&amp;alpha;&lt;sub&gt;1&lt;/sub&gt;-Blockers for BPH: Are There Differences?

Mey, Christian de

doi:10.1159/000052349

Cited by 23 publications

(17 citation statements)

References 78 publications

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“…Thus, the hypothesis of ␣ 1A -selectivity correlating to clinical uroselectivity remains unproved. 1 Interest in the role of ␣ 1D -adrenoceptors in the lower urinary tract has increased based on studies showing that this subtype predominates in human bladder (Lowe, 1999;Schwinn and Michelotti, 2000) and may play a role in detrusor instability (Fitzpatrick, 2000;Schwinn and Michelotti, 2000), a frequent and major component of BPH symptomatology (DeMey, 1999).…”

mentioning

confidence: 99%

“…Cardiovascular sequelae of ␣ 1 -adrenoceptor blockade are generally attributed to actions primarily at ␣ 1B -adrenoceptors, because neither ␣ 1A -nor ␣ 1D -adrenoceptors appear to predominate in any vascular bed (DeMey 1999). Although selective ␣ 1A -adrenoceptor antagonists have been shown to potently block increases of noradrenaline-induced resistance in isolated preparations, effects on MAP are observed only with very high doses, suggesting some non-␣ 1A -adrenoceptors regulate blood pressure control.…”

mentioning

confidence: 99%

“…In addition, the ratio of ␣ 1A -to ␣ 1B -adrenoceptors decreases with age in blood vessels (Fitzpatrick, 2000), suggesting that vascular function could be maintained in the absence of blockade of ␣ 1B -adrenoceptors (Fitzpatrick, 2000). Thus, compounds that are highly selective for the ␣ 1A -/␣ 1D -subtypes relative to ␣ 1B -adrenoceptors could have the potential for enhanced clinical uroselectivity compared with available ␣ 1 -adrenoceptor antagonists (DeMey, 1999;Fitzpatrick, 2000;Schwinn and Michelotti, 2000).…”

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confidence: 99%

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Modeling of Relationships between Pharmacokinetics and Blockade of Agonist-Induced Elevation of Intraurethral Pressure and Mean Arterial Pressure in Conscious Dogs Treated with α₁-Adrenoceptor Antagonists

Witte¹,

Brune²,

Katwala³

et al. 2002

J Pharmacol Exp Ther

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Fiduxosin is a new ␣ 1 -adrenoceptor antagonist targeted for the treatment of symptomatic benign prostatic hyperplasia. The purpose of this study was to determine and compare the potencies of the ␣ 1 -adrenoceptor antagonists terazosin, doxazosin, tamsulosin, and fiduxosin, based on relationships between plasma drug concentrations and blockade of phenylephrine (PE)-induced intraurethral (IUP) and mean arterial pressure (MAP) responses after single oral dosing in conscious male beagle dogs. Magnitude of blockade and plasma concentrations were evaluated at selected time points over 24 h. All drugs produced dose-dependent antagonism of PE-induced IUP and MAP responses. When IUP and MAP blockade effects were plotted against drug plasma concentrations, direct relationships were observed that were well described by the sigmoidal maximal effect model. IUP IC 50 values for terazosin, doxazosin, tamsulosin, and fiduxosin were 48.6, 48.7, 0.42, and 261 ng/ml, respectively. MAP IC 50 values were 12.2, 13.8, 1.07, and 1904 ng/ml, respectively. Uroselectivity index values, defined as MAP IC 50 /IUP IC 50 , were 0.25, 0.28, 2.6, and 7.3, respectively. These results extend previous observations with terazosin in this model, showing that doxazosin exhibits a uroselectivity index comparable to terazosin, consistent with the lack of ␣ 1 -adrenoceptor subtype selectivity or uroselectivity of these drugs. Tamsulosin, an ␣ 1a -/␣ 1d -subtype selective agent, had an index value approximately 10-fold greater than the nonselective drugs. Based on its pharmacokinetic profile and a relative uroselectivity 29-fold greater than the nonselective drugs, fiduxosin is expected to exhibit greater selectivity for urethral compared with vascular ␣ 1 -adrenoceptors in human and should be a novel, long-acting, uroselective ␣ 1 -adrenoceptor antagonist.␣ 1 -Adrenoceptor antagonists represent first-line therapy for the pharmacological treatment of benign prostatic hyperplasia (BPH), in part by relaxing prostatic smooth muscle (Lowe, 1999). Fiduxosin (ABT-980) is a novel ␣ 1 -adrenoceptor antagonist. Compared with other clinical agents, such as terazosin, doxazosin, and tamsulosin, fiduxosin exhibits a somewhat different ␣ 1 -adrenoceptor subtype selectivity profile. Radioligand binding potencies at human ␣ 1a -, ␣ 1b -, and ␣ 1d -adrenoceptors are reported to be 1.81, 1.16, and 0.67 nM for terazosin; 0.79, 0.80, and 0.81 nM for doxazosin; 0.03, 0.60, and 0.06 nM for tamsulosin; and 0.16, 24.89, and 0.92 nM for fiduxosin, respectively (Hancock et al., 1998b(Hancock et al., , 2002, showing fiduxosin to be selective for ␣ 1a -and ␣ 1d -adrenoceptors compared with ␣ 1b -adrenoceptors to a greater extent than tamsulosin.Accumulating data suggest that extraprostatic ␣ 1 -adrenoceptors in bladder, spinal cord, ganglia, or nerve terminals may also contribute to ameliorating the irritative and voiding symptoms of BPH (Fitzpatrick, 2000;Schwinn and Michelotti, 2000). Three subtypes of ␣ 1 -adrenoceptors are known to exist, ␣ 1A -, ␣ 1B -, and ␣ 1D -adr...

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Modeling of Relationships between Pharmacokinetics and Blockade of Agonist-Induced Elevation of Intraurethral Pressure and Mean Arterial Pressure in Conscious Dogs Treated with α₁-Adrenoceptor Antagonists

Witte¹,

Brune²,

Katwala³

et al. 2002

J Pharmacol Exp Ther

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“…Alfa-1 reseptör blokörlerinin yan etki profilleri birbirinden farklılık göstermektedir (16). Tamsulosin, alfuzosin kardiyovasküler yan etkileri terazosin ve doksazosine göre anlamlı olarak daha az olmakla beraber tamsulosinin ejakülasyon üzerine olan olumsuz etkileri daha fazladır (17). Alfa blokörler etki mekanizmalarından dolayı erektil disfonksiyon üzerine olumlu etkilere sahipken ejakülasyon üzerine olumsuz etkide bulunmaktadırlar (18).…”

Section: Alfa-1 Adrenerjik Blokörlerunclassified

The Effects of Medical Treatments Used for Benign Prostatic Hyperplasia on Ejaculation

Kayikci¹,

Kacagan²,

Tekın³

2015

uob

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Tedavi gerektiren benign prostat hiperplazisi (BPH) ile ilişkili ciddi alt üriner sistem semptomları (AÜSS) 50 yaş üzerindeki erkeklerde yaşla birlikte artmaktadır. Yaşla birlikte azalma göstermekle birlikte bu popülasyondaki bireylerin önemli bir kısmı aktif cinsel yaşamlarını devam ettirmektedir. BPH tedavisinde yaygın kullanılan ilaçların birçoğu ejakülasyon dahil olmak üzere cinsel fonksiyonları olumsuz etkileyebilir. BPH tedavisinde en yaygın kullanılan medikal tedavi grubu olan alfa 1 adrenerjik reseptör (α1-AR) blokörlerinden ejakülasyon disfonksiyonu ile en fazla ilişkilendirilen ilaçlar silodosin ve tamsulosindir. Silodosin plaseboya göre 32,5 kat (p<0,00001), tamsulosin ise 8,6 kat (p=0,006) daha fazla ejakülasyon bozukluğuna neden olur. Terazosin, doksazosin ve alfuzosin gibi bu gruptaki diğer ilaçların ejakülasyon üzerine etkileri minimaldir. α1-AR blokörlerin ejakülatuvar disfonksiyon etkileri ile tedavi etkinliği arasında pozitif istatistiksel bir ilişki söz konusudur. 5-alfa redüktaz inhibitörleri (5ARİ) libido ve penil ereksiyonda değişiklikler ile birlikte ejakülasyon bozukluğu da oluşturabilir. Finasterid ve dutasterid tedavilerinin ejakülatuvar disfonksiyon oranları birbirine benzerdir ve plaseboya göre yaklaşık 3 kat fazladır (p<0,0001). α1-AR blokör ve 5ARİ kombinasyon tedavisi bu ilaçların tek başına olduğuna göre daha fazla anormal ejakülasyona neden olur. Sonuç olarak α1-AR blokörler, 5ARİ ve bunların kombinasyonu değişen derecelerde ejakülatuvar disfonksiyona neden olabilir. Yaşam kalitesini olumsuz etkileyebileceğinden BPH'ya bağlı AÜSS nedeniyle medikal tedavi planlanan bireylere bu bilgi verilerek ilaç tercihinde dikkate alınmalıdır. Anahtar Kelimeler: Benign prostat hiperplazisi, alfa 1 adrenerjik reseptör blokör, 5-alfa redüktaz inhibitörleri, ejakülasyonIn men, significant lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) requiring treatment increase with aging. Though declining with aging, many individuals in this population sustain their sexual activities. Many drugs commonly used to treat LUTS may have significant adverse effects on sexual functions including ejaculatory function. Among alpha 1 adrenergic receptor (α1-AR) blockers, the most commonly used drugs for treatment of BPH, silodosin and tamsulosin have been associated significantly with ejaculatory dysfunction. Silodosin and tamsulosin lead to ejaculatory problems respectively 32.5 (p<0.0001) and 8.6 times (p=0.006) higher than placebo does. Other drugs in this class such as terazosin, alfuzosin and doxazosin have minimal effects on ejaculation. There seems to be a positive association between development of ejaculatory dysfunction and therapeutic efficacy of the α1-AR blockers. In addition to alterations in libido and penile erection, 5-alpha reductase inhibitors (5ARI) can cause ejaculatory dysfunction. The rate of abnormal ejaculation with finasteride and dutasteride is similar and three times more than placebo (p<0.0001). Abnormal ejaculation is more common with combination therapy of α1-...

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“…These results are consistent with the observation that the α 1a / α 1d AR-selective antagonist tamsulosin has been reported to have less effect on blood pressure in elderly men than a nonsubtype-selective α 1 AR antagonist. [46][47][48][49] Thus, although any α 1 AR antagonist that has α 1a blocking effects (the nonsubtype-selective agents and/or α 1a AR/α 1d AR-selective drugs) may affect blood pressure in younger patients, elderly patients appear to benefit in terms of minimal cardiovascular adverse effects when the α 1b AR is not blocked (as in α 1a AR/ α 1d AR-selective drugs). In fact, a study of pharmacy databases in Europe suggests that administration of α 1 AR blockers increases the incidence of hip fractures (chosen as a surrogate for clinically important orthostatic hypotension), 50 and further examination of the exact α 1 AR antagonist prescribed suggests that avoidance of α 1b AR blockade may result in less overall incidence of hip fractures.…”

Section: Vascular α α α α α 1 Ar Subtypes and Modulation With Agementioning

confidence: 99%

α1-Adrenoceptor Subtype Selectivity and Lower Urinary Tract Symptoms

Schwinn

Price

Narayan

2004

Mayo Clinic Proceedings

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Benign prostatic hyperplasia is a common cause of urinary flow obstruction in aging men and may lead to lower urinary tract symptoms (LUTS). Benign prostatic hyperplasia has 2 physiological components: a static component related to increased prostate size and a dynamic component related to increased prostate smooth muscle tone. alpha1-Adrenoceptors (alpha1ARs) maintain prostate smooth muscle tone; hence, alpha1-antagonists (blockers) relax prostate smooth muscle and decrease urethral resistance, ultimately leading to relief of LUTS. This review focuses on alpha1AR subtypes and their location in lower urinary tract tissues involved in LUTS (prostate, bladder, spinal cord); it also summarizes major clinical trials published to date on the efficacy of alpha1AR blockers for LUTS. Benefits and adverse effects of clinically available alpha1AR antagonists are reviewed, followed by recent information on interactions between alpha1AR subtype antagonists and type 5 phosphodiesterase inhibitors used for impotence. alpha1-Adrenoceptor antagonists have become the mainstay of therapy for LUTS; knowledge about specific alpha1AR subtypes should facilitate rational choice of alpha1AR blocker therapy by clinicians.

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α<sub>1</sub>-Blockers for BPH: Are There Differences?

Cited by 23 publications

References 78 publications

Modeling of Relationships between Pharmacokinetics and Blockade of Agonist-Induced Elevation of Intraurethral Pressure and Mean Arterial Pressure in Conscious Dogs Treated with α₁-Adrenoceptor Antagonists

Modeling of Relationships between Pharmacokinetics and Blockade of Agonist-Induced Elevation of Intraurethral Pressure and Mean Arterial Pressure in Conscious Dogs Treated with α₁-Adrenoceptor Antagonists

The Effects of Medical Treatments Used for Benign Prostatic Hyperplasia on Ejaculation

α1-Adrenoceptor Subtype Selectivity and Lower Urinary Tract Symptoms

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&alpha;<sub>1</sub>-Blockers for BPH: Are There Differences?

Cited by 23 publications

References 78 publications

Modeling of Relationships between Pharmacokinetics and Blockade of Agonist-Induced Elevation of Intraurethral Pressure and Mean Arterial Pressure in Conscious Dogs Treated with α1-Adrenoceptor Antagonists

Modeling of Relationships between Pharmacokinetics and Blockade of Agonist-Induced Elevation of Intraurethral Pressure and Mean Arterial Pressure in Conscious Dogs Treated with α1-Adrenoceptor Antagonists

The Effects of Medical Treatments Used for Benign Prostatic Hyperplasia on Ejaculation

α1-Adrenoceptor Subtype Selectivity and Lower Urinary Tract Symptoms

Contact Info

Product

Resources

About

α<sub>1</sub>-Blockers for BPH: Are There Differences?

Modeling of Relationships between Pharmacokinetics and Blockade of Agonist-Induced Elevation of Intraurethral Pressure and Mean Arterial Pressure in Conscious Dogs Treated with α₁-Adrenoceptor Antagonists

Modeling of Relationships between Pharmacokinetics and Blockade of Agonist-Induced Elevation of Intraurethral Pressure and Mean Arterial Pressure in Conscious Dogs Treated with α₁-Adrenoceptor Antagonists