CURRENT ISSUES IN ALPHA1-ADRENERGIC BLOCKER THERAPY: INTEGRATION OF PHARMACOLOGICAL APPROACH AND CLINICAL EXPERIENCE


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Abstract

Four successive stages in the action of the alpha1-adrenergic blocker (a1-AB) are discussed in the article. When describing the pharmaceutical and pharmacokinetic stages, the features of absorption, bioavailability and distribution of three a1-AB are discussed: alfuzosin, tamsulosin and silodosin. From a practical point of view, it is important that the bioavailability of alfuzosin and tamsulosin will increase during transit through the gastrointestinal tract, which means that extended-release dosage form (Alfuprost MR) has advantages compared to conventional immediate-release tablets. Alfuzosin has the highest volume of distribution among a1-AB (2.5 l/ kg), which indicates its maximum prostatotropic index compared to other a1-AB. The clinical uro selectivity of a1-AB directly depends on their pharmacological profile, in accordance with the chemical structure and pharmacological properties. The clinical uroselectivity of alfuzosin is provided mainly by unique pharmacokinetic/functional properties (volume of distribution, prostatotropism), while tamsulosin and silodosin are dominated by the receptor/pharmacodynamic component. Controlled studies have shown that a1-AB reduce I-PSS by about 30-40% and increase Qmax by about 20-25%. Evaluation of the safety of a1-AB includes monitoring for side effects, including asthenia, dizziness, and (orthostatic) hypotension. According to a meta-analysis, the vasodilatory effect is most pronounced with doxazosin and terazosin, but is much less common and with comparable alfuzosin and tamsulosin. For personalized approach in choosing an a1-AB for the drug therapy of LUTS in BPH one should takes into account, on the one hand, the individual characteristics of the patient (the presence of concomitant pathologies: arterial hypertension, coronary heart disease, diabetes mellitus), and on the other hand, the individual pharmacological profile of a1-AB, the risk of developing drug interactions. Based on the results of extensive clinical experience, including data from recent clinical trials, Alfuprost® MR (alfuzosin 10 mg in the form of extended-release tablets) demonstrated a pronounced clinical uroselectivity, high efficiency in the relief of LUTS and cardiovascular safety in comorbid patients, including those with cardiovascular diseases.

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About the authors

A. G Martov

A.I. Burnazyan SRC FMBC, FMBA of Russia; City clinical hospital named after D.D. Pletnev of the Health Department c. Moscow”

Email: martovalex@mail.ru
corr. member of RAS, Ph.D., MD, professor, head of the Department of urology and Andrology of Federal Medical and Biological Center named after A.I. Burnazyan FMBA RF; Head of the Urology Department of City clinical hospital named after D.D. Pletnev of the Health Department c. Moscow” Moscow, Russia

A. S Dukhanin

Pirogov Russian National Research Medical University

Email: das03@rambler.ru
Ph.D., MD, professor of the Department of the Molecular Pharmacology Moscow, Russia

A. N Bernikov

A.I. Evdokimov Moscow State University of Medicine and Dentistry of Minzdrav of Russia

Email: bernikov@mac.com
Ph.D. Moscow, Russia

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