淺 談 姙 娠 高 血 壓 台 南 新 樓 醫 院 藥 劑 科 藥 師 陳 湘 婷 林 家 伊. 5-10% 3.9% 140 mmhg 90 mmhg 30 mmhg 15 mmhg methyldopa labetalol nifedipine hydralazine (MgSO4)

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1 繼 續 教 育 Therapeutics of Clinical Drugs 淺 談 姙 娠 高 血 壓 台 南 新 樓 醫 院 劑 科 師 陳 湘 婷 林 家 伊 摘 要 5-10% 3.9% 140 mmhg 90 mmhg 30 mmhg 15 mmhg methyldopa labetalol nifedipine hydralazine (MgSO4) (deep tendon reflexes, DTR) gestational hypertension preeclampsia eclampsia HELLP syndrom 1 壹 前 言 (gestational hypertension) 5-6% 16% 2 The Working Group classification of hypertensive disorders complicating pregnancy (preeclampsia) (eclampsia) pregnancy-induced hypertension mmhg 90 mmhg ( ) % 12 ( ) 104 THE JOURNAL OF TAIWAN PHARMACY Vol.31 No.3 Sep

2 4 表 一 子 癲 前 症 的 診 斷 標 準 Preeclampsia 20 ( 140/90 mmhg) (> 300 mg/24hr > 100 mg/ dl/6hr 1 ) Severe preeclampsia 160/110 mmhg creatinine 1.2 mg/dl / L LDH ALT AST HELLP syndrome: Hemolytic anemia Elevated Liver enzymes Low Platelet count 1 表 二 子 癲 前 症 的 危 險 因 子 Moderate High 1. First pregnancy 1. Hypertensive disease during 2. Age 40 years Previous pregnancy 3. Pregnancy interval > 2. Chronic kidney disease 10 years 3. Autoimmune disease 4. BMI 35 kg/m 2 at such as systemic lupus first visit erythematosus or antiphospholipid syndrome 5. Family history of preeclampsia 4. Type 1 or type 2 diabetes 6. Multiple pregnancy 5. Chronic hypertension If at least 2 moderate or at least 1 high risk factor for preeclampsia: Advise woman to take Aspirin75 mg/day from 12 weeks until birth (Unlicensed indication) 5,6 貳 致 病 機 轉 及 臨 表 徵 (nitric oxide) prostacyclin (PGI 2 ) thromboxane A 2 angiotension II Endothelins Aantiangiogenic factors soluble Fms-like tyrosinekinase 1(sFlt-1) soluble endoglin (seng) 7 參 低 劑 量 aspirin 用 於 預 防 的 研 究 (PIGF) A (PAPP-A) (Uterine PI) (MAP) 95% aspirin aspirin ( mg/kg) thromboxane prostacyclin prostacyclin RCTs metaanalysis 27,000 ( 16 weeks) aspirin (RR 0.47, 95% CI = ; 7.6 versus 17.9%) (RR 0.18, 95% CI = ; 1.5 versus 12.3%) (RR 0.46, 95% CI = ; 8.0 versus 17.6%) (RR 0.35, 95% CI = ; 臨 31 3 Sep 雜 誌

3 繼 續 教 育 Therapeutics of Clinical Drugs 4.8 versus 13.4%) aspirin 16 (RR 0.41, 95% CI = versus 0.93, ) 肆 分 類 (BP 160 /110 mmhg) ( ) 8 acuity severity 一 抗 高 血 壓 ( 表 三 ) 9 ( 一 )Methyldopa mild (3-6 ) 250 mg, bid-tid 3000 mg/day ( 二 )β-blockers 2013 ( 13 population-based case-control cohort studies) -blockers (major congenital malformations) (OR 0.90, 95% CI = ) organ-specific malformations cardiovascular defects (OR 2.01;95% CI = ) cleft lip/palate (OR 3.11; 95% CI = ) neural tube defects (OR 3.56; 95% CI = ) labetalol adrenergic blocking activity ( 2 ) 20 mg ( 2 ) mg (at 10 min intervals) 300 mg 100 mg, bid mg, bid 2400 mg/day ( 三 )Calcium channel blockers (CCB) nifedipine (sustained release tablet) mg qd 120 mg/day mg 30 ( 四 )Hydralazine hydralazine ( 五 )Others thiazide clonidine Clonidine methyldopa mild clonidine 106 THE JOURNAL OF TAIWAN PHARMACY Vol.31 No.3 Sep

4 表 三 抗 高 血 壓 分 類 Anti-hypertensive drugs Mehtyldopa Labetalol Nifedipine Hydralazine Onset 3-6 < Oral: 250 mg bid-tid Max: 3000 mg/day MgSO4 IV bolus: 20 mg IV push over 2 min ; may administer 40 to 80 mg at 10 min intervals; Max:300 mg IV infusion: 2 mg/min; titrate to response up to 300 mg IV to oral: mg bid mg bid; Max: 2400 mg/day Urgent : Immediate release IV bolus: 5 mg IV ( mg; may repeat in 30 min) 5-10 mg/ 20 min if needed, then mg/ min as necessary Q2-6H Max bolus dose: 20 mg Chronic: Extended release for a total dose of 30 tablet mg daily mg Oral: mg/day bid-qid Max: 300 mg Anti-convulsion drug Raising the seizure threshold by its action at the n-methyl d-aspartate (NMDA) receptor, membrane stabilization in the central nervous system loading dose of 4-6 g IV (> 20 min) and maintenance dose of 1-3 g/hr (DTR) 臨 10 二 抗 痙 攣 (magnesium sulfate) n-methyl d-aspartate (NMDA) 4-6 g ( 20 ) 1-3 g/ hr mg/dl ( mmol/l) (deep tendon reflexes, DTR) 1 g calcium gluconate parathyroid hormone (PTH) 伍 結 論 HELLP 31 3 Sep 雜 誌

5 繼 續 教 育 Therapeutics of Clinical Drugs Management of Hypertensive Disorders in Pregnancy Hsiang-Ting Chen 1, Chia-Yi Lin 2 Department of Pharmacy, Sin-Lau Hospital 1,2 Abstract Hypertensive disorders are the most common medical complication of pregnancies, with an incidence of 5 10%, and a common cause of maternal mortality all over the world. Most cause of death is patients diagnosed with gestational hypertension will subsequently develop into pre-eclampsia, or severe features. In addition, these pregnancies may result in preterm delivery, fetal intrauterine growth restriction, and placental abruption. Hypertension is defined as a systolic blood pressure (BP) 140 mmhg or a diastolic BP 90 mmhg or both. In the absence of strong evidence supporting the use of antihypertensive therapy for mild-to-moderate hypertension during pregnancy, initiation of pharmacological therapy is not recommend unless BP approaches severe hypertention range. The choice of antihypertensive agents include methyldopa labetalol nifedipine and hydralazine. Patients should receive an intravenous magnesium sulfate for eclamptic seizures or seizure prophylaxis. Because of the side effects, we recommend to monitor the serum magnesium concentration, DTR, respiration and urine output when using magnesium sulfate. 參 考 資 料 : ;20: Dadelszen P, Magee LA: Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: an updated metaregression analysis. J Obstet Gynaecol Can 2002;24: Hutcheon JA, Lisonkova S, Joseph KS: Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol 2011;25: Abalos E, Cuesta C, Grosso AL, et al: Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol 2013;170:1. 5. Thangaratinam S, Koopmans CM, Iyengar S, et al: Accuracy of liver function tests for predicting adverse maternal and fetal outcomes in women with preeclampsia: a systematic review. Acta Obstet Gynecol Scand 2011;90: Thangaratinam S, Koopmans CM, Iyengar S, et al: How accurate are maternal symptoms in predicting impending complications in women with preeclampsia? A systematic review and meta-analysis. Acta Obstet Gynecol Scand 2011;90: Villa PM, Kajantie E, Räikkönen K, et al: Aspirin in the prevention of pre-eclampsia in high-risk women: a randomised placebo-controlled PREDO Trial and a metaanalysis of randomised trials. BJOG 2013;120: Abalos E, Duley L, Steyn DW: Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev. 2014; 2:CD Moussa HN, Arian SE, Sibai BM: Management of hypertensive disorders in pregnancy. Womens Health (Lond Engl) 2014;10: Visintin C, Mugglestone MA, Almerie MQ, et al: Management of hypertensive disorders during pregnancy: summary of NICE guidance. BMJ 2010; 341:c THE JOURNAL OF TAIWAN PHARMACY Vol.31 No.3 Sep