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1.
Article in English | IMSEAR | ID: sea-162163

ABSTRACT

In Fontan patients, reduced exercise capacity due to diminished cardiac output is a common finding with important prognostic implications. Beneficial effects have been shown for sildenafil treatment and regular exercise, but data comparing both strategies is scarce. We report on a female patient with Fontan circulation who underwent repeated cardiopulmonary exercise tests with either placebo or a single dose of 50mg sildenafil before and after 6months of supervised aerobic and resistance exercise. At baseline, V O2peak was 29.1ml/min/kg, and a marked increase to 32.8ml/min/kg was observed after administration of sildenafil. After the training period, V O2peak was 34.5ml/kg/min in the placebo test, and no further increase by sildenafil was possible (33.7ml/kg/min). Similar results were observed for exercise capacity at the ventilatory anaerobic threshold. In summary, this Fontan patient showed that regular exercise might use up and probably exceed the acute sildenafil effects on exercise capacity. Exercise should be considered as a primary treatment strategy within secondary prevention and rehabilitation after the Fontan procedure.


Subject(s)
Exercise Tolerance/drug effects , Female , Fontan Procedure/methods , Heart Defects, Congenital/drug therapy , Heart Defects, Congenital/epidemiology , Heart Defects, Congenital/rehabilitation , Heart Defects, Congenital/surgery , Heart Ventricles/abnormalities , Heart Ventricles/surgery , Humans , Piperazines/administration & dosage , Purines/administration & dosage , Sulfonamides/administration & dosage , Young Adult
2.
Int. braz. j. urol ; 40(3): 373-378, may-jun/2014. tab
Article in English | LILACS | ID: lil-718250

ABSTRACT

Objective To compare the safety and efficacy of combined therapy using sildenafil and tamsulosin for management of acute urinary retention (AUR) with tamsulosin alone in patients with benign prostate hyperplasia (BPH). Materials and Methods 101 patients were enrolled in a randomized placebo-controlled study from June 2009 to April 2012. Patients presenting with an initial episode of spontaneous AUR underwent urethral catheterization and then prospectively randomized to receive tamsulosin 0.4mg plus sildenafil 50mg in group A and tamsulosin 0.4mg plus placebo in group B for three days. Urethral catheter was removed three days after medical treatment and patient’s ability to void assessed at the day after catheter removal and seven days later. Patients who voided successfully were followed at least for three months. Results Mean age of patients was 59.64 ± 3.84 years in group A and 60.56 ± 4.12 years in group B (p value = 0.92). Mean prostate volume and mean residual urine were comparable between both groups (p value = 0.74 and 0.42, respectively). Fifteen patients in group A (success rate: 70%) and nineteen patients in group B (success rate: 62.7%) had failed trial without catheter (TWOC) at 7th day following AUR (p value = 0.3). No significant difference was noted between both groups regarding the rate of repeated AUR at one month and three month follow-up period (p = 0.07 and p = 0.45, respectively). Conclusion It seems that combination therapy by using 5-phosphodiesterase inhibitor and tamsulosin has no significant advantages to improve urinary retention versus tamsulosin alone. .


Subject(s)
Humans , Male , Middle Aged , Adrenergic alpha-1 Receptor Antagonists/administration & dosage , /administration & dosage , Piperazines/administration & dosage , Prostatic Hyperplasia/drug therapy , Sulfonamides/administration & dosage , Sulfones/administration & dosage , Urinary Retention/drug therapy , Acute Disease , Analysis of Variance , Drug Synergism , Drug Therapy, Combination , Lower Urinary Tract Symptoms/physiopathology , Prostatic Hyperplasia/physiopathology , Purines/administration & dosage , Time Factors , Treatment Outcome , Urinary Catheterization , Urinary Catheters , Urinary Retention/physiopathology
3.
Indian J Biochem Biophys ; 2013 Jun; 50(3): 215-220
Article in English | IMSEAR | ID: sea-147305

ABSTRACT

The aim of the present study was to investigate serum homocysteine levels in patients with erectile dysfunction and to evaluate the relationship between serum homocysteine levels and response to the standard 50 mg phosphodiesterase 5 inhibitor treatment. Twenty-eight erectile dysfunction patients having normal vascular parameter according to Penile Doppler Ultrasonography and twenty healthy subjects were enrolled in the study. All subjects filled The International Index of Erectile Function (IIEF) questionnaire. A total of 4-6 doses of phosphodiesterase 5 inhibitor (sildenafil 50 mg) were given to patients. Later, they were divided into two groups as sildenafil responder and non-responder. Serum homocysteine levels were compared in groups based on sildenafil response. Compared with healthy subject, higher homocysteine levels were observed in patients with erectile dysfunction (p = 0.005), especially in sildenafil non-responder group (p = 0.005). There was significant negative correlation between homocysteine and IIEF scores in group responder to sildenafil treatment (r = -0.698, p = 0.008). Mean IIEF scores of patients with non-responder to sildenafil 50 mg were lower than those of controls (p = 0.0001), but mean IIEF scores of patients with responders approached values observed in control subjects (p = 0.002). The results indicated that measurement of serum homocysteine levels could be used as a marker for the evaluation of efficacy of phosphodiesterase 5 inhibitor and the selection of efficacious alternative therapies.


Subject(s)
Adult , Biomarkers/blood , Erectile Dysfunction/blood , Erectile Dysfunction/drug therapy , Homocysteine/blood , Humans , Male , Middle Aged , Outcome Assessment, Health Care/methods , Phosphodiesterase 5 Inhibitors/administration & dosage , Piperazines/administration & dosage , Purines/administration & dosage , Reproducibility of Results , Sensitivity and Specificity , Sulfones/administration & dosage , Treatment Outcome , Vasodilator Agents/administration & dosage
4.
Int. braz. j. urol ; 39(2): 268-275, Mar-Apr/2013. tab, graf
Article in English | LILACS | ID: lil-676268

ABSTRACT

Purpose Recently, the effect of phosphodiesterase inhibitors (PDE5i) in the lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia have been studied thoroughly. However, it remains unclear how the PDE5i improve LUTS. Therefore, the aim of the present study was to evaluate the potential of acute administration of the PDE5i sildenafil to improve detrusor overactivity (DO) induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), an nitric oxide sinthase (NOS) inhibitor, in rats. Materials and Methods Twenty-seven MALE adult Wistar Rats were divided into the following groups: (1) control, (2) L-NAME, (3) sildenafil alone, and (4) L-NAME + sildenafil. The NOS blocker L-NAME (20 mg/rat/day) was given in the drinking water. Sildenafil (100µg/kg) was administrated intravenously (i.v.) acutely, diluted in cremophor, propylene glycol and water. All animals underwent to anesthetized cystometograms. Results The chronic and systemic administration of L-NAME markedly increased the number of non voiding contractions (2.62 (± 0.89)), and frequency of micturition (1.97 (± 0.78)), as well increased volume threshold (2.83 mL (± 1.64)) compared with control group, the number of non voiding contractions (1.17 (± 0.75)), frequency of micturition (1.08 (± 0.65)) and volume threshold (1.16 mL (± 0.38)), p < 0.001, p = 0.01, and p = 0.04, respectively. Sildenafil infusion decreased the number of micturition cycles significantly from the baseline to end point (-0.93 (± 0.34)) in nitric oxide (NO) deficient animals compared with sildenafil infusion alone (control) in animals with normal NO level (0.13 (± 0.25)), p = 0.03. Conclusion Systemic reduction of nitric oxide causes detrusor overactivity and acute infusion of sildenafil reduces the number of micturition cycles in chronic NO-deficient rats. .


Subject(s)
Animals , Male , Rats , Nitric Oxide/deficiency , Phosphodiesterase Inhibitors/administration & dosage , Piperazines/administration & dosage , Sulfones/administration & dosage , Urinary Bladder, Overactive/drug therapy , NG-Nitroarginine Methyl Ester/administration & dosage , Nitric Oxide Synthase/antagonists & inhibitors , Phosphodiesterase Inhibitors/pharmacology , Piperazines/pharmacology , Purines/administration & dosage , Purines/pharmacology , Random Allocation , Rats, Wistar , Sulfones/pharmacology , Urinary Bladder, Overactive/etiology , Urination/drug effects
5.
Braz. j. med. biol. res ; 44(8): 778-785, Aug. 2011. ilus, tab
Article in English | LILACS | ID: lil-595713

ABSTRACT

Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration) on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica) aged 12 to 72 h (1660 ± 192 g) received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT). Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57 percent, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.


Subject(s)
Animals , Humans , Infant, Newborn , Male , Extravascular Lung Water/drug effects , Hypertension, Pulmonary/prevention & control , Meconium Aspiration Syndrome/drug therapy , Piperazines/administration & dosage , Sulfones/administration & dosage , Vasodilator Agents/therapeutic use , Animals, Newborn , Disease Models, Animal , Lung/drug effects , Lung/pathology , Meconium Aspiration Syndrome/pathology , Purines/administration & dosage , Sus scrofa , Time Factors , Thermodilution/methods
6.
Arq. bras. cardiol ; 97(1): e8-e10, jul. 2011. ilus, tab
Article in Portuguese | LILACS | ID: lil-597674

ABSTRACT

Um homem de 33 anos com hipertensão arterial pulmonar hereditária teve um diagnóstico confirmado de venopatia oclusiva e microvasculopatia. O paciente permaneceu estável por 3 anos e meio recebendo sildenafila via oral, 75 mg 3x/dia (teste de caminhada de seis minutos de 375 m vs 105 m basal), mas necessitou da adição de bosentana (125 mg 2x/dia) posteriormente. A despeito do desfecho fatal após 5 anos, as observações sugerem um utilidade potencial dos vasodilatadores como uma ponte para o transplante de pulmão em casos selecionados com envolvimento venocapilar significante. A ocorrência de lesões veno-oclusivas e capilares na forma familiar da hipertensão arterial pulmonar enfatiza as dificuldades com a atual classificação da doença.


A 33-year-old male with severe hereditary pulmonary arterial hypertension had a confirmed diagnosis of occlusive venopathy and microvasculopathy. He remained stable for three and a half years on oral sildenafil, 75 mg t.i.d. (six-minute walked distance of 375 m vs 105 m at baseline), but required addition of bosentan (125 mg b.i.d.), subsequently. Despite the fatal outcome at five years post-diagnosis, the observations suggest a potential usefulness of vasodilators as a bridge for lung transplant in selected cases with significant venous/capillary involvement. The occurrence of veno-occlusive and capillary lesions in the familial form of pulmonary arterial hypertension reinforces the difficulties with the current classification of the disease.


Un hombre de 33 años con hipertensión arterial pulmonar hereditaria tuvo un diagnóstico confirmado de venopatía oclusiva y microvasculopatía. El paciente permaneció estable 3,5 años recibiendo sildenafila vía oral, 75mg 3x/ día (test de caminata de seis minutos de 375m vs. 105m basal), pero necesitó adición de bosentánana (125mg 2x/día) posteriormente. A despecho del desenlace fatal después de 5 años, las observaciones sugieren una utilidad potencial de los vasodilatadores como un puente para el transplante de pulmón en casos seleccionados con compromiso venocapilar significativo. La ocurrencia de lesiones veno-oclusivas y capilares en la forma familiar de la hipertensión arterial pulmonar enfatiza las dificultades con la actual clasificación de la enfermedad.


Subject(s)
Adult , Humans , Male , Hypertension, Pulmonary/pathology , Lung/pathology , Pulmonary Veno-Occlusive Disease/pathology , Biopsy , Fatal Outcome , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/genetics , Phenotype , Piperazines/administration & dosage , Purines/administration & dosage , Sulfones/administration & dosage , Vasodilator Agents/administration & dosage
7.
Clinics ; 66(1): 137-142, 2011. ilus, tab
Article in English | LILACS | ID: lil-578610

ABSTRACT

OBJECTIVES: This study was designed to investigate prevention of contralateral testicular injury with sildenafil citrate after unilateral testicular torsion/detorsion. METHODS: Thirty-seven adult male rats were divided into four groups: sham operated (group 1, n = 7), torsion/detorsion + saline (group 2, n = 10), torsion/detorsion + 0.7 mg of sildenafil citrate (group 3, n = 10) and torsion/detorsion + 1.4 mg of sildenafil citrate (group 4, n = 10). Unilateral testicular torsion was created by rotating the right testis 720º in a clockwise direction for 2 h in other groups, except for group 1, which was served as sham group. After torsion (2 h) and detorsion (2 h) periods, rats were killed. RESULTS: The level of reduced glutathion (GSH) (p<0.05) and the activities of catalase (p<0.01) and glutathione peroxidase (p<0.05) in the contralateral testis from group 2 were significantly lower and nitric oxide (NO) (p<0.05) level in the contralateral testis were significantly higher than those of group 1. Administration of low-dose sildenafil citrate (group 3) prevented the increases in malondialdehyde and NO levels and decreases in glutathione peroxidase activities and GSH values induced by testicular torsion. However, administration of high-dose sildenafil citrate (group 4) had no effect on these testicular parameters (p>0.05). Histopathological changes were detected in groups 2, 3 and 4. CONCLUSION: These results suggest that biochemically and histologically torsion/detorsion injury occurs in the contralateral testis following 2-h torsion and 2-h detorsion and that administration of low-dose sildenafil citrate before detorsion prevents ischemia/reperfusion cellular damage in testicular tissue.


Subject(s)
Animals , Male , Rats , /administration & dosage , Piperazines/administration & dosage , Reperfusion Injury/prevention & control , Spermatic Cord Torsion/prevention & control , Sulfones/administration & dosage , Testis/injuries , Catalase/analysis , Lipid Peroxidation , Malondialdehyde/analysis , Nitric Oxide/analysis , Protective Agents/administration & dosage , Purines/administration & dosage , Rats, Wistar , Testis/blood supply , Testis/pathology
8.
Clinics ; 66(8): 1407-1412, 2011. ilus, tab
Article in English | LILACS | ID: lil-598396

ABSTRACT

INTRODUCTION: Results from our laboratory have demonstrated that intracerebroventricular administration of sildenafil to conscious rats promoted a noticeable increase in both lumbar sympathetic activity and heart rate, with no change in the mean arterial pressure. The intracerebroventricular administration of sildenafil may have produced the hemodynamic effects by activating sympathetic preganglionic neurons in the supraspinal regions and spinal cord. It is well documented that sildenafil increases intracellular cGMP levels by inhibiting phosphodiesterase type 5 and increases cAMP levels by inhibiting other phosphodiesterases. OBJECTIVE: To examine and compare, in conscious rats, the hemodynamic response following the intrathecal administration of sildenafil, 8-bromo-cGMP (an analog of cGMP), forskolin (an activator of adenylate cyclase), or dibutyryl-cAMP (an analog of cAMP) in order to elucidate the possible role of the sympathetic preganglionic neurons in the observed hemodynamic response. RESULTS: The hemodynamic responses observed following intrathecal administration of the studied drugs demonstrated the following: 1) sildenafil increased the mean arterial pressure and heart rate in a dose-dependent manner, 2) increasing doses of 8-bromo-cGMP did not alter the mean arterial pressure and heart rate, 3) forskolin did not affect the mean arterial pressure but did increase the heart rate and 4) dibutyryl-cAMP increased the mean arterial pressure and heart rate, similar to the effect observed following the intrathecal injection of the highest dose of sildenafil. CONCLUSION: Overall, the findings of the current study suggest that the cardiovascular response following the intrathecal administration of sildenafil to conscious rats involves the inhibition of phosphodiesterases other than phosphodiesterase type 5 that increase the cAMP level and the activation of sympathetic preganglionic neurons.


Subject(s)
Animals , Male , Rats , Blood Pressure/drug effects , Bucladesine/pharmacology , Cyclic GMP/analogs & derivatives , Colforsin/administration & dosage , Heart Rate/drug effects , Piperazines/administration & dosage , Sulfones/administration & dosage , Vasodilator Agents/administration & dosage , Bucladesine/administration & dosage , Cyclic GMP/administration & dosage , Injections, Spinal , Purines/administration & dosage , Rats, Wistar
9.
Arq. bras. cardiol ; 92(2): 122-126, fev. 2009. graf, tab
Article in Portuguese | LILACS | ID: lil-511103

ABSTRACT

FUNDAMENTO: A hipertensão pulmonar (HP) é fator de mau prognóstico no pós-operatório de transplante cardíaco (TC) e, desta forma, o estudo do grau de reversibilidade a vasodilatadores é obrigatório durante avaliação pré-operatória. OBJETIVO: Avaliar os efeitos hemodinâmicos pulmonares e sistêmicos do sildenafil como droga vasodilatadora durante o teste de reversibilidade da HP em candidatos a transplante cardíaco. MÉTODOS: Pacientes em fila para TC foram submetidos à medida de variáveis hemodinâmicas sistêmicas e pulmonares antes e após a administração de 100mg dose única e sublingual de sildenafil, durante cateterização cardíaca direita. RESULTADOS: Quatorze pacientes (idade: 47±12 anos, 71,4 por cento homens) com insuficiência cardíaca avançada, Fração de Ejeção (FE) 25 ± 7 por cento, Classe Funcional (CF- NYHA) CF III - 6 e CF IV - 8, foram avaliados neste estudo. A administração aguda de sildenafil mostrou ser eficaz na redução das pressões sistólica (62,4 ± 12,1 vs. 51,5 ± 9,6 mmHg, IC=95 por cento, p<0,05) e média (40,7 ± 7,3 vs. 33,8 ± 7,6 mmHg, IC=95 por cento, p <0,05) da artéria pulmonar. Houve também uma redução significativa da resistência vascular pulmonar (4,2 ± 3 vs. 2,0 ± 0,9 uWood, IC=95 por cento, p<0,05) e sistêmica (22,9 ± 6,8 vs. 18,6 ± 4,1 Wood, IC=95 por cento, p<0,05), associada a uma elevação do débito cardíaco (3,28 ± 0,79 vs. 4,12 ±1,12 uWood, IC=95 por cento, p<0,05) sem, no entanto, interferir de maneira significativa na pressão arterial sistêmica (87,8 ± 8,2 vs. 83,6 ± 9,1 mmHg, IC=95 por cento, p=0,3). CONCLUSÃO: O sildenafil sublingual é uma alternativa eficaz e segura como droga vasodilatadora durante o teste de reversibilidade da HP em portadores de insuficiência cardíaca e em fila para transplante cardíaco.


BACKGROUND: Pulmonary hypertension (PH) is a factor of poor prognosis in the postoperative period of heart transplant (HT) and thus, the study of the degree of reversibility to vasodilators is mandatory during the preoperative assessment. OBJECTIVE: To evaluate the pulmonary and systemic hemodynamic effects of sildenafil as a vasodilator during the PH reversibility test in patients that are candidates to HT. METHODS: Patients awaiting HT were submitted to the measurement of systemic and pulmonary hemodynamic variables before and after the administration of a single sublingual dose of 100 mg of sildenafil during right heart catheterization. RESULTS: Fourteen patients (age: 47±12 years, 71.4 percent men) with advanced heart failure Ejection Fraction (EF) 25 ± 7 percent, Functional Class (FC - NYHA) FC III - 6 and FC IV - 8, were evaluated in this study. The acute administration of sildenafil showed to be effective in decreasing the systolic (62.4 ± 12.1 vs 51.5 ± 9.6 mmHg, CI=95 percent, p<0.05) and mean (40.7 ± 7.3 vs 33.8 ± 7.6 mmHg, CI=95 percent, p <0.05) pressures of the pulmonary artery. There was also a significant decrease in the pulmonary (4.2 ± 3 vs 2.0 ± 0.9 uWood, CI=95 percent, p<0.05) and systemic vascular resistance (22.9 ± 6.8 vs 18.6 ± 4.1 Wood, CI=95 percent, p<0.05), associated to an increase in the cardiac output (3.28 ± 0.79 vs 4.12 ±1.12 uWood, CI=95 percent, p<0.05) without, however, significantly interfering in the systemic arterial pressure (87.8 ± 8.2 vs 83.6 ± 9.1 mmHg, CI=95 percent, p=0.3). CONCLUSION:The sublingual administration of sildenafil is an effective and safe alternative as a vasodilator during the PH reversibility test in patients with heart failure and awaiting a HT.


FUNDAMENTO: La hipertensión pulmonar (HP) se muestra factor de mal pronóstico en el postoperatorio de transplante cardiaco (TC) y, de esta forma, el estudio del grado de reversibilidad a vasodilatadores se vuelve obligatorio durante evaluación preoperatoria. OBJETIVO: Evaluar los efectos hemodinámicos pulmonares y sistémicos del Sildenafil como droga vasodilatadora durante la prueba de reversibilidad de la HP en candidatos a transplante cardiaco. MÉTODOS: Pacientes en fila para TC fueron sometidos a la medición de variables hemodinámicas sistémicas y pulmonares, antes y luego de la administración de 100mg en dosificación única y sublingual de Sildenafil, durante cateterización cardiaca derecha. RESULTADOS: Se evaluaron en este estudio a 14 pacientes (edad: 47±12 años, el 71,4 por ciento varones) con insuficiencia cardiaca avanzada, fracción de eyección (FE) 25 ± 7 por ciento, clase funcional (CF-NYHA) CF III - 6 y CF IV - 8. La administración aguda de Sildenafil se mostró eficaz en la reducción de las presiones sistólica (62,4 ± 12,1 vs 51,5 ± 9,6 mmHg, IC=95 por ciento, p<0,05) y media (40,7 ± 7,3 vs 33,8 ± 7,6 mmHg, IC=95 por ciento, p <0,05) de la arteria pulmonar. Hubo también una reducción significativa de la resistencia vascular pulmonar (4,2 ± 3 vs 2,0 ± 0,9 uWood, IC=95 por ciento, p<0,05) y sistémica (22,9 ± 6,8 vs 18,6 ± 4,1 Wood, IC=95 por ciento, p<0,05), asociada a una elevación del débito cardiaco (3,28 ± 0,79 vs 4,12 ±1,12 uWood, IC=95 por ciento, p<0,05) sin, con todo, interferir de manera significativa en la presión arterial sistémica (87,8 ± 8,2 vs 83,6 ± 9,1 mmHg, IC=95 por ciento, p=0,3). CONCLUSIÓN: El Sildenafil sublingual resulta una alternativa eficaz y segura como droga vasodilatadora durante la prueba de reversibilidad de la HP en portadores de insuficiencia cardiaca y en fila para transplante cardiaco.


Subject(s)
Female , Humans , Male , Middle Aged , Heart Failure , Hypertension, Pulmonary/drug therapy , Piperazines/administration & dosage , Sulfones/administration & dosage , Vasodilator Agents/administration & dosage , Administration, Sublingual , Heart Transplantation , Heart Failure/physiopathology , Heart Rate/drug effects , Hypertension, Pulmonary/physiopathology , Purines/administration & dosage
10.
Journal of Korean Medical Science ; : 1033-1038, 2008.
Article in English | WPRIM | ID: wpr-8810

ABSTRACT

The possible characteristics of spinal interaction between sildenafil (phosphodiesterase 5 inhibitor) and morphine on formalin-induced nociception in rats was examined. Then the role of the opioid receptor in the effect of sildenafil was further investigated. Catheters were inserted into the intrathecal space of male Sprague-Dawley rats. For induction of pain, 50 microliter of 5% formalin solution was applied to the hindpaw. Isobolographic analysis was used for the evaluation of drug interaction between sildenafil and morphine. Furthermore, naloxone was intrathecally given to verify the involvement of the opioid receptor in the antinociception of sildenafil. Both sildenafil and morphine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. The isobolographic analysis revealed an additive interaction after intrathecal delivery of the sildenafil-morphine mixture in both phases. Intrathecal naloxone reversed the antinociception of sildenafil in both phases. These results suggest that sildenafil, morphine, and the mixture of the two drugs are effective against acute pain and facilitated pain state at the spinal level. Thus, the spinal combination of sildenafil with morphine may be useful in the management of the same state. Furthermore, the opioid receptor is contributable to the antinocieptive mechanism of sildenafil at the spinal level.


Subject(s)
Animals , Male , Rats , Analgesics/administration & dosage , Analgesics, Opioid/administration & dosage , Behavior, Animal/drug effects , Dose-Response Relationship, Drug , Drug Synergism , Formaldehyde/toxicity , Injections, Spinal , Morphine/administration & dosage , Naloxone/administration & dosage , Narcotic Antagonists/administration & dosage , Pain/chemically induced , Pain Measurement/drug effects , Phosphodiesterase Inhibitors/administration & dosage , Piperazines/administration & dosage , Purines/administration & dosage , Rats, Sprague-Dawley , Sulfones/administration & dosage , Time Factors
11.
Indian Heart J ; 2007 Jul-Aug; 59(4): 342-5
Article in English | IMSEAR | ID: sea-2756

ABSTRACT

OBJECTIVE: The purpose of this study was to evaluate the effects of oral Sildenafil for treatment of pulmonary hypertension secondary to congenital heart diseases. METHODS & RESULTS: Twelve patients with un-repaired congenital heart diseases resulting in significant pulmonary hypertension were enrolled in a prospective trial of oral Sildenafil treatment for 12 weeks. The outcomes measured were change in the systemic oxygen saturations, 6-minute walk test distance, and New York Heart Association class. The systemic blood pressure and visual symptoms were monitored for evaluating the tolerability of Sildenafil. The mean age was 25.7+/-14.4 years. The mean pulmonary vascular resistance before treatment was 17.4 Wood units. After 12 weeks of sildenafil, an increase in oxygen saturations (87.8+/-5.3%-90.25+/-4%, p=0.04) with an associated increase of one New York Heart Association class (p=0.009) was noted. A non-statistically significant increase in the 6-minute walk test distance (310.33+/-42-333.75+/-54.6 meters, p=0.47) was also noted. Sildenafil was well-tolerated with no significant change in systemic blood pressure or visual side-effects. CONCLUSION: Oral Sildenafil is well-tolerated and produces some improvement in the oxygenation and functional status of patients with pulmonary hypertension secondary to congenital heart diseases.


Subject(s)
Administration, Oral , Adolescent , Adult , Child , Exercise Test , Female , Heart Defects, Congenital/complications , Humans , Hypertension, Pulmonary/drug therapy , Male , Middle Aged , Phosphodiesterase Inhibitors/administration & dosage , Piperazines/administration & dosage , Prospective Studies , Purines/administration & dosage , Sulfones/administration & dosage , Treatment Outcome
12.
Rev. chil. urol ; 72(2): 181-184, 2007. tab, graf
Article in Spanish | LILACS | ID: lil-545956

ABSTRACT

La disfunción eréctil es una patología de alta frecuencia, especialmente en población masculina de mayor edad. La erección está dada fundamentalmente por la activación del sistema parasimpático, por acción del óxido nítrico y aumento de GMP cíclico; es así como fármacos como Sildenafil que disminuyen la eliminación de GMP cíclico al inhibir la actividad de la 5 fosfodiesterasa, potencian la mantención de dicha erección. Recientemente se lanzó al mercado la presentación masticable de este fármaco, lo que eliminaría el primer paso hepático de la presentación oral clásica. En este estudio, se analizaron 20 pacientes con disfunción eréctil sin comorbilidad asociada, los que consumieron la forma masticable; con el objetivo de evaluar eficacia clínica y efectos adversos. Los resultados obtenidos muestran que existe un alto grado de satisfacción de usuario en cuanto a forma de presentación, tiempo de administración y eficacia, y que los efectos adversos no difieren a los de la presentación tradicional. Se propone realizar estudios prospectivos comparativos de ambas presentaciones y otros inhibidores de la 5 fosfodiesterasa, para confirmar estos resultados preliminares.


Erectil dysfunction is a very frequent pathology in the elderly male. Erections are activated mainly by the parasympathic system, caused by nitric oxide and the increase of cyclic cGMP; it is because of this that drugs like Sildenafil improve partial erections by inhibiting the enzyme that facilitates the reduction of cyclic guanosine monophosphate (cGMP). Recently a chewable new form of this drug entered the market,it is deemed to avoid hepatic transformation of the drug. In this study we analyzed 20 patients witherectile dysfunction without other associated comorbidities that were treated with this drug. Results showed that patients were highly satisfied with the form of presentation, the dosage regimen, and efficacy. Side effects are no different from the other and more traditional version. We will conduct prospective comparative studies of both versions of the drugs and other inhibitors of the cGMP specific phosphodiesterase type 5,to confirm these preliminary results.


Subject(s)
Humans , Male , Erectile Dysfunction/drug therapy , Phosphodiesterase Inhibitors/administration & dosage , Piperazines/administration & dosage , Purines/administration & dosage , Sulfones/administration & dosage , Administration, Oral , Prospective Studies , Phosphodiesterase Inhibitors/adverse effects , Data Collection , Patient Satisfaction
13.
Arq. bras. cardiol ; 76(6): 463-472, June 2001. ilus, tab
Article in Portuguese, English | LILACS | ID: lil-286364

ABSTRACT

OBJECTIVE: To evaluate the effects of diet and medication, either isolated or associated, on serum levels of uric acid in patients with hyperuricemia. METHODS: We studied patients from the Hypertension Unit of the University of Goias who had hyperuricemia (men > or = 8.5mg/dL and women > or = 7.5mg/dL). We divided the patients into three groups: G1 (low purine diet), G2 (low purine diet + medication), and G3 (medication only). Patients received allopurinol, 150mg/day titrated up to 300mg/dL when necessary. Patients were evaluated with regards to their lifestyles (diet, smoking, physical, activity, alcohol consumption), uric acid, blood pressure, use of medication, body mass index, cholesterol, and triglyceride. Follow-up took place in weeks 0 (M1), 6 (M2), 12 (M3) during the intervention and in week 36(M4) after the study was completed. RESULTS: Fifty-five patients participated in the study, 31 women, mean age 54.4 + or - 10.6 years, body mass index 28.6 + or - 3.9kg/m². A similar reduction (p<0.001) in uric acid levels occurred in the three intervention groups. In week 36 (M4), after 24 weeks without intervention, a tendency toward elevation of uricemia was noted in G2 and G3, and a continuous drop in uricemia was noted in G1. No significant modifications were observed in the other variables analyzed. CONCLUSION: Considering the cost x benefit relationship, a diet low in purine should be the 1st therapeutic option for controlling hyperuricemia in patients with similar characteristic to the ones presented in this study


Subject(s)
Humans , Male , Female , Middle Aged , Allopurinol/administration & dosage , Diet , Hypertension/physiopathology , Purines/administration & dosage , Uric Acid/blood , Cardiovascular Diseases/etiology , Energy Intake , Ethanol/adverse effects , Exercise , Follow-Up Studies , Hypertension/drug therapy , Risk Factors , Smoking/adverse effects , Sodium Chloride Symporter Inhibitors/therapeutic use , Treatment Outcome
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