Use of an autorhythmometric experimental design to achieve individual adjustment of antihypertensive treatment
Romano, S.; Gizdulich, P.; Scarpelli, P.T.
Methods and Findings in Experimental and Clinical Pharmacology 3(4): 223-231
1981
ISSN/ISBN: 0379-0355 PMID: 7024688 Document Number: 170821
The therapeutic success of a new antihypertensive drug in man is generally tested by the significance of the average decrease of blood pressure (BP) induced in patients measured 1 at a time, before and after some treatment schedule designed with a proper protocol. A chronobiologic protocol is proposed which is based on 5-times-a-day autometric data gathering and weekly processing by appropriate computerized methods. The protocol was used in 1 renovascular and 4 primary hypertensive patients treated with prazosin [maximum dose 24 mg/day]. The aim to obtain the best individual control of BP was pursued by dose-doubling only when the comparison between the average mean BP for 2 successive wk revealed no significant decrease. A linear regression model containing a simple 24 h period sinusoidal component was used to validate individual responsiveness of systolic and diastolic BP. Heart rate (HR) self-measurements were processed in the same way to document any increase, sometimes observed as a prazosin-related side effect. Very scattered types of responses were observed in the 5 patients, but the major difference was found between the renovascular and the other 4 patients. The former exhibited an acute response both in systolic and diastolic BP and no significant HR modification. He was the only patient whose BP average decrease was accompanied by a .apprx. 3-fold augmentation of the circadian BP amplitude. In 2 of the other 4, an interesting significant 6-8 h acrophase delay shift of HR circadian rhythm was documented. The proposed intermediate chronobiologic approach may be useful for individual therapeutic purposes and in pharmacological clinical characterization of drug efficacy. The different behavior observed between the renovascular and the primary hypertensive patients and the possible interference of prazosin with the circadian organization of the circulation controlling factors needs further study.