Efecto del manejo farmacológico del sistema nervioso autónomo en la pancreatitis aguda inducida por el veneno de escorpión Tityus zulianus en un modelo ex vivo / Effect of the pharmacological management of the autonomic nervous system in the acute pancreatitis induced by the venom of Tityus zulianus scorpion in an ex vivo model

La pancreatitis es una de las consecuencias principales del envenenamiento escorpiónico producido por el género Tityus. El manejo farmacológico mediante el uso de agonistas y antagonistas α adrenérgicos en modelos experimentales in vivo e in vitro, permiten establecer una aproximación del papel del Sistema Nervioso Simpático (SNS) en el desarrollo de la pancreatitis. Objetivo: determinar el papel del SNS en el desarrollo de la pancreatitis aguda inducida por el veneno de escorpión Tityus zulianus (TzV), por medio del uso de simpaticolíticos como la clonidina y el prazosin. Métodos: La Extravasación de Proteínas Plasmáticas (EPP) en el páncreas se evaluó mediante el método de Azul de Evans (AE), modificado de Saria y Lundberg (1983) a 620 nm; n=3 ratones NIH en cada grupo experimental. Las comparaciones se hicieron por ANOVA de una vía y las pruebas post HOC por Tukey-Kramer. Resultados: Ambos fármacos (1mg/Kg), disminuyeron significativamente p< 0,01 (**) la EPP en el páncreas inducida por el TzV, en comparación con los animales inoculados solo con TzV. No hubo diferencias significativas entre los animales del grupo control y los grupos tratados con los fármacos más el TzV. Conclusiones: El efecto pancreatotóxico del TzV en ratones podría tener un componente autonómico dado que drogas simpaticolíticas al disminuir la actividad noradrenérgica reducen la magnitud del edema. Esto sugiere que ambos fármacos pueden usarse como estrategia terapéutica en estos casos(AU)

Pancreatitis is one of the main consequences of scorpionic poisoning produced by the genus Tityus. The pharmacological management through the use of agonists and α adrenergic antagonists in experimental models in vivo and in vitro, allow us to establish an approximation of the role of the Sympathetic Nervous System (SNS) in the development of pancreatitis. Objective: to determine the role of SNS in the development of acute pancreatitis induced by the scorpion venom Tityus zulianus (TzV), through the use of sympatholytics such as clonidine and prazosin. Methods: Plasma Protein Extravasation (PPE) in the pancreas was evaluated by the method of Evans Blue (EA), modified by Saria and Lundberg (1983) at 620 nm; n = 3 NIH mice in each experimental group. Comparisons were made by one-way ANOVA and post-HOC tests by Tukey-Kramer. Results: Both drugs (1mg / Kg) significantly decreased p <0.01 (**) the EPP in the pancreas induced by TzV, compared to animals inoculated only with TzV. There were no significant differences between the animals in the control group and the groups treated with drugs plus TzV. Conclusions: The pancreatotoxic effect of TzV in mice could have an autonomic component since sympatholytic drugs by decreasing noradrenergic activity reduce the magnitude of edema. This suggests that both drugs can be used as a therapeutic strategy in these cases(AU)

Impact of Metabolic Syndrome on Response to Medical Treatment of Benign Prostatic Hyperplasia

PURPOSE: To investigate the effect of metabolic syndrome (MetS) on the response to medical therapy of benign prostatic hyperplasia (BPH) after a 3-month period of treatment. MATERIALS AND METHODS: This was a cohort study of 100 patients, 47 with MetS and 53 without MetS, referred to either the primary care unit or referral hospital with BPH who had moderate lower urinary tract symptoms of prostate involvement and were candidates for medical treatment. Our main outcome was response to medical treatment with prazosin 1 mg twice a day and finasteride 5 mg daily in patients with BPH on the basis of International Prostate Symptom Score (IPSS). Multivariate analysis of covariance was used to compare BPH treatment response in patients with and without MetS before and after receiving treatment. RESULTS: The mean volume of the prostate was significantly higher in MetS patients than in patients without MetS (57+/-32.65 mL compared with 46.00+/-20.19 mL, p=0.036). The control group demonstrated an 11-unit reduction in IPSS, whereas those with MetS showed a reduction in the symptom score of only 6 units (p<0.001). Regarding the components of MetS separately, triglyceride (p<0.001), fasting blood sugar (p=0.001), and waist circumference (p=0.028) significantly affected the clinical progression of BPH. The observational nature of this study may be a limitation in comparison with an interventional study. CONCLUSIONS: The results of the present study showed that MetS can negatively affect the response to medical treatment of BPH. Therefore, it is necessary to consider MetS in selecting patients with BPH for drug therapy.

Effects of Terazosin and Tolterodine on Ureteral Stent Related Symptoms: A Double-Blind Placebo-Controlled Randomized Clinical Trial

Objective To evaluate the effects of terazosin and tolterodine on ureteral stent discomfort. Materials and Methods Of 163 patients assessed for eligibility, 104 patients were randomly assigned to receive placebo, 2 mg of terazosin twice daily, 2 mg of tolterodine daily, or both terazosin plus tolterodine during the stenting period. Prior to stenting and at stent removal, the International Prostate Symptom Score (IPSS), the IPSS quality of life (QoL) subscore and the Visual Analog Scale for Pain were determined. The patients also reported their analgesic use during the stenting period. Results Ninety-four patients completed the study. We noted significant decreases in the total IPSS scores (p = 0.002), irritative subscore (p = 0.039), QoL (p = 0.001), flank pain (p = 0.013), voiding pain (p = 0.01) and amount of analgesics used (p = 0.02) in the groups. However, neither the obstructive subscore nor the suprapubic pain improved significantly (p = 0.251 and p = 0.522, respectively). The patients receiving terazosin plus tolterodine experienced significant reductions in the total IPSS, irritative symptoms, QoL, flank pain, voiding pain and decreased analgesics use compared with those patients receiving placebo. However, compared with placebo, terazosin monotherapy did not affect pain levels, and tolterodine monotherapy did not improve QoL, flank pain or analgesics use. Conclusions Terazosin plus tolterodine improves ureteral stent-related complications, including irritative symptoms, the amount of analgesics used, QoL, flank pain and voiding pain but does not decrease obstructive symptoms or suprapubic pain. This trial was registered at www.clinicaltrials.gov as NCT01530243. .

Efficacy and safety of propiverine and terazosine combination for one year in male patients with luts and detrusor overactivity

Purpose To evaluate the long term efficacy and safety of the use of propiverine and terazosine combination in patients with LUTS and DO by a placebo controlled study. Materials and Methods One hundred patients were enrolled in the study. They were randomized into two groups (each group consisted of 50 patients). Terazosine and placebo were administered to the patients in Group 1 and terazosine plus propiverine HCL was administered to Group 2. The patients were evaluated by international prostate symptom score (IPSS), the first four questions of IPSS (IPSS4), the 8th question of IPSS (quality of life-QoL), overactive bladder symptom score questionnaire (OAB-q V8), PSA test, urodynamic studies, post voiding residue (PVR). All patients were followed for one year and were reassessed for comparison. Results IPSS, IPSS4, OAB symptoms, QoL score, PVR, and Qmax scores of the groups did not differ. After one year treatment, there was significant improvement in IPSS, IPSS4, OAB symptoms, QoL and Qmax values in Group 2. No significant improvement was noted for the same parameters in Group 1. Conclusion This is the first study to show long term safety and efficacy of anticholinergic therapy for patients with LUTS. In patients with OAB or DO, long term anticholinergic treatment may be regarded as a treatment option. .

Prazosina de liberação lenta para pacientes com transtorno do estresse pós-traumático resistentes aos ISRS / Slow-release prazosin for SSRI-resistant posttraumatic stress disorder patients

CONTEXTO: Prazosina, um antagonista de receptores alfa-1 adrenérgicos, é utilizada no tratamento de pesadelos e insônia relacionados com TEPT. Apesar das evidências sugerindo sua eficácia também no tratamento de sintomas gerais de TEPT, sua curta meia-vida (2-3 horas) pode limitar seus efeitos terapêuticos.OBJETIVO: Descrever quatro casos de pacientes com TEPT resistentes aos inibidores de recaptação de serotonina ou de serotonina e adrenalina (terapia convencional) tratados com uma apresentação de prazosina de liberação lenta.MÉTODOS: Quatro pacientes com TEPT grave, resistentes à terapia convencional, tiveram a prazosina de liberação lenta (meia-vida de 10,8 horas) adicionada as suas prescrições por pelo menos três meses. Os sintomas de TEPT foram avaliados pela PCL-C e pelos itens referentes a pesadelos e insônia da CAPS, na linha de base e no final do período de observação de cada paciente.RESULTADOS: Dois pacientes mostraram melhora dos sintomas gerais de TEPT (redução de 35,7% e 11,9% nos escores da PCL-C), e três mostraram melhora de pesadelos e insônia (nos escores da CAPS). O único paciente que recebeu doses da prazosina pela manhã e ao deitar-se foi o que mostrou a maior melhora dos sintomas gerais de TEPT.CONCLUSÃO: Possivelmente, a sustentação do bloqueio da atividade noradrenérgica no sistema nervoso central promovida pela prazosina de liberação lenta durante o dia se faz necessária para a melhora de sintomas residuais de TEPT em pacientes em tratamento convencional com antidepressivos.

BACKGROUND: Prazosin is an antagonist of alpha-1 adrenergic receptor used to treat PTSD-related nightmares and insomnia. Although evidence suggests that it is also effective in the treatment of general symptoms of PTSD, its short half-life (2-3 hours) may limit its therapeutic effects.OBJECTIVE: To describe four cases of patients with PTSD resistant to selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/noradrenaline reuptake inhibitor (SNRIs) therapy (conventional therapy) treated with slow-release prazosin presentation.METHODS: Four patients with severe PTSD resistant to conventional therapy received slow-release prazosin (half-life of 10.8 hours) added to their prescription for at least three months. PTSD symptoms were evaluated by the PCL-C, together with nightmares and insomnia items of CAPS, at baseline and at the last observation of each patient.RESULTS: Two patients showed improvement in general symptoms of PTSD (reduction of 35.7% and 11.9% in PCL-C scores), and three showed relief from nightmares and insomnia (CAPS scores). The only patient who received morning and bedtime doses of prazosin showed the greatest improvement in general symptoms of PTSD.DISCUSSION: It is possible that the sustained blockade of noradrenergic activity in the central nervous system provided by slow-release prazosin during the day is necessary to further ameliorate residual PTSD symptoms in patients receiving conventional antidepressant therapy.

Efficacy of three different alpha 1-adrenergic blockers and hyoscine N-butylbromide for distal ureteral stones

PURPOSE: To evaluate hyoscine N-butyl bromide (HBB) and three different alpha-1 blockers in the treatment of distal ureteral stones. MATERIALS AND METHODS: A total of 140 patients with stones located in the distal tract of the ureter with stone diameters of 5 to 10mm were enrolled in the present study and were randomized into 4 equal groups. Group 1 received HBB, Group 2 received alfuzosin, Group 3 received doxazosin and Group 4 received terazosin. The subjects were prescribed diclofenac injection (75 mg) intramuscularly on demand for pain relief and were followed-up after two weeks with x-rays of the kidneys, ureters, bladder and urinary ultrasonography every week. The number of pain episodes, analgesic dosage and the number of days of spontaneous passage of the calculi through the ureter were also recorded. RESULTS: The average stone size for groups 1, 2, 3 and 4 was comparable (6.13, 5.83, 5.59 and 5.48 mm respectively). Stone expulsion was observed in 11 percent, 52.9 percent, 62 percent, and 46 percent in groups 1, 2, 3 and 4 respectively. The average time to expulsion was 10.55 ± 6.21 days in group 1, 7.38 ± 5.55 days in group 2, 7.85 ± 5.11 days in group 3 and 7.45 ± 5.32 days in group 4. Alpha blockers were found to be superior to HBB (p < 0.05). CONCLUSIONS: Medical treatment of distal ureteral calculi with alfuzosin, doxazosin and terazosin resulted in a signi?cantly increased stone-expulsion rate and decreased expulsion time when compared with HBB. HBB seems to have a negative effect on stone-expulsion rate.

Pheochromocytoma in children and adolescents.

Eleven subjects aged <20 yr with histologically proven pheochromocytoma between 1987 and 2006 were analyzed. Family history was present in 18%. In 2 patients, pheochromocytoma was part of VHL and in one it was associated with MEN 2. Twenty four hour urine VMA level was elevated in 100% and metanephrine level in 73%. CT/ MRI were showing the tumor in all. Prazosin extended release tablets (maximum 30 mg/day) were used in 73% and doxazosin (maximum 12 mg/ day) in 27%. Intraoperative BP fluctuations were seen in 27%. All were biochemically cured after surgery. Preoperative á blockade with extended release prazosin and doxazosin were effective in controlling perioperative BP fluctuations. Hence these drugs can be used in children and adolescents without fear of postoperative hypotension.

Antipsicóticos, anticonvulsivantes, antiadrenérgicos e outras drogas: o que fazer quando o transtorno do estresse pós-traumático não responde aos inibidores seletivos da recaptação da serotonina? / Antipsychotics, anticonvulsants, antiadrenergics and other drugs: what to do when posttraumatic stress disorder does not respond to selective serotonin reuptake inhibitors?

OBJETIVOS: Nesta revisão narrativa, o objetivo foi descrever as opções farmacológicas para o tratamento do transtorno de estresse pós-traumático nos casos de intolerância, resistência, refratariedade ou impossibilidade de utilizar antidepressivos, especialmente inibidores seletivos da recaptação da serotonina. MÉTODO: Consulta às bases de dados ISI Web of Science e PubMed em busca de estudos originais sobre o tratamento farmacológico do transtorno de estresse pós-traumático em diferentes cenários clínicos. RESULTADOS: Evidências preliminares apontam para a utilidade de drogas como a risperidona, a olanzapina, a lamotrigina e o prazosin como estratégias para o cenário clínico em tela. A escolha do medicamento de segunda linha deve levar em conta não só os sintomas, como também as comorbidades, os tratamentos prévios, as interações farmacológicas, os efeitos colaterais e as condições físicas do paciente. CONCLUSÕES: Futuros ensaios clínicos randomizados ainda são necessários para estabelecer com clareza alternativas farmacológicas aos antidepressivos para o tratamento do transtorno de estresse pós-traumático.

OBJECTIVES: In this narrative review, we aimed to describe different pharmacological strategies for the treatment of patients with post-traumatic stress disorder who display different levels of intolerance, resistance, refractoriness, or who are unable to take to antidepressants, especially serotonin reuptake inhibitors. METHOD: We searched the ISI web of science and the PubMed for original studies focusing in the treatment of PTSD in different clinical scenarios. RESULTS: Preliminary evidence pointed towards the efficacy of drugs such as risperidone, olanzapine, lamotrigine and prazosin as strategies to be employed in the above mentioned clinical scenarios. The choice of a specific "second line" drug should take into account not only symptoms, but also pattern of comorbidities, previous response to other treatments, pharmacological interactions, side-effects, and patient's physical conditions. CONCLUSIONS: Future randomized controlled trials should be performed in order to unveil which drugs should be prescribed in the absence of adequate treatment and response to serotonin reuptake inhibitors.

Utility of scorpion antivenin vs prazosin in the management of severe Mesobuthus tamulus (Indian red scorpion) envenoming at rural setting.

BACKGROUND : Scorpion antivenom (SAV) is specific antidote to scorpion venom..SAV did not prevent the cardiovascular morbidity and mortality (autonomic storm), hence its utility in the management for severe scorpion envenomingmay be limited. Since 1983 the advent of prazosin revolutionized the management of severe scorpion sting. Since 2002 SAV against Indian red scorpion (IRS) for the treatment of scorpion sting cases is available at primary health centers. We compared the effects of SAV Vs Prazosin (PRA) in the management of severe scorpion stung cases at rural setting in a non-randomised open label manner. METHODS : From January 2002 to December 2004, 53 patients accidentally stung by scorpion were admitted in hospital at Mahad. Of these 25 patients received intravenous SAV at primary health centers and were referred to Mahad for further management. 28 patients directly reported to Mahad were treated with oral prazosin (PRA). Time interval between sting and hospitalization, the total dose of SAV and PRA administered was noted. Clinical manifestations were noted in a standard protocol. Details of SAV patients were noted from referred letters or in case of a doubt, details were obtained by direct communication with the medical officer who first saw and examined the case. All 53 cases were evaluated clinically for improvement, deterioration or fatal outcome. RESULTS : SAV Vs PRA ( 25 Vs 28) cases reported to hospital within 11/2 -3 (1.4) Vs 1/2-4 (1.3) hours after stung. On arrival 21 (84%) Vs 26 (92%) had hypertension, 2 (8%) Vs 1 (3.5%) had hypotension, 2 (8%)Vs 1 (3.5%) had normal blood pressure. Heart rate 58-102 (82) Vs 48-120 (80.2) respectively. 9 cases received 20 ml, 1 case 30 ml and remaining 15 cases were given 10 ML of SAV on arrival to PHC, while 28 cases received oral prazosin. 20 (80%) Vs 2 (7.5%) had acute pulmonary edema, 5 (20%) Vs 8 (30%) had persistent raised blood pressure. 4 (16%) Vs 0% died. Recovery time was 11-4 (2.26) Vs 1-2 (1.25) days respectively. CONCLUSION : We found that SAV is no more effective to alleviate or reverse the cardiovascular effects of scorpion venom actions in severe case as against prazosin prevents and cures the cardiovascular manifestations in a severe scorpion envenomation. Therefore role of SAV in severe scorpoin venomation needs to be relooked and prazosin needs to be a standard of care in such cases to overcome the autonomic storm.

The use and rationale of selective alpha blockade in children with non-neurogenic neurogenic bladder dysfunction

INTRODUCTION: We present here a long-term observation of 2 children with a rare syndrome with a non-neurogenic neurogenic bladder dysfunction (Hinman's syndrome), and we investigated the safety and efficacy of long-term use of terazosine in association with prophylactic antibiotics, timed voiding and a bowel regimen. MATERIALS AND METHODS: Two children, 7 years-old (22 kg) and 11 years-old (36 kg) presented in 1997 to our pediatric urology clinic with symptoms of urgency, frequency, urge incontinence and nocturnal enuresis. Both children were placed in a regimen of terazosine (starting with 0.5 mg increasing until 2 mg). RESULTS: There were no significant side effects throughout the entire treatment. The first 7-year old boy however developed some dizziness when the dose of terazosine was increased to 2 mg (after 4 weeks of administrating 1 mg), and this disappeared immediately when the dosage was reduced back to 1 mg daily. The urgency symptoms improved in both boys after 3 weeks of 1 mg terazosine. The secondary enuresis in the 11 year-old boy resolved after 2 months of 2 mg terazosine. CONCLUSION: It is possible to say that the alpha-blocker medication, terazosine can be administered safely to children with a non-neurogenic bladder dysfunction, also known as the Hinman's syndrome. These results have shown that dysfunctional voiding, postvoiding residual and upper tract involvement can disappear over time when long term terazosine is given in combination with timed voiding, prophylactic antibiotic therapy and treatment of the associated constipation. Our observations also suggest a permanent effect after discontinuing the medication.

Tratamiento de la hiperplasia prostática benigna / Treatment of benign prostatic hyperplasia

En el campo de la Urología, una de las causas més frecuentes de consulta la constituye la patología prostática y dentro de ésta, la hiperplasia benigna de la próstata. Esta consiste en un incremento de células en el área periuretral prostática, lo que puede ser debido a una proliferación celular aumentada, a una alteración de la apoptosis, o a una combinación de ambos mecanismos. Entre las principales opciones terapÚuticas actuales para la hiperplasia prostática benigna están: - Tratamiento quirúrgico, que continua siendo la principal alternativa de terapia, representado principalmente por la resección transuretral. Tratamiento farmacológico, utilizado como alternativa y/o complemento a la cirugía y representado por dos grandes grupos de fármacos: los antagonistas adrenÚrgicos y la terapia endocronológica (finasteride). El presente trabajo es una revisión bibliográfica actualizada sobre las distintas opciones de tratamiento disponibles para la hiperplasia prostática benigna y sus respectivas indicaciones.

Management of men with a first episode of acute urinary retention due to benign prostatic enlargement.

OBJECTIVE: To determine the effect of the existing management protocol of patients presenting with acute urinary retention due to benign prostatic enlargement on clinical efficacy and surgical practice. DESIGN: Prospective study. SETTING: The Urology Unit at the Teaching Hospital, Karapitiya, Galle. PATIENTS: 100 consecutive patients with a first episode of acute urinary retention due to a clinically benign enlarged prostate. MEASUREMENTS: Success of voiding urine after one week of treatment with an alpha adrenoceptor blocker (prazosin). Incidence of subsequent urinary retention during the follow up period of 6 months despite continuing treatment with the drug. RESULTS: Of the 94 patients who completed the follow up period of 6 months, 56 voided successfully after the initial trial without catheter at one week. However, 12 of them developed urinary retention during the follow up and required surgery. CONCLUSION: Treatment with an alpha adrenoceptor blocker followed by a single trial without catheter can avoid prostatic surgery in 40% of patients with acute urinary retention due to benign prostatic enlargement.

Prazosin therapy and scorpion envenomation.

BACKGROUND: 25-30% fatality due to acute pulmonary oedema in victims of Indian red scorpion (Mesobuthus tamulus) sting have been reported from Western Maharashtra, India. The advent of prazosin in recent years has revolutionized the management of severe scorpion sting cases. Majority of cases developed acute pulmonary oedema in 4-8 hours in a hospital setting irrespective of control of their arterial blood pressure with six hourly oral prazosin regimen, these cases recovered with extra dose of prazosin. We developed a standardised protocol for acute phase of treatment of these cases with the aim of preventing the development of pulmonary oedema. METHOD: We compared scorpion sting cases managed by non-protocol conventional (NPC) treatment and those by standardised protocol (SP) that included three hourly dose of oral prazosin. SP group included severe scorpion sting cases admitted to general hospital at Mahad in the year 1998 (Jan.-Dec.). While those admitted in the year 1997 (Jan.-Dec.) before the SP was implicated were the NPC group. FINDING: Characteristics on arrival of severe scorpion sting patients SP (n-17) and NPC (n-15) groups were similar that more case 6 (35%) from SP group had several hypertension on arrival. On arrival two cases from SP group and one from NPC group had pulmonary oedema. 16 (94.11%) patients from SP group recovered uneventfully, compared with 8 (53.33%) in NPC group (p-0.05). 0% Vs 5 (38.46%) developed acute pulmonary oedema (p < 0.0001) from SP and NPC group respectively, three (one had on arrival two patients during hospitalization) from NPC group had massive pulmonary oedema recovered with i.v. nitroprusside drip (SNP). While from SP group one had massive pulmonary oedema on arrival recovered with i.v. SNP, other one had pulmonary oedema recovered with oral prazosin. Cool extremities (vasoconstriction) persisted 11.5 (5-20) VS 18 (12-26) hours in SP and NPC group respectively. INTERPRETATION: Compared with NPC management; development of acute pulmonary oedema prevented by standardised protocol regimen at rural setting.

Indian red scorpion envenoming.

The clinical course and treatment outcome of scorpion envenoming in 293 children was studied in a hospital at Mahad in Raigad district of Maharastra. 111 (38%) children who reported 1-10 hours (mean 3.5 hours) after sting had hypertension, 87 (29.6%) with tachycardia reported within 1-24 hours (mean 6.7 hours) of being envenomed and 72 (24.5%) children developed acute pulmonary edema after 6-24 hours (mean 8 hours) of sting. Six victims were brought dead, while 17 (6%) died later owing to multiorgan failure with loss of consciousness and convulsions (who reported after 24 hours of sting). Early administration of prazosin (125-250 ug orally) improved the clinical symptoms. Morbidity and mortality due to scorpion envenoming depends upon time lapse between sting and administration of post synaptic alpha-1 blocker, prazosin hydrochloride.

Tratamiento médico de la hiperplasia prostática con prazosin en pacientes hipertensos complicados / Medical treatment of the prostatic hiperplasia with prazosin in patients hypertension complicated

En el presente estudio se procedió a valorar la respuesta sobre los síntomas de obstrución urinaria baja con un bloqueador adrenérgico alfa*-1 Post-sináptico (Prazosin); para ello se seleccionaron 18 pacientes con diagnóstico clínico, radiológico y urodinámico de hiperplasia prostático benigna (HPB), asociada a hiperplasia arterial complicada en quienes el riesgo operatorio estaba incrementado