Review Article J Clin Nutr 2014;6(1):11-18 ISSN 2289-0203 노인환자에서의약물과영양소의상호작용 노주현 분당서울대학교병원약제부 Drug-nutrient Interactions in Elderly Patients Department of Pharmacy, Seoul National University Bundang Hospital, Seongnam, Korea Physiological changes associated with aging affect the absorption, distribution, metabolism, and excretion of drugs and thus therapeutic outcomes. These changes may be further amplified by interactions with nutrients. The purpose of this review was to summarize drug-nutrient interactions found in elderly patients. Mechanisms of the interactions can be categorized as ex vivo bio-inactivations, interactions in absorption and elimination phases, and physiological interactions. The goal of enteral nutrition (EN) is to maximize the therapeutic response of medication without adversely affecting EN tolerance. Therefore, to ensure safety, consistent monitoring is necessary for enteral feeding of patients receiving medication via an enteral tube. Elderly patients receiving parenteral nutrition (PN) are often treated concomitantly with medication via the parenteral route. The stability and compatibility of PN formulations infused with other additives, including medication, may be influenced. Limitation of the number of prescriptions to essential medications only during the minimum period along with periodic re-evaluations of the treatment are thus necessary to minimize undesirable drug-nutrient interactions in elderly patients. Key Words: The elderly, Drug-food interactions, Nutritional support 서 론 노화가진행될수록신체구성이변하고질병에대해취약할뿐만아니라사회적고립, 경제적생활변화, 심리적위축등이동반된다. 또한독거가구, 치매, 뇌졸중등은일상생활능력을감소시켜불량한영양상태를초래할수있다. 미국조사에따르면지역사회에서노인의 5% 10% 가영양불량상태이며요양시설 Received Dec 2, 2013; Revised Feb 14, 2014; Accepted Feb 18, 2014 Correspondence to Department of Pharmacy, Seoul National University Bundang Hospital, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam 463-707, Korea Tel: +82-31-787-3886, Fax: +82-31-787-4034, E-mail: 30031@snubh.org Conflict of interest: None. 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. 에장기체류하는경우에는 37% 85% 으로영양불량상태비율이큰폭으로증가된다고보고된바있다. 1 우리나라의경우에도 65세이상노인중 41% 가권장량보다적은열량섭취를하고있으며단백질섭취가부족한노인도 35.8% 에이르는것으로조사되었다. 2 노인환자는영양불량으로인해질환이환율이나사망률을증가시킬수있으므로적절한영양지원이필요하다. 뿐만아니라다약제복용과생리학적변화로인해약물상호작용이나약물유해반응위험성이증가하므로안전한약물요법이필요하다. 지금까지약물상호작용에대한연구는많이진행되었고관심이많았지만약물과영양소의상호작용에대해서는간과되어왔다. 약물과영양소의상호작용은약물과영양소간에물리적 (physical), 화학적 (chemical), 생리학적 (physiological), 병태생리학적 (pathophysiologic) 상호작용으로인해약물이나영양소의약물동태학적 (pharmacokinetic) 또는약물동력학적 (pharmacodynamic) 변화가발생하는것을말한다. 3 약물과영 c 2014, The Korean Society for Parenteral and Enteral Nutrition. All Rights Reserved.
양소간에는밀접한상관관계가있어약물요법으로인해영양소의생체내항상성 (homeostasis) 이깨질수있으며반대로섭취된영양소에의해약물의효과가감소되거나부작용이발생할수도있다. 그러므로노인환자에서주의해야하는약물과영양소의상호작용에대해알아보고자한다. 본론 1. 노화과정 (aging process) 에따른약물과영양소의변화노화에따른약동학적특성의변화는흡수, 분포, 대사, 배설의모든과정에서발생하므로단계별생체내변화를이해해야약물과영양소간의상호작용을예측하고예방할수있다 (Fig. 1). 먼저흡수단계에서는노화가진행되면서치아의소실, 침분비감소로인해저작이나연하 (swallowing) 능력이저하된다. 특히, 고령의암환자에서는항암요법과방사선요법으로인해미각과후각능력이저하되며우울증, 치매가동반된경우에는식욕부진이발생하여음식이나약을섭취하는데방해가된다. 그외에도장연동운동 (peristalsis), 위산분비, 위장관의혈류량, 소장표면적이감소되어약물이나음식의생체이용률이감소될수있다. 예를들면위축성위염에서위내저산증을유발하고칼슘, 철분, 엽산, 비타민 B 12, 비타민 B 6 의생체이용률 (bioavailability) 이저하될수있다. 분포단계에서는제지방체중 (lean body mass), 수분, 혈장알부민농도는감소되는반면체지방은증가하며혈액뇌장벽 (blood-brain barrier) 의투과율이증가하게된다. 대사를담당하는간 (liver) 의경우간실질세포와대사효소의감소, 간혈류량감소로인해대사능이저하된다. 마지막으로배설의주된경로인신장에서는사구체여과율 (glomerular filtration rate) 이감소되어신배설되는약물이나영양소의대사산물의배설이되지않아독성이나부작용등이 발생할수있다. 3 노인환자의영양불균형혹은부족증의원인은매우다양하다 (Table 1). 4 치아를포함한구강상태불량은노인환자의경구섭취를어렵게하는주된원인이되며노화로인한미각, 후각, 시각능력저하는식욕감소의원인이된다. 또한, 동반하고있는당뇨병, 고혈압, 관절염등만성질환은그자체로영양부족을유발할수있다. 만성질환을치료하는여러가지약물들이식욕저하를유발하고약물과영양소의상호작용또한영양소의이용률을변화시킨다. 특히, 시설에거주하는노인환자의경우다량영양소 (macronutrients) 에비해미량영양소 (micronutrients) 의결핍이자주발생한다고보고된바있다. 5 시설에거주하는노인환자의 90% 이상이비타민 E, calcium, 엽산의일일권장량 (recommended daily allowance) 보다부족하게섭취하였으며비타민 B 6, 아연은 80% 이상이권장량보다부족하게섭취하였다. 6 이러한영양불균형은면역기능의감소로감염위험이증가할수있으며지역획득성폐렴 (community-acquired Table 1. Risk factors for drug-nutrient interactions in the elderly Appetite suppression (anorexia) Appetite stimulation Diminished nutrient absorption; toxicity to mucosal cells Facilitate renal elimination Decreased nutrient use Inhibition or facilitation with metabolism or transport system Hormonal effects of nutrients Received enteral nutrition Multiple medications Indirect effect due to components of drug formulation Antagonism/competitive interaction (e.q., warfarin vs. vitamin K) Socioeconomic status Adapted from the article of Morley et al. Ann Intern Med 1988; 109(11):890-904. 4 Fig. 1. Overview of pathophysiologic conditions in the elderly. 12 Journal of Clinical Nutrition
Drug-nutrient Interactions in Elderly Patients pneumonia) 에감염된노인환자의 85% 가영양불량상태임을보고한바있다. 7 신체적인문제외에도사회경제적문제도노인의영양불량을악화시키는원인이될수있다. 예를들면경제적어려움, 독거와일상생활능력의저하로인해식사를거르거나복약순응도가감소될수있으므로사회경제적지지도매우중요하다. 8 2. 약물과영양소간의상호작용기전 9,10 약물과영양소간의상호작용은기전이나생리학적반응에따라 4가지유형으로구분되며, 대표적인예들은 Table 2에제시되어있다. 먼저, 유형 1은체외에서발생하는생체불활성화 (ex vivo bio-inactivations) 로약물이나영양소가체내투여되기전물리화학적반응이발생하는것이다. 이반응은경장액이나정맥영양액에약물을혼합하면서발생하는경우가빈번하다. 유형 1의상호작용을예방하는가장좋은방법은상호작용이확인되지않은약물들은별도로투여하는것이다. 유형 2는흡수단계에서의상호작용 (absorption phase-associated interactions) 으로, 약물이나영양소가경구나경관을통해섭취된후위장관에서흡수되는단계에발생한다. 이상호작용은임상에서가장 흔하게접하는상호작용으로원인이되는약물이나영양소가효소 (enzyme, type IIA) 나수송단백질 (transport protein, type IIB) 의기능을변형시켜전신순환이되기전에대상물질이생체내변화 (biotransformation) 가발생하는것이다. 또한, 위장관에서이동하는동안복합화 (complexation) 되거나결합또는불활성화과정 (type IIC) 이발생할수있다. 그러나, 대부분의경우해당약물이나영양소를따로복용하도록투여스케줄을계획하면유형 2 상호작용은최소화할수있다. 유형 3은생리학적반응으로인한상호작용 (physiologic action-associated interactions) 으로흡수된후약물이나영양소가분포, 대사되는과정에서발생할수있으며유형 2와다르게별도로복용하더라도상호작용이발생할수있으므로적절한치료효과와부작용예방을위해서약물변경및용량조절이필요하다. 유형 4 는배설단계에서의상호작용 (elimination phase-associated interactions) 은변형, 길항작용에의해신장이나장간 (enterohepatic) 배설이원활하게진행되지않는경우이다. 3. 약물이영양상태나대사에미치는영향노인환자에게흔한만성질환에는암, 만성폐쇄성폐질환, 심부 Table 2. Examples of drug-nutrient interactions according to the mechanism-based classification system Interaction type Precipitant agents Object agents Proposed mechanism Clinical outcome Type I Type IIA Type IIB Type IIC Type III Type IV Continuous enteral nutrition Grapefruit juice Valproic acid Oral calcium supplements Tyramine (large amount) Dietary sodium restriction Levothyroxine Cyclosporine L-carnitine Ciprofloxacin (oral) Rasagiline Lithium Poor dissolution of levothyroxine tablets; possible absorption to tubings Inhibition of intestinal CYP3A4 enzyme by grapefruit juice, leading to an increased oral bioavailability of cyclosporine Competitive inhibition of intestinal SLC22A transport protein, leading to malabsorption of dietary carnitine Chelation and complexation of ciprofloxacin by calcium ions Rasagiline is MAOI-B. Although the interaction potential with tyramine is lower than that of MAOI-A, ingestion of a large amount of tyramine may still lead to the cheese reaction Sodium restriction can enhance the renal tubular reabsorption of drugs such as lithium Adapted from the article of Chan. JPEN J Parenter Enteral Nutr 2013;37(4):450-9. 10 MAOI-B = type B monoamine oxidase inhibitor; MAOI-A = type A monoamine oxidase inhibitor. Risk of developing subclinical to overt hypothyroidism overtime Elevation of blood cyclosporine concentration that may lead to symptomatic toxicity Symptomatic carnitine deficiency (hyperammonemia and acute altered mental status without evidence of hepatic injury) in susceptible patients Significant reduced oral bioavailability of ciprofloxacin; possible treatment failure Hypertensive crisis secondary to the presence of a large amount of epinephrine in the systemic circulation Lithium toxicity Volume 6, Number 1, April 2014 13
전, 관상동맥질환, 치매, 당뇨, 고혈압그리고골다공증등이있으며이런만성질환들의치료를위해복용하는여러가지약제들에의해영양상태나대사에변화를줄수있다. 예를들면, theophylline, digoxin에의해오심, 식욕감소가발생하고이뇨제, 항히스타민제, 항콜린제에의해구강건조증이발생할수있다. 마약성진통제, 항콜린제, 항정신병약제등에의해위장관운동이감소되는반면 erythromycin, 위장관운동촉진제 (prokinetics) 에의해위장관운동이항진될수있다. Phenytoin의경우 folic acid 대사를항진시켜결핍이유발될수있고, isoniazid 는 vitamin B 6 의활성형으로의전환을길항하여 vitamin B6의결핍이발생할수있다 (Table 3). 11 이와같이노인환자의경우, 기저질환으로인해다약제를복용하거나노화에따른생체내변화로인해여러가지약물부작용이빈번하게나타나고약물부작용으로인해영양상태나대사에다양한영향을미칠수있으므로주의가필요하다. 4. 영양소가약물의효과에미치는영향반대로음식이나영양소에의해약물의흡수나대사가영향을받아약물의효과가변할수있다. 심혈관계약제중에서 captopril은 음식에의해생체이용률이약 30% 40% 까지감소될수있어식전 1시간또는식후 2시간복용이추천되며 nifedipine, felodipine을자몽이나자몽주스와함께섭취할경우생체이용률이약 30% 이상증가되어부작용이나독성이증가할수있으므로물과함께복용하도록추천한다. Vitamin K 길항체인 warfarin은청국장과같은고함량의 vitamin K가포함된식이를할경우 warfarin의효과가길항되어항응고효과가감소될수있으므로 warfarin 복용환자의경우일일 vitamin K 섭취량을 150 mcg 이하로제한하고있다. 12 뇌신경계약물중에서파킨슨병의일차치료제인 levodopa/carbidopa는고단백식이를할경우 levodopa가위장관과혈액뇌장벽 (blood brain barrier) 으로수송될때경쟁적으로저해되어항파킨슨효과가감소될수있다. 결핵약제인 rifampin, isoniazid는음식에의해흡수가감소될수있으므로공복에복용하도록추천한다. Fluoroquinolone계항생제는 2가, 3가양이온이포함된식이를할경우양이온과킬레이트화 (chelation) 가발생하여항생제의흡수가저해되므로식사 2시간전또는식후 6시간복용을추천한다 (Table 4). 13 Table 3. Effects of drugs on nutrition and metabolism Metabolic alteration Predisposing medication Appetite or taste Anorexia Stimulate appetite Xerostomia Bad taste Decrease taste Affect taste acuity GI effects Nausea/Vomiting Gastritis or ulcers Intestinal motility Intestinal motility Damage GI tract mucosa Diarrhea Pancreas Exacerbate pancreatitis Alter pancreatic secretion Alter pancreatic hormone release Liver function Induce drug-metabolizing enzymes Inhibit drug-metabolizing enzymes Diuretics, estrogens, sympathomimetics (including decongestants), serotonin selective reuptake inhibitors (e.g., fluoxetine, sertraline), cardiac glycosides (digoxin), xanthine derivates (theophylline) Methylprogesterone, cyproheptadine, tricyclic antidepressants (amitriptyline, imipramine) Anticholinergics, diuretics, methyldopa, antihistamines Metronidazole, penicillins, other antibiotics Azathioprine, phenytoin Angiotensin converting enzyme inhibitors (e.g., captopril), chlorpromazine Anticholinergics, autonomic agents, beta blockers, emetogenic chemotherapeutic agents Corticosteroids, methylprednisolone, hydrocortisone, non-steroidal anti-inflammatory agents, serotonin selective reuptake inhibitors Opiates, anticholinergics, phenothiazines (e.g., chlorpromazine) Metoclopramide, erythromycin Colchicine, cytotoxic agents Antibiotics, digoxin, theophylline Diuretics, estrogens, anticonvulsants, corticosteroids, azathioprine, cyclosporine, alcohol, antibiotics, asparaginase Octreotide Insulin, asparaginase, beta blockers, corticosteroids, octreotide Barbiturates, rifampin, alcohol, theophylline, diazepam Cyclosporine, isoniazid, amphotericin B, cimetidine, erythromycin Adapted from the article of Jacqelyn et al. The Nutrition Screening Initiative;2002. 11 GI = gastrointestinal. 14 Journal of Clinical Nutrition
Drug-nutrient Interactions in Elderly Patients Table 4. Effects of food on medication Medications Effects of food Potential clinical implications Cardiovascular agents Digoxin Amiodarone Captopril Felodipine, Nifedipine HMG-CoA reductase inhibitors (statins) CNS medications Levodopa/carbidopa Lithium Anti-infective agents Isoniazid Rifampin Fluoroquinolones Ciprofloxacion Levofloxacin Moxifloxacin Itraconazole Respiratory agents SR theophylline Absorption with high-fiber products Absorption with GFJ Absorption (30% 40%) (substantial) absorption with GFJ Absorption with high-protein meals High Na diet Li blood levels Low Na diet Li blood levels Absorption (substantial) absorption with cation (Ca, Fe, Mg, Zn) (significant) absorption (overall) absorption High caffeine intake mpairs metabolism Failed management of CHF/Afib Significant enhanced effects/ toxicities Benefits in HTN/CHF management Enhanced effects/toxicities Anti-Parkinson s effects Altered drug actions Anti-tubercular effects Significantly reduced antibacterial effects; treatment failure Enhanced anti-fungal effects Reduced drug effects Risk of drug toxicity Adapted from the article of Leibovitch et al. Geriatrics 2004;59:19-22. 13 CHF = congestive heart failure; Afib= atrial fibrillation; GFJ = grapefruit juice; HTN = hypertension; CNS = central nervous system; SR = sustained-released. 5. 경장영양요법 (enteral nutrition) 에서의약물과의상호작용노인환자의경우경구식사량이불충분하거나신경학적장애로인한연하곤란, 흡인성폐렴의위험이큰경우가빈번하며이런경우경장영양 (enteral nutrition) 을시행한다. 경장영양을하는환자에게서약물요법을할때가장중요한목적은경장영양의순응도에영향을주지않으면서약물의치료적효과는최대화하는것이다. 그중에서흡수단계는약물이위장관을거쳐전신순환을하는첫번째단계로약물의치료효과를결정짓는중요한단계이다. 약물의흡수에영향을주는요인들은병용약물, 위배출시간 (gastric emptying time), 경장영양관 (tube) 이거치된위치등여러가지가있다. 특히, 고령일수록위배출시간및대장통과시간 (colonic transit time) 이지연되고장연동운동이감소되어약물의생체이용률이변하거나경관영양액의순응도가감소될수있다. 14 그리고공장조루술 (jejunostomy) 을통해약물이공장 (jejunum) 으로바로전달되는경우에는약물의용출 (dissolution) 량이감소될뿐만아니라약물의위장관통과시간이단축되어생체이용률이감소된다. 공장루관으로투여할경우약물의흡수가감소되는대표적인약물로 itraconazole, ciprofloxacin 등이있다. 경장영양액을혼합하거나함께투여할때발생할수있는약 물의배합금기 (incompatibility) 에는기전에따라물리학적배합금기 (physical incompatibility), 생리학적배합금기 (physiologic incompatibility), 약물학적배합금기 (pharmacological incompatibility), 약물동력학적배합금기 (pharmacokinetic incompatibility), 약제학적배합금기 (pharmaceutical incompatibility) 로구분된다. 15 물리학적배합금기는 2가지물질을배합하였을때물리적변화가발생하는것으로가장흔한예가침전형성 (precipitation) 이다. 이침전물들은경장영양액의점도를증가시켜관을막게되므로침전생성을예방하기위해약을직접경관액에혼합하지않는것을추천한다. 또한, 제조사마다출시한경관액의조성이다르므로경관액과약제들과의물리학적배합금기에대한자료를참고해야있다. 생리학적배합금기는약물자체나약물을희석한매개체에의해발생하는비약물학적작용이다. 액상약제의삼투압이 1,000 mosm/kg을초과하는경우설사를유발할수있으며액상약제의감미를개선하고안전성을높이기위해추가하는 sorbitol은삼투압을높여설사를발생할수있다. 약물학적배합금기는약물의작용기전으로인해경장영양의순응도를감소시키는것이다. 예를들면, 마약성진통제를투여한후위배출속도가지연되어경장영양진행이어렵거나위장관운동촉진제인 metoclopramide를투여한후설사가발생할수있다. 약물동력학적배합금기는경장영양으로 Volume 6, Number 1, April 2014 15
인해약물의흡수, 분포, 대사, 배설에변화가생기는것이다. 그예로, phenytoin의경우경관으로투여시관에흡착될수있어유효혈중농도를유지하기위해서더많은용량이필요하며 phenytoin 투여 2시간전후로는경관영양투여를잠시중단하고 60 ml 정도의물로충분히세척해주어야한다. 16 마지막으로약제학적배합금기는약물이분쇄되거나제형이파괴될경우효과가감소되거나부작용이발생하는경우이다. 예를들어장용정 (enteric coated) 을분쇄할경우위에서급격히용해되어위장점막을자극할수있으며서방정 (sustained-released) 을분쇄하면약물의방출속도가급격히증가하여부작용이나독성을유발할수있다. 건강보험심사평가원에서는고시에따라분할, 분쇄불가의약품에대하여사유를지정하여처방을제어하고있으며본원에서는분할, 분쇄불가의약품을공지하여불가사유및안전한대체약을추천하며필요한경우전산으로산제처방제어를하고있다 (Table 5). 경장영양을하는환자에게안전한약물요법을위한가이드라인은첫째, 경장영양을하는환자를위해다학제적접근으로실용적인프로토콜을정립해놓는것이필요하며둘째, 약사는경장관으로약이투여되기전환자가복용하는약물의프로파일을미리검토해야한다. 셋째, 경장관이적절한위치에있는지확인하고경관액에약을직접혼합하지않으며약물마다분리하여투여한다. 넷째, 경장관으로약을투여할때에는투여전후 30 ml 정도의물로세척한다. 다섯째, 환자가호소하는증상이약물에의한위장관계부작용인지경장영양으로인한위장관계부작용인지를감별한다. 마지막으로경구로투여되는약 물들은효과나부작용등을지속적으로모니터링한다. 15 6. 정맥영양요법 (total parenteral nutrition) 에서의약물과의상호작용고령환자의경우경구섭취가불량하거나경장영양의순응도가낮은경우가흔해 total parenteral nutrition (TPN) 으로영양지원을자주하게된다. 다만, 정맥으로 TPN 뿐만아니라약물, 전해질, 수액등도함께투여되어다양한상호작용이발생하기때문에 TPN과약물간의상호작용에대한정확한이해가필요하다. TPN의구성성분은포도당, 아미노산, 지질, 전해질, 비타민, 무기질등매우복잡한혼합물이므로안전성 (stability) 이나배합적합성 (compatibility) 을확인하는데많은제한이따른다. 그러므로 TPN과약물간의배합적합성을확인하는가장근본적인원칙은의심된다면절대혼합하지않는것이다. TPN 의배합적합성을결정짓는요인들은약물의농도, 온도, ph, TPN과혼합된시간, TPN의조제순서등이있다. 17 TPN과약물과의상호작용은 TPN 투여세트와 Y-site로약물이혼합 (piggybag) 되거나 TPN에직접약을혼합하는경우에발생할수있다. TPN 투여세트의 Y-site로약물을동시에투여하는방법은약물과 TPN이접촉하는시간이짧아서물리화학적배합변화를최소화할수있다. 그러나물리화학적배합변화는접촉시간뿐만아니라농도에따라발생할수있으므로배합적합성이검증되지않았다면함께투여해서는안된다. 그 Table 6. Y-site incompatibility with parenteral nutrition 18-20 Table 5. Oral dosage forms that should not be crushed (example of Do not crush list) Drugs Alendronate, Risedronate Aspirin protect Oxycodone SR Sevelamer Reasons Irritant: chewed, crushed, or sucked tablets may cause oropharyngeal irritation Enteric coated tablet Slow-release: tablet disruption may cause a potentially fatal overdose of oxycodone Sevelamer tablets expand when they are wet, and breaking the pill may cause a tube occlusion Therapeutic alternative No alternatives Should not lie down at least 30 minutes after taking the tablets Soluble micro-coated aspirin tablet Immediate-release d tablet The alternative phosphate binders Y-site incompatibility with 2-in-1 TPN Acyclovir Amphotericin B Cefazolin sodium Ciprofloxacin Cisplatin Cyclosporine Cytarabine Doxorubicin HCl Fluorouracil Furosemide Ganciclovir sodium Methotrexate sodium Metoclopramide HCl Midazolam HCl Mitoxantrone HCl Potassium phosphate Sodium bicarbonate Y-site incompatibility with 3-in-1 TPN Acyclovir Amphotericin B Cyclosporine Dopamine Doxorubicin HCl Fluorouracil Ganciclovir sodium Haloperidol lactate Heparin sodium (100 IU/mL) Hydromorphone Lorazepam Midazolam HCl Morphine sulfate (15 mg/ml) Nalbuphine HCl Ondansetron HCl Pentobarbital sodium Phenobarbital sodium Potassium phosphate Sodium bicarbonate Aspirin protect (Bayer Korea, Seoul, Korea). SR = sustained-released. TPN = total parenteral nutrition. 16 Journal of Clinical Nutrition
Drug-nutrient Interactions in Elderly Patients 리고포도당, 단백질, 전해질, 미량원소들로만구성된 2-in-1제형은수용성으로상대적으로안전성이큰반면지질유제가더추가된 3-in-1제형은유화제가추가되어불안정하다. 유화제는 ph 5 8에서지질유제를가장안전한음전화의형태로유지해주므로양이온이포함된약물이나강산성, 강알칼리성약물을 3-in-1제형과혼합해서는안된다. 그외에도 3-in-1제형의안전성은중성지방의근원, 아미노산의조성, 포도당의점도, 전해질과미량원소의농도, ph에영향을받는다. 2-in-1제형과 3-in-1제형의 Y-site 배합적합성은별도로여러문헌과제조회사의정보등을이용해야한다 (Table 6). 18-20 TPN에약을직접혼합하는경우에도상호작용이발생할수있으므로 TPN을절대로약물의운반수단으로써사용해서는안된다. 그러나투여가능한정맥투여경로가제한되거나많은약물투여가필요한경우에는부득이하게 TPN에약을직접혼합하게된다. 1가이온들은고농도로 TPN에혼합되더라도특별한물리화학적배합변화가일어나지않으나 2가, 3가양이온들 (Ca 2+, Mg 2+ ) 은물리화학적반응성이커서 TPN 중에포함된성분들과침전을생성할수있다. 특히, 배합변화의대표적인예인 Ca과 P가서로혼합될경우 calcium phosphate (CaHPO 4) 침전물이생성되어카테터 (catheter) 폐색의주요원인이되며색전증 (embolism) 으로인한사망에까지이를수있다. CaHPO 4 생성을예방하기위해서조제된 TPN은낮은온도에서보관하고 Ca제형은안전성이높은 Ca. gluconate염으로사용하며 ph를낮추어용해도를증가시키고 Ca과 P 이온농도를제한하며 P를먼저가하고 Ca을이후에가하는순서로혼합한다. 마지막으로이미혼합조제된 TPN은되도록빠른시일내에투여한다. 17 그외에산염기평형을위해정맥으로투여하는 sodium bicarbonate (NaHCO 3) 도 TPN과혼합하는경우불용성인 calcium carbonate (CaCO 3) 침전물이형성되므로배합금기되는대표적약물이다. Sodium bicarbonate를투여할때에는 TPN 과별도로투여되거나 sodium bicarbonate 대신침전물이형성되지않는 sodium acetate를 TPN에혼합해서사용할수있다. 지질유제가포함된 3-in-1제형은 2-in-1제형보다불안정하며불투명하기때문에침전물이생성되더라도육안으로확인이어렵기때문에주의해야한다. 정맥영양요법을하는환자에게안전한약물요법을위한가이드라인을정리해보면첫째, TPN을투여하는환자의경우정맥으로투여되는약물들이많기때문에내강 (lumen) 이여러개인카테터를사용하는것이좋다. 둘째, 3-in-1제형은매우복잡한조성을가질뿐아니라기본적으로불안정하므로각별한주의가필요하다. 셋째, 정맥으로약물을투여할때에는수액으로충 분히세척해준다. 넷째, TPN은되도록투여직전에혼합하고, 다섯째, 혼합된약제의효과를확인하여안전성을예측한다. 마지막으로배합적합성이검증된 TPN과약물프로토콜을병원마다정리하여통일된지침서를사용함으로써안전한약물투여를기대할수있을것이다. 21 결론 노인환자는불량한영양상태로인해경장영양과정맥영양을시행하는경우가흔하고여러가지약물을함께투여하기때문에주의가필요하다. 특히, 약물과영양소간의상호작용으로인해영양상태의변화나질환의예후를결정지을수있으므로정확한이해가필요하다. 그러므로적절한영양지원을수행하고약물과영양소의상호작용을예방하기위해불필요한약물사용은피하고되도록단기간만투여하며약물의치료효과나영양지원의순응도를주기적으로평가하는것을추천한다. REFERENCES 1. Furman EF. Undernutrition in older adults across the continuum of care: nutritional assessment, barriers, and interventions. J Gerontol Nurs 2006;32(1):22-7. 2. Ministry of Health & Welfare. Korean Health Statistics 2009. Korea National Health and Nutrition Examination Survey (KNHANES IV-3) [Internet]. Cheongwon:Ministry of Health & Welfare;2010 [cited Jul 1, 2013]. Available from: https://knhanes. cdc.go.kr/. 3. Akamine D, Filho MK, Peres CM. Drug-nutrient interactions in elderly people. Curr Opin Clin Nutr Metab Care 2007;10(3): 304-10. 4. Morley JE, Mooradian AD, Silver AJ, Heber D, Alfin-Slater RB. Nutrition in elderly. Ann Intern Med 1988;109(11):890-904. 5. Aghdassi E, McArthur M, Liu B, Mcgeer A, Simor A, Allard J, et al. A comparison of the diet in a population of institutionalized Canadian elderly to the dietary reference intake. Am J Clin Nutr 2002;75(2):339S-40S. 6. High KP. Nutritional strategies to boost immunity and prevent infection in elderly individuals. Clin Infect Dis 2001;33(11): 1892-900. 7. Riquelme R, Torres A, el-ebiary M, Mensa J, Estruch R, Ruiz M, et al. Community-acquired pneumonia in the elderly. Clinical and nutritional aspects. Am J Respir Crit Care Med 1997;156(6): 1908-14. 8. Baik HW. Nutritional disorder. In: Yoo HJ, Kim SY, Nam HW, Rho YK, Shin SH, Yoon JL, et al., eds. Textbook of geriatric medicine. 2nd ed. Seoul:Medicine Publishing Company;2005:378-90. 9. Chan LN. Drug-nutrient interactions. In: Shils ME, Shike M, Ross Volume 6, Number 1, April 2014 17
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