Efficacy of tamsulosin versus tadalafil as medical expulsive therapy on stone expulsion in patients with distal ureteral stones: A randomized double-blind clinical trial

ABSTRACT Purpose: To compare the effects of tadalafil, tamsulosin, and placebo as a medical expulsive therapy (MET) for distal ureteral calculi. Materials and Methods: This prospective randomized double-blind clinical trial was conducted on 132 renal colic patients with distal ureteric stones (≤10mm) over a period of 12 months. Patients were randomly divided into three groups. Patients in group A received tamsulosin 0.4mg, in group B received tadalafil 10mg, and in group C received placebo. Therapy was given for a maximum of 4 weeks. The rate of stone expulsion, duration of stone expulsion, the dose and the duration of nonsteroidal anti-inflammatory drugs (NSAIDs), analgesic use, and adverse effects of drugs were recorded. Results: Demographic profiles were comparable between the 3 groups. Although the stone expulsion rate in group A (72.7%) was higher in comparison to group B(63.6%) and group C(56.8%), it was not considered statistically significant (P=0.294). Shorter mean time to stone expulsion was significantly observed in group A (17.75±75), than group B(21.13±1.17) and group C(22.25±1.18) (P=0.47). The mean number of analgesic use was 9.8±5.09 days in group A, 14.6±7.9 days in group B, and 12.6±22.25 days in group C, this difference was significant (P=0.004). The analgesic requirement (doses of NSAIDs and pethidine) in group A was significantly lower than other groups (P<0.05). Also, patients in group A reported fewer headaches compared to other groups (P=0.011). Conclusion: Tamsulosin as medical expulsive therapy is more effective for distal ureteric stones with less need for analgesics and less stone expulsion time than tadalafil.

Effect of Shanhaidan Granules combined with tadalafil on erectile dysfunction: A multi-center clinical trial / 中华男科学杂志

Objective@#To observe the clinical effect and safety of Shanhaidan Granules (SHDG) combined with tadalafil tablets (TT) in the treatment of ED.@*METHODS@#In this open multi-center case-control clinical trial, we enrolled 247 ED patients according to the designed criteria, and treated them orally with SHDG at 10 g per time tid (n = 74), TT at 5 mg per time bid (n = 52), or SHDG + TT at the above doses (n = 121), all for 8 weeks. Before and after medication, we recorded the IIEF-6, erection hardness scores (EHS), traditional Chinese medicine syndromes (TCMS) scores, penile cavernous blood flow parameters and adverse reactions, and compared them between the 3 groups of patients.@*RESULTS@#After 8 weeks of treatment, all the patients showed significantly increased IIEF-6, EHS and TCMS scores in comparison with the baseline (P < 0.05). The total effectiveness rates in the SHDG, TT and SHDG + TT groups were 60.8%, 67.3% and 69.4% respectively based on the IIEF-6 scores, remarkably higher in the TT and SHDG + TT groups than in the SHDG group (P < 0.05), and 40.5%, 32.7% and 63.6% respectively according to the TCMS scores, markedly higher in the SHDG and SHDG + TT groups than in the TT group (P < 0.05). Single-center data manifested significantly increased peak systolic velocity (PSV) of the penile artery in the SHDG + TT and TT groups (P < 0.05). The improvement values of relevant parameters were remarkably higher in the SHDG + TT group than in the TT and SHDG groups, so were IIEF-6 scores in the TT than in the SHDG group, and TCM syndromes in the SHDG than in the TT group. No medication-related adverse events were found in any of patients after treatment, except for some mild side effects including muscle soreness and gastrointestinal reactions in a few cases, all soon relieved, none with abnormalities in blood and urine routine tests or hepatic and renal function indicators.@*CONCLUSIONS@#Shanhaidan Granules combined with tadalafil can significantly improve the erectile function and reduce TCM syndromes in ED patients, and therefore can be applied effectively and safely in clinical practice./.

Tadalafil protector effect during ischemia-reperfusion in rats

Abstract Purpose: To evaluate histological parameters in rat renal tissue after tadalafil use during hot ischemia for 45 minutes and reperfusion for 24 hours. Methods: Twenty rats were divided into 2 groups. In the experimental group 10 mg/kg of tadalafil was used per gavage before the procedure. All cases underwent left partial nephrectomy, followed by 45 minutes of warm ischemia. Left nephrectomy of the remaining kidney was performed after 24 hours from the initial procedure. The histological parameters analyzed were: detachment of tubular cells, accumulation of desquamated cells in the proximal tubule, loss of brush border, tubular cylinders, interstitial edema, leukocyte infiltration, capillary congestion, vacuolization, tubular dilatation, necrosis and collapse of the capillary tuft. Results: Two rats from each group died and were excluded from the study. Tadalafil significantly reduced leukocyte infiltration (p = 0.036). The remaining histological parameters did not show statistical difference between the groups. Conclusion: The use of tadalafil during warm ischemia and reperfusion demonstrates statistically significant reduction of leukocyte infiltration in the renal interstitium.

Tadalafil: protective action against the development of multiple organ failure syndrome

Abstract Introduction: Multiple organ failure syndrome (MOFS) is a pathology associated to unspecified and severe trauma, characterized by elevated morbidity and mortality. The complex inflammatory MOFS-related reactions generate important ischemia-reperfusion responses in the induction of this syndrome. Nitric oxide elevation, through the activation of cyclic guanosine monophosphate (cGMP), has the potential of counteracting the typical systemic vasoconstriction, and platelet-induced hypercoagulation. Tadalafil would possibly act protectively by reducing cGMP degradation with consequent diffuse vasodilatation, besides reduction of platelet-induced hypercoagulation, thus, preventing multiple organ failure syndrome development. Methods: The experimental protocol was previously approved by an institution animal research committee. Experimental MOFS was induced through the stereotaxic micro-neurosurgical bilateral anterior hypothalamic lesions model. Groups of 10 Wistar rats were divided into: a) Non-operated control; b) Operated control group; c) 2 hours after tadalafil-treated operated group; d) 4 hours after tadalafil-treated operated group; e) 8 hours after post-treated operated group. The animals were sacrificed 24 hours after the neurosurgical procedure and submitted to histopathologic examination of five organs: brain, lungs, stomach, kidneys, and liver. Results: The electrolytic hypothalamic lesions resulted in a full picture of MOFS with disseminated multiple-organs lesions, provoked primarily by diffusely spread micro-thrombi. The treatment with tadalafil 2 hours after the micro-neurosurgical lesions reduced the experimental MOFS lesions development, in a highly significant level (P<0.01) of 58.75%. The treatment with tadalafil, 4 hours after the micro-neurosurgically-induced MOFS lesions, also reduced in 49.71%, in a highly significant level (P<0.01). Finally, the treatment with tadalafil 8 hours after the neurosurgical procedure resulted in a statistically significant reduction of 30.50% (P<0.05) of the experimentally-induced MOFS gravity scores. Conclusion: The phosphodiesterase 5 inhibitor, tadalafil, in the doses and timing utilized, showed to protect against the experimentally-induced MOFS.

The effect of tadalafil therapy on kidney damage caused by sepsis in a polymicrobial septic model induced in rats: a biochemical and histopathological study

ABSTRACT Introduction Sepsis is an inflammatory reaction to bacteria involving the whole body and is a significant cause of mortality and economic costs. The purpose of this research was to determine whether tadalafil exhibits a preventive effect on sepsis in a septic model induced in rats with cecal ligation and puncture (CLP). Materials and Methods Rats were randomly separated into groups, 10 rats in each: (i) a sham (control) group, (ii) an untreated sepsis group, (iii) a sepsis group treated with 5mg/kg tadalafil and (iv) a sepsis group treated with 10mg/kg tadalafil. A polymicrobial sepsis model was induced in rats using CLP. Rats were sacrificed after 16h, and blood and kidney tissues were collected for biochemical and histopathological study. Results Levels of the inflammatory parameter IL-6 decreased significantly in the sepsis groups receiving tadalafil in comparison with the untreated sepsis group (p<0.05). In terms of histopathology, inflammation scores investigated in kidney tissues decreased significantly in the sepsis groups receiving tadalafil compared to the untreated sepsis group (p<0.05). In addition, levels of creatinine and cystatin C measured in septic rats receiving tadalafil were lower by a clear degree than in septic rats (p<0.05). Conclusion In this study, tadalafil exhibited a preventive effect for sepsis-related damage by suppressing inflammation in serum and kidney tissue of septic rats in a polymicrobial sepsis model induced with CLP.

Análisis de impacto presupuestal de las terapias combinadas bosentan + sildenafil, ambrisentan + tadalafil e iloprost + bosentan en pacientes diagnosticados con hipertensión pulmonar grupo 1 (HAPG1 idiopática-HAPI y asociada-HAPA) de clase funcional II, I / Budget impact analysis of the combination therapies bosentan + sildenafil, ambrisentan + tadalafil and iloprost + bosentan in patients diagnosed with pulmonary hypertension group 1 (idiopathic HAPG1-HAPI and associated-HAPA) functional class II, I

Tecnologías evaluadas: Nueva: ambrisentan (principal) + tadalafil (complementario) Nueva: iloprost (principal) + bosentan (complementario), Actual: bosentan (principal) + sildenafil (complementario). Población: Pacientes diagnosticados con hipertensión pulmonar grupo 1 (HAP idiopática-HAPI y asociada-HAPA) de clase funcional II, III y IV de la NYHA/WHO en Colombia. Perspectiva: La perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el Sistema General de Seguridad Social en Salud (SGSSS) en Colombia. Horizonte Temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costo promedio ponderado de l mg de a mbrisentán, tadalafil, bosentan y sildenafil y costo promedio del mcg del iloprost en Colombia; Costo de las dosis individuales y en terapia combinada de ambrisentan, tadalafil, bosentan, sildenafil e iloprost para la población objetivo del AIP Colombia. Fuentes de Costos: Precios de ambrisentan, tadalafil, bosentan, sildenafil e iloprost en sus diferentes CUM s reportados por SISMED. Escenarios: Escenario 1: la participación de mercado de iloprost se reduce significativamente mientras que ambrisentan gana un espacio importante y bosentan disminuye ligeramente su participación en el primer año y la conserva \r\nen los dos años siguientes debido a que i) iloprost no es más efectivo que bosentan o ambrisentan, ii) la terapia combinada ambrisentan + tadalafil reduce hospitalizaciones, iii) ambrisentan es más barata que iloprost y iv) el sistema de salud en Colombia viene ganando eficiencia. Además, en la práctica la mayoría \r\nde los pacientes inician con terapia combina da y con seguridad 100% de ellos hace tránsito a terapia combinada si comenzaron con monoterapia; Escenario 2: la participación de mercado de ambrisentan se incrementa de manera pausada y llega a un nivel no superior a la participación de mercado de iloprost, que mantiene un segmento importante del mercado por la fuerte formulación de ese medicamento. En este escenario bosentan conserva su participación de mercado inalterada dada su comprobada efectividad en el tratamiento de HAPG1 y a que es la tecnología más antigua y conocida en el mercado. Resultados:\r\nEl costo de la tecnología actual de la terapia combinada bosentan + sildenafil, es de 98.773 millones COP en el año base. Bajo el escenario 1, el costo de adopción de las terapias combinadas nuevas analizadas, ambrisentan + tadalafil e iloprost + bosentan, implica un esfuerzo financiero adicional de 12.318 millones COP, mientras que bajo el escenario 2 el esfuerzo adicional es de 40.645 millones COP, es decir, 3.3 veces más. Para el segundo año el es fuerzo adicional requerido decrece con relación al año 1 ubicándose en 2.734 y de 3.071 millones COP en los escenarios 1 y 2 respectivamente. En el tercer año el impacto adicional se incrementa en 3.215 y 7.055 millones COP en cada caso.(AU)

Inhibidores de fosfodiesterasa-5 para el tratamiento de la hipertensión arterial pulmonar / Phosphodiesterase-5 inhibitors for the treatment of pulmonary arterial hypertension

En cardiología clínica y experimental, los inhibidores de fosfodiesterasa-5 (PDE-5) han atraído el interés científico en años recientes como herramienta terapéutica para el tratamiento de la HAP. Las fosfodiesterasas son una superfamilia de enzimas que inactivan el adenosín monofosfato cíclico y el guanosín monofosfato cíclico, los segundos mensajeros de la prostaciclina y del óxido nítrico. El razonamiento para utilizar los inhibidores de PDE-5 en HAP se basa en su relativa selectividad por la circulación pulmonar y en su capacidad para sobreexpresar la vía del óxido nítrico por inhibición de la hidrólisis del guanosín monofosfato cíclico e incrementar sus concentraciones, lo cual produce efectos vasodilatadores, antiproliferativos y proapoptóticos que pueden revertir el remodelado vascular pulmonar. Además, pueden aumentar el inotropismo ventricular derecho al incrementar el adenosín monofosfato cíclico mediado por la inhibición de la fosfodiesterasa tipo 3 sensible al guanosín monofosfato cíclico. El sildenafil, el tadalafil y el vardenafil son 3 inhibidores de PDE-5 actualmente en uso clínico que comparten similar mecanismo de acción aunque presentan algunas diferencias significativas en potencia, selectividad por la PDE-5 y propiedades farmacocinéticas. Para el tratamiento de la HAP en pacientes en clase funcional II y III (NYHA/WHO), el sildenafil fue aprobado por la Food and Drug Administration y la European Medicines Agency en 2005; y tadalafil por la Food and Drug Administration y la European Medicines Agency en 2009. En México, el sildenafil y el tadalafil recibieron la aprobación por parte de la Comisión Federal para la Protección contra Riesgos Sanitarios para la misma indicación en 2010 y 2011 respectivamente.

In experimental and clinical cardiology, phosphodiesterase type 5 (PDE-5) inhibitors have brought scientific interest as a therapeutic tool in pulmonary arterial hypertension (PAH) management in recent years. Phosphodiesterases are a superfamily of enzymes that inactivate cyclic adenosine monophosphate and cyclic guanosine monophosphate, the second messengers of prostacyclin and nitric oxide. The rationale for the use of PDE-5 inhibitors in PAH is based on their capacity to overexpresss the nitric oxide pathway pursued inhibition of cyclic guanosine monophosphate hydrolysis. By increasing cyclic guanosine monophosphate levels it promotes vasodilation, antiproliferative and pro-apoptotic effects that may reverse pulmonary vascular remodeling. There is also evidence that these drugs may directly enhance right ventricular contractility through an increase in cyclic adenosine monophosphate mediated by the inhibition of the cyclic guanosine monophosphate -sensitive PDE-3. Sildenafil, tadalafil and vardenafil are 3 specific PDE-5 inhibitors in current clinical use, which share similar mechanisms of action but present some significant differences regarding potency, selectivity for PDE-5 and pharmacokinetic properties. Sildenafil received approval in 2005 by the Food and Drug Administration and the European Medicines Agency and tadalafil in 2009 by the Food and Drug Administration and the European Medicines Agency for the treatment of PAH in patients classified as NYHA/WHO functional class II and III. In Mexico, sildenafil and tadalafil were approved by Comisión Federal de Protección contra Riesgos Sanitarios for this indication in 2010 and 2011, respectively.