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Urology Journal Apr 2021The present study aims to assess and compare the effects of carvedilol and terazosin plus enalapril on lower urinary tract symptoms (LUTS), the urine flow, and blood... (Comparative Study)
Comparative Study Randomized Controlled Trial
A Randomized Crossover Pilot Study Examining the Effect of Carvedilol and Terazosin plus Enalapril on Urinary Symptoms of Patients with Hypertension and Benign Prostatic Hyperplasia.
PURPOSE
The present study aims to assess and compare the effects of carvedilol and terazosin plus enalapril on lower urinary tract symptoms (LUTS), the urine flow, and blood pressure (BP) in patients with moderate hypertension (HTN) and benign prostatic hyperplasia (BPH).
MATERIALS AND METHODS
In this randomized crossover trial, a total of 40 men with HTN and LUTS symptoms were enrolled. The first group was treated with carvedilol, and the second one received terazosin plus enalapril. After eight weeks of treatment, the patients experienced a one-month washout period, and the treatments changed and continued for eight weeks. To diagnose BPH in the study, the international prostate symptom score (IPSS) questionnaire was used. Moreover, the prostate-specific antigen (PSA), the post-void residual (PVR) urine volume, and the maximum urinary flow rate (Q-max using the uroflowmetry test) were measured.
RESULTS
Effect assessment results in this crossover trial illustrated neither carryover effects nor significant treatment effects on all primary outcomes (P > 0.05). Moreover, the results for the period effect indicated a significant reduction in BP (systolic and diastolic), PVR, and IPSS, yet a significant raise in Qmax.
CONCLUSION
The effects of carvedilol are similar to those of the combination of terazosin and enalapril in patients with moderate HTN and BPH in controlling LUTS. Carvedilol could be used as an appropriative drug in patients with moderate HTN and cardiac problems with LUTS of BPH. Further studies are recommended to be conducted to investigate and compare the efficacy of carvedilol with that of other alpha-blockers with a larger sample size and over a longer period of time.
Topics: Adrenergic alpha-1 Receptor Antagonists; Aged; Antihypertensive Agents; Carvedilol; Cross-Over Studies; Drug Therapy, Combination; Enalapril; Humans; Hypertension; Male; Middle Aged; Pilot Projects; Prazosin; Prostatic Hyperplasia; Single-Blind Method
PubMed: 33840085
DOI: 10.22037/uj.v18i.5678 -
European Journal of Hospital Pharmacy :... Jul 2022Surgery is the primary strategy for treating phaeochromocytoma (PCC), but it can lead to severe hypertension and heart failure. Although valsartan is effective in...
OBJECTIVE
Surgery is the primary strategy for treating phaeochromocytoma (PCC), but it can lead to severe hypertension and heart failure. Although valsartan is effective in reducing high blood pressure, clinical data on the potential role of valsartan in PCC are currently limited. Therefore, the aim of this study was to investigate the effects of pretreatment with terazosin and valsartan on patients with PCC.
METHODS
In this retrospective cohort study, 50 patients who underwent laparoscopic resection of PCC were enrolled. During preoperative preparation, the patients (n=25) in the control group were treated with terazosin, while those (n=25) in the combination treatment group were treated with terazosin and valsartan. The levels of catecholamine hormones before and after surgery were determined, and the intraoperative blood pressure and the incidence of complications were compared between the two groups.
RESULTS
The results showed no significant differences in baseline patient characteristics or surgical conditions between the two groups (p>0.05). However, on the third day after surgery, the levels of catecholamine hormones in the two groups were significantly lower than those before surgery (p<0.05), while the levels in the combination treatment group were notably lower than those in the control group (p<0.05). The patients in the combination treatment group showed lower intraoperative blood pressure fluctuations and incidence of perioperative complications compared with the control group (p<0.05).
CONCLUSIONS
Terazosin combined with valsartan can effectively improve perioperative haemodynamic instability and reduce postoperative complications in the preoperative management of PCC.
Topics: Adrenal Gland Neoplasms; Catecholamines; Hemodynamics; Hormones; Humans; Pheochromocytoma; Prazosin; Retrospective Studies; Valsartan
PubMed: 32895230
DOI: 10.1136/ejhpharm-2020-002375 -
British Journal of Pharmacology Feb 2008Paracetamol, a major cause of acute liver failure (ALF) represents a significant clinical problem. Adrenoceptor stimulation or antagonism can modulate chemical-induced...
BACKGROUND AND PURPOSE
Paracetamol, a major cause of acute liver failure (ALF) represents a significant clinical problem. Adrenoceptor stimulation or antagonism can modulate chemical-induced hepatotoxicity. We investigated the role of endogenous catecholamines and alpha(1)-adrenoceptors in the development of paracetamol- induced hepatotoxicity.
EXPERIMENTAL APPROACH
Paracetamol (3.5 mmol kg(-1)) was administered to male CD-1 mice, with and without alpha(1)-adrenoceptor antagonists (prazosin, doxazosin, terazosin and tamsulosin; 35.7 micromol kg(-1)). Serum transaminases and hepatic glutathione (GSH) levels were assessed as markers of hepatic damage. Paracetamol bioactivation was assessed by covalent binding, hepatic and urinary conjugate formation and uridine glucuronosyltransferase activity. Plasma catecholamines levels and hepatic congestion were also analysed.
KEY RESULTS
Plasma catecholamine levels were significantly elevated 5 h post paracetamol administration. Prazosin prevented hepatotoxicity when administered 1 h before a toxic paracetamol insult and importantly, when administered up to 1 h post paracetamol injection. Prazosin had no effect on paracetamol-induced depletion of hepatic GSH, paracetamol bioactivation or paracetamol-induced transcription of defence genes. Paracetamol toxicity is associated with marked accumulation of erythrocytes within hepatic sinusoids and prazosin completely prevented this accumulation.
CONCLUSION AND IMPLICATIONS
Paracetamol-induced hepatocellular damage is associated with increased circulating catecholamines. alpha(1)-Adrenoceptor antagonists conferred complete protection from paracetamol -induced hepatotoxicity. Protection was associated with absence of hepatic erythrocyte accumulation. Increased catecholamine levels may contribute to the pathophysiology of paracetamol-induced hepatotoxicity by compromising hepatic perfusion. Protection against paracetamol toxicity by alpha(1) antagonists in mice has implications for therapeutic management of patients presenting with paracetamol overdose and ALF.
Topics: Acetaminophen; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Animals; Catecholamines; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Doxazosin; Erythrocytes; Gene Expression Regulation, Enzymologic; Glutamate-Cysteine Ligase; Glutathione; Heme Oxygenase-1; Liver; Liver Circulation; Liver Diseases; Male; Membrane Proteins; Mice; Prazosin; Protein Binding; Receptors, Adrenergic, alpha-1; Sulfonamides; Tamsulosin; Time Factors; Transaminases
PubMed: 18071297
DOI: 10.1038/sj.bjp.0707620 -
British Journal of Pharmacology Mar 19941. The electrophysiological effects of prazosin, a highly specific alpha 1-adrenoceptor antagonist, on transmembrane action potential characteristics were studied in... (Comparative Study)
Comparative Study
1. The electrophysiological effects of prazosin, a highly specific alpha 1-adrenoceptor antagonist, on transmembrane action potential characteristics were studied in guinea-pig papillary muscles. 2. At concentrations between 10(-6) M and 10(-5) M, prazosin produced a concentration-dependent decrease in the maximum upstroke velocity (Vmax) and a progressive lengthening of the action potential duration at 50% (APD50) and 90% (APD90) of repolarization. The prolongation of the APD50 and APD90 values was independent of the frequency of stimulation. The prolongation of the ADP90 was accompanied by a parallel lengthening of the effective refractory period (ERP) and thus, the ERP/APD90 ratio remained unaltered at all drug concentrations tested. 3. In the presence of prazosin, 5 x 10(-6) M, the percentage of Vmax block increased with the frequency of stimulation, the inhibitory effect being more marked at fast driving rates (frequency-dependent Vmax block). At 3 Hz, the onset kinetics of the frequency-dependent Vmax block was better fitted by a biexponential function, the K values of the fast (K1) and slow components (K2) being 0.254 +/- 0.037 AP-1 and 0.045 +/- 0.010 AP-1, respectively. However, prazosin did not produce tonic Vmax block. 4. The recovery time constant (tau re) from the frequency-dependent Vmax block was prolonged from 19.6 +/- 2.5 ms to 24.4 +/- 5.5 s. This result indicated that prazosin can be considered as a slow kinetics Na channel blocker. 5. Prazosin, 5 x 10(-6) M, shifted the membrane responsiveness curve in a hyperpolarizing direction, which indicated that the blockade of sodium channels increased at less negative potentials (voltage-dependent Vmax block). 6. It is concluded that in guinea-pig papillary muscles, prazosin inhibited the Vmax and lengthened the duration of the action potentials, thus exhibiting both class I and class III antiarrhythmic actions,respectively, that were possibly unrelated to blockade of myocardial alpha l-adrenoceptors.
Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Electric Stimulation; Electrophysiology; Female; Guinea Pigs; Kinetics; Male; Membrane Potentials; Papillary Muscles; Prazosin; Sodium Channels
PubMed: 8019750
DOI: 10.1111/j.1476-5381.1994.tb14796.x -
Alcoholism, Clinical and Experimental... Jun 2014Evidence suggests that activation of the noradrenergic system may contribute to alcohol drinking in animals and humans. Our previous studies demonstrated that blocking...
Combining the α1 -adrenergic receptor antagonist, prazosin, with the β-adrenergic receptor antagonist, propranolol, reduces alcohol drinking more effectively than either drug alone.
BACKGROUND
Evidence suggests that activation of the noradrenergic system may contribute to alcohol drinking in animals and humans. Our previous studies demonstrated that blocking α1 -adrenergic receptors with the antagonist, prazosin, decreased alcohol drinking in rats under various conditions. As noradrenergic activation is also regulated by β-adrenergic receptors, we now examine the effects of the β-adrenergic receptor antagonist, propranolol, alone or in combination with prazosin, on alcohol drinking in rats selectively bred for high voluntary alcohol intake and alcohol preference (P line).
METHODS
Two studies were conducted with male P rats. In study 1, rats were allowed to become alcohol-dependent during 14 weeks of ad libitum access to food, water, and 20% alcohol, and the effect of propranolol (5 to 15 mg/kg, intraperitoneally [IP]) and prazosin (1 to 2 mg/kg, IP) on alcohol intake during withdrawal was assessed. In study 2, the effect of propranolol (5 mg/kg, IP) and prazosin (2 mg/kg, IP) on alcohol intake following prolonged imposed abstinence was assessed.
RESULTS
Alcohol drinking following propranolol treatment was variable, but the combination of propranolol + prazosin consistently suppressed alcohol drinking during both alcohol withdrawal and following prolonged imposed abstinence, and the combination of these 2 drugs was more effective than was treatment with either drug alone.
CONCLUSIONS
Treatment with prazosin + propranolol, or a combination of other centrally active α1 - and β-adrenergic receptor antagonists, may assist in preventing alcohol relapse in some individuals.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-Antagonists; Alcohol Drinking; Alcoholism; Animals; Drug Therapy, Combination; Male; Prazosin; Propranolol; Rats
PubMed: 24891220
DOI: 10.1111/acer.12441 -
The Biochemical Journal Oct 1999We have identified from human liver eight alpha(1A)-adrenoceptor (alpha(1A)-AR) splice variants that were also expressed in human heart, prostate and hippocampus. Three...
We have identified from human liver eight alpha(1A)-adrenoceptor (alpha(1A)-AR) splice variants that were also expressed in human heart, prostate and hippocampus. Three of these alpha(1A)-AR isoforms (alpha(1A-1)-AR, alpha(1A-2a)-AR and alpha(1A-3a)-AR) gave rise to receptors with seven transmembrane domains (7TMalpha(1A)-AR). The other five (alpha(1A-2b)-AR, alpha(1A-2c)-AR, alpha(1A-3c)-AR, alpha(1A-5)-AR and alpha(1A-6)-AR) led to truncated receptors lacking transmembrane domain VII (6TMalpha(1A)-AR). The 7TMalpha(1A)-AR isoforms transiently expressed in COS-7 cells bound [(3)H]prazosin with high affinity (K(d) 0.2 nM) and mediated a noradrenaline (norepinephrine)-induced increase in cytoplasmic free Ca(2+) concentration, whereas the 6TMalpha(1A)-AR isoforms were incapable of ligand binding and signal transduction. Immunocytochemical studies with N-terminal epitope-tagged alpha(1A)-AR isoforms showed that the 7TMalpha(1A)-AR isoforms were present both at the cell surface and in intracellular compartments, whereas the 6TMalpha(1A)-AR isoforms were exclusively localized within the cell. Interestingly, in co-transfected cells, each truncated alpha(1A)-AR isoform inhibited [(3)H]prazosin binding and cell-surface trafficking of the co-expressed 'original' 7TMalpha(1A-1)-AR. However, there was no modification of either the [(3)H]prazosin-binding affinity or the pharmacological properties of alpha(1A-1)-AR. Immunoblotting experiments revealed that co-expression of the alpha(1A-1)-AR with 6TMalpha(1A)-AR isoforms did not impair alpha(1A-1)-AR expression. Therefore the expression in human tissues of many truncated isoforms constitutes a new regulation pathway of biological properties of alpha(1A)-AR.
Topics: Amino Acid Sequence; Animals; Biological Transport; Blotting, Western; COS Cells; Cloning, Molecular; DNA, Complementary; Humans; Liver; Molecular Sequence Data; Prazosin; Protein Binding; Protein Isoforms; Radioligand Assay; Receptors, Adrenergic, alpha-1; Sequence Homology, Amino Acid; Subcellular Fractions; Tritium
PubMed: 10493934
DOI: No ID Found -
Alcoholism, Clinical and Experimental... Feb 2009Preliminary evidence suggest that noradrenergic signaling may play a role in mediating alcohol drinking behavior in both humans and rats. Accordingly, we tested the...
BACKGROUND
Preliminary evidence suggest that noradrenergic signaling may play a role in mediating alcohol drinking behavior in both humans and rats. Accordingly, we tested the hypothesis that blockade of alpha(1)-adrenergic receptors will suppress alcohol drinking in rats selectively bred for alcohol preference (P line).
METHODS
Adult male P rats were given 24-hour access to food and water and scheduled access to a 15% (v/v) alcohol solution for 2 hours daily. Rats were injected IP with the alpha(1)-adrenergic receptor antagonist, prazosin (0, 0.5, 1.0, 1.5, or 2.0 mg/kg body weight), once a day at 15 minutes prior to onset of the daily 2-hour 2-bottle choice, alcohol versus water, access period for 2 consecutive days and then 3 weeks later for 5 consecutive days.
RESULTS
Prazosin significantly reduced (p < 0.01) alcohol intake during the initial 2 daily administrations, and this reduction of alcohol intake was maintained for 5 consecutive days by daily prazosin treatment in the subsequent more prolonged trial (p < 0.05). The prazosin-induced reduction of alcohol intake was not dependent upon drug-induced motor impairment since increases in water drinking (p < 0.05) were exhibited during the 2-hour access periods during both 2- and 5-day prazosin treatment.
CONCLUSIONS
The results indicate that the noradrenergic system plays a role in mediating alcohol drinking in rats of the P line and suggest that prazosin--a safe, well-characterized, and well-tolerated drug--may be an effective pharmacotherapeutic agent for the treatment of alcohol use disorders.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Alcohol Drinking; Animals; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Drinking; Male; Prazosin; Rats
PubMed: 19032582
DOI: 10.1111/j.1530-0277.2008.00829.x -
PloS One 2013ρ-Da1a is a three-finger fold toxin from green mamba venom that is highly selective for the α1A-adrenoceptor. This toxin has atypical pharmacological properties,...
ρ-Da1a is a three-finger fold toxin from green mamba venom that is highly selective for the α1A-adrenoceptor. This toxin has atypical pharmacological properties, including incomplete inhibition of (3)H-prazosin or (125)I-HEAT binding and insurmountable antagonist action. We aimed to clarify its mode of action at the α1A-adrenoceptor. The affinity (pKi 9.26) and selectivity of ρ-Da1a for the α1A-adrenoceptor were confirmed by comparing binding to human adrenoceptors expressed in eukaryotic cells. Equilibrium and kinetic binding experiments were used to demonstrate that ρ-Da1a, prazosin and HEAT compete at the α1A-adrenoceptor. ρ-Da1a did not affect the dissociation kinetics of (3)H-prazosin or (125)I-HEAT, and the IC50 of ρ-Da1a, determined by competition experiments, increased linearly with the concentration of radioligands used, while the residual binding by ρ-Da1a remained stable. The effect of ρ-Da1a on agonist-stimulated Ca(2+) release was insurmountable in the presence of phenethylamine- or imidazoline-type agonists. Ten mutations in the orthosteric binding pocket of the α1A-adrenoceptor were evaluated for alterations in ρ-Da1a affinity. The D106(3.32)A and the S188(5.42)A/S192(5.46)A receptor mutations reduced toxin affinity moderately (6 and 7.6 times, respectively), while the F86(2.64)A, F288(6.51)A and F312(7.39)A mutations diminished it dramatically by 18- to 93-fold. In addition, residue F86(2.64) was identified as a key interaction point for (125)I-HEAT, as the variant F86(2.64)A induced a 23-fold reduction in HEAT affinity. Unlike the M1 muscarinic acetylcholine receptor toxin MT7, ρ-Da1a interacts with the human α1A-adrenoceptor orthosteric pocket and shares receptor interaction points with antagonist (F86(2.64), F288(6.51) and F312(7.39)) and agonist (F288(6.51) and F312(7.39)) ligands. Its selectivity for the α1A-adrenoceptor may result, at least partly, from its interaction with the residue F86(2.64), which appears to be important also for HEAT binding.
Topics: Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-1 Receptor Antagonists; Animals; Binding Sites; Binding, Competitive; CHO Cells; Cricetulus; Elapid Venoms; Elapidae; Humans; Kinetics; Ligands; Models, Molecular; Mutation; Prazosin; Protein Binding; Radioligand Assay; Receptors, Adrenergic, alpha-1; Tetralones
PubMed: 23935897
DOI: 10.1371/journal.pone.0068841 -
International Journal of Urology :... Jun 2000The objective of this open randomized clinical study was to compare the short-term efficacy and safety of three alpha-1 blockers, prazosin, terazosin and tamsulosin, in... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Comparison of prazosin, terazosin and tamsulosin in the treatment of symptomatic benign prostatic hyperplasia: a short-term open, randomized multicenter study. BPH Medical Therapy Study Group. Benign prostatic hyperplasia.
BACKGROUND
The objective of this open randomized clinical study was to compare the short-term efficacy and safety of three alpha-1 blockers, prazosin, terazosin and tamsulosin, in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).
METHODS
The study comprised 121 patients with symptomatic BPH who were randomized to receive 0.5 mg of prazosin twice daily, 0.5 mg of terazosin twice daily or 0.1 mg of tamsulosin once daily for the initial 2 weeks. The doses were doubled for the next 2 weeks. The primary variables assessed were a symptom score, changes in maximum and average urinary flow rate (Qmax and Qave), postvoid residual urine volume and blood pressure.
RESULTS
The percentage changes in the total symptom score from baseline were 38, 39 and 26% at 4 weeks by prazosin, terazosin and tamsulosin, respectively. Terazosin produced significantly higher improvement in four out of nine individual symptoms than tamsulosin (P < 0.05). A significant increase in Qmax or Qave in uroflowmetry was obtained in the prazosin and tamsulosin groups. Blood pressure remained unchanged in normotensive patients, but significantly decreased in hypertensive patients except for the tamsulosin group. Adverse events were minimal in all treatment groups.
CONCLUSIONS
The efficacy and safety profiles were different among the alpha-1 blockers at standard doses. Tamsulosin appears to be safer than the others for aged patients or patients with hypertension who have impaired blood pressure regulation, while terazosin is significantly effective in improving symptomatic score when compared with the others examined. It is recommended that the alpha-1 blocking agent and its optimal dose are selected on the basis of the baseline characteristics of the patients with symptomatic BPH.
Topics: Adrenergic alpha-Antagonists; Aged; Blood Pressure; Humans; Male; Prazosin; Prostatic Hyperplasia; Sulfonamides; Tamsulosin; Urodynamics
PubMed: 10843450
DOI: 10.1046/j.1442-2042.2000.00175.x -
Neurochemical Research Nov 2022Phenylephrine (PE) is a canonical α-adrenoceptor-selective agonist. However, unexpected effects of PE have been observed in preclinical and clinical studies, that...
Phenylephrine (PE) is a canonical α-adrenoceptor-selective agonist. However, unexpected effects of PE have been observed in preclinical and clinical studies, that cannot be easily explained by its actions on α-adrenoceptors. The probability of the involvement of α- and β-adrenoceptors in the effect of PE has been raised. In addition, our earlier study observed that PE released noradrenaline (NA) in a [Ca]-independent manner. To elucidate this issue, we have investigated the effects of PE on [H]NA release and α-mediated smooth muscle contractions in the mouse vas deferens (MVD) as ex vivo preparation. The release experiments were designed to assess the effects of PE at the presynaptic terminal, whereas smooth muscle isometric contractions in response to electrical field stimulation were used to measure PE effect postsynaptically. Our results show that PE at concentrations between 0.3 and 30 µM significantly enhanced the resting release of [H]NA in a [Ca]-independent manner. In addition, prazosin did not affect the release of NA evoked by PE. On the contrary, PE-evoked smooth muscle contractions were inhibited by prazosin administration indicating the α-adrenoceptor-mediated effect. When the function of the NA transporter (NAT) was attenuated with nisoxetine, PE failed to release NA and the contractions were reduced by approximately 88%. The remaining part proved to be prazosin-sensitive. The present work supports the substantial indirect effect of PE which relays on the cytoplasmic release of NA, which might explain the reported side effects for PE.
Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Cytoplasm; Male; Mice; Norepinephrine; Phenylephrine; Prazosin; Receptors, Adrenergic, alpha-1
PubMed: 35945308
DOI: 10.1007/s11064-022-03681-2