How important is 24-hour control of blood pressure?
Control of blood pressure over the full 24-hour period is important to prevent, or allow resolution of, cardiac and vascular hypertrophy. In addition, the peak incidence of sudden death, myocardial infarction and stroke occurs at the time of the blood pressure increase associated with awakening and arising. There is at present no objective evidence that "good' 24-hour blood pressure control will improve prognosis. Once-daily therapy has created problems in hypertension management. The problem in assessing new drugs was that, in order to achieve blood pressure control before the next drug dose, excessive falls in blood pressure occurred at peak drug concentrations or excessive blood drug concentrations were produced. This led to the concept of a trough: peak ratio. This is not a unique property of a drug and if drugs have an Emax effect (i.e. the drug produces a plateau response) it is dose dependent. Interpreting a trough: peak ratio requires an understanding of the interaction between the pharmacokinetics and pharmacodynamics of a drug. The answer is to use drugs with an elimination half-life close to or greater than the dose interval (24 hours); to use drugs with an "effective' half-life close to or greater than the dose interval, which can be achieved either by modification of the pharmaceutical delivery system or by using drugs that produce a persistent effect because of physiological changes induced; or to give drugs more frequently than once a day. 24-hour blood pressure control is important and the trough: peak ratio of a drug gives a guide as to whether it can be achieved.
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
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D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D001795:Blood Pressure Determination; D002561:Cerebrovascular Disorders / Q000453:epidemiology; D003645:Death, Sudden / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D009203:Myocardial Infarction / Q000453:epidemiology
D000959:Antihypertensive Agents