Prescribing in Pregnancy

unchanged, decrease, increases, decreased, increased, CYP, output, glomerular, renal, uterine

ADME Changes in Pregnancy

• Absorption

  • May be _________

  • May _________ d/t decreased peristalsis and delayed gastric emptying

• Distribution

  • Plasma volume __________ by up to 50% (bag of water)

  • Increased plasma volume = _______ drug levels

  • Decreased protein binding = increased free drug levels = __________ drug effects

• Metabolism

  • ____ enzymes change dramatically from trimester to trimester

• Elimination

  • Maternal physiologic changes that affect pharmacokinetics by trimester of pregnancy

    • Cardiac _______, _________ filtration rate, effective ______ plasma flow, creatinine clearance, _________ blood flow

caffeine, acetaminophen, codeine, fluoxetine, warfarin, omeprazole, progesterone, bilirubin

Representative drugs metabolized by CYP450 enzymes

• CYP1A1/2

  • _________, aflatoxin B1, ___________

• CYP2D6

  • _________, hydrocodone, flecainide, propranolol, carvedilol, ___________

• CYP2C9

  • Phenytoin, _______, tolbutamide

• CYP2C19

  • __________, pantoprazole, phenobarbital, diazepam, propranolol, clopidogrel, citalopram, bupropion

• CYP3A4

  • Fentanyl, midazolam, cyclosporin, tacrolimus, carbamazepine, ___________

• UGT1A1

  • _________, irinotecan

pregnancy, lactation, reproductive

New Labeling for Specific Population Use

• _________ → includes Labor and Delivery

• _________ → includes Nursing Mothers

• Females and Males of ___________ potential

genotype, developmental stage, embryogenesis, deleterious, environmental, dosage

Wilson’s Principles of Teratology

• 1st Principle

  • Susceptibility to a teratogen depends on the _________ of the conceptus

• 2nd Principle

  • Susceptibility of the conceptus to teratogenic agents varies with the _____________ _______ at the time of exposure

• 3rd Principle

  • Teratogenic agents act in a specific way on developing cells and tissues in initiating abnormal ___________

• 4th Principle

  • Irrespective of the specific ___________ agent, the final manifestations of abnormal development are death, malformation, growth restriction, and/or functional disorder

• 5th Principle

  • Access of adverse ___________ influences to developing tissues depends on the nature of the influence

• 6th Principle

  • Manifestations of abnormal development increase in degree from the no-effect level to the lethal level as ________ increases

androgens, lithium, thalidomides, cytotoxic, retinoids, warfarin, streptomycin, valproate/topiramate, mycophenolate

1st Trimester Exposure to Teratogens in Pregnancy

• _________

  • Virilization

• ________

  • Ebsteins anomaly (cardiac)

• _________

  • Limb reduction

• ____________ drugs

  • Abortion, Growth stunting, Stillbirth

• ________

  • Craniofacial, cardiac, CNS defects

• ________

  • Nasal hypoplasia, skeletal defects

• ___________

  • Deafness

• ____________/__________

  • facial and neurobehavioral effects, renal

• ___________

  • Cardiac, ear, eye, orofacial, renal

warfarin, NSAIDs, salicylates, sulfonamides, tetracyclines, aminoglycosides, narcotics, lithium, ACEi, phenothiazines, benzodiazepines, antidepressants

2nd and 3rd Trimester Exposure to Teratogens in Pregnancy

• ________

  • Fetal hemorrhage, CNS abnormalities

• _________ and __________

  • prolongation of gestation and labor, neonatal pulmonary HTN

• ___________

  • kernicterus, hyperbilirubinemia

• _________

  • Staining of teeth, impaired bone growth

• ___________

  • deafness, vestibular damage

• _________

  • withdrawal and respiratory depression

• _________

  • Hypotonia and hyporeflexia

• ____

  • Growth stunting, lung and kidney deformities, convulsions, hypotension

• ___________

  • Withdrawal

• ____________

  • Withdrawal, respiratory depression

• _____________

  • Withdrawal

pyridoxine, ginger, doxylamine, dimenhydrinate, diphenhydramine, promethazine, ondansetron, metoclopramide

N/V Pharmacologic Options

• Vitamins and nutritional supplements

  • Vitamin B6 (__________)

  • ________

• Antihistamines

  • _________ (Unisom)

  • _________ (Dramamine)

  • ____________ (Benadryl)

• Combination medication that is expensive when OTC products exist

• Phenothiazine Antipsychotics

  • __________

  • Prochlorperazine

  • Chlorpromazine

• Serotonin (5HT3) receptor antagonists

  • ___________

• Dopamine antagonist

  • ______________

folic acid, ginger, pyridoxine, doxylamine, prochlorperazine

N/V Pharmacologic Options

• First Line

  • Nonpharmacologic Therapy

    • Use ______ _____ supplement only

    • _________ capsules 250 mg four times daily (reduces nausea)

• Second line

  • __________ with or without _____________

• Third line

  • ____________

  • Dimenhydrinate

  • Promethazine

dehydrated, oral, B6, doxylamine, dimenhydrinate, metoclopramide, ondansetron

N/V → Have you had any water?

• Pts who are _________ are treated differently from those who are hydrated

• Hydrated

  • ______ medications

  • Vitamin ____ + __________

  • If sx persist, add one oral agent at a time:

    • Antihistamines (__________)

    • Dopamine antagonists

      • ____________

      • Promethazine

    • ___________ (secondary/third line per guidelines)

hydration, parenteral, normal, lactated ringers, thiamine, dextrose, electrolytes, antiemetics, ondansetron, promethazine, corticosteroids, 10, feeding

N/V → Dehydrated Patient

• Inpatient or ED management

  • Focus shifts to IV __________ and __________ medications

• IV Fluid resuscitation

  • ________ saline or ________ _________

    • Add IV __________ BEFORE giving __________ if prolonged vomiting

    • Correct __________ (K+, Mg2+)

Parenteral ___________

• Given IV or IM because PO cannot be tolerated

  • ____________ IV

  • Metoclopramide IV

  • ___________ IV

  • Dimenhydrinate IV

• Escalation (if vomiting is uncontrolled):

  • ____________ (methylprednisolone) after __ weeks of gestation

  • Consider enteral tube _________ if severe

• MONITOR

neural tube, brain, spina bifida, anencephaly

Why is folate important?

• _______ _____ defects are serious birth defects that affect the spine, spinal cord, or ______ and may cause death

• These include

  • _______ ________ →

    • Condition happens when an unborn baby’s spinal column does not fully close during development in the womb, leaving the spinal cord exposed

  • _________ →

    • Most or all of the brain and skull does not develop in the womb. Almost all babies with this condition die before or soon after birth.

bypass, diabetes, malabsorptive, alcohol, methotrexate

Folate Deficiency Risk Factors

• Medical Conditions

  • Hx of gastric _______

  • Pre-pregnancy _________

  • _________ disorders

  • ________ use disorder

• Medications

  • Anticonvulsants

  • __________

  • Sulfasalazine

early, treat, cure, 5-7

Asymptomatic Bacteriuria in Pregnancy → Treatment and Screening

• Screen once in ______ gestational visit

• _______ if colony counts >100,000 CFU/mL

• Unclear if test of _____ is needed

• Treat for _-_ days, shorter duration may not be adequate

nitrofurantoin, bactrim, cephalexin, fosfomycin, amoxicillin

Asymptomatic Bacteriuria in Pregnancy Treatment Options

• ___________

  • Avoid during weeks 38-42 gestation

• ________

  • Consider avoiding during 1st and 3rd trimester

• __________

• _________

• ___________ (± clavulanate)

  • Only if culture shows sensitivity

high, less, weak, lipid, diffuse, basic, acidic, lower

Medications and Breastmilk

• Plasma protein binding

  • Drugs with ____ plasma protein binding are ____ likely to be transferred into breast milk

• Ionization

  • Most drugs are _____ acids or bases that are present in solution as both nonionized and ionized species

  • The nonionized molecules are usually ______ soluble and can _______ across the milk-plasma membrane

• Acidity

  • ______ drugs are more likely to be transferred into breast milk d/t milk being more ________ than plasma

• Molecular weight

  • The _______ the molecular weight the more easily the drugs will be transferred

yes, yes, no, yes, yes, no, yes, yes, no

Medications in Breastmilk

• Acetaminophen and ibuprofen

  • Breastfeeding friendly? ___

• Claritin and Benadryl

  • Breastfeeding friendly? ___

  • Note: observe infant for drowsiness

• Sudafed

  • Breastfeeding friendly? ___

  • Notes: Can decrease milk supply

• Amoxicillin, ampicillin, cephalexin, erythromycin, penicillin, zithromax

  • Breastfeeding friendly? ___

• Fluconazole

  • Breastfeeding friendly? ___

• Prozac

  • Breastfeeding friendly? ___

  • Notes: Zoloft or Paxil are preferred alternatives

• Zoloft and Paxil

  • Breastfeeding friendly? ___

• Depo-Provera and Progestin-only oral contraceptivs

  • Breastfeeding friendly? ___

• St. John’s Wort

  • Breastfeeding friendly? ___