Secretory immunoglobulin A and cardiovascular reactions to mental arithmetic, cold pressor, and exercise: effects of alpha-adrenergic blockade

The mechanism underlying acute changes in secretory immunoglobulin A (sIgA) remains to be determined. In this experiment, sIgA and cardiovascular activity were monitored at rest and while participants performed a mental arithmetic task, cold pressor, and submaximal cycle exercise following placebo or 1 mg of the alpha-adrenergic blocker, doxazosin. Under placebo, the tasks produced patterns of cardiovascular activity indicative of combined alpha- and beta-adrenergic, alpha-adrenergic, and beta-adrenergic activation, respectively. Doxazosin was associated with reduced blood pressure during cold pressor, but not during arithmetic or exercise. Mental arithmetic elicited increases in sIgA concentration and exercise produced increases in both sIgA concentration and secretion rate; these changes were unaffected by alpha blockade. In contrast, the cold pressor was associated with decreases in both sIgA concentration and secretion rate, which were blocked by doxazosin. These data suggest that acute decreases, but not increases, in sIgA are mediated by alpha-adrenergic mechanisms.     

Effect of doxazosin on insulin sensitivity in hypertensive non-insulin dependent diabetic patients

Summary The effect of doxazosin, an a,-adrenoceptor blocking drug, on blood pressure, sensitivity to insulin and serum lipids has been evaluated in 14 hypertensive, non-insulin dependent diabetic patients. The dose was titrated individually upwards from 1 mg until the diastolic blood pressure was below 90 mm Hg, side-effects precluded further dosage increase or the maximum daily dose of 16 mg was achieved.After 12 weeks of treatment (mean doxazosin dose 5.6 ± 5.1 mg daily), the supine and standing diastolic blood pressure of the patients had declined by about 7 mmHg, whereas their systolic blood pressure and heart rate were not significantly changed. The metabolic clearance rate of glucose increased from 2.35 to 3.37 ml - min^–1 - kg^–1 during treatment, suggesting improved sensitivity to insulin. Fasting plasma glucose was 11.9 mmol·1^–1 before and 10.9 mmol·l^–1 after doxazosin therapy (NS). Serum electrolytes and lipids did not change significantly but serum uric acid decreased from 305 to 281 mol · 1^–1 Doxazosin may be a useful alternative for the treatment of hypertension in NIDDM patients.     

多沙唑嗪治疗轻中度高血压的疗效及其对血浆内皮素和降钙素基因相关肽的影响

目的观察多沙唑嗪治疗轻、中度原发性高血压的疗效,探讨多沙唑嗪对血浆内皮素(ET)和降钙素基因相关肽(CGRP)的影响。方法采用随机、对照、双盲法,将轻、中度原发性高血压48例分为两组各24例,治疗组和对照组分别给予多沙唑嗪和特拉唑嗪,均为2mg,po,qd,共治疗8周。结果治疗组和对照组降血压有效率分别为835%,783%,差异无显著性(P>005)。治疗组总胆固醇亦明显下降(P<005)。两组治疗后ET浓度下降、CGRP水平升高。结论多沙唑嗪为一安全有效的降血压药物,在降血压的同时有降血脂作用;多沙唑嗪的降血压作用可能部分与其拮抗ET、升高CGRP的浓度有关。     

In vivo studies on the effects of α1-adrenoceptor antagonists on pupil diameter and urethral tone in rabbits

α₁-Adrenoceptors mediate contraction of iris dilator smooth muscle and hence pupil dilatation. We compared the ability of i.v. bolus injections of alfuzosin, doxazosin, naftopidil, prazosin, tamsulosin and terazosin to antagonise phenylephrine-induced mydriasis relative to their potency for inhibiting phenylephrine-induced elevations of intraurethral pressure (IUP) in rabbits. Moreover, we compared the ability of these drugs to induce miosis in conscious rabbits in the absence of phenylephrine. All antagonists inhibited the effects of phenylephrine on pupil size and IUP, and the ratio of the respective ED₅₀ values was close to unity in all cases. The doses required to induce statistically significant miosis in the absence of phenylephrine were 30- to 100-fold higher than those inhibiting phenylephrine-induced mydriasis for all antagonists, except for naftopidil. Moreover, the miotic effects of all α₁-adrenoceptor antagonists were fully reversible within 8 h. We conclude that alfuzosin, doxazosin, naftopidil, prazosin, tamsulosin and terazosin inhibit phenylephrine-induced mydriasis in the same dose range as they inhibit elevations in IUP. Higher doses of all antagonists are required to induce miosis in the absence of an exogenous agonist, and such miosis is always reversible within hours.     

非那雄胺与多沙唑嗪联用对鼠前列腺增生模型的影响

目的:探讨非那雄胺与多沙唑嗪联用对鼠前列腺增生模型的影响。方法:将34只雄性W istar大鼠,随机分为模型组(28只)、假手术组(6只)。造模成功后将24只模型鼠随机分为非那雄胺与多沙唑嗪联用、非那雄胺、多沙唑嗪组、阴性对照组,继续予皮下注射丙酸睾酮4mg/d.kg造模,连续4周;假手术组继续予皮下注射等量橄榄油4周。各组实验鼠分别于注射4周后处死,取出前列腺,光镜下观察其形态学变化,计算各实验组前列腺指数(PI)。免疫组化检测bax、fas、bcl-2蛋白表达情况。结果:与阴性对照组相比,给药4周后非那雄胺与多沙唑嗪联用、非那雄胺组PI、bcl-2表达下降(P<0.05),bax、fas表达增加(P<0.05)。结论:两种药物联用显著地降低了鼠前列腺增生的进展,有望成为临床治疗前列腺增生的新方法。     

Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Prazosin, Terazosin, and Doxazosin in Pharmaceutical Formulations

The current study was carried out with an attempt to separate similarly structured title drugs by liquid chromatography. Spectrophotometric techniques were generally insufficient under these conditions because of the spectral overlapping of drugs with similar functional groups. The pharmaceutical drugs prazosin, terazosin, and doxazosin contain the same parent quinazoline nucleus, thus making it especially difficult to separate the former two drugs because of their very similar structures. A simple and sensitive method for the routine determination of these drugs in pharmaceutical formulations was attempted. We found that the mobile phase consisting of A: ACN–diethylamine (0.05 ml), B: methanol, and C: 10 mM Ammonium acetate separated these drugs effectively. Separations were carried out on a new Kromasil C18 column (250 × 4.6 mm, 5.0 μm) at 254 nm wavelength. The calibration curve was found to be linear in the range of 2–500 μg/ml. The stated method was then validated in terms of specificity, linearity, precision, and accuracy. Additionally, the proposed method reduced the duration of the analysis.     

多沙唑嗪的多晶型研究

多沙唑嗪是一种抗高血压药物，本文通过选用不同的溶剂对其进行多晶型的制备，并利用差热分析法、红外分光光度法、Ｘ－射线粉末衍射法等确证其至少存在三种晶型。此外，还利用差热分析法研究比较了它们的固体稳定性。     

Long-term treatment with doxazosin in men with benign prostatic hyperplasia: 10-year follow-up

INTRODUCTION AND OBJECTIVES: Benign prostatic hyperplasia (BPH) is a progressive condition that is characterized by an increased risk of acute urinary retention and BPH-related surgery. This study evaluates the safety and efficacy of doxazosin over 10 years in men with BPH. MATERIAL AND METHODS: The trial enrolled men (aged 49-83 years--mean 64.0) with symptomatic BPH (clinical stage II according to Alken) and no evidence of prostate cancer. The trial involved a 1.5 year controlled efficacy study with doxazosin (4 mg/day) 64 ambulatory patients with BPH, followed by a 5-year extension. During the study after 1 year 11 pts discontinued it (expense given as reason) and 6 pts underwent surgery. Then 47 pts (100%) receiving doxazosin continued therapy. After 5 years 32 pts (60%) aged 54-92 years--mean 69.4 years continued to be followed for further 5 years, giving a total follow-up of 10 years (next 8 pts underwent surgery; total 14 (26%) pts; and 14 (26%) pts died. RESULTS: Twenty (38%) of the 47 pts (100%) enrolled into doxazosin were judged as being successfully treated during the 10-year follow-up. In further 5 years only 2 pts underwent surgery and 7 pts (13%) died for reasons unrelated to doxazosin treatment. Three pts after 6 years therapy left study. Excluding 14 pts who died plus 14 pts who left the trial it means that after 10 years 20 pts remained successfully treated and 16 pts who had to be surgically treated. Assuming that all group make 36 pts (100%) than long term follow-up showed effective results in doxazosin treated 20 pts (56%) and thus can obviate surgery. Adverse events associated with doxazosin therapy were insignificant. 10 years therapy proved effective in increasing urina flow rates and decreasing residual urine volume--respectively 14.6 ml/s and 57.0 ml (mean value). CONCLUSIONS: 1. Long-term 10 years doxazosin (4 mg/daily) therapy has demonstrated that appropriately selected BPH patients are likely to have an excellent response. 2. The a/m trial indicates that surgery can be obviated in up to half of BPH treated patients. 3. The results of the trial demonstrate that doxazosin is safe, efficacious and well-tolerated.     

脑梗死二级预防联用阿托伐他汀和强肝胶囊降脂及安全性析因分析

目的评估动脉粥样硬化性脑梗死( ACI)二级预防病人联用不同剂量阿托伐他汀和强肝胶囊的降脂效果及其安全性。方法选择 2017年 8月至 2018年 1月于冀中能源峰峰集团有限公司总医院神经内科住院的急性脑梗死病人 180例,病因分型为 TOAST大动脉粥样硬化型或小动脉闭塞型,合并高脂血症,既往无类似发作。入选病人按随机数字表法分为 10 mg对照组、 20 mg对照组、 40 mg对照组和 10 mg观察组、 20 mg观察组、 40 mg观察组,均给予对应剂量的阿托伐他汀钙片,口服,每晚 1次;观察组额外加用强肝胶囊 2g,口服,每天 2次;疗程均为 3个月。测定治疗前后病人血脂［三酰甘油( TG)、总胆固醇( TC)、低密度脂蛋白胆固醇( LDL?C)］和谷丙转氨酶( ALT)数值。析因分析比较用药种类、阿托伐他汀剂量对上述指标的影响。结果治疗后阿托伐他汀相同剂量组间比较: 20 mg观察组 TC水平显著低于 20 mg对照组［( 4.04±0.77)比( 4.69±0.91)mmol/L,P＜ 0.01］,差异有统计学意义。关于 LDL?C和 ALT水平, 10 mg观察组显著低于 10 mg对照组［(2.98±0.49)比( 3.34±0.42)mmol/L、     

甲磺酸多沙唑嗪片人体生物等效性试验研究

目的：建立HPLC—MS／MS法测定人体血浆中甲磺酸多沙唑嗪浓度的方法。方法：以KromasilC_18（4．6mm×250mm,5μm）为色谱柱,流动相为乙腈：20mM乙酸胺（含0．3％甲酸）水溶液（55：45）,流速为0．30mL·min-1,柱温为25℃,进样器温度为4℃,进样量为10μL,内标物为吡格列酮。结果：甲磺酸多沙唑嗪在血浆浓度0．3～100ng／mL范围内线性良好,定量下限为0．3ng／mL,日内RSD≤6．0％,日间RSD≤6．3％,回收率为96．58％～100．16％。结论：该法灵敏,检测结果准确,适用于甲磺酸多沙唑嗪片的人体生物等效性研究。