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Drugsinpregnancy&Drugsinpregnancy&lactationlactationByByDrAttiaMJabrDrAttiaMJabrDrAmalHassanainDrAmalHassanainFacultyofMedicineFacultyofMedicineQassimUniversityQassimUniversity1TherearetwomajorTherearetwomajorconsiderationsregardingdrugconsiderationsregardingdruguseinpregnantwomen:useinpregnantwomen:EffectofpregnancyonEffectofpregnancyon::drugsdrugs(pharmacokinetics)(pharmacokinetics)EffectofdrugsonEffectofdrugson::pregnancy(fetus)pregnancy(fetus)IntroductionIntroduction1.1.About40%About40%ofpregnantwomentakeofpregnantwomentakedrugs(atleast1drug)drugs(atleast1drug)2.2.6%6%takedrugsduring1takedrugsduring1ststtrimestertrimester(excludefolic,iron,vitamins)(excludefolic,iron,vitamins)3.3.ThemostcommondrugsareThemostcommondrugsareanalgesics,analgesics,antibacterial,antacids.antibacterial,antacids.4.4.Whataboutnewdrugs?Whataboutnewdrugs?4I.EffectofpregnancyonI.Effectofpregnancyondrugsdrugs((PharmacokineticsPharmacokinetics))A.A.AbsorptionAbsorption::TherateTheratemaybemaybereducedreducedbecauseofdelayedbecauseofdelayedgastricemptyinggastricemptyingTheextentTheextentmaynotbeabsorbedmaynotbeabsorbedVomitingVomitingiscommoniscommon.Effect?.Effect?ReducedbioavailabilityReducedbioavailability5EffectofpregnancyonEffectofpregnancyondrugsdrugsB)Distribution:B)Distribution:11..MaternalMaternalplasmavolumeplasmavolume&ECF&ECF▲50%(3▲50%(3rdrdtrimester)trimester)2.2.TotalbodywaterTotalbodywater▲20%&totalbodyfat▲20%&totalbodyfat3.3.WhatistheeffectonVd&steadystateWhatistheeffectonVd&steadystateconcentration?concentration?4.4.SerumalbuminSerumalbumin▼▼byabout20%(inpre-eclampsiabyabout20%(inpre-eclampsia35%)35%)5.5.Alpha1-acidglycoproteinAlpha1-acidglycoprotein▲▲Byabout40%(inpre-Byabout40%(inpre-eclampsia100%)eclampsia100%)6.Thefreefractionof6.Thefreefractionofacidicdrugsacidicdrugs▲▲7.Thefreefractionof7.Thefreefractionofbasicdrugsbasicdrugs▼▼8.E.G.Diazepam,phenytoin,valproate.What?8.E.G.Diazepam,phenytoin,valproate.What?Whatistheeffectont½ofthedrug?E.g.phenytoinWhatistheeffectont½ofthedrug?E.g.phenytoin6A.A.Drugmetabolism:Drugmetabolism:1.1.▲▲HepaticmicrosomalmixedfunctionoxidaseHepaticmicrosomalmixedfunctionoxidase2.2.Increasedduringpregnancy(2Increasedduringpregnancy(2ndnd,3,3rdrd))3.3.ExplainwhyherateofclearanceofExplainwhyherateofclearanceofphenytoin,phenytoin,valproate,carbamazepinevalproate,carbamazepineisincreasedduringisincreasedduringpregnancypregnancy4.4.ThereisnochangeinThereisnochangeinhepaticbloodflowhepaticbloodflow..Effect?DrugsofEffect?Drugsoffirstpasseffectfirstpasseffect.Examples.Examplespropranololpropranolol7EffectofpregnancyondrugsB.B.Excretion:Excretion:1.1.EffectiverenalplasmaflowEffectiverenalplasmaflow▲(doubles)▲(doubles)2.2.GFRGFR▲▲by70%by70%3.3.Clearancerateincreasese.g.ampicillin.Clearancerateincreasese.g.ampicillin.Solve?Solve?WhataboutdoseinUTI?WhataboutdoseinUTI?4.4.ExplainwhythedosagesofdigoxinandExplainwhythedosagesofdigoxinandlithium,areincreasedduringpregnancy?lithium,areincreasedduringpregnancy?DoyouthinkthatpregnancycanalsoaffectdrugDoyouthinkthatpregnancycanalsoaffectdrugpharmaco-dyamics?pharmaco-dyamics?▲▲B.blockersB.blockers8EffectofpregnancyondrugsII.II.EffectofdrugsonEffectofdrugsonfetusfetusDrugscaninfluencefetalDrugscaninfluencefetaldevelopmentat3separatestages:developmentat3separatestages:1.1.Fertilization&implantati...