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1 개원의와함께하는임상강좌 2011 신기능저하환자에서의약물처방 경희대학교의과대학신장내과학교실 정경환 내용 1. 국내만성콩팥병환자현황 2. 만성콩팥병환자에서의약물대사 3. 신기능의판단 4. 신기능감소에따른약물처방의실제 국내만성콩팥병환자현황 68 개원의와함께하는임상강좌 2011

2 정경환 : 신기능저하환자에서의약물처방 Prevalence of ESRD, PMP USRDS 2010 국내투석환자의원인질환및연령대별비교 당뇨병환자에서만성콩팥병의발생률 개원의와함께하는임상강좌

3 맞춤진료 만성콩팥병환자의증가 1. 노인인구의증가 2. 당뇨병, 고혈압유병률의증가 3. 신기능검사의증가 Effect of Chronic Kidney Disease on Drug Pharmacokinetics 70 개원의와함께하는임상강좌 2011

4 정경환 : 신기능저하환자에서의약물처방 Effect of Absorption 위산도의증가 Furosemide, ketoconazole, ferrous sulfate 등과같이 acidic 한환경에서 dissolution, ionisation 되는약제들의경구투여시 bioavailability 감소 Gastroparesis, vomitting, diarrhea 등의위장관장애동반 Bowel wall edema Intestinal CYP450 activity 의감소 Effects on Distribution Protein binding 알부민감소와 uremic substance 의증가에의해단백결합이감소되어 drug 의유리분획이증가 Phenytoin, warfarin, salicylate, valproate 등의약물농도에영향 Volume of Distribution Total body water, adipose tissue 의증가, muscle mass 의감소로인한분포용적의변화 Digoxin 의경우분포용적이감소하여 loading dose 를감소시켜줘야함 Effects of Metabolism Hepatic biotransformation 의변화 Phase I hydrolysis, reduction reaction 의감소 Phase II metabolic reaction 의변화 Acetylation (hydralazine, isoniazid), glucuronidation (acetaminophen, morphine, lorazepam, oxazepam), sulfation (e.g., acetaminophen, minoxidil, dopamine, albuterol) 의감소 개원의와함께하는임상강좌

맞춤진료 Effects of Elimination GFR, renal tubular secretion, absorption 에따라 renal excretion 이결정됨 Biologic active or toxic metabolites 가축적될수있음 Meperidine 이 normeperidine 으로 biotransformation 된후신기능저하시축적되어

5 맞춤진료 Effects of Elimination GFR, renal tubular secretion, absorption 에따라 renal excretion 이결정됨 Biologic active or toxic metabolites 가축적될수있음 Meperidine 이 normeperidine 으로 biotransformation 된후신기능저하시축적되어 seizure threshold 를낮추는부작용이발생할수있음 Midazolam 의 metabolite 인 alphahydroxymidazolam 이축적되면 excessive sedation 을유발할수있음 Effects of Aging Elderly people (>68 세 ) 의 15-30% 가 CKD stage 3 이상 Aging kidney Renal parenchymal loss (10%/per decade of age) Renal plasma flow 감소 Tubular dysfunction Age related GFR loss: 0.40~1.02 ml/min per year Cyt P450 의기능및 metabolic clearance, absorption, distribution 등의감소에의한 pharmacokinetics 의변화 Nolin TD et al. Clin Pharmacol Therap, 개원의와함께하는임상강좌 2011

6 정경환 : 신기능저하환자에서의약물처방 신기능의평가 신기능의평가 Creatinine: age, sex, race, weight 에영향 Creatinine based estimation of Kidney Function for Prescription Medication Dosage in Adults Creatinine clearance (ml/min) : 24hr urine collection or Cockcroft-Gault equation Estimated glomerular filtration rate (egfr): Modification of Diet in Renal Disease (MDRD) Study equation egfr, ecrcl 모두 extreme body size, muscle mass, unusual dietary habits 시에는부정확 Narrow therapeutic, high toxicity drug 주의필요 Effects of age on renal function (constant serum creatinine of 1.2 mg/dl) GFR Age 개원의와함께하는임상강좌

7 맞춤진료 신기능의평가 Cockcroft & Gault 공식 Creatinine clearance (ml/min) (140-Age)x Body weight = x 0.85 ( 여성 ) 72x serum creatinine Ex) 68세 70kg 여성의 Creatinine = 1.5 mg/dl 인경우, Creatinine clearence = 39mL/min MDRD egfr 공식 ** GFR, in ml/min /1.73 m 2 = 175 x SCr (exp[-1.154]) x Age (exp[-0.203]) x (0.742 if female) 신기능감소에따른약물처방의실제 74 개원의와함께하는임상강좌 2011

8 정경환 : 신기능저하환자에서의약물처방 고혈압약제 RAAS 차단제 : bilateral renal artery stenosis 가있는경우 renal dysfunction 과 hyperkalemia 를더욱악화시킬수있음 ACE inhibitor GFR < 50mL/min : % dose reduction Angiotensin II receptor blocker Beta blocker : ESRD 환자에서 hyperkalemia 유발가능 Carvedilol, labetalol 혈당강하제 (I) Sulfonylurea Hypoglycemia risk 증가 반감기가짧은약선택, 저용량부터사용후, titration Glipizide, Gliclazide Meglitinide 반감기가짧음 Repaglinide Dipeptidyl peptidase-iv inhibitor (Sitagliptin, Vildagliptin) Sitagliptin (januvia) 30< GFR <50mL/min : 50mg once daily GFR < 30mL/min : 25mg once daily 혈당강하제 (II) Metformin Lactic acidosis risk 증가 Contraindication S cr >1.5 mg/dl in males, or >1.4 mg/dl in females Alpha-glucosidase inhibitor (Acarbose, Voglibose) S cr >2 mg/dl 에서 avoid Thiazolidinedione (Pioglitazone) No adjustment but, 체중증가와 edema 주의 개원의와함께하는임상강좌

9 맞춤진료 항생제 Ampicillin-Sulbactame GFR에따른시간간격조절 Cephalosporin Cefaclor, cefuroxime : dose reduction 불필요 Macrolide Erythromycin, Azythromycin : dose reduction 불필요 Clarithromycin : GFR < 50mL/min : 50% dose reduction Quinolone Ciprofloxacin : GFR < 50mL/min : 50% dose reduction Levofloxacin : GFR < 50mL/min : q48hrs Acyclovir 시간간격조절 진통제 (I) Non-Steroid Anti-Inflammatory Drugs (NSAIDs) Homodynamically mediated ARF Prostacyclin, prostaglandin E2가 volume depleted status 에서 GFR 유지에중요한역할을함 Volume depleted status 에서투여 3-7일후renal ischemia 유발가능 진통제 (II) Non-Steroid Anti-Inflammatory Drugs (NSAIDs) Acute interstitial nephritis, nephrotic syndrome Analgesic nephropathy Neparoxen, celecoxib: GFR 30ml/min avoid Acetaminophen Nonnarcotic analgesic of choice for mild to moderate pain Metabolite accumulation GFR <10ml/min administer every 8hr Tramadol Bladder sphincter tone 증가시켜 urinary retention 가능성 76 개원의와함께하는임상강좌 2011

Proton pump inhibitor dose reduction 불필요 Prokinetics Metoclopramide : GFR < 40mL/min 50%

10 정경환 : 신기능저하환자에서의약물처방 위장약 H 2 Blocker Cimetidine : GFR < 50mL/min : 50% dose reduction Ranitidine : GFR < 50mL/min : 150mg q 24hrs Famotidine : GFR < 50mL/min : 50% dose reduction Proton pump inhibitor dose reduction 불필요 Prokinetics Metoclopramide : GFR < 40mL/min 50% dose reduction 개원의와함께하는임상강좌

11 맞춤진료 78 개원의와함께하는임상강좌 2011

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056~064........6.............. 병원약사회지(2012), 제 29 권 제 1 호 J. Kor. Soc. Health-Syst. Pharm., Vol. 29, No. 1, 56 ~ 64 (2012) 회원학술보고 신기능에 따른 Sitagliptin의 처방용량 적정성 평가 경성대학교 약학대학 Drug Use Evaluation of Sitagliptin Renal Dosing Kie Ho Sohn