Alpha¹‐Adrenergic Blockers: Current Usage Considerations

Abstract

Alpha1-adrenergic-blocking drugs are effective in reducing blood pressure and do so in a fashion comparable to most other antihypertensive drug classes. These compounds are most effective in patients in the upright position, reducing systolic and diastolic pressures by 8%-10%. Alpha1-adrenergic-blocking drugs incrementally reduce blood pressure when combined with most drug classes and are the only antihypertensive drug class to improve plasma lipid profiles. Alpha1-adrenergic-blocking drugs are also accepted as important elements of the treatment plan for symptomatic benign prostatic hypertrophy. Dose escalation of an alpha1-adrenergic-blocking drug can trigger renal Na+ retention, and the ensuing volume expansion can attenuate its blood pressure-lowering effect. Orthostatic hypotension can occur with these compounds, particularly when a patient is volume-contracted. Dizziness, headache, and drowsiness are common side effects with alpha1-adrenergic blockers. A modest decline in the use of doxazosin and other alpha1-adrenergic-blocking drugs has occurred coincident to the early termination of the doxazosin treatment arm in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

“…a 1 -ARs are found in vascular beds throughout the body, including smooth muscle cells in arteries of the heart, brain, kidneys, and gut, as well as in smooth muscle in the prostate and bladder (Michelotti et al, 2000). By virtue of their ability to block a 1 -AR-mediated smooth muscle contractions, a 1 -AR antagonists (a 1 -blockers) are used to treat hypertension (Lund-Johansen and Omvik, 1991;Frishman and Kotob, 1999;Sica, 2005) and benign prostatic hyperplasia (Caine et al, 1976(Caine et al, , 1978Schwinn and Roehrborn, 2008;Michel, 2010).…”

α-Adrenoceptor antagonistic and hypotensive properties of novel arylpiperazine derivatives of pyrrolidin-2-one

“…Knowing that dual a 1A -and a 1B -ARs antagonists 11,12 could be beneficial in the therapy of hypertension, compounds 10d and 10h were selected for further in vivo tests. The hypotensive activities of compounds 10d and 10h were determined after their iv administration to normotensive anaesthetized rats at doses between 1.0 and 5.0 mg/kg.…”

“…This is consistent with a reduced effect of a 1A /a 1D -AR selective blockers on blood pressure. 11,12 The arylpiperazine fragment costituates one of the most versatile templates for constructing new molecules with affinity for a 1 -AR. The second component of an a 1 -AR antagonist is a hydrogen bond acceptor, which may or not be incorporated into a heterocyclic terminal ring.…”

Hypertension: An Overview

“…Alpha-1 receptor antagonist Α1-adrenergic blocking drugs are effective in reducing blood pressure and do so in a fashion comparable to most other antihypertensive drug classes. 75 Initially, for many years α1-adrenergic antagonists had been considered suitable initial drugs for uncomplicated early-stage hypertension. But guidelines including the European Society of Hypertension/European Society of Cardiology and the authors of the JNC 7 no longer include α1-adrenergic antagonists as initial agents for the treatment of hypertension.…”