INHIBITION OF PROSTAGLANDIN SYNTHESIS ALTERS ~-BlOCKER EFFECTS

The effect of indomethacin-induced inhibition of endogenous prostaglandin synthesis on the antihypertensive activity of pindolol OSms/cta)') and propranolol (SO- 160mgl day) was studied in 7 hypertensive patients (good respon~ers to ~.blockers) in 4 ten-day test phases. All patients. whether on pindo!ol or propranolol. had similar SP changes during the study. Mean pretreatment BP fell from \7\ ± 9/ 109 ± 2mm Hg to 139 ± 6/8 1 ± 2mm Hg during the run·in period and stayed constant during phase I on ~­blockade alone. During tbeplacebo phase OJ). average systolic and diastolic pressures rose to 158 ± 6mm Hg and 98 ± Jrnm

Hg. respectively. In phase 111, while on ~-blocker plus indomethacin, mean systolic DP fell slightly (to I SO·± 6mm Hg), and diastolic DP remained raised at 96 ± 3mrn Hg. In phase IV, after withdrawal of indomethacin, mean systOlic BP fell to 136 ± 6mm Hg and diastolic SP to 83 ± 3mm Hg -i.e. similar levels to those in phase I. Diastolic DP values with indomethacin were not signifteantly dilTerent from those with placebo, but ~ere signiflCantly different from values in both phases with ~-blockers alone (p < 0.0 I). Changes in systOlic BP and pulse rate were oot signifICant. These preliminary results suggest tha~ the antihypertensive elTect of these a-blockers may be related to the endogenous prostaglandin system. Aspirin, sal icylates and reJat;.d analgesic-antipyretic drugs and non-steroidal anti-inflammatory agents are widely used. All inhibit endogenolls prostaglandin synthesis, making interaction (with reduction of antihypenensive effect) likely in some hyperten.~ive patients.

'We suggest that salk:ylate-like agents and non-sterotdalanti-inflammatory drugs should be avoided. if possible. in hypertensive patients on a-blockers.'

Ol,lrao, V. et al : IAnetl 2: 1005 (12 NoY 1977)

INPHARMA 3rd December: 1977 p14