Dose-titration study of alfuzosin, a new alpha1-adrenoceptor blocker, in essential hypertension

Abstract

An open, dose-titration study of alfuzosin, a new selective post-synaptic alpha 1-adrenoceptor antagonist with additional direct vasodilator properties has been performed. After a 3-week run-in placebo period, 12 patients with essential hypertension received alfuzosin 5 mg oral b.d., and then the dose was doubled every week, up to a maximum of 20 mg q.i.d. if the supine diastolic blood pressure was greater than 90 mm Hg. The study lasted for 4 weeks. Supine blood pressure (SBP) decreased from 160/102 (Day 0) to 148/89 mm Hg and upright blood pressure (UBP) from 151/102 (Day 0) to 137/84 mm Hg. Alfuzosin did not cause any significant change in supine or upright heart rate. In addition, after the first dose of alfuzosin, supine and upright blood pressure and heart rate (SHR and UHR) were measured every 30 min for 5 h. The fall in blood pressure was significant after 90 min and it lasted up to the 5th hour; the maximum effect was observed after 3 h: SBP decreased from 159/103 (time 0) to 137/84 mm Hg and UBP from 150/102 (time 0) to 123/79 mm Hg. SHR was increased from 72 (time 0) to 81 beats/min at the 5th hour and UHR from 87 to 101 beats/min at the 4th hour. A weak but significant correlation was observed between the hypotensive effect 12 h after drug intake and the plasma concentration of the drug at that time. A 10% decrease in supine diastolic blood pressure was found at a drug plasma concentration higher than 7 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

α₁-Adrenoceptor Selectivity: The North American Experience

“…A similar conclusion can be drawn from the comparative study of tamsulosin and alfuzosin, in which both agents significantly reduced hypertensive blood pressure [3]. Likewise, dependent on the vascular tone, both alfuzosin [22]and tamsulosin [23]can significantly depress blood pressure. This dependency of blood pressure response on the haemodynamic baseline, and thereby on the pre-drug sympathetic drive, is key to understanding claims of physiological selectivity.…”

Who Should Be Treated and How? Evidence-Based Medicine in Symptomatic BPH

“…For terazosin and doxazosin, the same doses are used to treat both LUTS and hypertension. For alfuzosin, similar or somewhat lower doses are recommended to treat LUTS compared to those shown to be efficacious for hypertension [135, 136]. Cardiovascular α-blockade and the related risks are inherent to their pharmacological profile.…”

Alpha-1 Blockers. A New Generation of Antihypertensive Agents

“…Although doxazosin is also found to have a longer half-life than prazosin, the benzodioxan moiety may not be as water-soluble as the tetrahydrofuran group in terazosin. There is a benzodioxan double-ring in the simple a-blocker piperoxan, but the exact identity of the substitute seems unimportant (84)(85)(86)(87).…”