Adverse Effects of ??1-Adrenergic Blocking Drugs

Abstract

Earlier nonselective alpha 1-adrenergic blocking drugs such as phentolamine and phenoxybenzamine are now restricted to the pharmacological management of alpha 1-adrenergic crisis and phaeochromocytoma. Prazosin, the first selective alpha 1-blocker approved for the treatment of hypertension, became available in the mid-1970s. Additional alpha 1-blockers such as doxazosin and terazosin have been introduced during recent years. The undesirable effects of all members of this class are similar. Most adverse events can be attributed to reversible competitive antagonism of postsynaptic alpha 1-adrenergic receptors in tissues that sustain high levels of alpha-adrenergic sympathetic tone, e.g. resistance arteries, capacitance veins and the urinary bladder outflow tract. Orthostatic hypotension with a sensation of intense faintness and occasional syncope, can occur shortly after the initial dose. Aggravating factors include upright posture, intravascular volume depletion and concurrent administration of other medications that lower blood pressure, including all other classes of antihypertensive drugs. The problem is reduced or avoided by the choice of low starting doses, beginning treatment at bedtime and by minimising other risks. Among overall adverse effects, asthenia, dizziness, faintness and syncope predominate and occur in 10 to 20% of patients, leading to discontinuation of therapy in about half that number. Infrequent adverse events include headache, drowsiness, palpitations, urinary incontinence and priapism. Some patients experience a 1 to 2kg bodyweight gain which may be associated with secondary hyperaldosteronism. Tolerance appears to develop to the benefits of alpha 1-blockade in patients with congestive heart failure, but not in hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

A Double-Blind Comparison of Terazosin and Tamsulosin on Their Differential Effects on Ambulatory Blood Pressure and Nocturnal Orthostatic Stress Testing

“…Many of the α 1 -adrenoceptor antagonists used for LUTS were primarily developed and/or are still used for the treatment of hypertension [17]. In hypertensives, these α 1 -adrenoceptor antagonists often cause dizziness, asthenia and orthostatic hypotension [18]. Comparatively little is known about their effects on blood pressure and the risk of orthostatic hypotension in normotensive patients with LUTS, especially in comparison with newer α 1 -adrenoceptor antagonists specifically developed to treat LUTS.…”

α₁-Blocker Therapy for Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Obstruction: What Are the Relevant Differences in Randomised Controlled Trials?

“…This distinction in terms of associated anti-hypertensive properties is relevant: anti-hypertensive α 1 -blockers are generally not well tolerated [117], and the capacity to reduce pathological blood pressure elevation is likely to result in an impairment of physiological blood pressure control (‘homeostasis’) in normotensives, resulting in orthostatic hypotension, dizziness, light-headedness, asthenia, etc. [118, 119].…”

“…As cardiovascular effects, especially in terms of blood pressure control, are a very important aspect of the overall safety of α 1 -blockade, several studies evaluated the interaction between α 1 -blockers and anti-hypertensive medication. Additionally, since hypertension is often associated with LUTS and since anti-hypertensive α 1 -blockade cannot be considered an appropriate first-choice for the treatment of associated hypertension, neither in terms of tolerability [117]nor in terms of outcome [146, 147], it is reassuring that selective α 1 -blockers without anti-hypertensive effects, such as tamsulosin, can be combined safely and efficaciously with suitable first-line anti-hypertensives [148, 149]. …”

α₁-Blockers for BPH: Are There Differences?

“…Often – but not always – these complications can be avoided by initiating the treatment slowly and in stepwise fashion and by administering these medications in the evening. These measures are inconvenient and α-blockers – although efficacious in reducing elevated blood pressure in patients with hypertension – are not well tolerated [2]. In consequence, they are not considered as a treatment of first choice for hypertension.…”