Sildenafil in Primary Pulmonary Hypertension

Prasad, Sanjay K.; Wilkinson, J. P. D.

doi:10.1056/nejm200011023431814

Cited by 308 publications

(155 citation statements)

References 4 publications

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“…50 These experimental data suggest that at least in certain conditions with increased pulmonary arterial pressure, PDE 5 inhibition might be of benefit, and the possibility of additional inhalative application of other agents used to lower pulmonary artery pressure might provide a unique approach to achieve site-specific, additive, or even overadditive effects. 51 Michelakis et al 52 investigated the effect of oral sildenafil in patients with severe primary or secondary pulmonary hypertension who were evaluated for potential heart-lung transplantation. They reported a reduction of pulmonary vascular resistance that was similar in extent to that observed after inhaled nitric oxide.…”

Section: Effects Of Pde 5 Inhibition On Pulmonary Vasculaturementioning

confidence: 99%

Therapeutic Potential of Phosphodiesterase 5 Inhibition for Cardiovascular Disease

2003

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Section: Effects Of Pde 5 Inhibition On Pulmonary Vasculaturementioning

confidence: 99%

Therapeutic Potential of Phosphodiesterase 5 Inhibition for Cardiovascular Disease

2003

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“…[11][12] Also case reports suggest that children and adults with pulmonary arterial hypertension have been treated successfully with oral SC. [13][14][15][16] A recent proof of concept randomized controlled trial suggests benefits of oral sildenafil in newborns with PPHN, 5 and an increasing number of infants are starting to be exposed to this drug. Nevertheless, much still needs to be learned about potential adverse effects of this systemic enzymatic inhibitor, and the effects in patients who receive nitrites or have hepatic insufficiency and/or in patients who receive drugs that interact with the cytochrome system.…”

Section: Introductionmentioning

confidence: 99%

Oral sildenafil citrate lacks genotoxicity and cytotoxicity in a primate model: Callithrix jacchus

et al. 2006

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Objective: To determine sildenafil citrate (SC) genotoxicity and cytotoxicity in the Callithrix jacchus.Study design: Fifteen organisms were assigned to one of three groups as follows: experimental (25 mg/kg of SC); negative control (glucose solution 5%); and positive control (3 mg/kg of cytocine arabinoside). Systemic hemodynamic changes were monitored in each animal before and after each treatment. A drop of blood was obtained before and after the treatment at 24-120 h. Smears were made and the frequency of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE) and polychromatic erythrocytes (PCE) was counted.Results: No significant differences in MNE, MNPCE and PCE were found in the group that received sildenafil and negative control. A significant increase in genotoxicity and cytotoxicity was observed in the positive control group. No changes were observed in systemic hemodynamic changes. Conclusion:The macro-dose of SC lacks genotoxic, cytotoxic or systemic hemodynamic changes effects in this species.

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“…Siklik guanozin monofosfat (GMP)-özgül fosfodiesteraz 5'in (PDE-5) seçici inhibitörü olan sildenafil etkisini hücre içindeki siklik GMP düzeyini artırarak gösterir (17). Siklik GMP düzeyinin artması vasküler düz kas hücrelerinde gevşemeye neden olur, ayrıca antiproliferatif etkileri de vardır (17,18).…”

Section: Fosfodiesteraz Inhibitörleriunclassified

“…Siklik GMP düzeyinin artması vasküler düz kas hücrelerinde gevşemeye neden olur, ayrıca antiproliferatif etkileri de vardır (17,18).…”

Section: Fosfodiesteraz Inhibitörleriunclassified

Therapeutic algorithms in pulmonary hypertension in the light of current guidelines

Okutucu¹,

Tokgözoğlu²

2010

Anadolu Kardiyol Derg

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Pulmonary arterial hypertension (PAH) is a clinical syndrome that is often diagnosed late and is associated with a progressive clinical deterioration and death. However, over the past ten years there has been a dramatic increase in the number of effective therapies. Identification of dysfunctional pathways in the pulmonary circulation provided novel therapeutic targets with the goal of reducing pulmonary vascular resistance and death from right ventricular failure. Treatment strategies are determined according to current guidelines. Pulmonary artery vasoreactivity, functional class and response to treatment are important concepts for initiation of medical therapy. With the availability of medications that target different pathologic processes, combination therapy has become a frequently used therapeutic option in PAH. In this paper, we aimed to review the therapeutic algorithms in pulmonary hypertension based on current guidelines. ( ÖZETPulmoner arter hipertansiyonu (PAH) sıklıkla geç tanınan ve ilerleyici klinik bozulma ve ölümle ilişkili klinik bir sendromdur. Bununla birlikte, son on yıl içinde etkin tedavi sayısında belirgin bir artış olmuştur. Pulmoner dolaşımdaki işlev bozukluğu olan yolakların saptanması, pulmoner vasküler direnci ve sağ ventrikül yetmezliğinden ölümü azaltacak yeni tedavi hedefleri sağlamıştır. Günümüzde PAH tedavi stratejileri yinelenen kılavuzlar çerçevesin-de belirlenmektedir. Tedavi seçeneklerinin uygulanmasında pulmoner arter vazoreaktivitesi, işlevsel kapasite ve tedaviye olan yanıt önem taşımakta-dır. Farklı patolojik süreçleri hedefleyen ilaçların varlığı sonucunda, kombinasyon tedavisi PAH'de sıkça kullanılan bir seçenek durumuna gelmiştir. Bu yazıda güncel kılavuzlar ışığında pulmoner hipertansiyonda tedavi algoritmalarının özetlenmesi amaçlanmıştır. GirişPulmoner arter hipertansiyonu (PAH) pulmoner arter basıncı ve pulmoner vasküler dirençte ilerleyici artış ile karakterize bir grup hastalığın oluşturduğu klinik tablodur (1, 2). Son on yılda PAH patogenezi ve tedavisinde elde edilen ilerlemeler kötü prognozlu bu hastalığa olan ilgiyi artırmış ve yeni umutlar doğurmuştur. Tüm bu ilerlemelere rağ-men, PAH tanısı hastalığın ancak geç seyrinde konulmaktadır. Ülkemizde de Avrupa geneline benzer bir şekilde, tanı anında hastaların çoğunun fonksiyonel kapasitesi Dünya Sağlık Örgütü (DSÖ) Sınıf III-IV'tür (3, 4). Hacettepe Üniversitesi Tıp Fakültesindeki deneyimimize göre tanı anında hastaların %82'si DSÖ fonksiyonel sınıf (FS) III-IV'tür (3). Halbuki hastalar erken tanı ve uygun tedaviden yarar görmektedir. PAH tedavisinde amaç; PAH şiddetini azaltmak, fonksiyonel kapasitesini, yaşam kalitesini düzeltmek, sağ ventrikül işlevle-rini iyileştirmek, oluşabilecek tromboembolik yükü azaltmak ve iyi prognoz sağlamaktır. Günümüzde PAH tedavi stratejileri; pulmoner arter vazoreaktivitesine, fonksiyonel kapasiteye ve tedaviye olan yanıta göre belirlenmektedir. Farklı patolojik süreçleri hedefleyen ilaçların varlığı sonucunda, kombinasyon tedavisi PAH' de sıkça kullanılan bir seçenek durumun...

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Sildenafil in Primary Pulmonary Hypertension

Cited by 308 publications

References 4 publications

Therapeutic Potential of Phosphodiesterase 5 Inhibition for Cardiovascular Disease

Therapeutic Potential of Phosphodiesterase 5 Inhibition for Cardiovascular Disease

Oral sildenafil citrate lacks genotoxicity and cytotoxicity in a primate model: Callithrix jacchus

Therapeutic algorithms in pulmonary hypertension in the light of current guidelines

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