Concentration-effect relationships and antihypertensive mechanisms: ketanserin in the treatment of essential hypertension.
Concentration-effect relationships were characterized in individual hypertensive patients treated with single and multiple doses of ketanserin. There were significant changes in the concentration-effect parameters during continued treatment, and overall there was a reduction in antihypertensive responsiveness, from -0.47 to -0.25 mmHg/ng per ml. The nature of the changes, however, raises the possibility that there were associated changes in the site and mechanism of the underlying antihypertensive action. It is possible that a peripheral mechanism, perhaps alpha 1-adrenoceptor antagonism, is relatively more pronounced after the first dose whereas a central mechanism, perhaps related to serotonergic antagonism, is relatively more important during chronic treatment. We conclude that this technique of concentration-effect analysis may be useful in exploring mechanisms of action and identifying issues which require further clarification.
Elliott
H L
HL
University Department of Medicine and Therapeutics, Stobhill General Hospital, Glasgow, UK.
Meredith
P A
PA
D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D007650:Ketanserin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged
D007650:Ketanserin