대한안과학회지 2015 년제 56 권제 9 호 J Korean Ophthalmol Soc 2015;56(9):1473-1478 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) http://dx.doi.org/10.3341/jkos.2015.56.9.1473 Case Report 실데나필시트르산염과다복용후발생한색각이상및시야감소 1 예 A Case of Transient Color Anomaly and Persistent Visual Field Defect after Sildenafil Citrate Overdose 김패트릭 김소영 Patrick Kim, MD, So Young Kim, MD 순천향대학교의과대학천안병원안과학교실 Department of Ophthalmology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea Purpose: Sildenafil citrate, is an oral tablet demonstrating efficacy for maintaining an erection in males with erectile dysfunction by inhibiting phosphodiesterase type 5 (PDE5). In the present study, we report 1 case of a transient color anomaly with visual field defect after an overdose of sildenafil citrate. Case summary: One patient, a 39-year-old female, with no significant medical history other than previous major depressive disorder, visited an outpatient department due to the visual field defect that began after taking 30 tablets of sildenafil citrate (50 mg) 3 days earlier. A number of ophthalmologic tests were administered including visual acuity test, color vision test, fundus photography and the measurement of retinal structure with optical coherent tomography and her condition was monitored. The best corrected visual acuity was 1.0 in both right and left eyes in her first visit. The color anomaly and a central scotoma of both eyes were detected in the visual field test, while significant signs were not observed after evaluation using optical coherent tomography and fundus photography. After 5 weeks, the visual acuity was not affected, the color anomaly symptom disappeared and the focal visual field defect was present although improved. Conclusions: Transient color anomaly and persistent central scotoma caused by an overdose ingestion of sildenafil has not been reported in Korea, The related mechanisms may involve the inhibition of PDE5 on ganglion cells and bipolar cells in the retina and interruption of phosphodiesterase type 6 (PDE6) function in both rods and cones. J Korean Ophthalmol Soc 2015;56(9):1473-1478 Key Words: Color anomaly, Sildenafil citrate, Visual field defect Sildenafil citrate는선택적으로 cyclic guanosine mono- phosphate (cgmp) 에특이적인 phosphodiesterase type 5 (PDE5) 를억제하여발기를지속시키는경구용발기부전 Received: 2015. 2. 27. Revised: 2015. 4. 21. 치료제이다. 또 sildenafil은망막의광수용체에도작용하여 Accepted: 2015. 7. 23. 신경신호로의전환을매개하는 phosphodiesterase type 6 Address reprint requests to So Young Kim, MD Department of Ophthalmology, Soonchunhyang University (PDE6) 억제를통해일시적인안증상등을유발할수있다 Cheonan Hospital, #31 Suncheonhyang 6-gil, Dongnam-gu, 고알려져있다. 1 현재해외에서 sildenafil 복용후발생된 Cheonan 31151, Korea Tel: 82-41-570-2114, Fax: 82-41-592-3810 비동맥염성앞허혈시신경병증, 망막분지동맥폐쇄, 동안신경 E-mail: ophdrkim@gmail.com * This study was presented as a poster at the 112th Annual Meeting 마비, 결막하출혈, 색각이상, 일시적인시력소실, 망막전위도변화등이보고된바있으며국내에서는망막출혈과급 of the Korean Ophthalmological Society 2014. 성폐쇄각발작, 하직근비대가보고된바있다. 2-7 * This work was supported by the Soonchunhyang University Research Fund. 저자들은 sildenafil citrate를과다복용한후발생한일시적 c2015 The Korean Ophthalmological Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 1473
- 대한안과학회지 2015 년제 56 권제 9 호 - A B Figure 1. Fundus photographs at the first visit. These show no specific lesion on the right eye (A) and left eye (B). 인색각이상및시야감소를경험하여이를보고하고자한다. 증례보고 39세여자환자는특별한전신적질환없이예전에주요우울장애로치료받았던과거력이있던환자로내원 4일전자살목적으로 sildenafil (Viagra, Pfizer, New York, NY, USA) 50 mg 30 tablets (1,500 mg) 를한번에복용후시작된시야가좁아진듯한증상으로내원하였다. 안증상이외에두통, 홍조, 소화불량, 코충혈등의전신적인증상은보이지않았다. 환자는특별한안과적과거력은없었고내원시나안시력은우안 0.4, 좌안 0.8, 교정시력은우안 (1.0), 좌안 (1.0) 이었다. 안압은우안 12 mmhg, 좌안 8 mmhg였고, 양안모두전안부나안저검사 (Fig. 1) 상특이소견은관찰되지않았으며빛간섭단층촬영 (Spectralis OCT, Heidelberg engineering, Heidelberg, Germany) (Fig. 2), 대광반사모두정상소견을보였고구심성동공장애는보이지않았다. 이시하라색각검사 (Ishihara s test for color deficiency, 24 plates edition, 2005, Kanehara & Co. Ltd., Tokyo, Japan) 에서전색약, 전색맹에해당하는소견을보였으며시야검사 (Humphrey Instruments, San Leandro, CA, USA) 에서중심암점이확인되었다. 내원 1주후에도색각이상은지속되었으며, 중심암점은약간호전되었지만여전히남아있는상태였다. 경과관찰약 5주후색각이상은소실되었으나시야검사는약간호전되는양상이었지만중심암점이지속되었다 (Fig. 3). 환자의시력변화는없었고빛간섭단층촬영도정상이었다. 고찰 Sildenafil citrate 는음경해면체의 cgmp 특이 PDE5 를 억제하여 cgmp 농도를증가시키며혈관평활근의확장을유도하는산화질소 (Nitric oxide) 의작용을증가시켜발기를지속시키는작용을한다. Sildenafil citrate는망막의광수용체에존재하는 PDE6도 10% 정도억제하는데 PDE6의경우 cgmp에서 guanosine monophosphate (GMP) 로의전환을유도하게되며억제시 cgmp의농도가일정수준이상으로지속되어일시적인색시증과 ( 주로청색, 청색-녹색착색 ) 광감수성증가를보일수있다. 또 sildenafil은심혈관계에작용하여전신적인혈압을낮추는것으로알려져있으며, 이를통해맥락막순환에영향을끼쳐망막출혈, 망막정맥폐쇄, 비동맥염성앞허혈시신경병증등을일으킬수있다. 1 현재전세계적으로 sildenafil 복용후발생한안합병증에대한보고는부족한상황이다. Fraunfelder et al 2 은 5명의 sildenafil 복용이후발생한 5예의허혈성시신경병증증례를보고하였는데저자들은 sildenafil 복용후생긴 nitric oxide 증가에따른혈관확장에의한혈류변화로인한시신경의허혈성변화로추정하고있다. Tripathi and O Donnell 3 은특별한과거력이없던 69세남자에서 sildenafil citrate 100 mg 복용수시간후발생한망막분지동맥폐쇄에대해처음으로보고하였는데저자들은갑작스런안압증가혹은일시적으로나타난부정맥으로인한색전현상에의한것으로추론했다. Donahue and Taylor 4 는 sildenafil citrate 50 mg을복용한 50갑년의흡연력이있는 56세남자에서 sildenafil citrate 복용 36시간후에동공을침범하지않는동안신경마비발생을보고한바있으며이는오랜흡연으로생긴미세혈관질환때문에발생한동안신경의일시적인관류저하를원인으로추론하였다. 국내에서는 Jang et al 5 이 71세남자환자에서 2달동안 100 mg의 sildenafil citrate를간헐적으로복용한지 2일후단안에서발생한망막출혈을보고한바있으며이를 2달간의다소고용량의 sildenafil 복용에따른전신적혈역동학적인변화에따른안 1474
- 김패트릭 김소영 : 약물과다복용후발생한시기능저하 - A B C D E F G H Figure 2. (A, B, C, D) Initial (upper) and (E, F, G, H) after 5 weeks (below) optical coherent tomography showed no abnormality on macula and optic disc. RNFL = retinal nerve fiber layer; TS = superotemporal; NS = superonasal; T = tempora ; G = general; N = nasal; TI = inferotemporal; NI = inferonasal; TMP = temporal; SUP = superior; NAS = nasal; INF = inferior. 내혈류의증가와울혈에기인하는현상이라추론하였다. Lee and Seong 6 은 63세남자환자에서 sildenafil citrate 복용 5시간후발생한양안급성폐쇄각발작을보고하였으며이를성적자극에의한동공확장, 중력에의한수정체의 전방이동, 맥락막혈류증가에따른맥락막의부피증가로인한홍채와수정체의전방이동등이복합적으로작용한결과라추정하였다. 또한 Jung et al 7 은 58세남자환자가 2 주전부터 3차례에걸친 sildenafil 복용이후발생한단안 1475
- 대한안과학회지 2015년 제 56 권 제 9 호 - A B C D E F Figure 3. The patient s visual field tests. (A, B) Initial (1st row), (C, D) after 1st week (2nd row) (E, F) and 5th week (3rd row) showed central scotoma on both eyes. POS = positive; NEG = negative; ASB = apostilb; SITA = Swedish Interactive Threshold algorithm; RX = prescription; DS = diopter sphere; DC = diopter cylinder; GHT = glaucoma hemifield test; M D = mean deviation; PSD = pattern standard deviation. 1476
- 김패트릭 김소영 : 약물과다복용후발생한시기능저하 - 의하직근비대를보고하였으며이에대한기전은명확치않으나약의부작용인과관계를평가하는 Naranjo probability scale에대입시 probable 의관계를보였다고보고하였다. Sildenafil을이용한임상시험에서경미한색각저하가 2% 에서보고되었으며, 8 이는일시적이고가역적인색구별의저하 ( 주로청색-녹색영역 ) 로나타난다. 9 이러한색각저하는 sildenafil의혈장농도가최고치에이르는복용후 1시간이후에잘나타나며 4-8시간이후되돌아오는것으로보고되었다. 10 색각저하는약물용량에의존하여변하는양상을보이는데약물용량이 25 mg 혹은 50 mg 정도의저용량에서는약 3% 정도로소수에서만나타나며, 100 mg에서는 11%, 200 mg에서는거의 50% 의환자에서나타난다. 광감수성증가나색각저하등의기전은아직확실하게밝혀지진않았지만, 추체광수용체의 cgmp의변화에따른색깔과빛정보의신경전달과정의변화에따른것으로추정하고있다. 1 PDE5는망막, 맥락막의혈관벽을포함하는혈관벽의내피세포, 평활근세포및망막의두극세포, 신경절세포에존재하며, 이중망막의두극세포와신경절세포는일종의필터역할로써시신호가신경신호로전환될때가장먼저작용하는것으로알려져있다. 11-14 본증례에서는특별한전신질환이없던환자가추천용량을초과하는고용량을한번에복용후발생한색각이상및시야감소로볼때 sildenafil에의한안증상으로사료되며, 복용후경과관찰 1주까지는색각이상과시야감소를동시에보였으나 5주후에는색각이상은소실되었으며지속되는중심암점을보였다. 이러한기전에관해서단언할수는없지만아마도과량의 sildenafil 복용후에주로황반의기능을보조하는신경절세포및두극세포에존재하는 PDE5 억제로발생된시신호전달과정의장애로인한시야감소및 PDE6 억제에따른추체광수용체의 cgmp 변화로인한색각이상으로추정할수있다. 결론적으로아직까지는세계적으로나국내에서나 sildenafil 복용과관련된안증상과합병증에관한증례보고나연구가부족한상황이며, sildenafil의추천용량을넘어서는 고용량을한번에복용할경우본증례와같이일시적인색각이상과지속적인중심암점과같은시기능저하가나타날수도있음을인지해야할것이다. REFERENCES 1) Marmor MF. Sildenafil (Viagra) and ophthalmology. Arch Ophthalmol 1999;117:518-9. 2) Fraunfelder FW, Pomeranz HD, Egan RA. Nonarteritic anterior ischemic optic neuropathy and sildenafil. Arch Ophthalmol 2006; 124:733-4. 3) Tripathi A, O Donnell NP. Branch retinal artery occlusion; another complication of sildenafil. Br J Ophthalmol 2000;84:934-5. 4) Donahue SP, Taylor RJ. Pupil-sparing third nerve palsy associated with sildenafil citrate (Viagra). Am J Ophthalmol 1998;126:476-7. 5) Jang YS, Ahn GS, Kim SD. Retinal hemorrhage associated with viagra (sildenafil citrate). J Korean Ophthalmol Soc 2002;43:1340-4. 6) Lee WJ, Seong M. Bilateral simultaneous acute angle closure glaucoma following sexual intercourse aided by sildenafil citrate. J Korean Ophthalmol Soc 2011;52:1123-7. 7) Jung YH, Lee NY, Yim HB. A case of inferior rectus muscle enlargement after taking sildenafil citrate. J Korean Ophthalmol Soc 2013;54:382-6. 8) Jackson G, Montorsi P, Cheitlin MD. Cardiovascular safety of sildenafil citrate (Viagra): an updated perspective. Urology 2006; 68(3 Suppl):47-60. 9) Laties A, Ellis P, Koppiker N, et al. Visual function testing in patients and healthy volunteers receiving VIAGRA. Ophthalmic Res 1998;30(Suppl 1):177. 10) Laties A, Zrenner E. Viagra (sildenafil citrate) and ophthalmology. Prog Retin Eye Res 2002;21:485-506. 11) Foresta C, Caretta N, Zuccarello D, et al. Expression of the PDE5 enzyme on human retinal tissue: new aspects of PDE5 inhibitors ocular side effects. Eye (Lond) 2008;22:144-9. 12) Trexler EB, Li W, Massey SC. Simultaneous contribution of two rod pathways to all amacrine and cone bipolar cell light responses. J Neurophysiol 2005;93:1476-85. 13) Dacey DM, Liao HW, Peterson BB, et al. Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN. Nature 2005;433:749-54. 14) Nirenberg S, Carcieri SM, Jacobs AL, Latham PE. Retinal ganglion cells act largely as independent encoders. Nature 2001;411: 698-701. 1477
- 대한안과학회지 2015 년제 56 권제 9 호 - = 국문초록 = 실데나필시트르산염과다복용후발생한색각이상및시야감소 1 예 목적 : Sildenafil citrate 는선택적으로 phosphodiesterase type 5 (PDE5) 를억제하여발기를지속시키는경구용발기부전치료제로널리사용되는약제이다. 본저자는 sildenafil citrate 과다복용이후에발생한색각이상및시야감소 1 예를보고하고자한다. 증례요약 : 특이전신질환이없던 39 세여자환자가내원 3 일전자살목적으로 sildenafil citrate 50 mg 30 알을복용후시작된시야감소를주소로내원하였다. 교정시력우안 (1.0), 좌안 (1.0) 이었으며빛간섭단층촬영및안저검사상특이소견은발견되지않았으나, 색각이상및시야검사에서중심암점이관찰되었다. 경과관찰 5 주간시력변화는없었으며색각이상은소실되었으나, 시야는호전되는양상이지만결손은남아있었다. 결론 : Sildenafil 의추천용량을넘어서는고용량을한번에복용할경우일시적인색각이상과지속되는중심암점과같은시기능저하가나타날수있다. < 대한안과학회지 2015;56(9):1473-1478> 1478