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Minoxidil is a potent antihypertensive used as an adjunctive agent in refractory hypertension. It exerts an antihypertensive effect through two mechanisms: selective arterial vasodilation by activation of potassium channels in the vascular smooth muscle and stimulation of carotid and aortic baroreceptors, leading to downstream release of renin and norepinephrine. Although frequently cited in reviews of antihypertensive agents, limited data about the use of minoxidil in neonates are available. We describe an infant girl, born at 35 weeks of gestation, who was diagnosed with idiopathic hypertension after extensive diagnostic evaluation. Adequate blood pressure control was not achieved with captopril, amlodipine, and clonidine. Oliguria secondary to captopril and rapid-onset congestive heart failure due to persistent hypertension led to the introduction of intravenous agents labetalol and nitroprusside. Although adequate blood pressure control was achieved, attempts to transition back to oral agents were unsuccessful, prompting the use of minoxidil as an alternative agent. Although good blood pressure control was achieved, the infant's oral intake plummeted from 210 to 63 ml/kg/day. The anorexia quickly resolved after stopping minoxidil, and she was discharged home at 5 months of age receiving propranolol, amlodipine, and doxazosin. Use of the Naranjo adverse drug reaction probability scale indicated a definite relationship (score of 10) between the patient's development of anorexia and minoxidil therapy. To our knowledge, there have been no previous reports of minoxidil-associated anorexia in preterm or term infants. Clinicians should be aware that anorexia is a possible adverse effect of minoxidil in this patient population when initiating the drug in similar patients.
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The urethral pressure of the anesthetized cat was increased by electric stimulation of the hypogastric nerve. The different effects of Alf or Dox on the arterial blood pressure and urethral pressure between intraduodenal administration (i.d.) and intravenous infusion (i.v.) were compared.
Benign prostatic hyperplasia is an increasingly prevalent condition affecting > 50% of men > 65 years of age. Although it is a condition that is unlikely to be life threatening, it can significantly affect quality of life with distressing lower urinary tract symptoms. Increasingly, medical therapy is being used as first-line treatment for men with moderate-to-severe lower urinary tract symptoms. Two main pharmacological classes of drugs are used: 5alpha-reductase inhibitors and alpha-1 selective blockers. Both these classes of drugs have shown good tolerability and clinical efficacy. This article examines the potential benefit of the use of combination therapy. In particular, what is the evidence for using doxazosin and finasteride therapy together?
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We conclude that the increase in heart rate caused by urapidil is less pronounced than that with doxazosin, a property that might favour urapidil in the treatment of arterial hypertension. In addition, only doxazosin (but not urapidil) increased the RPP at rest, a finding that might be helpful to explain why this drug was never shown to improve outcome in the treatment of arterial hypertension.
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A 16-week, open, noncomparative, multicenter, prospective study of patients with hypertension (> or = 140/> or = 90 mm Hg). Doxazosin GITS 4 mg/d was added to entry medication and increased to 8 mg/d at Week 4 in cases of inadequate blood pressure (BP) control.
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Systemic and regional hemodynamics (radionuclide-labeled microspheres), left and right ventricular weight, hydroxyproline concentration, and aortic weight were measured at age 35 weeks. Doxazosin reduced arterial pressure and total peripheral resistance without changing left ventricular mass and collagen content, whereas monotherapies with the beta-1 antagonist metoprolol or a subdepressor dose of the ACE inhibitor enalapril were effective in reducing left ventricular mass and hydroxyproline without altering pressure. Doxazosin combined with the same low-dose ACE inhibitor reduced left ventricular mass and hydroxyproline without potentiating the hypotensive effect of doxazosin. By contrast, the combination of beta-1 antagonist with the low-dose ACE inhibitor reduced pressure, unlike either agent alone. Aortic weight index was significantly reduced only by doxazosin whether when used alone or with the ACE inhibitor. Low-dose ACE inhibitor with doxazosin or the beta-1 receptor antagonist as well as doxazosin alone decreased renal vascular resistance.
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A randomized, parallel-controlled, multicenter clinical trial was conducted. From September 2002 to December 2003 906 BPH patients were enrolled into 7 therapeutic groups, including selective-adrenoceptor antagonist (terazosin, doxazosin tamsulosin and naftopidil), 5 alpha-reductase inhibitor (finasteride and epristeride) and natural product (cernilton). International Prostate Symptom Score (IPSS) and Quality of Life (QOL), uroflowmetry, total prostatic volume (TPV) and transitional zone volume and residual urine were used as efficacy criteria.
A sample pre-concentration method based on the in-line coupling of in-tube solid-phase microextraction and electrophoretic sweeping was developed for the analysis of hydrophobic compounds. The sample pre-concentration and electrophoretic separation processes were simply and sequentially carried out with a (35%-phenyl)-methylpolysiloxane-coated capillary. The developed method was validated and applied to enrich and separate several pharmaceuticals including loratadine, indomethacin, ibuprofen and doxazosin. Several parameters of microextration were investigated such as temperature, pH and eluant. And the concentration of microemulsion that influences separation efficiency and microextraction efficiency were also studied. Central composite design was applied for the optimization of sampling flow rate and sampling time that interact in a very complex way with each other. The precision, sensitivity and recovery of the method were investigated. Under the optimal conditions, the maximum enrichment factors for loratadine, indomethacin, ibuprofen and doxazosin in aqueous solutions are 1355, 571, 523 and 318, respectively. In addition, the developed method was applied to determine loratadine in rabbit blood sample.
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Effects of exogenous and endogenous noradrenaline, released by tyramine and lower body negative pressure (LBNP), on vascular post-synaptic alpha 1- and alpha 2-adrenoceptors have been compared in healthy volunteers. Intra-arterial (i.a.) infusions of noradrenaline and tyramine into the forearm were given in the presence of saline, of yohimbine and of doxazosin, and changes in forearm blood flow (FBF) were measured. Lower body negative pressure of -40 mmHg was applied without and with a continuous i.a. infusion of yohimbine and of doxazosin, and changes in FBF in both forearms were compared. Forearm blood flow was measured by venous occlusion plethysmography. Noradrenaline and tyramine reduced FBF dose-dependently and to the same extent. Both these vasoconstrictions were significantly reduced by yohimbine (P < 0.001 for both) as well as by doxazosin (P < 0.05 for noradrenaline and P < 0.001 for tyramine). The tyramine-induced vasoconstriction was more effectively reduced by doxazosin, whereas yohimbine reduced the noradrenaline-induced vasoconstriction more effectively. Lower body negative pressure reduced FBF in both forearms to the same extent. Doxazosin effectively inhibited the LBNP induced decrease in FBF (P < 0.05) whereas yohimbine had no effect (P > 0.05). These results are in accordance with a predominant intrasynaptic location of post-synaptic alpha 1-adrenoceptors and a predominant extrasynaptic location of post-synaptic alpha 2-adrenoceptors in human blood vessels.
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The NIH-CPSI initial and sixth-month total scores were 23.1 and 10.7, respectively, in group 1, and 21.9 and 9.2, respectively, in group 2. The initial and sixth-month scores remained stable in group 3 (22.9 and 21.9, respectively). There was no statistically significant difference between two treatment arms with respect to efficiency of treatment (p>0.05). The responses in groups 1 and 2 were found durable at the end of 12 mo.
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Doxazosin mesylate is an alpha1-adrenoceptor antagonist that was used to treat hypertension until a major study (ALLHAT; Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) showed that it increased the risk of progressing to heart failure. Doxazosin is now being used to treat benign prostatic hyperplasia (BPH). Noradrenaline acts on alpha1-adrenoceptors to contract the smooth muscle in the prostate and bladder, and by opposing these actions, doxazosin is beneficial in BPH. Doxazosin also increases apoptosis in the prostate. Although the standard preparation is suitable for once-daily dosing in BPH, it has to be titrated through three steps to its final dose. The controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin is more convenient to use as it only has to be titrated through one step. In the treatment of BPH, standard doxazosin reduced both obstructive and irritative symptoms and increased peak urinary flow rate. The main side effects with doxazosin are those commonly associated with lowering blood pressure, although doxazosin lowers blood pressure to a lesser extent in normotensives than hypertensives. There is some evidence that in addition to being easier to use, doxazosin GITS may cause less adverse effects than the standard preparations. The benefits of doxazosin and the 5alpha-reductase inhibitor, finasteride, may be additive in BPH especially in men with large prostates. Further trials are necessary in order to determine whether doxazosin GITS is superior to other alpha1-adrenoceptor antagonists in BPH.
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To compare the effects of doxazosin on blood pressure when used for the treatment of benign prostatic hyperplasia (BPH) in men who are either physiologically or pharmacologically normotensive.
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Alpha1-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 alpha1-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.
Recent data suggest that the bladder urothelium may have a sensory function by way of release of adenosine triphosphate (ATP) during stretch, which then acts as a sensory neurotransmitter. Because benign prostatic hyperplasia (BPH) can give rise to irritative (hypersensory) voiding patterns, we questioned whether the bladder urothelium from patients with BPH released more ATP during in vitro stretch and whether doxazosin, an alpha(1)-adrenoceptor blocker, affects this purinergic mechanism.
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Recent studies and analyses have confirmed that baseline prostate volume is related to progression of benign prostatic hyperplasia (BPH) as well as to negative outcomes related to BPH, such as acute urinary retention (AUR) and need for surgery, and can also predict response to therapy. Other investigations have determined that prostate-specific antigen (PSA) level has good predictive value for assessing prostate volume. Strong evidence exists that baseline serum PSA level, like baseline prostate volume, predicts future prostate growth. Randomized placebo-controlled finasteride trials have shown that men with larger prostate volumes and higher PSA levels experience a clinically significant response to therapy compared with those with smaller prostate volumes and lower PSA levels. It has also been demonstrated that men with larger prostate glands and higher PSA levels are at increased risk for AUR and BPH-related surgery but that finasteride reduces these risks. Moreover, doxazosin and finasteride, alone and in combination, have been shown to significantly reduce BPH clinical progression.
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Since it is not known for certain which alpha-adrenergic receptors mediate renal vasoconstriction in human essential hypertension, we infused either doxazosin (n = 7) or yohimbine (n = 7) into the renal arteries of hypertensive subjects immediately prior to diagnostic angiography. Both agents caused an increment in renal blood flow as assessed with the xenon-washout technique. Doxazosin increased renal flow from 342 +/- 36 to 360 +/- 55 ml/min per 100 g (0.05 less than p less than 0.10). Yohimbine enhanced flow from 380 +/- 41 to 485 +/- 63 ml/min per 100 g (p less than 0.01). The effect of yohimbine was significantly greater than that of doxazosin. In a control group (n = 7) receiving only saline, no changes in renal blood flow occurred. Doxazosin enhanced renin secretion in the kidney by 10 +/- 4% over levels in controls (0.05 less than p less than 0.10), whereas yohimbine increased renin release by 80 +/- 23% (p less than 0.01). The latter increase was apparently not due to alterations in flow alone, since the arteriovenous gradient for renin also widened. We conclude that in resting conditions, neurogenic vascular tone in the kidney depends mainly upon activation of alpha 2-adrenergic receptors. Moreover, these receptors exert a tonic inhibitory influence on renin release.