Pharmacokinetics and drug safety of oral infectious disease during pregnancy

doi:10.7518/hxkq.2018.03.017

Abstract

Abstract:

Pregnancy is a time of particular vulnerability in terms of physiologic changes resulting in higher risk of oral infectious diseases. There is emerging evidence showing that irrational dental treatment and drug therapy are associated with adverse pregnancy outcomes, including infant malformation or spontaneous abortion. This article reviews the pharmacokinetics of medications in pregnant women and the fetus and introduces a guideline for drug therapy and common dental drugs used during pregnancy.

Key words: pregnancy, oral health, pharmacokinetics, medication

CLC Number:

R988.2

Hongyu Li, Yachuan Zhou, Xue-dong Zhou, Liwei Zheng. Pharmacokinetics and drug safety of oral infectious disease during pregnancy[J]. West China Journal of Stomatology, 2018, 36(3): 319-324.

Figures/Tables 2

Tab 1

Tab 2

References 33

[1]	Strafford KE, Shellhaas C, Hade EM.Provider and patient perceptions about dental care during pregnancy[J]. J Matern Fetal Eonatal Med, 2008, 21(1): 63-71.
[2]	杨湘晖. 孕妇口腔疾病的药物选择[J]. 国外医学(妇幼保健分册), 2000, 11(2): 63-66.
	Yang XH.Drug selection for oral diseases of pregnant wo-men[J]. Foreign Med Sci (Sect Mater Child Health), 2000, 11(2): 63-66.
[3]	Honein MA, Gilboa SM, Broussard CS.The need for safer medication use in pregnancy[J]. Expert Rev Clin Pharmacol, 2013, 6(5): 453-455.
[4]	Singla V, Arora A, Tyagi P, et al.Failed common bile duct cannulation during pregnancy: rescue with endoscopic ultra-sound guided rendezvous procedure[J]. Endosc Ultrasound, 2016, 5(3): 201-205.
[5]	马玉燕, 马丽娟, 高凌雪. 妊娠及哺乳期药物代谢特点[J]. 中国实用妇科与产科杂志, 2008, 24(6): 462-464.
	Ma YY, Ma LJ, Gao LX.Characteristics of drug metabolism during pregnancy and lactation[J]. Chin J Pract Gynecol Obstetr, 2008, 24(6): 462-464.
[6]	Gaipov A, Solak Y, Zhampeissov N, et al.Renal functional reserve and renal hemodynamics in hypertensive patients[J]. Ren Fail, 2016, 38(9): 1391-1397.
[7]	黄醒华. 孕期药物动力学的改变[J]. 中国实用妇科与产科杂志, 1998, 14(5): 271-273.
	Huang XH.Changes in pharmacokinetics during pregnancy[J]. Chin J Pract Gynecol Obstetr, 1998, 14(5): 271-273.
[8]	道毅俊, 焦正, 李中东, 等. 妊娠引起的药动学变化[J]. 中国新药与临床杂志, 2006, 25(11): 861-864.
	Dao YJ, Jiao Z, Li ZD, et al.Changes of pharmacokinetics during pregnancy[J]. Chin J New Drug Clin Remed, 2006, 25(11): 861-864.
[9]	Pavek P, Smutny T.Nuclear receptors in regulation of bio-transformation enzymes and drug transporters in the pla-cental barrier[J]. Drug Metab Rev, 2014, 46(1): 19-32.
[10]	吴澄清. 胎儿药动学特点及药物对胎儿的影响[J]. 儿科药学杂志, 2004, 10(4): 26-28.
	Wu CQ.Pharmacokinetics property of foetus and effect of drug in foetus[J]. J Pediatr Pharm, 2004, 10(4): 26-28.
[11]	陈绪柳. 妊娠期妇女用药研究进展[J]. 临床合理用药杂志, 2012, 5(12): 151-152.
	Chen XL.Advances in the pharmacy study of women in pregnancy[J]. Chin J Clin Ration Drug Use, 2012, 5(12): 151-152.
[12]	王怀良. 妊娠用药与药物的致畸作用[J]. 中国社区医师, 2003, 19(5): 22-23.
	Wang HL.The teratogenic effect of medication and drugs in pregnancy[J]. Chin Commun Dr, 2003, 19(5): 22-23.
[13]	游燕. 中药在妊娠期的安全应用探讨[J]. 陕西中医学院学报, 2010, 33(2): 58-59.
	You Y.Discussion on the safe application of traditional chi-nese medicine in pregnancy[J]. J Shanxi Coll Tradit Chin Med, 2010, 33(2): 58-59.
[14]	戴钟英. 妊娠期用药FDA五级分类法[J]. 中国实用妇科与产科杂志, 2004, 20(6): 377-378.
	Dai ZY.FDA five grade classification for pregnancy[J]. Chin J Pract Gynecol Obstetr, 2004, 20(6): 377-378.
[15]	Wyszynski DF, Shields KE.Frequency and type of medi-cations and vaccines used during pregnancy[J]. Obstet Med, 2016, 9(1): 21-27.
[16]	梁莉. 孕期用药对妊娠影响的分析[J]. 中国产前诊断杂志(电子版), 2012, 4(1): 38-42.
	Liang L.Analysis of the pregnancy effects of the drug used during the pregnancy[J]. Chin J Prenat Diagn (Electron Vers), 2012, 4(1): 38-42.
[17]	Barak S, Oettinger-Barak O, Oettinger M, et al.Common oral manifestations during pregnancy: a review[J]. Obstet Gynecol Surv, 2003, 58(9): 624-628.
[18]	王晓琳, 戴杰, 阮方超. 妊娠期口腔疾病患者的治疗[J]. 中国医药指南, 2014, 12(35): 50-51.
	Wang XL, Dai J, Ruan FC.Oral disease in pregnancy patient care treatment[J]. Guide Chin Med, 2014, 12(35): 50-51.
[19]	Jeffcoat MK, Geurs NC, Reddy MS, et al.Periodontal in-fection and preterm birth: results of a prospective study[J]. J Am Dent Assoc, 2001, 132(7): 875-880.
[20]	郑黎薇, 邹静, 游泳, 等. 孕期口腔疾病管理[J]. 华西口腔医学杂志, 2017, 35(2): 113-118.
	Zheng LW, Zou J, You Y, et al.Management of oral diseases during pregnancy[J]. West Chin J Stomatol, 2017, 35(2): 113-118.
[21]	陈琛, 程敏, 刘彤, 等. 妊娠期口腔疾病与治疗用药指导[J]. 中国妇幼保健, 2011, 26(17): 2706-2708.
	Chen C, Cheng M, Liu T, et al.Oral diseases in pregnancy and guidance for the treatment of drugs[J]. Mater Child Health Care Chin, 2011, 26(17): 2706-2708.
[22]	古丽尼尕·扎克尔, 艾则孜·安不都. 妊娠期口腔疾病患者的治疗[J]. 世界最新医学信息文摘, 2016, 16(99): 53.
	Gulini Zacher, Azizi Abdul.Treatment of patients with oral diseases in pregnancy[J]. World Latest Med Inform, 2016, 16(99): 53.
[23]	易洁梅, 曾毅, 谢伟乾, 等. 妊娠妇女用药安全性研究进展[J]. 实用药物与临床, 2008, 11(4): 249-250.
	Yi JM, Zeng Y, Xie WQ, et al.Advances in the study of drug safety in pregnant women[J]. Pract Drug Clin, 2008, 11(4): 249-250.
[24]	戴钟英. 妊娠期用药的基本原则[J]. 实用妇产科杂志, 2007, 23(10): 581-582.
	Dai ZY.Basic principles of drug use during pregnancy[J]. J Pract Obstet Gynecol, 2007, 23(10): 581-582.
[25]	杨勇, 陈诚, 刘心霞. 妊娠期药物在母体和胎儿的药动学特点与用药安全[J]. 医药导报, 2017, 36(9): 951-955.
	Yang Y, Chen C, Liu XX.Pharmacokinetics and safety of drugs in mother and fetus during pregnancy[J]. Her Med, 2017, 36(9): 951-955.
[26]	Foundation CDA. Oral health during pregnancy and early childhood: evidence-based guidelines for health professionals[J]. J California Dent Assoc, 2010, 38(6): 391-403, 405-440.
[27]	Trønnes JN, Lupattelli A, Nordeng H.Safety profile of med-ication used during pregnancy: results of a multinational European study[J]. Pharmacoepidemiol Drug Saf, 2017, 26(7): 802-811.
[28]	Moore PA.Selecting drugs for the pregnant dental patient[J]. J Am Dent Assoc, 1998, 129(9): 1281-1286.
[29]	Becker DE, Rosenberg M.Nitrous oxide and the inhalation anesthetics[J]. Anesth Prog, 2008, 55(4): 124-130.
[30]	卢博一, 刘冰, 徐浩, 等. 口服镇静药在口腔疾病治疗中的临床应用[J]. 实用口腔医学杂志, 2015, 31(3): 300-302.
	Lu BY, Liu B, Xu H, et al.Clinical application of oral seda-tive drugs in the treatment of oral diseases[J]. J Pract Sto-matol, 2015, 31(3): 300-302.
[31]	Burtin P, Taddio A, Ariburnu O, et al.Safety of metronida-zole in pregnancy: a meta-analysis[J]. Am J Obstet Gynecol, 1995, 172(2 Pt 1): 525-529.
[32]	Dreyer NA, Blackburn SC, Mt-Isa S, et al.Direct-to-patient research: piloting a new approach to understanding drug safety during pregnancy[J]. JMIR Public Health Surveill, 2015, 1(2): e22.
[33]	何平, 叶金梅, 郭芳, 等. 妊娠期口腔疾病患者的治疗[J]. 国际口腔医学杂志, 2014, 41(5): 500-509.
	He P, Ye JM, Guo F, et al.Treatment of patients with oral diseases in pregnancy[J]. Int J Stomatol, 2014, 41(5): 500-509.

药物动力学参数		妊娠期的改变
吸收	胃排空	降低
	肠动力	降低
	肺功能	上升
	心输出量	上升
	皮肤血流量	上升
分布	水体积	上升
	血浆蛋白	降低
	体脂	上升
代谢	肝代谢	上升或降低
	肝外代谢	上升或降低
	血浆蛋白浓度	降低
排泄	肾血流量	上升
	肾小球滤过率	上升

药物		FDA分级	禁忌/注意事项
解热镇痛抗炎类	阿司匹林	C	短期使用;避免在孕早、晚期使用
	对乙酰氨基酚	B	解热镇痛首选
	布洛芬	B	避免在孕早、晚期使用;使用时间不能超过48 h
	萘普生	B	避免在孕早、晚期使用;使用时间不能超过48 h
	可待因	C	避免孕晚期使用（致胎儿动脉导管未闭）^[27]
	吗啡	B/D	长期服用的人群导致婴儿出现戒断症状;对于长期服用人群药物分类D类
	哌替啶	B/D	对于长期服用人群药物分类D类
抗菌药物	盘尼西林	B	无限制
	阿莫西林	B	无限制
	头孢菌素	B	无限制
	克林霉素	B	暂无
	红霉素	B	依托红霉素因对母体有肝毒性而禁止使用
	四环素	D	孕期禁止服用,孕后25周服用将导致牙齿着色严重甚至影响骨质沉积
	克拉霉素	待定	当暴露因素不能证明无风险,是可作为供选择的抗生素
	喹诺酮类	C	孕期禁用,动物学实验表明影响软骨形成
局部麻醉类	利多卡因	B	无限制
其他	洗必泰	C	未评估其是否对孕妇有不良影响
	木糖醇	暂无	没有证据证明其对孕妇有不良影响