의약품안전성 노인환자들에서낙상의위험을증가시킬수있는약물들 저자최선서울성모병원약제부 UM 약학정보원학술자문위원 개요 전세계적으로증가추세를보이고있는노인인구는의학적인측면에서는입원을요하거나장기적인의료서비스를필요로하는인구집단이다. 노인환자들에게중요한의학적이슈들은여러가지가있겠지만이

Size: px

Start display at page:

Download "의약품안전성 노인환자들에서낙상의위험을증가시킬수있는약물들 저자최선서울성모병원약제부 UM 약학정보원학술자문위원 개요 전세계적으로증가추세를보이고있는노인인구는의학적인측면에서는입원을요하거나장기적인의료서비스를필요로하는인구집단이다. 노인환자들에게중요한의학적이슈들은여러가지가있겠지만이"

윤영 목
5 years ago
Views:

1 의약품안전성 노인환자들에서낙상의위험을증가시킬수있는약물들 저자최선서울성모병원약제부 UM 약학정보원학술자문위원 개요 전세계적으로증가추세를보이고있는노인인구는의학적인측면에서는입원을요하거나장기적인의료서비스를필요로하는인구집단이다. 노인환자들에게중요한의학적이슈들은여러가지가있겠지만이중낙상관련상해는많은경우치명적일수있다. 낙상의위험요인은여러가지가있지만노인환자의경우는약물에의한낙상도주요원인중의하나인데, 이는연령이증가할수록복용하는약물이증가하는경향과함께특정약물군에의한낙상위험자체가증가하기때문일수있다. 노인환자들에서특히주의하여야할약물들의특징은기존에보고되어왔으나, 최근노인인구집단을기반으로하여흔히처방되는약품들과관련하여낙상으로입원한사례에대한연구결과가발표되어이를소개하고자한다. 키워드 노인환자, 낙상, 약물요법 1. 연구설계 1) 연구집단연구대상자들은스웨덴총인구등록부 (Swedish Total Population Register) 를사용하여 2006년 3월부터 2009년 12월까지낙상으로인해입원하게된 65세이상의노인환자 64,399명에대해진행되었다. 각시험대상자들에대해서는코호트군이사례별로연령, 생년월일, 주거지에의해매치된 4명의대조군이배정되었다. 2) 각사례및대조군의정의 - 사례 (case): 입원결과를가져온낙상상해를지속적으로보인환자로 ICD-10 질병분류에의해 W00-W19의상병명을가진환자로, 연구기간동안최초의낙상만을연구대상으로포함하였다. - 대조군 : 연구기간동안낙상으로입원한경력이없는사람들로이뤄진코호트군중에서무작위로선택하였다. 3) 약물에대한노출 - 일반적인약물 (common medications): 연구의색인날짜 (index date) 로부터 30일이전기간동안사용한약물을중심으로 20개의다빈도약물 ( 전산화된스웨덴처방약물시스템인스웨덴처방약등록부 (Swedish Prescribed Drug Register: SPDR) 를사용하여분류함 ) 1

2 2. 연구결과 총 64,399사례 ( 남성 22,190명, 여성 42,209명 ) 가선별되었으며이중 257,596명이대조군이었다. 이중 80-85세연령이 30.4% 로가장많은비중을차지하였으며그다음이 65-79세연령으로 29.4% 를차지하였다. 1) 다빈도처방약물 ( 표1) 시험대상자들에게처방된 20종의다빈도약물군의처방빈도는 0.5% 에서 15.3% 사이였으며, 대부분의경우 case 군이대조군보다높은약물처방빈도를나타내었고, 남성이여성보다높은빈도를나타내었다. 약물군중가장많이처방된약물군은항혈소판제제 ( 남성및여성에서각각 17.0% 및 14.4%) 와소화성궤양치료제 ( 남성및여성에서각각 8.6% 및 9.6%) 였다. 표 1. 성별로층화된가장일반적으로처방된약물의경향 Ref. The European Journal of Public Health Advance Access published July 31, ) 가장흔하게처방된약물에대한낙상상해오즈비 ( 표2) 시험대상자들에게처방된약물들중대부분의심혈관계약물과에스트로겐제제를제외하고는대부분의약물이낙상상해에대해양의상관관계를나타내었고, 이는성별간에차이가있었다. 약물수에대한보정전오즈비비교에서낙상상해에대한가장높은오즈비를보인약물군은남녀모두아편류제제 ( 남성및여성에서각각 OR=3.54 및 2.73) 이었고, 두번째로높은오즈비는항우울제에서나타났다 ( 남성및여성에서각각 OR=2.82 및 2.04). 약물군별로살펴보면심혈관계약물중남성및여성모두에서고효능이뇨제 ( 남성및여성에서각각 OR=1.94 및 1.52) 와항혈소판제제 ( 남성및여성에서각각 OR=1.63 및 1.56) 가낙상상해와높은상관관계를보였다. 또한비타민제제중에서 B12가비교적높은오즈비를보였다. 이외에도변비약, 항혈소판제제, 당뇨약, 갑상선제제등에서도이러한약물을복용하지않은환자군들에비해약물을처방받았던환자들에서오즈비가높게나타났다. 총약물수에대한보정이후에는이러한상관관계는유사하게유지되었으나, 남성환자의경우당뇨약과 2

3 NSAIDs 는약물수에대한보정이후해당약물로인해낙상에대한오즈비가증가되지않았다. 표 2. 노인환자에게서처방된약물에대한다빈도약물의낙상상해오즈비 a: 효과분류가수행되었음. PubMed 에서다음검색어를사용하여이전연구들이검색되었음 :name of the medications, fall injuries, fall risk and/or elderly b: 약물수에의해보정함, na: 해당사항없음 Ref. The European Journal of Public Health Advance Access published July 31, 고찰 본연구에서는대규모노인환자인구집단에대해노인환자군의건강에대한주요위험인자로작용할수있는낙상과처방약물간의상관관계를분석하였다. 다양한이유로노인환자들에게사용이제한되는약물들이많으나, 본연구에특히본연구에서는이전연구에서보고되지않았던, 항혈소판제제, 궤양치료제및비타민 B12와낙상상해간의양의상관관계가나타났으며, 이는환자들의기저질환도하나의인자로작용했을가능성이있다. 그러나이연구는일반의약품, 재원기간동안복용한약물에대한데이터는누락되었다는점과실제복약순응도가반영되지않았다는한계점이있음을고려하여야한다. 4. 결론 본연구에따른 노인에서빈번히처방되는약물들중낙상의위험증가로인해그사용의안전성에많은문 제를가진약물은매우소수였다. 또한, 본연구에서주의하여야할약물군들과기존에노인환자들에게처방시주의해야하는약물기준으로알려져있는미국노인병학회 (American Geriatric Society) 가제안하는 Beers Criteria( 표3) 에서제시된노인에서사용을제한해야하는약물군 ( 삼환성항우울제, 부정맥치료제, 발비츄레이트계열약제, 벤조디아제핀계항불안약등 ) 의오즈비가다소차이를보였다. 그러나낙상상해는노인환자들에게건강에있어중요한위험인자로작용하기때문에임상현장에서이러한약물들을사용하여야할때에는사용의이익과이에따른위험을평가하여신중하게사용할필요가있겠다. 3

4 표 American Geriatric Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adult Organ System or Therapeutic Category or Drug Anticholinergics (excludes TCAs) First-generation antihistamines (as single agent or as part of combination products) Brompheniramine Carbinoxamine Chlorpheniramine Clemastine Cyproheptadine Dexbrompheniramine Dexchlorpheniramine Diphenhydramine (oral) Doxylamine Hydroxyzine Promethazine Triprolidine Rationale Recommendation Quality of Evidence Highly anticholinergic clearance reduced with advanced age, and tolerance develops when used as hypnotic greater risk of confusion, dry mouth, constipation, and other anticholinergic effects and toxicity. Use of diphenhydramine in special situations such as acute treatment of severe allergic reaction may be appropriate Avoid Hydroxyzine and promethazine: high All others: moderate Strength of Recommendation Antiparkinson agents Benztropine (oral) Trihexyphenidyl Not recommended for prevention of extrapyramidal symptoms with antipsychotics more-effective agents available for treatment of Parkinson disease Avoid Antispasmodics Belladonna alkaloids Clidinium-chlordiazepoxide Dicyclomine Hyoscyamine Propantheline Scopolamine Highly anticholinergic, uncertain effectiveness Avoid except in short-term palliative care to decrease oral secretions Antithrombotics Dipyridamole, oral short acting* (does not apply to extendedrelease combination with aspirin) Ticlopidine* Anti-infective May cause orthostatic hypotension more-effective alternatives available intravenous form acceptable for use in cardiac stress testing Safer effective alternatives available Avoid Avoid Nitrofurantoin Potential for pulmonary toxicity safer alternatives available lack of efficacy in patients with CrCl < 60 ml/min due to inadequate drug concentration in the urine Avoid for long-term suppression avoid in patients with CrCl < 60 ml/min Cardiovascular Alpha1 blockers Doxazosin Prazosin Terazosin High risk of orthostatic hypotension not recommended as routine treatment for hypertension alternative agents have superior risk/benefit profile Avoid use as an antihypertensive Alpha agonists, central Clonidine Guanabenz* Guanfacine* Methyldopa* Reserpine (> 0.1 mg/d)* High risk of adverse CNS effects may cause bradycardia and orthostatic hypotension not recommended as routine treatment for hypertension Avoid clonidine as a first-line antihypertensive. Avoid others as listed Low 4

5 표 3. 계속 Organ System or Therapeutic Category or Drug Antiarrhythmic drugs (Class Ia, Ic, III) Amiodarone Dofetilide Dronedarone Flecainide Ibutilide Procainamide Propafenone Quinidine Sotalol Disopyramide* Dronedarone Digoxin > mg/d Nifedipine, immediate release* Rationale Recommendation Quality of Evidence Data suggest that rate control yields better balance of benefits and harms than rhythm control for most older adults. Amiodarone is associated with multiple toxicities, including thyroid disease, pulmonary disorders, and QT-interval prolongation Disopyramide is a potent negative inotrope and therefore may induce heart failure in older adults strongly anticholinergic other antiarrhythmic drugs preferred Worse outcomes have been reported in patients taking dronedarone who have permanent atrial fibrillation or heart failure. In general, rate control is preferred over rhythm control for atrial fibrillation In heart failure, higher dosages associated with no additional benefit and may increase risk of toxicity slow renal clearance may lead to risk of toxic effects Potential for hypotension risk of precipitating myocardial ischemia Avoid antiarrhythmic drugs as first-line treatment of atrial fibrillation High Avoid Low Avoid in patients with permanent atrial fibrillation or heart failure Strength of Recommendation Avoid Avoid High Spironolactone > 25 mg/d In heart failure, the risk of hyperkalemia is higher in older adults especially if taking > 25 mg/d or taking concomitant NSAID, angiotensin converting-enzyme inhibitor, angiotensin receptor blocker, or potassium supplement Avoid in patients with heart failure or with a CrCl < 30 ml/min Central nervous system Tertiary TCAs, alone or in combination: Amitriptyline Chlordiazepoxide-amitriptyline Clomipramine Doxepin > 6 mg/d Imipramine Perphenazine-amitriptyline Trimipramine Antipsychotics, first (conventional) and second (atypical) generation (see Table 8 for full list) Thioridazine Mesoridazine Highly anticholinergic, sedating, and cause orthostatic hypotension safety profile of low-dose doxepin ( : 6 mg/d) is comparable with that of placebo Increased risk of cerebrovascular accident (stroke) and mortality in persons with dementia Highly anticholinergic and risk of QT-interval prolongation Avoid High Avoid use for behavioral problems of dementia unless nonpharmacological options have failed and patient is threat to self or others Avoid 5

6 표 3. 계속 Organ System or Therapeutic Category or Drug Barbiturates Amobarbital* Butabarbital* Butalbital Mephobarbital* Pentobarbital* Phenobarbital Secobarbital* Benzodiazepines Short and intermediate acting: Alprazolam Estazolam Lorazepam Oxazepam Temazepam Triazolam Long acting: Clorazepate Chlordiazepoxide Chlordiazepoxide-amitriptyline Clidinium-chlordiazepoxide Clonazepam Diazepam Flurazepam Quazepam Rationale Recommendation Quality of Evidence High rate of physical dependence tolerance to sleep benefits risk of overdose at low dosages Older adults have increased sensitivity to benzodiazepines and slower metabolism of long-acting agents. In general, all benzodiazepines increase risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents in older adults May be appropriate for seizure disorders, rapid eye movement sleep disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, periprocedural anesthesia, end-of-life care Chloral hydrate* Tolerance occurs within 10 days, and risks outweigh benefits in light of overdose with doses only 3 times the recommended dose Meprobamate Nonbenzodiazepine hypnotics Eszopiclone Zolpidem Zaleplon Ergot mesylates* Isoxsuprine* Endocrine Androgens Methyltestosterone* Testosterone Desiccated thyroid Estrogens with or without progestins Growth hormone High rate of physical dependence very sedating Benzodiazepine-receptor agonists that have adverse events similar to those of benzodiazepines in older adults (e.g., delirium, falls, fractures) minimal improvement in sleep latency and duration Avoid High Avoid benzodiazepines (any type) for treatment of insomnia, agitation, or delirium High Strength of Recommendation Avoid Low Avoid Avoid chronic use (> 90 days) Lack of efficacy Avoid High Potential for cardiac problems and contraindicated in men with prostate cancer Concerns about cardiac effects safer alternatives available Evidence of carcinogenic potential (breast and endometrium) lack of cardioprotective effect and cognitive protection in older women Evidence that vaginal estrogens for treatment of vaginal dryness is safe and ffective in women with breast cancer, especially at dosages of estradiol < 25 lg twice weekly Effect on body composition is small and associated with edema, arthralgia, carpal tunnel syndrome, gynecomastia, impaired fasting glucose Avoid unless indicated for moderate to severe hypogonadism Weak Avoid Low Avoid oral and topical patch. Topical vaginal cream: acceptable to use low-dose intravaginal estrogen for the management of dyspareunia, lower urinary tract infections, and other vaginal symptoms Avoid, except as hormone replacement after pituitary gland removal Oral and patch: high Topical: moderate High Oral and patch: strong Topical: weak 6

7 표 3. 계속 Organ System or Therapeutic Category or Drug Insulin, sliding scale Megestrol Sulfonylureas, long duration Chlorpropamide Glyburide Gastrointestinal Metoclopramide Mineral oil, oral Trimethobenzamide Pain Meperidine Non COX-selective NSAIDs, oral Aspirin > 325 mg/d Diclofenac Diflunisal Etodolac Fenoprofen Ibuprofen Ketoprofen Meclofenamate Mefenamic acid Meloxicam Nabumetone Naproxen Oxaprozin Piroxicam Sulindac Tolmetin Indomethacin Ketorolac, includes parenteral Pentazocine* Skeletal muscle relaxants Carisoprodol Chlorzoxazone Cyclobenzaprine Metaxalone Methocarbamol Orphenadrine Rationale Recommendation Quality of Evidence Higher risk of hypoglycemia without improvement in hyperglycemia management regardless of care setting Minimal effect on weight increases risk of thrombotic events and possibly death in older adults Chlorpropamide: prolonged half-life in older adults can cause prolonged hypoglycemia causes syndrome of inappropriate antidiuretic hormone secretion. Glyburide: greater risk of severe prolonged hypoglycemia in older adults Can cause extrapyramidal effects including tardive dyskinesia risk may be even greater in frail older adults Potential for aspiration and adverse effects safer alternatives available One of the least effective antiemetic drugs can cause extrapyramidal adverse effects Not an effective oral analgesic in dosages commonly used may cause neurotoxicity safer alternatives available Increases risk of GI bleeding and peptic ulcer disease in high-risk groups, including those aged > 75 or taking oral or parenteral corticosteroids, anticoagulants, or antiplatelet agents. Use of proton pump inhibitor or misoprostol reduces but does not eliminate risk. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 6 months and in approximately 2 4% of patients treated for 1 year. These trends continue with longer duration of use Increases risk of GI bleeding and peptic ulcer disease in high-risk groups. (See above Non-COX selective NSAIDs.) Of all the NSAIDs, indomethacin has most adverse effects Opioid analgesic that causes CNS adverse effects, including confusion and hallucinations, more commonly than other narcotic drugs is also a mixed agonist and antagonist safer alternatives available Most muscle relaxants are poorly tolerated by older adults because of anticholinergic adverse effects, sedation, risk of fracture effectiveness at dosages tolerated by older adults is questionable Avoid Avoid Avoid High Avoid, unless for gastroparesis Strength of Recommendation Avoid Avoid Avoid High Avoid chronic use unless other alternatives are not effective and patient can take gastroprotective agent (proton pump inhibitor or misoprostol) Avoid Indomethacin: moderate Ketorolac: high Avoid Low Avoid * Infrequently used drugs. CNS = central nervous system; COX = cyclooxygenase; CrCl = creatinine clearance; GI = gastrointestinal; NSAID = nonsteroidal anti-inflammatory drug; TCA = tricyclic antidepressant. 7

8 약사 Point - 노인환자에서낙상상해는일반적으로처방받는다빈도약물에의해서도빈번히발생할수있는약물이상반응이다. - 노인환자에게약물치료를시행함에있어다빈도처방약물에의한낙상상해이상반응을유의하여야할필요가있다. 참고문헌 1. The European Journal of Public Health Advance Access published July 31,

<B3EBC0CEC8AFC0DAC0C75FBEE0B9B0BFE4B9FD FC0FAC0DAB0CBC5E4BFCFB7E12E687770>

<B3EBC0CEC8AFC0DAC0C75FBEE0B9B0BFE4B9FD FC0FAC0DAB0CBC5E4BFCFB7E12E687770> 노인환자의약물요법 (1) 저자남궁형욱분당서울대학교병원특수조제팀장약학정보원학술자문위원 개요 노인환자에서약물과관련된부작용은매우흔하게발생하며, 이로인해치료비용은증가하고치료결과에도나쁜영향을미치게된다. 이전연구에따르면외래및장기요양시설에서발생한부작용의약 40% 는예방이가능하며노인환자에서약물과관련된부작용을감소시키기위해서는고위험약물과부적절한약물의사용을피하는것이단순하면서가장효과적인방법인것으로알려져있다.