9 Pregnancy and Lactation.pptx

Pregnancy and Lactation:
Therapeutic Considerations

Introduction
• Covers many complex issues that affect both
the mother and her child from planning for
pregnancy through lactation
• The duration of pregnancy is approximately
280 days
• Pregnancy is divided into three
periods/trimesters; each 3-months

Pharmacokinetic changes during
pregnancy
• Drug absorption during pregnancy may be
altered by delayed gastric emptying and
vomiting.
• An increased gastric pH may affect absorption
of weak acids.
• Higher estrogen and progesterone levels may
alter liver enzyme activity and increase
elimination of some drugs

PK…cont’d
• Maternal plasma volume, cardiac output, and
glomerular filtration increase by 30% to 50%
during pregnancy, possibly lowering the plasma
concentration of renally cleared drugs.
• Body fat increases; thus volume of distribution of
fat-soluble drugs may increase.
• Plasma albumin concentrations decrease; thus
volume of distribution of highly protein bound
drugs may increase.
• However, the net effect may not be affected

PK…cont’d
• Factors that determine placental transfer of
drugs
– Drug with molecular weights less than 500 daltons
cross readily while molecular weights greater than
1,000 daltons (e.g., insulin and heparin) do not
cross in significant amounts.
– Lipophilic drugs (e.g., opiates and antibiotics)
cross more easily than do water-soluble drugs

Teratogenic effect of drugs
• More than half of pregnant women take
prescription or nonprescription (over-the-
counter) drugs or use social drugs (such as
tobacco and alcohol) or illicit drugs at some
time during pregnancy.
• Drugs use during pregnancy should be
avoided unless absolutely necessary

Teratogenic effect…cont’d
• The incidence of congenital malformation is
approximately 3% to 5%, and about 2% to
3% of all birth defects are caused by
medication exposure.
• Adverse fetal drug effects depend on
– Dosage, route of administration
– Concomitant exposure to other agents
– Stage of pregnancy

• Exposure to the fetus in the first 2 weeks after
conception -“all or nothing” effect.
• Exposure during the period of organogenesis (18 to
60 days postconception) may result in structural
anomalies (e.g., methotrexate, cyclophosphamide,
diethylstilbestrol, lithium, retinoids, thalidomide,
certain antiepileptic drugs, and coumarin
derivative).

• Exposure after the period of organogenesis
may result in growth retardation, skeletal and
CNS abnormalities, or death (e.g., NSAIDs,
ACEIs and tetracycline)

Time Frame Possible Drug Effects Status of the Fetus
Within the first
2weeks after
fertilization
An ‘all-or-nothing’ effect
(death of the fetus or no
effect at all)
The fetus is highly
resistant to birth
defects.
3-8 weeks after
fertilization
Possibly no effect, A
miscarriage, An obvious
birth defect, A permanent
but subtle defect that is
noticed only later in life
The fetus's organs are
developing, making the
fetus particularly
vulnerable to birth
defects.
2nd and 3rd
trimesters
Changes in the growth and
function of normally
formed organs and tissue
Unlikely to cause obvious
birth defects Unknown
long-term effects
Organ development is
complete

FDA category for Teratogenic Effects of
Drugs
• Most widely used system to grade the
teratogenic effects of medications
• Categorizes medications by using a 5-letter
system: A, B, C, D, and X
• This safety category must be displayed on the
labels of all drugs

FDA category …cont’d
• Category A
• Adequate and well-controlled studies have
failed to demonstrate a risk to the fetus in the
first trimester of pregnancy (and there is no
evidence of risk in later trimesters).
• levothyroxine, folic acid

• Category B
• Animal reproduction studies have failed to
demonstrate a risk to the fetus and there are
no adequate and well-controlled studies in
pregnant women.
• metformin, hydrochlorothiazide, amoxicillin,
pantoprazole

• Category C
• Animal reproduction studies have shown an
adverse effect on the fetus and there are no
adequate and well-controlled studies in
humans, but potential benefits may warrant
use of the drug in pregnant women despite
potential risks.
• tramadol, gabapentin, prednisone,
Duloxetine, Tinidazole

• Category D
• There is positive evidence of human fetal risk
based on adverse reaction data from
investigational or marketing experience or studies
in humans, but potential benefits may warrant
use of the drug in pregnant women despite
potential risks.
• lisinopril, alprazolam, losartan, clonazepam,
lorazepam, Aminoglycosides, first-
generationAnticonvulsants, Aspirin, Atenolol,
Fluoxetine, Fluconazole, Tetracyclines

• Category X
• Studies in animals or humans have demonstrated fetal
abnormalities and/or there is positive evidence of
human fetal risk based on adverse reaction data from
investigational or marketing experience, and the risks
involved in use of the drug in pregnant women clearly
outweigh potential benefits.
• atorvastatin, simvastatin, warfarin, methotrexate,
flurazepam, temazepam, triazolam, oral
contraceptives, Misoprostol, Retinoids, Thalidomide

Drug selection during pregnancy
• Principles for selecting medications for use during
pregnancy include:
✓ Select drugs that have been used safely for long
periods of time.
✓ Prescribe doses at the lower end of the dosing range.
✓ Eliminate nonessential medication and discourage self-
medication.
✓ Avoid medications known to be harmful.
✓ Adjust doses to optimize health of mother while
minimizing risk to fetus.

Preconception planning
• Ingestion of folic acid by all women of
childbearing potential should be encouraged, as
it reduces the risk for neural tube defects.
– low risk should take 400 mcg/day throughout the
reproductive years
– high risk (e.g., those who take certain seizure
medications or who have had a previously affected
pregnancy) should take 4 mg/day
• Avoid use of alcohol, tobacco, and other
substances prior to pregnancy

Pregnancy induced illnesses
Constipation
• Nondrug modalities such as education,
physical exercise, and increased intake of
dietary fiber and fluid should be instituted
first.
• use of supplemental fiber with or without a
stool softener (Lactulose, sorbitol, bisacodyl,
or senna) is appropriate.
• Castor oil and mineral oil should be avoided

Gastroesophageal Reflux Disease
• lifestyle and dietary modifications such as small,
frequent meals; alcohol, tobacco, and caffeine
avoidance; food avoidance 3 hours before
bedtime; and elevation of the head of the bed.
• Drug therapy, if necessary, may be initiated with
aluminum, calcium, or magnesium antacids;
sucralfate; or cimetidine or ranitidine.
Lansoprazole, omeprazole, and metoclopramide
are also options
• Sodium bicarbonate and magnesium trisilicate
should be avoided

Hemorrhoids
• Hemorrhoids during pregnancy are common.
• Therapy includes high intake of dietary fiber,
adequate oral fluid intake;
• Topical anesthetics, skin protectants and
astringents may also be used.
• Treatment for refractory hemorrhoids includes
rubber band ligation, sclerotherapy, and
surgery

Nausea and Vomiting
• Up to 80% of all pregnant women experience some
degree of nausea and vomiting.
• Eating small, frequent meals; avoiding fatty foods
decreases N & V.
• Antihistamines (e.g., doxylamine), vitamins (e.g.,
pyridoxine, cyanocobalamin), anticholinergics (e.g.,
dicyclomine, scopolamine), dopamine antagonists
(e.g., metoclopramide). Ondansetron can be used
when other agents have failed, and ginger is
considered safe and effective.
• Dexamethasone or prednisolone have been effective
for hyperemesis gravidarum, but the risk of oral
clefts is increased

Gestational diabetes
• Screening for gestational diabetes mellitus utilizes
the oral glucose challenge test.
• Non pharmacologic: nutritional and exercise
interventions for all women, and caloric restrictions
for obese women
• If nutritional intervention fails therapy with
recombinant human insulin should be instituted;

Hypertension
• Hypertension during pregnancy includes
gestational hypertension (pregnancy-induced
hypertension without proteinuria),
preeclampsia (hypertension with proteinuria),
and chronic hypertension (diagnosed prior to
pregnancy with or without overlying
preeclampsia).
• Eclampsia, a medical emergency, is
preeclampsia with seizures.

Hypertension…cont’d
• For women at high risk for preeclampsia, low-
dose aspirin after 12 weeks’ gestation reduces
the risk for preeclampsia by 19%. Aspirin may
reduce the risk of preterm birth by 7% and
fetal or neonatal death by 16%.
• Calcium, 1 g/day, is recommended for all
pregnant women, as it may help prevent
hypertension in pregnant women and reduce
the risk of preeclampsia by 31% to 67%.

Hypertension…cont’d
• Commonly used drugs for hypertension in
pregnancy include methyldopa, labetalol, and
calcium channel blockers.
• ACEIs should be avoided throughout
pregnancy.
• Other drugs to avoid are magnesium sulfate
(except for eclampsia prevention and to treat
eclamptic seizures), high-dose diazoxide,
nimodipine, and chlorpromazine.

Venous Thromboembolism
• Risk factors for venous thromboembolism in
pregnancy include increasing age, history of
thromboembolism, hypercoagulable conditions,
operative vaginal delivery or cesarean section,
obesity, and a family history of thrombosis.
• low-molecularweight heparin or unfractionated
heparin should be used for the duration of
pregnancy and for 6 weeks after delivery.
• Warfarin should be avoided after the first 6
weeks of gestation

ACUTE CARE ISSUES IN PREGNANCY
HEADACHE
• Nonpharmacologic: -exercise, rest, reassurance,
ice packs, and massage.
• If drug therapy is needed, acetaminophen is the
first choice
• NSAIDs are contraindicated after 37 weeks’
gestation.
• For refractory migraines, narcotics may be used.
• Salicylates and indomethacin should be avoided
throughout pregnancy if possible.
• The use of sumatriptan is controversial.

Urinary tract infection
• Cephalexin is considered safe and effective.
• Nitrofurantoin should not be used after week 37 due
to concern for hemolytic anemia in the newborn.
• Sulfa-containing drugs may increase risk for kernicterus
in the newborn and should be avoided during the last
weeks of gestation.
• Folate antagonists, such as trimethoprim, are
relatively contraindicated during the first trimester
because of their association with cardiovascular
malformations.
• Fluoroquinolones and tetracyclines are
contraindicated

Sexually transmitted infections
Chlamydia
• The current recommendation for the
treatment of Chlamydia cervicitis is
azithromycin, 1 g orally as a single dose, or
amoxicillin, 500 mg three times daily for 7
days.
• Other options include erythromycin base or
ethylsuccinate.

Sexually transmitted…cont’d
Syphilis
• Penicillin is the drug of choice, and it is effective
for preventing transmission to the fetus. No
alternatives to penicillin are available for the
pregnant woman who is allergic to penicillin.
Neisseria gonorrhoeae
• The treatment of choice is ceftriaxone, 125 mg
intramuscularly (IM) as a single dose or cefixime,
400 mg orally in a single dose. Spectinomycin 2 g
IM as a single dose is appropriate as a second
choice.

Sexually transmitted…cont’d
Genital Herpes
• Acyclovir can be used safely. For valacyclovir and
famciclovir, safety data are more limited.
Bacterial Vaginosis
• The recommended regimen for treatment is
metronidazole, 500 mg twice daily for 7 days;
metronidazole, 250 mg three times daily for 7
days; or clindamycin, 300 mg twice daily for 7
days.

Management of chronic diseases
during pregnancy
EPILEPSY
• Malformations occur in 6% to 20% of pregnancies
affected by epilepsy.
• Major malformations occur in 4% to 6% of the
offspring of women taking benzodiazepines,
carbamazepine, phenobarbital, phenytoin, or valproic
acid.
• Ways to minimize teratogenic risk
– Drug therapy should be optimized prior to conception
– Antiepileptic drug monotherapy is recommended
– All women with epilepsy should take a folic acid
supplement, 0.4 to 5 mg daily
– Women should take 10 mg oral vitamin K1 daily during the
last month of gestation

HIV/AIDS
• Pregnant women should start ART regardless of CD4
count or stage
• TDF + 3TC + EFV is recommended as first-line ART in
pregnant women the first trimester of pregnancy
• Infants of mothers who are receiving ART and are
breastfeeding should receive six weeks of infant
prophylaxis with daily NVP.

Depression
• If antidepressants are used, the lowest
possible dose should be used for the shortest
possible time to minimize adverse fetal and
maternal pregnancy outcomes.

Labor and delivery
Preterm Labor
• labor before 37 weeks of gestation
• Tocolytic Therapy
– To postpone delivery long enough to allow for
administration of antenatal corticosteroids
– Magnesium sulfate, β-adrenergic agonists (terbutaline),
NSAIDs, and calcium channel blockers (nifedipine)
• Antenatal Glucocorticoids
– For fetal lung maturation to prevent respiratory distress
syndrome, intraventricular hemorrhage, and death in
infants delivered prematurely
– betamethasone, 12 mg IM every 24 hours for two doses,
or dexamethasone, 6 mg IM every 12 hours for four doses

Cervical ripening and labor induction
• For cervical ripening: Prostaglandin E2 analogs
(e.g., dinoprostone) is the most commonly
used.
• Misoprostol, a prostaglandin E1 analog is used
effective for cervical ripening and labor
induction
• Oxytocin is the most commonly used agent
for labor induction after cervical ripening.

Labor analgesia
• The IV or IM administration of parenteral
narcotics (meperidine, morphine, fentanyl) is
commonly used to treat the pain associated
with labor

Drug use during breast feeding
• Factors that can affect medications entry into
breast milk:
– Molecular weights
– Lipid solubility
– Ionization
– Protein binding
– Concentration of drug in the mother’s serum
– Timing and frequency of feedings

Drug use during breast feeding…
• Medications enter breast milk via passive
diffusion
– Nonionized and non–protein-bound medication
can enter into the milk

• Principles for selecting medications during
breastfeeding
– Select medications for the mother that is safe for
use in the infant
– Choose medications with shorter half-lives
– Select those that are more protein bound, have
lower bioavailability, and have lower lipid
solubility

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9 Pregnancy and Lactation.pptx

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