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Lifecycle Unit 2 > Drug Use in Pregnancy/Lactation > Flashcards

Drug Use in Pregnancy/Lactation Flashcards

1
Q

Pharmacokinetic Changes in Pregnancy

A

SUMMARY: generally unnecessary to make a priori changes in maternal drug dosing but pay attention to therapeutic endpoints/if plasma drug levels should be obtained/adjust dosing–esp for narrow therapeutic index drugs

ABSORPTION: increased GI motility/gastric pH

DISTRIBUTION:

  • increased plasma volume
  • decreased serum albumin binding capacity (more unbound drug) but net impact negligible due to increased metabolism/excretion

ELIM:

  • maternal hormones can increase/decrease metabolism
  • Biliary excretion slowed (cholestasis)
  • Renal excretion may be increased (increased RBF and GFR)
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2
Q

Absorption/placental transfer

A
  • rule of thumb: drugs with good oral availability will readily cross placenta
  • properties of drugs allowing access to maternal circulation also allow access to embryonic/fetal circulation
  • highly lipophilic drugs diffuse readily
  • highly ionized drugs (succinylcholine/turbocurarine) used in C-sections cross placenta slow and have negligible plasma levels in newborn
  • SIZE important. mw of 250-500 cross easily, 500-1000 with more difficulty, > 1000 poorly

HEPARIN DRUG OF CHOICE FOR ANTICIOAG (very large, polar molecule)

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3
Q

Distribution in fetus

A
  • free drug equilibrates across placenta
  • Total drug levels depends on protein binding/degree of ionization for weak acid/base drugs
  • protein binding of some drugs decreased in fetal circulation relative to mom due to lower binding affinity of fetal proteins–total drug will be lower but free drug will equilibrate (sulfonamides, barbituates, phenytoin, local anesthetic agents)
  • Fetal pH lower (7.25) than mom (7.35+)– can cause ion trapping and accumulation in fetal circulation; worse in fetal distress–lowers pH more
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4
Q

Oxytocic agents

A

Dinoprostone, misoprostol, oxytocin, methylergonovine

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5
Q

Tocolytic agents

A
  • Prostaglandin synthesis inhibitor (indomethacin)
  • Beta2 adrenergic agonists (Terbutaline)
  • Mg sulfate
  • Ca channel blocker
  • ethanol
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6
Q

Abortifacient agents

A

Mifepristone, misoprostol, methotrexate

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7
Q

Erectile dysfunction agents

A

Sildenafil (viagra), vardenafil, tadalafil

‘FIL’ that penis!

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8
Q

FDA drug categories for pregnancy

A

5 categories based on animal/human data

  • A, B, C, D, X
  • A = safe vs X =proven teratogenicity
  • most in categories B/C/D where evidence often confusing/ambiguous

Proposed change to have 3 sections on labels( effective 6/2015):

  • Fetal Risk Summary (describe known effects on fetus/risk)
  • Clinical Considerations (info re: effects of use of drug and risks of the disease to Mom/baby)
  • Data (details on data about use of drugs in humans and animal studies used to develop Fetal Risk Summary)
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9
Q

Metabolism

A

placental/fetal metabolism limited but important

  • placenta has enzymes for metabolizing xenobiotics but most cross without being metabolized.
  • placental enzymes for steroids give fetus protection against maternal hormones like cortisol, prednisolone via oxidation (want NO metabolism when want to give fetus steroids, i.e. surfactant production)
  • drugs enter via umbilical vein; 40-60% to gen circulation but rest to liver for “first pass” emtabolism
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10
Q

Pharmacodynamics

A
  • exposure timing important factor (first 4 months most critical regarding malformations vs later for functional/behavioral deficits AND effects on labor/delivery
  • judgement essential in weighing benefits vs harm to fetus
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11
Q

Pharm of labor/Delivery

A
  • progesterone inhibits smooth muscle of uterus through most of pregnancy
  • Prostaglandins E2 and E2a play critical role in labor initiation–strongly contract uterine smooth muscle and promote gap junction formation between cells (made by amnion, chorion, decidua but degraded only but decidua/choroion)
  • —Drugs inhibitiont PG synthesis will delay labor and prolong gestation, which is generally contraindicated in late stage pregnancy (NSAIDs, or COS-2 selective inhibitors)

-Oxytocin probably not involved in initiation but helps maintain labor. Uterus insensitive to it until 20-36 weeks when HUGE increase in receptors (thanks to estrogen)

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12
Q

Stages of labor

A

Stage I: cervical effacement and dilation
- inhibited by progesterone/stim by descent of fetal head and prostaglandins. Cervical dilation dependent on PGs

Stage II: Descent of presenting part and delivery of fetus

  • Prostaglandins/oxytocin stimulate uterine contraction
  • Uterus has beta 2 adrenergic receptors–relaxation when stimulated

Stage III: Separation and delivery of placenta
- postpartum hemorrhage conrolled via contraction of uterus (oxytocin promotes hemostasis)

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13
Q

Induction of labor, when and what do you use

A
  • prego-induced HTN, HELLP syndrome, maternal diabetes

PGE

  • Prostaglandin tolerated poorly systemically, so PGE2 gels applied vaginally for “ripening”–Dinoprostone
  • PGE1 analogs (misoprostol) given orally to induce uterine contractions

OXYTOCIN

  • IV or IM: produces uterine/mammary contractions but NO effect on cervical dilation
  • most commonly used agent for labor induction AFTER cervical ripening
  • effective for post-partum hemorrhage
  • ADR: can get water intoxication with higher doses

Ergonovine/Methylergonovine

  • ergot alkaloids that act via adrenergic/serotoninergic receptors– cause contraction of smooth muscle (vascular and uterine)
  • ONLY for control late uterine bleeding NEVER before delivery
  • Oxytocin PREFERREDpostpartum hemorrhage but can be given if oxy ineffective
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14
Q

Drugs for labor inhibition

A
  • Ca channel blockers (oral Nifedipine): relax uterine muscle; fewer maternal side effects than others
  • Beta2 adrenergic agonists (Terbutaline); higher maternal side effects (HR, palpitations, hypokalemia)–DO NOT USE PARENERALLY AFTER 48-72 hrs for serious maternal heart problems/death and oral not effective
  • Mg Sulfate: No longer used at UCH—found to hvae NO benefit in preventing preterm birth/increased total pediatric mortality
  • Prostaglandin synthesis inhibitors (indomethacin)—limited use since worry about ductus arteriosus closure in utero leading to pulm HTN after birth
  • Ethanol -theoretical but no longer used!
  • 17alpha OH-progesterone caproate (IM): progesterone metabolite given 1x/week to women at high risk for preterm delibery
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15
Q

Pregnancy termination drugs

A
  • Mifepristone (oral): progesterone derivative acting as competitive antagonist for termination up to 9 weeks. Blocks P receptors and lead to detachment of blastocyst, increased PGE levels, and PGE-sensitized myometrium). Single dose followed by prostaglandin (PO Misoprostol > IM/PO agents); approaches 95% success rate

Misoprostol: PGE1 analogue–uterotonic; use in combo with misopristone; many have abd pain/cramps, nausea, diarrhea

Methotrexate: folic acid antagnoist disrupts tissue growth, esp trophoblast—NOT FDA APPROVED but occasional use
- single dose IM, for pregnancies up to 8 weeks followed by vaginal Misoprostol

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16
Q

HELLP syndrome

A

Hemolysis
Elevated Liver enzymes
Low Platelet count

17
Q

Leading cause of infant mortality

A

prematurity

18
Q

Drugs causing sexual dysfunction

A
  • anticholinergic agents
  • 1st gen antihistamines
  • Antiparkinsonian agents
  • TCAs–less ED with SSRIs but anorgasmia/difficulty in ejaculation
  • Pneothiazine antipsychotics
  • CNS depressants (benzos, barbituates, opioids, ethanol)
  • Antihypertensive agents decreasing penile blood flow (diuretics, beta blockers, clonidine, methyldopa)
19
Q

Algorithm for sexual dysfunction treatment

A
  • if drug-induced– discontinue or reduce dose
  • Psychogenic impotence: psychotherapy or behavior modification
  • if organic – oral phosphodiesterase inhibitors or vacuum erection devices
20
Q

Oral phosphodiesterase inhibitors (PDEIs)

A
  • first line therapy for ED
  • oral; hepatically metabolized/ renal and fecal excretion
  • Sildenafil, Vardenafil, Tadalafil
  • Nitric oxide (NO) released from cholinergically-stimulated endothelial cells and nonadrenergic-noncholinergic neurons in presence of sexual stimulation. Activates guanylyl cyclase– increase cGMP–increased vasodilation in penile tissue. cGMP metabolized by PDE type 5 in penis
  • **block cGMP breakdown – enhance vasodilation – more blood flow
21
Q

PDEI adverse reactions/DDI

A

Sildenafil: lower BP, increased light sensitivity/blurred vision/loss blue-green color discrimination

Vardenafil- decreased BP

Tadalafil: back/muscle pain

DDI with nitrate vasodilators, slpha adrenergic blockers, inhibitors of CYP450 drug metabolism

22
Q

“Other” drugs for ED

A 
Alprostadil (only one FDA approved)
Trazodone
Yohimbine
Papaverine
Phetolamine
23
Q

Drugs in breast milk

A
  • most drugs cross but usually low levels and infant plasma level way below therapeutic level

Limit infant exposure by:

  • desynchronize breastfeeding and peak milk drug concentrations
  • milk more acidic and will accumulate basic compounds
  • lipid soluble–generally increased milk concentration
  • high protein binding: decreased milk concentration

Total dose of drugs administered to infants via breast milk generally minimal.
- Possible for drugs to accumulate in infants not clearing them well so maybe measure plasma levels of drug in infant with unexplained sxs.
- Measuring breast milk levels of drug not clinically useful
-

24
Q

Treatment of Nausea/vomiting

A

Nonpharm treatments: dietary changes, acupuncture, avoid triggers, hyponosis

  • can take drug if other methods fail.

Ginger, pyridoxine decrease nausea but NOT vomiting. Pyridoxine most often used with Doxylamine

H1 antagonists (Doxylamine)= first line for decreasing vomiting.

Dopamine antagonists (Prochlorpenrazine, Metoclopramide, Promethazine)
***- Metoclopramide effective in women with hyperemesis

5HT3 antagonists (Ondansetron)– reduce nausea and vomiting

25
Q

Antibiotics to avoid in pregnancy

A
  • TMP/SMX
  • Clarithromycin
  • Fluoroquinolones
  • Tetracyclines
  • Fluconazole (avoid in 1st trimester)
  • Metronidazole (in 1st trimester–possible deformations); stop breastfeeding for 12-24 hrs for 1 dose use
  • Nitrofurantoin: avoid close to delivery (hemolytic anemia in newborn)

Lifecycle Unit 2 (16 decks)

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