. G
• Format: Article
• Language: English
• Subjects: Adult; Atenolol - adverse effects; Atenolol - pharmacology; Attention - drug effects; Bendroflumethiazide - adverse effects; Bendroflumethiazide - pharmacology; Biological and medical sciences; Blood Pressure - drug effects; Diazepam - pharmacology; Double-Blind Method; Drug toxicity and drugs side effects treatment; Flicker Fusion - drug effects; Humans; Male; Medical sciences; Memory, Short-Term - drug effects; Mental Recall - drug effects; Pharmacology. Drug treatments; Psychomotor Performance - drug effects; Reaction Time - drug effects; Toxicity: nervous system and muscle
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/BF00315311

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.