多沙唑嗪与特拉唑嗪治疗原发性高血压的疗效比较

目的:比较甲磺酸多沙唑嗪和特拉唑嗪治疗原发性高血压的疗效和安全性.方法:采用随机单盲平行对照试验,将符合条件的轻、中度高血压患者63例随机分为试验组(多沙唑嗪)和对照组(特拉唑嗪).试验剂量从2 mg开始逐渐递增至2～8 mg/d,疗程4周.治疗前后分别行心电图、常规体检、血尿常规和生化检查.结果:①治疗4周后,多沙唑嗪组降压总有效率80.7%,特拉唑嗪组降压总有效率70.0%.两组间无显著性差异.②多沙唑嗪组治疗前后收缩压、舒张压的下降幅度分别为10.81%、10.70%,特拉唑嗪组为10.01%、11.47%.两组间无显著性差异.③多沙唑嗪组有效剂量2～6 mg/d,平均3.04 mg/d,特拉唑嗪组有效剂量2～8 mg/d,平均4.19 mg/d.④每组不良事件发生率相似,多沙唑嗪组25.8%,特拉唑嗪组33.3%(P>0.05).最常见的不良反应为头晕、头痛、心悸、体位性低血压等,多为轻度,可迅速缓解,多沙唑嗪组未发生体位性低血压.结论:甲磺酸多沙唑嗪2～6 mg/d,一天一次口服治疗轻、中度高血压安全有效.     

Short-term subjective efficacy of doxazosin in predicting probability of prostatectomy in the management of benign prostatic hyperplasia in patients with severe symptoms

BACKGROUND: The severity of symptoms still constitutes the major indication for transurethral prostatectomy, despite the extensive utilization of medical treatments. The aim of the study presented here was to investigate the impact of doxazosin on symptoms in relation to the probability of consequent surgery in severely symptomatic patients. METHODS: Patients with an International Prostate Symptom Score (IPSS) between 18 and 35 were included in the study. The patients received 4 mg/day doxazosin, and subjective efficacy was assessed by IPSS at the first and third months. In addition, the patients were classified at the third month according to a single question regarding satisfaction with medical treatment in terms of symptom relief as 'ineffective, no change, and effective'. RESULTS: A total of 178 patients constituted the study group. Mean total symptom scores were 24, 19 and 17 at baseline, first and third months, respectively (P < 0.05). According to results of the questionnaire, 23% of the patients claimed the treatment was ineffective, and subsequently, the majority of this group (93%) underwent prostatectomy in a year. In addition, 33% of the patients reported no change in their symptoms, while 44% reported that the medication was effective. However, after 1 year, 59% and 15% of these cases underwent surgical treatment, respectively. The probability of surgery in the 'ineffective' group was significantly higher compared to the remaining groups (P < 0.05). CONCLUSION: The majority of patients with severe symptoms who were not satisfied with the medication at the 3rd month underwent surgery. This observation may provide a predictor for subsequent probability of prostatectomy. Therefore, reassessment of patients would be a cost-effective approach for the treatment of BPH in severely symptomatic patients.     

国产甲磺酸多沙唑嗪Ⅰ期临床耐受性试验

目的：评价国产多沙唑嗪片剂口服的耐受性,为临床应用的剂量范围提供依据。方法：24例健康成年人,随机分为五组,分别单次口服1mg,2mg,4mg,6mg,8mg多沙唑嗪片,观察服药前,服药后2,4,6,8,10和24小时的坐,卧,立位血压,心率变化及不良反应,服药前及服药后24小时验血,尿常规及肝肾功能,心电图,结果：多沙唑嗪2－8mg口服均有明显降压作用,体位性低血压 其主要不良反应, 总发生率达70．83％,伴随头军,恶心,心悸,耳鸣等不适,发生率与用药剂量明显正相关,6mg组发生晖厥1例,平卧后意识立即恢复,无后遗症状,其他不良反应有头痛和鼻塞,均轻微,在试验剂量范围内对肝肾功能无明显影响。血WBC有轻度降低,结论：多沙唑唪口服推荐2－4mg,每日1次。首次服药注意体位性低血压发生。     

多沙唑嗪及其手性对映体对离体兔血管α_1 受体的拮抗特性(英文)

目的　分析α1 肾上腺素受体阻断药多沙唑嗪手性对映体对兔胸主动脉和颈总动脉的选择性作用 ,以探讨作为良性前列腺增生症治疗药物的可能性。方法　测定去甲肾上腺素 (NE)诱发兔离体胸主动脉和颈总动脉收缩反应 ,并采用Schild作图法计算rac 多沙唑嗪、R 多沙唑嗪和S 多沙唑嗪的pA2 值。结果　在兔胸主动脉和颈总动脉 ,0 .0 3 ,0 .1和 0 .3μmol·L-1 的rac 多沙唑嗪、R 多沙唑嗪和S 多沙唑嗪均使NE诱发的血管收缩反应量效曲线平行右移 ,Emax不变 ;由Schild作图法计算得到的多沙唑嗪及其手性对映体的斜率值 ,经统计学分析符合竞争性拮抗。3种拮抗剂pA2 值的强度顺序为 :R 多沙唑嗪 >rac 多沙唑嗪 >S 多沙唑嗪。结论　与多沙唑嗪及其手性对映体对人前列腺组织作用的报道结果不同 ,S 多沙唑嗪对兔胸主动脉和颈总动脉α1 肾上腺素受体拮抗作用的选择性显著低于rac 多沙唑嗪和R 多沙唑嗪     

多沙唑嗪联合双氯芬酸钠治疗前列腺电切术后膀胱痉挛的安全性和有效性

目的：观察多沙唑嗪联合双氯芬酸钠治疗前列腺电切术（TURP）后膀胱痉挛（BS）的安全性和有效性。方法：以2017年1月-2018年1月某院经TURP治疗的良性前列腺增生患者126例作为研究对象，采用随机数表法，将126例患者分为观察组和对照组，每组63例。对照组于TURP术后口服甲磺酸多沙唑嗪缓释片进行治疗，观察组口服甲磺酸多沙唑嗪片联合双氯芬酸钠栓肛塞进行治疗。比较2组BS时间和次数、视觉模拟评分量表（VAS）评分、汉密尔顿抑郁量表（HAMD）评分、汉密尔顿焦虑量表（HAMA）评分、膀胱冲洗液变淡时间、导管留置时间、术后住院天数和不良反应的发生率。结果：观察组BS发生频率、BS持续时间和VAS评分均较对照组高，差异有显著性（P<0.05）。观察组HAMD评分和HAMA评分均高于对照组，差异有显著性（P<0.05）。2组膀胱冲洗液变淡时间、导管留置时间和术后住院天数的比较无显著差异（P>0.05）。126例患者均成功完成手术，术后服用期间未见任何药物相关不良反应。结论：多沙唑嗪联合双氯芬酸钠治疗TURP术后BS安全和有效。     

多沙唑嗪对映体对兔四种血管α受体的作用

多沙唑嗪(doxazosin，DOX)作为高选择性α₁受体阻断药，是临床上治疗良性前列腺增生(benign prostatic hyperplasia, BPH)的一线药物，但同时引起心血管系统的不良反应。本研究采用兔离体动脉环张力实验及电场刺激兔离体隐动脉诱发交感嘌呤能血管收缩实验观察R-多沙唑嗪(R-doxazosin，R-DOX)和S-多沙唑嗪(S-doxazosin，S-DOX)对兔耳动脉、肠系膜动脉和肺动脉血管平滑肌α₁受体的作用，以及较高浓度R-DOX和S-DOX对兔隐动脉交感神经突触前膜α₂受体的作用。结果表明，在兔耳动脉、肠系膜动脉和肺动脉，R-DOX和S-DOX竞争性拮抗去甲肾上腺素(noradrenaline，NA)诱发的血管收缩反应；其pA₂值分别为7.91±0.03和7.53±0.05，7.80±0.05和7.29±0.07以及8.32±0.06和7.97±0.07；且S-DOX的pA₂值均明显小于R-DOX的pA₂值(P<0.01)。R-DOX和S-DOX(0.1～10 μmol·L^-1)对电刺激诱发的血管收缩反应无明显影响；R-DOX或S-DOX(100 μmol·L^-1)显著抑制电刺激诱发的血管收缩反应，完全抑制外源性NA诱发的血管收缩反应，但对1 mmol·L^-1腺苷三磷酸诱发的血管收缩反应无明显影响。上述结果提示，R-DOX和S-DOX对NA诱发兔耳动脉、肠系膜动脉和肺动脉收缩反应具有竞争性拮抗作用，对上述三种血管S-DOX拮抗NA的pA₂值均明显小于R-DOX。此外，R-DOX和S-DOX的浓度升至10 μmol·L^-1时，对血管交感神经末梢突触前膜α₂受体仍无明显影响。     

多沙唑嗪对映体对大鼠血压和排尿功能的影响

目的观察十二指肠给予多沙唑嗪(rac-DOX)及其对映体(S-DOX、R-DOX)对麻醉大鼠血压和膀胱排尿功能的影响。方法采用八道生理仪记录麻醉大鼠颈总动脉血压、心率以及膀胱排尿压、排尿间隔,并测量排尿量。结果十二指肠给予S-DOX、R-DOX和rac-DOX均可剂量依赖性降低颈总动脉收缩压、舒张压和平均动脉压,1.0mg.kg-1时3者对平均动脉压的降低幅度分别达到23.5%±4.6%、38.5%±8.9%和42.6%±7.5%,3者降低平均动脉压的ED30值依次为(2.0±0.8)、(0.6±0.7)、(0.6±0.5)mg.kg-1。S-DOX降低收缩压、舒张压和平均动脉压的作用均弱于rac-DOX和R-DOX(P<0.05),rac-DOX与R-DOX的降压作用差异无显著性(P>0.05)。rac-DOX在0.1～3.0mg.kg-1剂量范围内剂量依赖性抑制麻醉大鼠心率,而S-DOX和R-DOX仅在3.0mg.kg-1剂量时对心率有抑制作用。十二指肠给予S-DOX、R-DOX和rac-DOX均剂量依赖性降低麻醉大鼠膀胱排尿压,3种药物对排尿压的最大降低幅度分别为13.4%±5.7%、14.5%±11.0%和10.9%±7.6%,3者降低排尿压的作用差异无显著性(P>0.05)。与S-DOX相比,R-DOX可缩短排尿间隔并减少排尿量(P<0.05),而S-DOX和rac-DOX对排尿间隔和排尿量无影响。结论与R-DOX和rac-DOX相比,S-DOX保留了对麻醉大鼠膀胱排尿压的有利作用,减轻了对血压、心率和膀胱排尿间隔的不良影响。     

Perioperative management of a child with severe hypertension from a catecholamine secreting neuroblastoma

Increased catecholamine secretion from neuroblastomas can occasionally be demonstrated, but severe hypertension is uncommon. We report the perioperative management of a 5 year old child with stage III adrenal neuroblastoma who presented with malignant hypertension and high norepinephrine and dopamine levels. Hypertensive crises occurred during anesthesia for surgical biopsy and during chemotherapy. After blood pressure control using phenoxybenzamine and enalapril, doxazosin was used successfully as the preoperative alpha-adrenergic receptor antagonist for surgical tumor resection.     

Patients with uncontrolled hypertension or concomitant hypertension and benign prostatic hyperplasia

At optimal doses, individual antihypertensive agents lower blood pressure (BP) by an average of 10 mmHg. Many patients with hypertension, including those with stage 3 hypertension, target organ damage, or those at high risk for cardiovascular events and/or adverse effects of high-dose monotherapy, are likely to require combination antihypertensive drug treatment to achieve the recommended systolic/diastolic BP (< 140/90 mmHg). Two studies, a placebo-controlled, double-blind trial (n = 70) and a community-based, open-label trial (n = 491) investigated the antihypertensive efficacy of doxazosin, a long-acting selective alpha1-adrenoceptor blocker, as add-on therapy for uncontrolled hypertension with other antihypertensive medications and in patients with concomitant benign prostatic hyperplasia (BPH) and treated but inadequately controlled hypertension, respectively. The addition of doxazosin to baseline antihypertensive medication(s) significantly lowered BP and had a significantly positive effect on the serum lipid profile. In patients with concomitant BPH, doxazosin significantly improved all BPH symptom scores, regardless of initial symptom severity. Add-on doxazosin sufficiently reduced systolic/diastolic BP such that many patients whose hypertension was previously uncontrolled by other antihypertensive medications were able to reach goal BP (< 140/90 mmHg). Doxazosin as add-on therapy was well tolerated. In conclusion, doxazosin as add-on therapy improves BP control in hypertensive patients not at goal BP and improves lower urinary tract symptoms in patients with concomitant BPH.     

Stromal/epithelial interactions of murine prostatic cell lines in vivo: a model for benign prostatic hyperplasia and the effect of doxazosin on tissue size

BACKGROUND: One of the major constraints in elucidating the mechanisms involved in the etiology of benign prostatic hyperplasia (BPH) is the lack of suitable model systems that are readily manipulable in vitro and in vivo. To address this issue, we have used murine prostatic cell lines to establish a novel in vivo model for studying prostatic cell interactions. METHODS: Luminal, basal, and smooth muscle (SM) cell lines were inoculated alone or in combinations under the renal capsule of intact or castrated male mice, and the growth and composition of prostatic tissue in the absence or presence of doxazosin was determined. RESULTS: Both the luminal and basal cell lines reconstituted prostatic tissue if co-inoculated under the renal capsule with normal SM cells, whereas none of the lines formed significant tissue when inoculated alone. Luminal cells produced and secreted prostatic secretory products. The growth of prostatic tissue formed from co-inoculation of basal and SM cells was androgen responsive. In addition, a significant reduction in prostatic tissue was noted in animals treated with doxazosin. CONCLUSION: We have established an in vivo model that uses prostatic epithelial and SM cell lines for investigating cellular interactions between epithelial and SM cells that regulate prostatic growth and function. This model will be useful for delineating the mechanisms by which prostatic cells interact and in determining the efficacy of new approaches aimed at interfering with prostatic stromal/epithelial interactions that result in abnormal cellular proliferation.