Research in Vestibular Science Vol. 15, No. 4, December 2016 Review pissn 2092-8882, eissn 2093-5501 https://doi.org/10.21790/rvs.2016.15.4.101 낙상위험을초래하는약물 계명대학교의과대학이비인후과학교실 이예원, 남성일 Medications as Risk Factor for Falls Ye Won Lee, Sung Il Nam Department of Otorhinolaryngology, School of Medicine, Keimyung University, Daegu, Korea Received Nov 15, 2016 Revised Nov 22, 2016 Accepted Nov 25, 2016 Corresponding Author: Sung Il Nam Department of Otorhinolaryngology, Keimyung University School of Medicine, 56 Dalseong-ro, Jung-gu, Daegu 41931, Korea Tel: +82-53-250-7715 Fax: +82-53-256-0325 E-mail: entnamsi@dsmc.or.kr Copyright c 2016 by The Korean Balance Society. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Falls are the most common cause of accidents among the older population, leading to both fatal and non-fatal injuries. Falls is a syndrome resulting from the cumulative effect of various extrinsic and intrinsic factors. It is considered to be a multifactorial disorder. Medication use is considered a risk factor for falls. We reviewed medications associated with falls in older individuals. In geriatrics populations, polypharmacy is associated with falls. Medical doctors should be aware of the possibility that starting a new medication, such as antihypertensive agents, benzodiazepine, antidepressants, opioid agents and antihistamines, may act as a trigger for the onset of a fall. Res Vestib Sci 2016;15(4):101-106 Keywords: Aged; Accidental falls; Polypharmacy; Medication 서론노인인구에서낙상은가장흔한사고중에하나로알려져있으며, 1 이사고로오랫동안지속되는통증과혹은불구로고생할수있으며, 또한사망에이를수도있다. 2 WHO의연령별발생률에의하면 64세이상노인에서 28% 35%, 70세이상에서는 32% 42% 의낙상이발생한다. 3 낙상은다양한내 외적인요인이축적되어나타나는사고이다. 내적요인으로는주로연령과관계된것으로시력저하, 청력감퇴, 골격근기능저하, 육체적활동감소, 만성병질환 ( 당뇨, 인지장애, 파킨슨병 ) 등을포함한다. 그리고외적요인으로는희미한불빛, 계단등의난간부족, 미끄 러지기쉬운바닥, 약물등이있다. 낙상의위험요인을줄이기위해서는다양한운동프로그램과환경평가와같은여러임상적인접근이필요하다. 4 여기에는보행과균형평가, 힘과균형운동그리고노인연령에서주로사용되고있는약제에대한평가가있다. 낙상예방을위한주요전략은수정가능한위험인자를확인하고변경하는것이다. 수정가능위험인자로는시력저하, 저혈압, 다중약물요법, 부적절한약물요법등이있다. 5 낙상의위험을증가시키는약물은주로심혈관계와중추신경계통약물이다. 예를들면향정신약물, 심장약, 진통제, 진정제, 항우울제, 벤조디아제핀, 항고혈압제, 디곡신등이다. 6-9 오랫동안처방을받은동일약물보다새롭게처 101
Res Vestib Sci Vol. 15, No. 4, Dec. 2016 음처방된약물로인해낙상의위험이좀더증가한다고한다. 또한노인층에서부적절한처방으로인해낙상이흔히발생한다고한다. 10,11 다중약물요법은특히노인층에서다양한노화와관련된질환을치료하기위해널리처방되고있는데 12 낙상의첫번째위험요소로여겨지고있다. 13,14 만성질환들로인해처방된많은약물들은다른약들간의상호작용으로인한부작용이일어남으로써낙상에이르게될수있다. 본고에서는현재까지알려진노인연령층에서의낙상위험을증가시키는다양한약물들을 (Table 1) 문헌고찰과함께살펴보고자한다. 본론 1. 다중약물요법 (polypharmacy) 낙상은노인에게서질병이환율및사망률증가와연관이깊은데, 특정한한개의약물혹은여러약물에의해발생할수있다. 65세이상노인중약 40% 이상이 5가지이상의약물을복용하고있다. 15 현재까지다중약물요법의정의에대한의견은아직분분하다 (Table 2). 16-20 문헌에는다중약물요법의약물개수를 2 9로다양하게기술하고있다. 21 약물부작용은청년연령보다노인연령에서 2 3배정도더높게발생하는데, 22 다중약물요법처방의빈도는연령이증가함에따라, 그리고허혈성심질환, 골다공증및고혈압과같은만성질환을많이앓을수록대체로증가한다. 16 Table 1. Drugs associated with increased risk of falls in older people Drug class Antihypertensives ACE inhibitors -blockers Diruretics Calcium channel blockers Type Ia antiarrhythmics Benzodiazepines Short acting Long acting Antidepressants Antiepileptics Antiparkinsonians Anticoagulants Narcotics/Opioids Antihistamine Examples Captopril,lisinopril, enalapril, perindopril, Ramipri Propronolol, atenolol, metoprolol Furosemide, spironolactone, amiloride Nipedipine, amlodipine, felodipine Quinidine, procainamide Lorazepam, alprazolam Diazepam, clonazepam SSRIs (fluoxetine, citalopram, Paroxetine) TCAs (imipramine, desipramine) Acetazolamide, carbamazepine, gabapentin Lovedopa, bromocriptine, pergolide, cabergoline Fentanyl, oxydodone, hydrocodone, morphine ACE, angiotensin converting enzyme; SSRIs, selective serotonin reuptake inhibitors; TCAs, tricyclic antidepressants. Table 2. Previously published definitions for polypharmacy Reference Veehof et al. 20 Brager and Sloand 17 Ziere et al. 18 Slabaugh et al. 16 Hovstadius et al. 19 Definitions of polypharmacy A long-term (240 days a year) simultaneous use of 2 drugs. They classified polypharmacy as minor (2 3 drugs), moderate (4 5 drugs), and major (>5 drugs) The use of 2 drugs to treat the same condition or the use of 2 drugs of the same chemical class; or the use of 2 agents with the same or similar pharmacologic actions to treat different conditions Use of 4 drugs with at 1 appropriate of fall-risk-increasing medications Simultaneous use of 5 drugs occurring for 1 day The use of multiple drugs with 5 drugs was termed as polypharmacy, whereas the use of 10 drugs was termed as excessive polypharmacy occurring within a period of 3 months. 102
이예원외 1 인. 낙상위험을초래하는약물 낙상한환자와낙상하지않은환자간의비교연구에서약물복용개수가많은환자에서낙상의위험률이증가했다. 23 문헌에의하면 4개, 5개이상 24 혹은 6개이상 25 의다중약물요법을하는경우에는통계적으로유의하게낙상의위험이높아진다고한다. 나이가들면생리기전의변화가생기며, 또한약역학및약물동력학에도변화를초래한다. 그래서신장및간청소율의감소로인해혈청내약물농도가상승되어약물독성으로발생할수있다. 그래서노인의경우다중약물요법으로인해상반된약물작용, 약물-약물간의상호작용과투약실수가생겨낙상의위험을증가시킬수있다. 26,27 반면에, 다중약물요법이낙상위험과연관성이없다는보고와적은수의약물을사용시에낙상이발생한다는보고도있다. 28 다중약물요법을단지약물개수에국한시켜의미를파악하기보다약물의부적절한처방과약물부작용에대한깊은연관성에대한평가가필요하다. 그리고다중약물요법은약동학을변경시켜예상치못한약물독성으로이어질수있으므로노인에게서약제사용에주의를요하는것은주의를요한다. 2. 항고혈압약물 (antihypertensive medication) 3. 정신과약물 (Psychotropic medication) 정신과약물과낙상위험의증가는깊은연관성이있다는보고들이많다. 25,30,38-40 특히, 진정제, 수면제, 항불안제및항우울제 sedatives and hypnotics, anxiolytics, antidepressants 는낙상위험증가와연관이많다. 그리고, 정신활성의약품을부적절히사용할경우비정신활성의약품보다낙상발생위험률이 60.3% 더증가할수있다. 41 1) 항우울약물항우울약물이낙상과상당한연관이있다는보고가있다. 25,31,32,39,42 종류에는 tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs) 와, SNRIs가있다. 특히 SSRIs는 TCAs 혹은 SNRIs 약제에비해더높은낙상발생률을나타낸다. 43,44 항우울약물로인해낙상이야기되는특별한기전이밝혀져있지는않지만흔한약물부작용 ( 기립성저혈압, 수면장애, 진정효과 ) 으로인해낙상이발생하며, 45 TCA 약물의부작용으로기립성저혈압이생길수있어또한낙상을일으킬수있다. 그러므로임상적으로노인에게안전하게항우울약물을권하기가어려우며약물투여시신중을기해야한다. 항고혈압약물은노인에서가장많이복용하는약물중에하나이며, 29 기립성저혈압을야기할수있기때문에낙상위험을증가시킨다. 하지만, 문헌을살펴보면항고혈압약물과낙상간에대립되는결과를나타내는보고들이있다. 즉, 항고혈압약제와낙상이통계학적으로유의한연관성이있다는보고 30-33 와, 낙상과는연관이없다는보고가있다. 34-37 이런상반된결과의이유는명백하진않지만각연구방법에서많은예상치못한변수들이있을것으로예상된다. 항고혈압제중칼슘채널차단제는낙상위험을감소시킨다는보고가있다. 30,31 반면에 angiotensin converting enzyme (ACE) 억제제는낙상위험을증가시킨다. 32 베타차단제는낙상위험을감소시키는데, 32 기전은미주신경성실신에대한베타차단제의보호효과로설명된다. 즉실신전카테콜라민함량이상승되는데베타차단제로인해감소된다. 이러한약물에작용들에는향후더연구가진행되어야할것으로생각된다. 2) 벤조디아제핀약물 (Benzodiazepines) 벤조디아제핀약물은노인낙상의주된위험요소중하나이다. 36 심지어저용량벤조디아제핀 ( 1 mg/day in diazepam) 이라도입원한노인환자인경우낙상과깊은연관이있으므로주의를요한다. 36 특히, 벤조디아제핀관련약물인 zolpidem, zolpiclone은주로수면장애시처방이되는데, 중추신경계부작용인혼란, 어지럼, 주간졸림등의부작용을일으켜입원환자에서상당한낙상위험을초래하는약물이다. 33,36 만성적인 zolpidem, temazepam약을복용하는경우는낙상의위험을증가시키지만급성치료로 lorazepam, alprazolam을사용할경우노인층의낙상을줄인다. 46 4. 마약성약물 opioids (narcotics) 마약성약물이낙상의위험을증가시킨다. 36,39,42 마약성약물은암환자의통증을조절해주는좋은이점도있지만약물부작용인어지럼증과졸림현상으로인해낙상의위 103
Res Vestib Sci Vol. 15, No. 4, Dec. 2016 험을증가시킨다. 암환자인경우마약성약물처방시적절한간호가필요하다. 5. 파킨슨, 치매치료약제들 Levodopa와같은파킨슨약물과 memantine과같은치매약물은낙상과연관이없다고한다. 34,46,47 한중요성을인식하지않고처방하는경우가많으므로, 노인의약용량과약물처방리스트를눈여겨볼필요가있다. 중심단어 : 노인, 낙상, 약물 CONFLICT OF INTEREST 6. 항히스타민제항히스타민제가낙상위험을증가시킨다. 36 항히스타민제의부작용인수면효과로수면제로도사용되는데인지장애 cognitive impairment를초래해낙상이될수있으므로노인에게처방시조심해야한다. 입원한노인암환자인경우 zolpidem, 벤조디아제핀, 마약성그리고항히스타민제는낙상과깊은연관이있음으로처방시감량과특별한주의를요한다. 36 7. 기타약물항혈소판제 antiplatelets가낙상위험이있다는뜻밖의보고가있다. 25,28 왜냐하면, 항혈소판제는심혈관계와중풍시혈관상태를완화시키는효과가있어서노인에게낙상위험이있다는보고는예상밖의일이다. 항부정맥제 antiarrhythmic agents, 대표적인 digoxin은낙상의위험을증가시킨다. 31 그리고, 기침혼합제와 28 실금 incontinence 조절약물이 46 낙상과연관이있다. 항간질약물 antiepileptics (anticonvulsants) 도낙상의위험을증가시킨다. 42 결론이상에서문헌에발표된약물들과노인에서의낙상위험연관성에대해정리를했다. 항고혈압제는아직논란의여지가있지만, 특히벤조디아제핀, 항우울제 (TCAs, SSRIs, SNRIs) 와마약제제는낙상의위험증가와밀접한관련이있다. 다중약물요법은노인에서만성질환을치료하기위해흔히처방되고있지만부적절하게처방될경우건강의적신호인낙상을야기할수있으므로노인에게약물사용은제한적이어야한다. 일반의사들은노인들이어지럼증을호소하지않을경우낙상의위험을증가시키는약물을처방할때낙상에대 No potential conflict of interest relevant to this article was reported. REFERENCES 1. Kwok T, Liddle J, Hastie IR. Postural hypotension and falls. Postgrad Med J 1995;71:278-80. 2. Centers for Disease Control and Prevention. Falls among older adults: an overview [Internet]. Atlanta: Centers for Disease Control and Prevention; 2013 [cited 2014 Jul 10]. Available from: http://www.cdc.gov/homeand RecreationalSafety/Falls/ adulttalis.html. 3. World Health Organization. Global report on falls prevention in older age [Internet]. Geneva: World Health Organization; 2007 [cied 2014 Sep 1]. Available from: http://www.who.int/ ageing/projects/falls_prevention_older_age/en/. 4. Panel on Prevention of Falls in Older Persons, American Geriatrics Society and British Geriatrics Society. Summary of the Updated American Geriatrics Society/British Geriatrics Society clinical practice guideline for prevention of falls in older persons. J Am Geriatr Soc 2011;59:148-57. 5. Ambrose AF, Paul G, Hausdorff JM. Risk factors for falls among older adults: a review of the literature. Maturitas 2013;75:51-61. 6. Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: I. Psychotropic drugs. J Am Geriatr Soc 1999;47:30-9. 7. Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: II. Cardiac and analgesic drugs. J Am Geriatr Soc 1999;47:40-50. 8. Gales BJ, Menard SM. Relationship between the administration of selected medications and falls in hospitalized elderly patients. Ann Pharmacother 1995;29:354-8. 9. Hendrich A, Nyhuis A, Kippenbrock T, Soja ME. Hospital falls: development of a predictive model for clinical practice. Appl Nurs Res 1995;8:129-39. 10. Bradley MC, Motterlini N, Padmanabhan S, Cahir C, Williams T, Fahey T, et al. Potentially inappropriate prescribing among older people in the United Kingdom. BMC Geriatr 2014;14:72. 11. Rognstad S, Brekke M, Fetveit A, Dalen I, Straand J. Prescription peer academic detailing to reduce inappropriate prescribing for older patients: a cluster randomised controlled trial. Br J Gen Pract 2013;63:e554-62. 104
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