patrick duff, m.d. · mechanisms of placental transfer ... drugs in pregnancy fda class explanation...

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Page 1: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

PATRICK DUFF, M.D.

Page 2: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

POWEROFTHEM.D.

May 2016

Page 3: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

POTENTIALFORHARM

Thalidomide

Valproic acidTopiramate

Page 4: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

MECHANISMSOFPLACENTALTRANSFER�Simple diffusion�Facilitated

diffusion�Active transport�Pinocytosis

Page 5: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

POSSIBLETERATOGENICEFFECTS�Anatomic abnormality

�Impaired growth

Page 6: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

TYPESOFTERATOGENS�Medications

�Thalidomide� Environmental agents

� Irradiation�Heat�Chemicals� Smoking�Microorganisms�Maternal diabetes

Page 7: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

TRIMESTEROFGREATESTFETALVULNERABILITY

Page 8: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

MOSTLIKELYORGANSYSTEMSAFFECTED

Page 9: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

ANIMALMODELSTOASSESSTERATOGENECITY

Page 10: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

ORIGINALFDACLASSIFICATIONOFDRUGSINPREGNANCYFDA CLASS EXPLANATIONA No harmB No harm but limited

human studiesC Animal studies suggest

riskD HarmfulX Absolutely

contraindicatedDiscontinued in the summer of 2015

Page 11: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

ACEINHIBITORSANDARBs�Most likely adverse

fetal effect?� Is the effect

reversible?� Is there a safe

period in pregnancy to use these drugs?

Page 12: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

BETABLOCKERS�Usual

indications?�Adverse fetal

effects?

Page 13: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

CARBEMAZEPINE�Possible

indications in the mother?

�Most likely harmful effects in the baby?

Page 14: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

COUMADIN�Most likely

adverse effect in the fetus?

�Alternative agents for anticoagulation in pregnancy?

Page 15: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

HEAT�How does the

fetus dissipate heat?

�Critical time of exposure?

�Most likely adverse fetal effect?

Page 16: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

ISOTRETINOIN�Most likely

prescriber?�Indication?�Adverse fetal

effects?

Page 17: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

LITHIUM�Usual

indication in the mother?

�Most likely harmful effect in the fetus?

Page 18: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

METHAMPHETAMINE�Most likely

adverse fetal effect?

�Most likely adverse neonatal effect?

�Effect on breast feeding?

Page 19: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

NARCOTICS�Two most likely

sources of exposure?

�Most likely adverse fetal effects?

�Most likely adverse neonatal effect?

Page 20: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

NSAIDS�Usual

indications?�Adverse maternal

effects?�Adverse fetal

effects?

Page 21: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

PHENYTOIN�Usual

indication?�Most likely

adverse fetal effects?

Page 22: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

QUINOLONES�Usual

indications?�Most likely

harmful effect in the fetus?

�Acceptable indications in pregnancy?

Page 23: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

RADIATION�Dose threshold?�Most likely

adverse fetal effect?

Page 24: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

SSRIs�Usual indication?�Most dangerous

of the SSRIs in pregnancy?

�Most likely adverse fetal effect?

Page 25: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

TETRACYCLINE/DOXYCYCLINE�Possible harmful

effect in the mother?

�Most likely adverse effect in the fetus?

Page 26: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

THALIDOMIDE�Original

indication?�Adverse fetal

effects?

Page 27: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

TOBACCO�Most likely adverse fetal effects?

�Most serious maternal complication?

Page 28: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

TOPIRAMATE�Possible

indications?�Newly described

adverse fetal effect?

Page 29: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

TRIMETHOPRIM-SULFAMETHOXAZOLE�Most likely adverse

fetal effect with first trimester exposure?

�Potential neonatal effect with exposure just prior to delivery?

Page 30: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

VALPROICACID�Usual

indications?�Most likely

adverse fetal effect?

Page 31: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

MICROORGANISMSMICROBE TERATOGENIC

EFFECTSRubellaVaricellaCMVParvovirusToxoplasmosis

Page 32: PATRICK DUFF, M.D. · MECHANISMS OF PLACENTAL TRANSFER ... DRUGS IN PREGNANCY FDA CLASS EXPLANATION A No harm B No harm but limited human studies C Animal studies suggest risk D Harmful

EXPOSURETOTERATOGENSCONCLUSIONS�Think carefully before prescribing any

drug in pregnancy, especially in the first trimester

�If you are unsure about the safety of a drug, ask for consultation from your obstetric colleague