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Clare J Fowler - One of the best experts on this subject based on the ideXlab platform.
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treatment of erectile dysfunction with Sildenafil citrate viagra in parkinsonism due to parkinson s disease or multiple system atrophy with observations on orthostatic hypotension
Journal of Neurology Neurosurgery and Psychiatry, 2001Co-Authors: Iqbal F Hussain, C J Mathias, C M Brady, Michael J Swinn, Clare J FowlerAbstract:OBJECTIVES—To assess the efficacy and safety of Sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy. METHODS—Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of Sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital. RESULTS—Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after Sildenafil, all patients with multiple system atrophy reported a good erectile response and were reluctant to discontinue the medication. CONCLUSIONS—Sidenafil citrate (50 mg) is efficacious in the treatment of erectile dysfunction in parkinsonism due to Parkinson's disease or multiple system atrophy; however, it may unmask or exacerbate hypotension in multiple system atrophy. As Parkinson's disease may be diagnostically difficult to distinguish from multiple system atrophy, especially in the early stages, we recommend measurement of lying and standing blood pressure before prescribing Sildenafil to men with parkinsonism. Furthermore, such patients should be made aware of seeking medical advice if they develop symptoms on treatment suggestive of orthostatic hypotension.
Dino A Giussani - One of the best experts on this subject based on the ideXlab platform.
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Sildenafil therapy for fetal cardiovascular dysfunction during hypoxic development studies in the chick embryo
The Journal of Physiology, 2017Co-Authors: Nozomi Itani, Katie L Skeffington, Christian Beck, Dino A GiussaniAbstract:Key points Common complications of pregnancy, such as chronic fetal hypoxia, trigger a fetal origin of cardiovascular dysfunction and programme cardiovascular disease in later life. Sildenafil treatment protects placental perfusion and fetal growth, but whether the effects of Sildenafil transcend the placenta to affect the fetus is unknown. Using the chick embryo model, here we show that Sildenafil treatment directly protects the fetal cardiovascular system in hypoxic development, and that the mechanisms of Sildenafil protection include reduced oxidative stress and increased nitric oxide bioavailability; Sildenafil does not protect against fetal growth restriction in the chick embryo, supporting the idea that the protective effect of Sildenafil on fetal growth reported in mammalian studies, including humans, is secondary to improved placental perfusion. Therefore, Sildenafil may be a good candidate for human translational antioxidant therapy to protect the chronically hypoxic fetus in adverse pregnancy. Abstract There is a need for developing clinically translatable therapy for preventing fetal origins of cardiovascular disease in pregnancy complicated by chronic fetal hypoxia. Evidence shows that Sildenafil protects placental perfusion and fetal growth. However, whether beneficial effects of Sildenafil transcend onto the fetal heart and circulation in complicated development is unknown. We isolated the direct effects of Sildenafil on the fetus using the chick embryo and hypothesised that Sildenafil also protects fetal cardiovascular function in hypoxic development. Chick embryos (n = 11 per group) were incubated in normoxia or hypoxia (14% O2) from day 1 and treated with Sildenafil (4 mg kg−1 day−1) from day 13 of the 21-day incubation. Hypoxic incubation increased oxidative stress (4-hydroxynonenal, 141.1 ± 17.6% of normoxic control), reduced superoxide dismutase (60.7 ± 6.3%), increased phosphodiesterase type 5 expression (167 ± 13.7%) and decreased nitric oxide bioavailability (54.7 ± 6.1%) in the fetal heart, and promoted peripheral endothelial dysfunction (70.9 ± 5.6% AUC of normoxic control; all P < 0.05). Sildenafil treatment after onset of chronic hypoxia prevented the increase in phosphodiesterase expression (72.5 ± 22.4%), protected against oxidative stress (94.7 ± 6.2%) and normalised nitric oxide bioavailability (115.6 ± 22.3%) in the fetal heart, and restored endothelial function in the peripheral circulation (89.8 ± 2.9%). Sildenafil protects the fetal heart and circulation directly in hypoxic development via mechanisms including decreased oxidative stress and enhanced nitric oxide bioavailability. Sildenafil may be a good translational candidate for human antioxidant therapy to prevent fetal origins of cardiovascular dysfunction in adverse pregnancy.
A. M. Y. Jaber - One of the best experts on this subject based on the ideXlab platform.
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Determination of Sildenafil citrate and related substances in the commercial products and tablet dosage form using HPLC.
Journal of pharmaceutical and biomedical analysis, 2001Co-Authors: Nidal Daraghmeh, Michael Omari, A A Badwan, A. M. Y. JaberAbstract:This study aimed at developing and validating an HPLC method for the assay of Sildenafil citrate and its related substances that might coexist in the drug commercial products and in tablets' formulation as impurities that originate from synthesis processes or degradation. A chromatographic system comprising a microBondapak C(18) (10 microm) column, a mobile phase of ammonium acetate (pH 7.0, 0.2 M)-acetonitrile (1:1, v/v), a flow rate of 1 ml/min and a UV detector set at 240 nm has shown good chromatographic separation for sildenfil and the other related substances. The degree of linearity of the calibration curves, the percent recoveries of Sildenafil and related substances, the limit of detection, LOD, and limit of quantitation, LOQ for the HPLC method have been determined. The HPLC method under study was found to be specific, precise, accurate, reproducible indicating stability and robust.
Iqbal F Hussain - One of the best experts on this subject based on the ideXlab platform.
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treatment of erectile dysfunction with Sildenafil citrate viagra in parkinsonism due to parkinson s disease or multiple system atrophy with observations on orthostatic hypotension
Journal of Neurology Neurosurgery and Psychiatry, 2001Co-Authors: Iqbal F Hussain, C J Mathias, C M Brady, Michael J Swinn, Clare J FowlerAbstract:OBJECTIVES—To assess the efficacy and safety of Sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy. METHODS—Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of Sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital. RESULTS—Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after Sildenafil, all patients with multiple system atrophy reported a good erectile response and were reluctant to discontinue the medication. CONCLUSIONS—Sidenafil citrate (50 mg) is efficacious in the treatment of erectile dysfunction in parkinsonism due to Parkinson's disease or multiple system atrophy; however, it may unmask or exacerbate hypotension in multiple system atrophy. As Parkinson's disease may be diagnostically difficult to distinguish from multiple system atrophy, especially in the early stages, we recommend measurement of lying and standing blood pressure before prescribing Sildenafil to men with parkinsonism. Furthermore, such patients should be made aware of seeking medical advice if they develop symptoms on treatment suggestive of orthostatic hypotension.
Sanjeev Ahuja - One of the best experts on this subject based on the ideXlab platform.
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a multicenter randomized double blind crossover study of patient preference for tadalafil 20 mg or Sildenafil citrate 50 mg during initiation of treatment for erectile dysfunction
Clinical Therapeutics, 2003Co-Authors: Fred E Govier, Jonathan Denne, Axeljuerg Potempa, Joel M Kaufman, Pavel Kovalenko, Sanjeev AhujaAbstract:Abstract Background: Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor approved in >30 countries for the treatment of erectile dysfunction (ED). It has been shown to improve erectile function compared with placebo in Phase III studies, but clinical experience comparing tadalafil with the PDE5 inhibitor Sildenafil citrate is lacking. Objective: This study compared patient preference for tadalafil 20 mg or Sildenafil 50 mg during initial treatment for ED. It also compared the tolerability of the 2 agents at these doses. Methods: This randomized, double-blind, fixed-dose, 2-period crossover trial took place at 13 sites in the United States and Germany. Patients were randomized 1:1 to receive 4 weeks of treatment with tadalafil 20 mg or Sildenafil 50 mg, followed by the alternative treatment, to be taken as needed up to once daily before sexual activity. Results: The study enrolled 215 men with ED, 109 randomized to the tadalafil-Sildenafil sequence and 106 to the Sildenafil-tadalafil sequence. Their mean age was 49.8 years; 84.7% were Sildenafil naive and 15.3% had undergone a previous inadequate trial of Sildenafil. Most patients had moderate ED (60.5%) of ≥1 year's duration (74.9%). Of 190 evaluable patients, 126 (66.3%) preferred to initiate treatment with tadalafil, compared with 64 (33.7%) with Sildenafil ( P Conclusions: Tadalafil 20 mg was preferred to Sildenafil 50 mg for the initiation of ED therapy in this study population. Both medications were well tolerated.