신생아의 지속성 폐동맥 고혈압증에서 Sildenafil 치료 경험

이연경,손수빈,김경아,윤소영,고선영,신손문 대한신생아학회 2011 Neonatal medicine Vol.18 No.1

Purpose: To evaluate the effect of oral sildenafil therapy in neonates with persistent pulmonary hypertension of the newborn (PPHN)Methods: We conducted a retrospective review of 32 neonates ≥35 weeks’ gestation and fraction of inspired oxygen (FiO2) 1.0with PPHN. The first dose (0.5 mg/kg) of oral sildenafil was started and 1 mg/kg was given every 6 hour thereafter. Mean airway pressure (MAP), FiO2, oxygenation index (OI), mean arterial blood pressure (MBP) were documented before and 6, 12, 24, and 48hours after sildenafil. For adverse effects, gastrointestinal symptoms, brain ultrasound, funduscopy and auditory brainstem response results were evaluated. Results: The underlying diseases of PPHN (n=32) were meconium aspiration syndrome (n=9), respiratory distress syndrome (n=8),pneumonia (n=3), and idiopathic (n=12). Thirty-one neonates survived; 3 neonates were transferred for inhaled nitric oxide (iNO)and all of them survived. In 28 infants, FiO_2 and OI improved significantly by 6 hours and MAP improved significantly by 48 hours after initiation of sildenafil. There were no clinically significant adverse effects of sildenafil. Conclusion: Sildenafil may be an effective and safe agent for near-term and term neonates with PPHN, providing significant improvement in oxygenation, and thus may be especially useful in the treatment of PPHN in hospitals without iNO. 목적: 최근 PPHN의 치료를 위해 iNO와 함께 많은 약물적 치료가 사용되고 있다. Sildenafil은 PDE5의 억제제로 선택적인폐혈관 확장제로 알려져 있으며 iNO에 비하여 접근성이 뛰어나 iNO에 대안적인 약제로 연구되어 왔다. 저자들은 본원에서sildenafil로 PPHN을 치료한 경험을 분석하였다. 방법: 심초음파를 통해 PPHN으로 진단된 재태 기간 35주 이상, FiO_2 1.0을 필요로 하는 32명의 환아를 대상으로 하였으며의무기록을 후향적으로 조사하였다. sildenafil은 0.5 mg/kg로시작하여 6시간마다 1 mg/kg로 투약하였으며, 투약 전과 후 6,12, 24, 48시간의 MAP, FiO2, OI, MBP를 비교하였다. 부작용을확인하기 위하여 환아들의 위장관 증상, 뇌초음파, 안저검사와청성뇌간유발반응 검사의 결과를 조사하였다. 결과: 대상 환아 32명 중 태변 흡인 증후군 9명, 호흡곤란증후군 8명, 폐렴 3명이었으며, 12명은 특발성이었다. 이 중 31명이생존하였으며 28명의 환아는 본원에서 sildenafil만으로 치료되었고 3명의 환아는 전원되어 iNO 치료 후 회복하였다. Sildenafil 단독으로 치료된 28명의 환아에서 FiO_2와 OI는 치료 6시간째부터 MAP는 48시간째부터 유의하게 감소하였다. 모든 환아에서 특별한 부작용은 관찰되지 않았다. 결론: Sildenafil은 35주 이상의 PPHN 환아에서 비교적 효과적이고 안전하게 시도해 볼 수 있는 대안 약제로서, 특히 iNO가가능하지 않은 병원에서 유용할 것으로 생각된다.

Trimix를 사용해오던 발기부전 환자에서 Sildenafil의 효과와 선호도

전혁준,김세철 大韓泌尿器科學會 2002 Korean Journal of Urology Vol.43 No.11

Effect of Sildenafil on Neuropathic Pain and Hemodynamics in Rats

Lan Ji Huang,최정일,김웅모,이형곤,김여옥,윤명하 연세대학교의과대학 2010 Yonsei medical journal Vol.51 No.1

Purpose: The inhibition of phosphodiesterase 5 produces an antinociception through the increase of cyclic guanosine monophosphate (cGMP), and increasing cGMP levels enhance the release of γ-aminobutyric acid (GABA). Furthermore, this phosphodiesterase 5 plays a pivotal role in the regulation of the vasodilatation associated to cGMP. In this work, we examined the contribution of GABA receptors to the effect of sildenafil, a phosphodiesterase 5 inhibitor, in a neuropathic pain rat, and assessed the hemodynamic effect of sildenafil in normal rats. Materials and Methods: Neuropathic pain was induced by ligation of L5/6 spinal nerves in Sprague-Dawley male rats. After observing the effect of intravenous sildenafil on neuropathic pain, GABAA receptor antagonist (bicuculline) and GABAB receptor antagonist (saclofen) were administered prior to delivery of sildenafil to determine the role of GABA receptors in the activity of sildenafil. For hemodynamic measurements, catheters were inserted into the tail artery. Mean arterial pressure (MAP) and heart rate (HR) were measured over 60 min following administration of sildenafil. Results: Intravenous sildenafil dose-dependently increased the withdrawal threshold to the von Frey filament application in the ligated paw. Intravenous bicuculline and saclofen reversed the antinociception of sildenafil. Intravenous sildenafil increased the magnitude of MAP reduction at the maximal dosage, but it did not affect HR response. Conclusion: These results suggest that sildenafil is active in causing neuropathic pain. Both GABAA and GABAB receptors are involved in the antinociceptive effect of sildenafil. Additionally, intravenous sildenafil reduces MAP without affecting HR.

Sildenafil Citrate의 복용 후 발생한 양안의 안압 상승과 단안의 비동맥염성 앞허혈시신경병증 1예

이동익(Dong Ik Lee),이미연(Mee Yon Lee),문남주(Nam Ju Moon) 대한검안학회 2013 Annals of optometry and contact lens Vol.13 No.2

목적: Sildenafil citrate (Viagra??)의 복용 후 양안의 안압 상승 및 단안의 비동맥염성 앞허혈시신경병증이 동시에 발생한 증례 1예를 보고하고자 한다. 증례요약: 62세 남자 환자가 2개월 전 발생한 좌안의 시력저하로 타 병원에서 전원되었다. 환자는 증상 발생 하루 전 Sildenafil citrate 50 mg을 복용하였으며 아침에 일어난 직후 좌안의 통증과 시력저하를 느꼈다. 타병원에서의 안압은 우안 48 mmHg, 좌안50 mmHg였다. 안압 하강제를 사용하여 안압조절을 시행하였으며, 치료 후에도 시야협착이 호전되지 않아 본원으로 의뢰되었다. 본원에 첫 방문 시의 안압은 정상이었으나 좌측 시야의 전반적 결손 및 좌안 시신경유두의 창백 소견을 보였다. 좌안의 비동맥염성 앞허혈시신경병증 의심하 시력과 안압에 대한 정기적 추적관찰을 시행하였다. 3개월의 추적관찰기간 동안 안압은 안정적이었으나 시야의 호전은 없었다. 결론: Sildenafil의 복용이 안압상승 및 시신경병증의 발생에 영향을 미친다는 여러 보고들이 있다. 본 증례는 Sildenafil의 복용 후 안압상승과 그에 의한 것으로 추정되는 시신경병증이 발생한 국내의 첫 보고로, 상기 질환들의 위험인자가 있는 환자에게서 Sildenafil citrate의 복용을 주의해야 할 것이다. Purpose: To report a patient who simultaneously developed bilateral increased intraocular pressure and unilateral non-arteritic anterior ischemic optic neuropathy (NAION) after Sildenafil citrate (Viagra??) use. Case summary: 60-year-old male was referred from other hospital by decreased vision of his left eye. 2 month ago, he visited other hospital’s ophthalmologic department by pain and sudden decrease of vision in left eye and. He had taken Sildenafil citrate 50 mg one day before, and symptom was first recognized after wake up in the morning. At that hospital, intraocular pressure (IOP) was 48 mm Hg and 50 mm Hg in his right and left eye. IOP was controlled by topical IOP-lowering agent. However, visual field constriction was not improved after treatment, the patient was referred to our ophthalmologic clinic. IOP was normal at the first visit, but diffuse constriction of visual field and pale optic disk was observed in his left eye. With the impression of NAION, regular outpatient follow up was done. During 3 months follow up period, IOP was stable but visual field was not improved. Conclusions: There are several reports about increased intraocular pressure or development of NAION after Sildenafil use. To our best knowledge, this is the first case of developed increased intraocular pressure and unilateral NAION after Sildenafil use in Korea. Those who predisposed towards these diseases, special concern should be taken in using Sildenafil citrate.

Life Science : RESEARCH ARTICLE ; Development of sildenafil-loaded orally disintegrating tablet with new lactate salt

( Si Young Jung ),( Dong Wuk Kim ),( Youn Gee Seo ),( Jong Soo Woo ),( Chul Soon Yong ),( Han Gon Choi ) 영남대학교 약품개발연구소 2012 영남대학교 약품개발연구소 연구업적집 Vol.22 No.0

To develop a sildenafil lactate-loaded orally disintegrating tablet with a faster drug effect onset and immediate action of erection, the orally disintegrating tablets were prepared with various amounts of menthol and colloidal silica using the direct compression technique followed by vacuum drying. Theirtablet properties such as friability, hardness, wetting time and disintegration time were investigated. The oral bioavailability of sildenafil in the orally disintegrating tablet was then compared with the sildenafil citrate-loaded commercial tablet (Viagra(®)) in rabbits. Sildenafil lactate was a new salt form with more improved solubility and alleviated bitterness compared with commercial salt, sildenafil citrate. As the amount of menthol in the orally disintegrating tablet increased, the friability increased and hardness decreased, resulting in a shorter wetting time and disintegration time. Colloidal silica did the opposite. The sildenafil lactate-loaded orally disintegrating tablet prepared with 45 mg/tab of menthol and 1.5 mg/tab of colloidal silica gave a hardness of 3-4 KP, friability less than 0.5% and disintegration time less than 30 s, suggesting that it was a practical and commercial product with goodtablet property and excellent efficacy. Furthermore, it gave higher AUC and C(max), and shorter T(max) values than did the commercial tablet, indicating that it improved the oral bioavailability of sildenafil in rabbits compared with the commercial tablet. Thus, the sildenafil lactate-loaded orally disintegratingtablet might induce a fast onset of action and immediate erection compared with the sildenafil citrate-loaded commercial tablet.

Ameliorative effect of hesperidin against high dose sildenafil-induced liver and testicular oxidative stress and altered gene expression in male rats

Ibrahim M. Ibrahim Laila,Samar HassabAllah Kassem,Marwa Salah ElDin Mohamed Diab 한국실험동물학회 2023 Laboratory Animal Research Vol.39 No.3

Background: The clinical use of sildenafil citrate (Viagra), a drug used to treat erectile dysfunction, is limited because of its many side effects on tissues. In this context, we aimed to investigate the protective effects of hesperidin, a citrus flavonoid, on hepatic and testicular damage induced by a high dose of sildenafil citrate in male rats. Rats were randomly divided into four groups. The first group was used as the control group. The second group was orally administered sildenafil citrate at a high dose of 75 mg/kg thrice a week. In the third group, hesperidin was administered orally at a dose of 50 mg/kg/day. The fourth group was administered 75 mg/kg sildenafil citrate three times a week with 50 mg/kg hesperidin daily. The experiment lasted for 28 days. Results: In the sildenafil-treated groups, blood indices were altered, liver function tests were deranged, and serum testosterone levels were reduced. In the liver and testicular tissue, sildenafil citrate treatment resulted in significant reductions in catalase and total antioxidant capacity; as well as increased malondialdehyde, reactive oxygen species, and nitrous oxide levels. In addition, sildenafil citrate treatment caused abnormal histopathological patterns in both the liver and the testes. Liver vascular endothelial growth factor and testicular steroidogenic acute regulatory protein gene expression were upregulated. Conclusions: Hesperidin attenuated the harmful effects of intensive sildenafil citrate treatment on liver and testicular functions, alleviated oxidative stress and normalized blood indices. Therefore, hesperidin could be protective against sildenafil citrate-induced oxidative damage that may develop over the long term.

Additive Antinociception between Intrathecal Sildenafil and Morphine in the Rat Formalin Test

윤명하,박경덕,이형곤,김웅모,안태훈,김여옥,Lan Ji Huang,Cui Jin Hua 대한의학회 2008 Journal of Korean medical science Vol.23 No.6

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 μL 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.

실데나필 복용 이후 발생한 청색시증에 대한 사례

이찬희,윤중식,지은희 한국임상약학회 2020 한국임상약학회지 Vol.30 No.1

The emergence of phosphodiesterase (PDE) 5 inhibitors gave rise to the solution for erectile dysfunction, starting with the development of sildenafil. Although their efficacy in treating erectile dysfunction has been shown, the side effects of PDE5 inhibitors, especially sildenafil, must be taken into consideration. A 64-year-old man received 100 mg of sildenafil and experienced blue vision in both eyes; however, after a day or so, his symptoms improved. The symptoms disappeared when he stopped administering sildenafil, but reappeared when the medication was re-administered. Therefore, he discontinued sildenafil treatment and was prescribed udenafil instead. After that, visual adverse events no longer occurred. Causality assessment showed that in this case, sildenafil-induced cyanopsia was “certain” under the World Health Organization-Uppsala Monitoring Center (WHO-UMC) criteria and Korean causality assessment algorithm (Ver.2), and was “probable” according to the Naranjo scale. In addition, sildenafil also led to abnormal visual reactions in other cases. Sildenafil can also inhibit PDE6, which is present in retinal cells, unlike other PDE5 inhibitors. Thus, visual adverse reactions, such as blue vision, are the unique results of sildenafil, and other PDE5 inhibitors may be used to prevent them.

발기부전에 처방된 Sildenafil이 식도 증상을 유발할 수 있다

심상군 ( Sang Goon Shim ),김범진 ( Beom Jin Kim ),이풍렬 ( Poong Lyul Rhee ),이성원 ( Seong Won Lee ) 대한소화기기능성질환·운동학회 2004 Journal of Neurogastroenterology and Motility (JNM Vol.10 No.2

목적: 발기부전의 치료제로 흔히 사용되는 sildenafil은 제5형 phosphodiesterase를 선택적으로 억제 시킨다. 최근 Sildenafil은 식도의 운동능에 변화를 일으키는 것으로 알려져 있으며, 이전의 우리연구에서도 하부식도괄약근의 기저압 및 식도 원위부 수축파의 진폭이 감소됨을 보였다. 그러나 sildenafil에 의한 식도운동이상이 증상을 유발하는 지는 확실치 않다. 본 연구는 sildenafil 복용에 의해 유발될 수 있는 식도증상 Background/Aims: Sildenafil, which is commonly prescribed for erectile dysfunction, is a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5. Recently, sildenafil has been found to induce changes in esophageal motility. However, it re

Positive Effects of Orally Administered Sildenafil on Skin Wound Healing of Rats

( Su Sung Park ),( Jin Il Yang ),( Seok Kwun Kim ),( Keun Cheol Lee ) 한국조직공학과 재생의학회 2010 조직공학과 재생의학 Vol.7 No.4

Purpose: Wound healing is a series of restoration processes developing after dermal and soft tissue injury that is regulated by various factors. Among them, angiogenesis is an essential process that increases the tensile strength of wound and plays an important role in tissue regeneration. Sildenafil is a phosphodiesterase-5 (PDE-5) inhibitor that has been used commonly as a therapeutics for erectile dysfunction. Sildenafil induces vasodilation by blocking the degradation of nitric oxide (NO). High NO concentration has been reported to play a positive role in wound healing by accelerating angiogenesis, inflammatory reaction, and the proliferation of vascular endothelial cells. The present study assessed the effect of sildenafil on the wound healing process by examining wound contraction, tensile strength, and histological changes in response to the oral administration of sildenafil. Methods: Rats (n=120) were divided into the experiment group (n=60) and the control group (n=60), abdominal skin was incised up to the fascia. On postoperative day 10, 10 mg/kg sildenafil was administered to the experiment group. On postoperative day 4, 7, 14, 21, and 35, specimens were obtained from the incisional wound of 12 animals of each group. The wound tensile strength of each wound surface was determined, a histological evaluation was performed, and the change of the incisional wound area of the experiment and control groups was measured. Results: The tensile strength of wound was higher at 4, 7, and 14 postoperative day in the sildenafil treated group than control. In histologic findings, acute and chronic inflammatory reactions were not significantly different. The formation of granulation tissues, collagen deposition, and reepithelialization did not show significant differences. Nonetheless, concerning the collagen deposition score, except on day 35, the averages were higher in the experiment group. The angiogenesis scores on postoperative day 4, 7, 14, 21, and 35 were higher in the experiment group. Postoperatively, wound contraction was significantly greater in the experiment group, although they were not significant from postoperative day 14 onward. Conclusion: In the rat abdominal wound model, orally administered sildenafil accelerates wound healing by facilitating angiogenesis, and is beneficial during the process of wound contraction.