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EFFECT OF ELIMINATION HALF-LIFE ON TROUGH:PEAK RATIO IN BETA-BLOCKERS: Maximal beta-adrenoceptor blockade and peak blood pressure reduction are achieved with plasma concentrations that are below the peak postdose concentrations observed when therapeutic doses are given. As a result, any trough:peak variation in the blood pressure response is likely to depend on the proportion of the dose interval during which maximal beta-blockade is maintained, and on the relationship between the elimination half-life of the drug, the dose and the dose interval. Acceptable trough:peak ratios (70%) for the blood pressure response to beta-blockade with a single daily dose are usually found with drugs that have an elimination half-life of over 6 h or when slow-release preparations are used for drugs with a shorter half-life. OTHER FACTORS THAT INFLUENCE THE TROUGH:PEAK RATIO: The interpretation of trough:peak ratios when beta-blockers are used may be complicated by circadian variations in the blood pressure response, with low blood pressure levels during sleep and an early morning rise upon waking. The blood pressure response-time relationships for beta-blockers with vasodilator properties appear to be similar to those for 'plain' beta-blockers, although there may be greater attenuation of the rise in blood pressure upon waking when multiple-action agents are used. Furthermore, the blood pressure of elderly patients with systolic hypertension may show an attenuated response to beta-blockers, resulting in a less favourable trough:peak ratio.It is not clear whether blood pressure 'responders' to beta-blockers have a pattern of response that is different from the mean of a heterogeneous group. Further studies with appropriate designs are required to clarify these issues. |
