Therapeutic effects of α-adrenergic receptor antagonists on benign prostatic hyperplasia: A network meta-analysis / 中华男科学杂志

<p><b>Objective</b>To investigate the therapeutic effects of commonly used selective α-adrenergic receptor antagonists (α-ARA) on benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>PubMed, Embase and CNKI databases were searched for the literature about selective α-ARAs for the treatment of BPH and the information was extracted on the common adverse reactions in the course of treatment. Multivariate meta-analysis was conducted to investigate the therapeutic effects of different α-ARAs.</p><p><b>RESULTS</b>The total rates of adverse effects of silodosin and tamsulosin were the highest, 51.9% and 34.0% respectively, with the highest incidences of headache (38.3%), weakness (23.6%) and dizziness (17.5%). Besides, tamsulosin ranked the first in inducing sexual dysfunction of the male patients with BPH (70.4%).</p><p><b>CONCLUSIONS</b>Doxazosin is preferable as the first-choice treatment of BPH for its therapeutic effect and improvement of the patient's quality of life. Silodosin and tamsulosin, however, can be selectively used according to the patient's specific tolerance to different adverse effects.</p>

Efficacy and Safety of Doxazosin GITS over 4 weeks for the Treatment of Non-neurogenic Voiding Dysfunction in Females: Short-term Outcomes

PURPOSE: We administered doxazosin gastrointestinal therapeutic system (GITS) to women with non-neurogenic voiding dysfunction to evaluate its therapeutic effects. MATERIALS AND METHODS: Women who had voiding dysfunctions for at least 3 mo were included. Inclusion criteria were age > or =18yr, an International Prostate Symptom Score (IPSS) > or =15, and a maximum flow rate (Qmax) or =150mL. Patients with neurogenic voiding dysfunction or anatomical bladder outlet obstruction were excluded. All patients were classified according to the Blaivas-Groutz nomogram. After 4 weeks, treatment outcomes were evaluated. RESULTS: Sixty-two patients were evaluated of mean age 53.8 (32-78)yr. According to the Blaivas-Groutz nomogram, 24 patients had no or mild obstruction (group A) and 38 had moderate or severe obstruction (group B). After treatment, mean IPSS decreased significantly and by more than 5 points in 42 (67.7%). Mean bother scores, Qmax, and PVR also changed significantly. Thirty-seven (59.7%) showed Qmax increases of more than 50%. No significant difference were observed between the groups in terms of IPSS, bother score, Qmax, PVR, micturition frequencies, or functional bladder capacity changes. Adverse effects related to medication were de novo stress urinary incontinence (SUI) (1 case) and underlying SUI aggravation (1 case). By satisfaction assessments, 16 patients (25.8%) were 'mainly satisfied', 31 (50%) were 'slightly satisfied', and 15 (24.2%) were 'dissatisfied'. CONCLUSION: Doxazosin GITS was found to be effective in female patients with voiding dysfunction regardless of obstruction grade. The alpha-adrenoceptor antagonists should be viewed as initial treatment option for women with a non-neurogenic voiding dysfunction.

Analyses of four?-adrenergic receptor antagonists in the treatment of chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS) / 中华泌尿外科杂志

Objective To investigate the efficacy and side effects of 4?-adrenergic receptor(?- AR)antagonists in the treatment of chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS).Meth- ods Totally,325 patients(mean age,33.2 year;disease history,2.4 years)with CP/CPPS were randomly divided into Prazosin(n=95),Terazosin(n=78),Phenoxybenzamine(n=27),and Doxazosin mesylate controlled release tablets(n=72)groups.Some antibiotics and medications were used for allopathy.In addi- tion,53 cases with no?-AR antagonist treatment served as control group.The efficacy and side effects in all the patients were observed and recorded.The chronic prostatitis symptom index(CPSI)was used to evaluate the efficacy.Results In control group,22(41.5%)patients responded well to the treatment( CPSI mark drop≥5)and 31(58.5%)failed to respond to the treatment(CPSI mark drop＜5).In study group,199 (73.2%)patients responded well to the treatment,and 73(26.8%)failed.The difference in efficacy be- tween?-AR antagonists and placebo treatment was significant(P＜0.01).In study group,specifically,the effective rate was 55.6% in Phenoxybenzamine,78.2% in Terazosin,76.4% in Doxazosin mesylate con- trolled release tablets,and 71.6% in Prazosin groups.The main side effects of?-AR antagonists were postur- al hypotension(a rate of 23.2% for Prazosin,17.9% for Terazosin,22.2% for Phenoxybenzamine,and 8.3% for Doxazosin mesylate controlled release tablets)and dysfunction of ejaculation(only in Phenoxy- benzamine group with a rate of 51.9%).The rates of withdrawing treatment due to side effects were in turn 18.5% of Phenoxybenzamine,7.4% of Prazosin,5.1% of Terazosin,and 0% of Doxazosin mesylate con- trolled release tablets.Conclusions As essential medications for the treatment of CP/CPPS,?-AR antag- onists can relieve the clinical symptoms(dropping NIH-CPSI mark significantly),but some side effects should be considered when some medications are selected.

Quantitative Autoradiography on Ontogenic Development of alpha-Adrenoceptor in the Rat Cerebral Cortex / 대한해부학회지

Adrenoceptors mediate response to catecholamines throughout the body. To investigate postnatal ontogenic development of alpha1- and alpha2- adrenoceptors in the rat cerebral cortex, in vitro autoradiography was done on frontal, parietal and temporal cortex in P0, P5, P10, P15, P20, P30 and adult animals. Binding sites for the alpha1-adrenergic receptor ligand, [3H]-prazosin, and the alpha2-adrenergic receptor ligand, [3H]-rauwolscine, were visualized by in vitro autoradiography, and anatomically localized by comparing the autoradiogram to Nissl-stained sections. Nonspecific binding was detected with unlabeled phentolamine (alpha1) and yohimbine (alpha2). There is uniform increase in alpha1- and alpha2- adrenoceptors from birth through first three or four postnatal weeks, followed by a decrease to adult level. Two alpha-adrenoceptors have very different ontogenic patterns of distribution during postnatal development. alpha1- adrenoceptors were expressed differentially in different cortical (frontal, temporal, parietal) regions and in different cortical layers (layers V, II-IV, VI) at same age. alpha2- adrenoceptor was expressed homogenously in throughout regions and layers. These findings may provide evidence that alpha1- adrenoceptors are involved in regulating cortical development or function more specifically than alpha2- adrenoceptors during postnatal development.

alpha-Adrenergic and cholinergic receptor agonists modulate voltage-gated Ca2+ channels

We investigated the effect of alpha-adrenergic and cholinergic receptor agonists on Ca2+ current in adult rat trigeminal ganglion neurons using whole-cell patch clamp methods. The application of acetylcholine, carbachol, and oxotremorine (50 muM each) produced a rapid and reversible reduction of the Ca2+ current by 17+/-6%, 19+/-3% and 18+/-4%, respectively. Atropine, a muscarinic antagonist, blocked carbachol-induced Ca2+ current inhibition to 3 +/- 1%. Norepinephrine (50 muM) reduced Ca2+ current by 18 +/- 2%, while clonidine (50 muM), an alpha2-adrenergic receptor agonist, inhibited Ca2+ current by only 4 +/- 1%. Yohimbine, an alpha2-adrenergic receptor antagonist, did not block the inhibitory effect of norepinephrine on Ca2+ current, whereas prazosin, an alpha1-adrenergic receptor antagonist, attenuated the inhibitory effect of norepinephrine on Ca2+ current to 6 +/- 1%. This pharmacology contrasts with alpha2-adrenergic receptor modulation of Ca2+ channels in rat sympathetic neurons, which is sensitive to clonidine and blocked by yohimbine. Our data suggest that the modulation of voltage dependent Ca2+ channel by norepinephrine is mediated via an alpha1-adrenergic receptor. Pretreatment with pertussis toxin (250 ng/ml) for 16 h greatly reduced norepinephrine- and carbachol-induced Ca2+ current inhibition from 17 +/- 3% and 18 +/- 3% to 2 +/- 1% and 2 +/- 1%, respectively. These results demonstrate that norepinephrine, through an alpha1-adrenergic receptor, and carbachol, through a muscarinic receptor, inhibit Ca2+ currents in adult rat trigeminal ganglion neurons via pertussis toxin sensitive GTP-binding proteins.

A study of alpha adrenergic receptors in human and rabbit corpus cavernosum tissue / 대한비뇨기과학회지

The relaxation of the corpus cavernosum smooth muscle, which is main process in penile erection, is controlled by nerves that release cholinergic and nonadrenergic-noncholinergic neurotransmitters as well as vascular endothelium derived relaxing factor(EDRF). But the adrenergically-induced tone maintains the penis in flaccid state. In order to define the physiological role of adrenergic neurotransmission in the local control of penile erection we studied the distribution of alpha adrenergic receptor subtypes and their pharmacological potency in human and rabbit corpus cavernosum tissue. In this study we used yohimbine as the alpha-2 antagonist, which is known to have beneficial therapeutic effect for organic impotence, to assess its neuropharmacological mechanism in the treatment of erectile dysfunction. The alpha-1 : alpha-2 receptor potency was approximately 7.4:1 and 2.2:1 in human and rabbit tissue respectively. These results indicate that the predominant alpha adrenergic receptor is alpha-1 type and alpha-2 receptor antagonist, yohimbine, can not play a main role on the local control of penile erection because of its low receptor potency especially in human corpus cavernosum tissue. It remains possible that yohimbine partially antagonizes the postsynaptic alpha-1 mediated effect or activation of central sympathetic pathway is necessary for the therapeutic effect of yohimbine in human.