Differential vascular alpha1-adrenoceptor antagonism by tamsulosin and terazosin

Abstract

Aims: In patients with lower urinary tract symptoms suggestive of benign prostatic obstruction the alpha1-adrenoceptor antagonist terazosin lowers blood pressure whereas only very small if any alterations were reported with the alpha1-adrenoceptor antagonist tamsulosin. Therefore, we have compared the vascular alpha1-adrenoceptor antagonism of tamsulosin and terazosin directly.

Methods: Ten healthy subjects were investigated in a randomized, single-blind, three-way cross-over design and received a single dose of 0.4 mg tamsulosin, 5 mg terazosin or placebo on 3 study days at least 1 week apart. Before and 1, 3, 5, 7, 10 and 23.5 h after drug intake, alterations of diastolic blood pressure and other haemodynamic parameters in response to a graded infusion of the alpha1-adrenoceptor agonist phenylephrine were determined non-invasively.

Results: At most time points tamsulosin inhibited phenylephrine-induced diastolic blood pressure elevations significantly less than terazosin (5 h time point: median difference in inhibition 35%, 95% CI: 18.7-50.3%). On the other hand, phenylephrine-induced changes of cardiac output, heart rate and stroke volume were similar during both active treatments.

Conclusions: In doses equi-effective for treatment of lower urinary tract symptoms tamsulosin causes less inhibition of vasoconstriction than terazosin.

Figure 1

Diastolic blood pressure elevations induced by infusion of phenylephrine. The figure shows original data from a representative subject obtained 5 h after intake of placebo (open circles), 0.4 mg tamsulosin (filled squares) or 5 mg terazosin (open squares). The inhibition index I_all (Figure 3) was calculated as [1—(D-C)/(B-A)]×100, while the inhibition index I_act (Figure 4) was calculated as [1—(E-C)/(B-A)]×100.

Figure 3

Inhibition of phenylephrine infusion-induced elevations of diastolic blood pressure by 0.4 mg tamsulosin (filled squares) or 5 mg terazosin (open squares). Inhibition was calculated at each time point relative to the highest phenylephrine dose which was reached on all study days including the placebo day (‘I_all’, 1 μg kg⁻¹ min⁻¹ in almost every case, for calculation see Figure 1) and is shown as medians with upper and lower quartiles. * and **: P<0.05 and <0.01, respectively, vs tamsulosin in a Wilcoxon signed rank test.

Figure 4

Inhibition of phenylephrine infusion-induced elevations of diastolic blood pressure by 0.4 mg tamsulosin (filled squares) or 5 mg terazosin (open squares). Inhibition was calculated at each time point relative to the highest phenylephrine dose which was reached on both study days during active treatment and compared with the highest phenylephrine dose on the placebo day (‘I_act’, for calculation see Figure 1) and is shown as medians with upper and lower quartiles. * and **: P<0.05 and <0.01, respectively, vs tamsulosin in a Wilcoxon signed rank test.

Figure 2

Number of responders with regard to diastolic blood pressure upon infusion of phenylephrine. Responders were defined as subjects with an increase of >7.6 mm Hg in diastolic pressure upon the highest agonist dose allowed in the protocol. Shown are the number of responders out of 10 subjects studied at the indicated times following intake of placebo (open circles), 0.4 mg tamsulosin (filled squares) or 5 mg terazosin (open squares).

Figure 5

Effects of 0.4 mg tamsulosin and 5 mg terazosin on phenylephrine-induced alterations of diastolic blood pressure (upper panel), mean arterial pressure (middle panel) and total peripheral resistance (lower panel) as determined 5 h following medication. Data are based on the highest phenylephrine dose achieved during both active treatments (‘I_act’, for calculation see Figure 1) and are shown as medians with upper and lower quartiles. * and **: P<0.05 and <0.01 vs tamsulosin in a Wilcoxon signed rank test. Phenylephrine effects during placebo treatment are shown for comparison; they were not compared statistically to the data obtained during active treatment since they were determined at a different phenylephrine dose.

Figure 6

Effects of 0.4 mg tamsulosin and 5 mg terazosin on phenylephrine-induced alterations of cardiac output (upper panel), heart rate (middle panel) and stroke volume (lower panel) as determined 5 h following medication. Data are based on the highest phenylephrine dose achieved during both active treatments (‘I_act’, for calculation see Figure 1) and are shown as medians with upper and lower quartiles. Effects of tamsulosin and terazosin were not significantly different in a Wilcoxon signed rank test. Phenylephrine effects during placebo treatment are shown for comparison; they were not compared statistically to the data obtained during active treatment since they were determined at a different phenylephrine dose.