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1、Drugsinpregnancy lactation ByDrAttiaMJabrDrAmalHassanainFacultyofMedicineQassimUniversity 1 Therearetwomajorconsiderationsregardingdruguseinpregnantwomen Effectofpregnancyon drugs pharmacokinetics Effectofdrugson pregnancy fetus Drugsinpregnancy Introduction About40 ofpregnantwomentakedrugs atleast1
2、drug 6 takedrugsduring1sttrimester excludefolic iron vitamins Themostcommondrugsareanalgesics antibacterial antacids Whataboutnewdrugs 4 I Effectofpregnancyondrugs Pharmacokinetics Absorption TheratemaybereducedbecauseofdelayedgastricemptyingTheextentmaynotbeabsorbedVomitingiscommon Effect Reducedbi
3、oavailability 5 Effectofpregnancyondrugs B Distribution 1 Maternalplasmavolume ECF 50 3rdtrimester 2 Totalbodywater 20 totalbodyfat3 WhatistheeffectonVd steadystateconcentration 4 Serumalbumin byabout20 inpre eclampsia35 5 Alpha1 acidglycoprotein Byabout40 inpre eclampsia100 6 Thefreefractionofacidi
4、cdrugs 7 Thefreefractionofbasicdrugs 8 E G Diazepam phenytoin valproate What Whatistheeffectont ofthedrug E g phenytoin 6 Drugmetabolism HepaticmicrosomalmixedfunctionoxidaseIncreasedduringpregnancy 2nd 3rd Explainwhyherateofclearanceofphenytoin valproate carbamazepineisincreasedduringpregnancyThere
5、isnochangeinhepaticbloodflow Effect Drugsoffirstpasseffect Examplespropranolol 7 Effectofpregnancyondrugs B Excretion Effectiverenalplasmaflow doubles GFR by70 Clearancerateincreasese g ampicillin Solve WhataboutdoseinUTI Explainwhythedosagesofdigoxinandlithium areincreasedduringpregnancy Doyouthink
6、thatpregnancycanalsoaffectdrugpharmaco dyamics B blockers 8 Effectofpregnancyondrugs II Effectofdrugsonfetus Drugscaninfluencefetaldevelopmentat3separatestages Fertilization implantationperiod fromconceptiontoabout17daysgestationOrganogenesis 18 55daysGrowth development 56thdayonward 9 Terminology D
7、ysmorphogenesis teratogenicity1 Teratogen agentthatinterfereswithnormalgrowth developmentofFoetus describedrugsorchemicalsthatcausemajororgrossbirthDefects2 Congenitalmalformations structuralabnormalitiesofprenataloriginthatarepresentatbirth 12 TeratogensAsubstance organism physicalagentsordeficienc
8、ystatecapableofinducingabnormalstructureorfunctionsuchas GrossstructuralabnormalitiesFunctionaldeficienciesIntrauterinegrowthrestrictionBehavioralaberrationsDemise TeratogenicFactors 13 TimingofexposureDevelopmentalstageduringexposureMaternaldoseanddurationMaternalpharmacokineticsGeneticfactors phen
9、otypesInteractionsbetweenagents 3 Congenitalanomaly non reversiblebirthdefectscausedbygeneticpredispositionordrugexposure maybe obviousatbirth hydrocephalus or delayedmanyyearstobeidentified behavioural intellectualdisorders withinutero alcoholexposure 4 Dysmorphogenesis structural functionaldefects
10、 Thalidomide Isotretinoin Warfarin ValproicAcid Carbamezepine Coumarin Phenytoin Effectofdrugsonpregnancy fetus 1 Placentaldrugtransfer Factorsaffectingtherateofdrugtransferacrossplacentaanditseffectonfetus 1 Physico chemicalpropertiesofthedrug a Molecularweight size DrugswithMW 600crosseasily Mostd
11、rugs DrugswithverylargeMWe gInsulin HeparinCannotcross b Lipidsolubility Lipidsoluble un ionized substancescrossrapidly Weaklybasicdrugsmaybecometrappedinfetalcirculation SlightlylowerpHcomparedtomaternalplasma e g thiopental c Ionization MoleculesthatareionizedatphysiologicalpHcrossslowly e g salic
12、ylates tubocurarine NB Consideranydrugcancrosstheplacenta E g atenolol d ProteinbindingOnlyfreeunbounddrugs crossplacenta2 Therateatwhichthedrugcrossestheplacentaandamountreachingthefetus a Uterine umbilicalbl flow Maternalbloodpressure Cordcompression Drugtherapy alpha stimulantb Maternaldiseases p
13、regnancy inducedhypertension DM changepermeabilityofplacenta c Placentaltransporters e g PGpwithanticancerdrugs proteaseinhibitorsd Placentalandfetaldrugmetabolisme g oxidationreactionsofplacenta fetalliver50 3 Thedurationofexposuretothedrug4 Distributioncharacteristicsindifferentfetaltissues5 Stage
14、ofplacentalandfetaldevelopmentatthetimeofexposuretothedrug6 Theeffectsofdrugsusedincombination 19 2 Pharmacologicaleffects Drugscrossingplacentamayexert directeffect corticosteroids adrenalsuppression indirecteffect anti hypertensives fetalhypoxia2rytomaternalhypotension Drugsmayaffect Organdevelopm
15、ent Organfunction 1 Fertilization implantationperiod Interferencebydrugsinthisstageleadstofailureofpregnancy deathoffetus ataveryearlyandprobablysub clinicalstage 21 ThemostsensitiveperiodtoTeratogeniceffectsTetragon anysubstancethatproducesdeformityDifferentinspecies animals humans ThalidomidePheny
16、toin5 warfarin25 ThemostcommonTeratogenicdrugsare 22 2 Organogenesis Predictabletoxicdrugactionsinthefetus Opioids dependenceoffetusandnewbornACEI irreversiblerenaldamageoffetusDiethylstilbosterol adenocarcinomaofvaginaafterpuberty 23 Definition Developmentalabnormality drugAnimalstudiesRateofspontaneousis1 2 Teratogenicmechanisms Poorlyunderstoodandmulti factorialDirecteffectonmaternaltissueswith2ryeffectonfetaltissues OxygenandnutrientsthroughplacentaDirectactionsonfetaltissuese g differentiat
