Pregnancy and Lactation th3

Pregnancy and Lactation: Therapeutic
Considerations
Physiology of Pregnancy
 Approximately only 50% of embryos survive after fertilization
losses occur early: in the first 2 weeks after fertilization
 Spontaneous loss of pregnancy later in gestation (after 12

weeks):15%
 Fertilization
 Occurs in the fallopian tube
 A sperm attaches to the outer protein layer of the egg, the zona
pellucida
 The egg becomes non-responsive to other sperm
 The attached sperm releases enzymes
 Allow the sperm to fully penetrate the zona pellucida and

 Contact the egg’s cell membrane
 Membranes combine to create a new, single cell: zygote
 The fertilized egg: Zygote
 travels down the fallopian tube over 2 days: with cell division
taking place
 By day 3: reaches the uterus
 Cell division continues for another 2 to 3 days: before
implantation
 Approximately 6 days after fertilization, the cell mass is termed
a blastocyst
 Human chorionic gonadotropin (hCG) is produced in
detectable amounts
Implantation
 Occurs at approximately 6 days after fertilization
 Begins with the blastocyst sloughing the zona pellucida
 Rest directly on the endometrium
 allowing initiation of growth into the endometrial wall
 By day 10 post fertilization
 The blastocyst receives nutrition from maternal blood

 Embryo: On the first day of the third week postfertilization
Periods of pregnancy
 The embryonic period: b/n weeks 2 and 8 post fertilization
 Formation of most body structures
 The fetal period: from the 8th week until term
 Formed body structures continue to grow and mature

 Definition of terms
 Gravidity: the number of times that a woman is pregnant
 A multiple birth is counted as a single pregnancy
 Parity: the number of pregnancies exceeding 20 weeks’
gestation
 Includes information regarding the outcome of each
pregnancy
 Definition of terms
 GaPbcde
 Signifies
 a: number of times that a woman is pregnant

 P
o b: term deliveries
o c: premature deliveries
o d: aborted and/or ectopic pregnancies
o e: number of living children
 E.g. G4P2113
Characteristics of Pregnancy
Pregnancy
lasts approximately 280 days (about 40 weeks or 9 months)
 measured from the first day of the last menstrual period to

birth
Gestational age: the age of the embryo or fetus
o Due date: add 7 days to the first day of the last

menstrual period then subtract 3 months
Divided into three periods of 3 calendar months: trimester
Early symptoms of pregnancy
 Fatigue
 Increased frequency of urination
 Signs include
 Cessation of menses
 Change in cervical mucus consistency
 Bluish discoloration of the vaginal mucosa
 Increased skin pigmentation, and
 Anatomic breast changes

At approximately 6 weeks’ gestation
 Nausea and vomiting
 Commonly called morning sickness
 can happen at any time of the day
 resolve at 12 to 18 weeks’ gestation
A pregnant woman can feel fetal movement in the lower abdomen
 At 16 to 20 weeks of gestation
Pharmacokinetic Changes During Pregnancy
Physiologic changes during pregnancy
 Begin in the first trimester and peak during the second trimester
 Includes
 30% to 50% or higher increase in
 Maternal plasma volume
 Cardiac output, and
 Glomerular filtration
Effect on clearance of drugs
 Increase in body fat
 Vd of fat-soluble drugs????
 Decrease in plasma albumin concentration
 Vd of albumin bound drugs???....... Increase in CO
Pharmacokinetic Changes During Pregnancy
Physiologic changes during pregnancy
 Increase in hepatic perfusion
 Alteration of GI activity
 Nausea and vomiting
 Delayed gastric emptying
 Increase in gastric pH
 Higher levels of estrogen and progesterone
o Alter liver enzyme activity
Transplacental Drug Transfer
The placenta
 Organ of exchange b/n the mother and fetus
 Most drugs move from the maternal to the fetal circulation by
diffusion
 Chemical properties of drugs determine the transfer across the
placenta
Molecular weight
 MW < 500 Da readily cross the placenta
 MW: 600 to 1,000 Da cross more slowly
 MW > 1,000 Da do not cross the placenta in significant
amounts
• E.g. insulin and heparin
Transplacental Drug Transfer
 Lipid solubility
 Lipophilic drugs cross the placenta more easily than do water-soluble
drugs
 E.g. opioids and antibiotics
 Fetal difference with the mother
 Fetal albumin increases while maternal albumin decreases
 Fetal pH is slightly more acidic than maternal pH
 Effect on weak bases????

Drug Selection During Pregnancy
 Risk for congenital malformations:3% to 6%
 Unknown causes: 65% to 75%
 Genetic causes:15% to 25%
 Environmental issues: 10%
 Medication exposure: <1% of all birth defects

Teratogenic effect of a drug is determined by
 The stage of pregnancy during exposure
 Route of administration, and
 Dose
 Stage of pregnancy during exposure and effect of
teratogen
 First 2 weeks following conception: “all-or-none” effect
 During organogenesis (18 to 60 days post-conception):
structural anomalies
E.g. methotrexate, cyclophosphamide, diethylstilbestrol,
lithium, retinoids, thalidomide, certain antiepileptic drugs,
and coumarin derivatives
 During fetal period: growth retardation, CNS abnormalities,
or death
E.g. NSAIDs and tetracycline derivatives
Drug Safety in Pregnancy
 Pregnant women: Not eligible for participation in clinical trials
 Risk associated with medication estimated
 By studies other than RCT
 Most commonly cohort or case control studies
 Pregnancy registries by pharmaceutical companies
 Voluntary reporting systems

 Sources of information
 www.motherisk.org
 www.toxnet.nlm.nih.gov
 tertiary compendia and
 textbooks
 Risk categories of drugs during pregnancy
 A, B, C, D, X
 A considered safe and X considered teratogenic

Preconception Planning
Pregnancy outcomes are influenced by
 Maternal health status
 Lifestyle, and
 History prior to conception
 Preconception planning
 Important to prevent adverse pregnancy outcome

Preconception risk Potential adverse Management or
factor pregnancy outcomes prevention options
Antiepileptic drugs  Known teratogens, • Use lowest possible dose

causes craniofacial, to maintain control
cardiac and limb defects • Folic acid 4 mg daily
 Neural tube defects
 Fetal hydantoin
syndrome
Isotretinoins • Miscarriage • Use effective pregnancy
• Known teratogen, causes prevention
CNS, craniofacial and
cardiac defects
Oral anticoagulants • Fetal warfarin syndrome • Switch to other
anticoagulants e.g.
LMWH before
becoming pregnant
Preconception risk Potential adverse Management or
factor pregnancy outcomes prevention options
Alcohol misuse  Fetal alcohol syndrome • Cease alcohol intake

before conception
Obesity • Neural tube defect • Weight loss with
• Preterm delivery appropriate nutritional
• Diabetes, hypertension, intake before pregnancy
VTE
• Cesarean section
Tobacco use • Preterm birth • Ideally, cease tobacco use
• Low birth weight before conception
• Spontaneous abortion • Non pharmacologic
• Increased perinatal therapies
mortality • Bupropion
• Nicotine replacement ???
 The most common major congenital abnormalities:
 Neural tube defects (NTDs)
 Cleft palate
 Lip and cardiac anomalies
 Neural tube defects (NTDs)
 Occur within the first month of conception
 Folic acid: 0.4 - 0.9 mg daily is recommended throughout a

woman’s reproductive years
 Reduces the incidence of NTDs in their offspring
Pregnancy-influenced Issues
GI Tract
Constipation
 affect 25% to 40% of women
 Contribute to the development or exacerbation of

hemorrhoids
 Treatment
 Non-pharmcologic
 Light physical exercise
 Increased intake of dietary fiber and fluid

GI Tract
Constipation
 Pharmacologic
 Osmotic laxatives
o For short term intermittent use

• polyethylene glycol: DOC
• lactulose, sorbitol and magnesium and sodium salts
GI Tract
Constipation
 Pharmacologic
 Occassionally: Senna and bisacodyl can be used
 Avoid
o Castor oil: Stimulate uterine contractions

o Mineral oil: impair maternal fat-soluble vitamin
absorption
GI Tract
Hemorrhoids
Conservative treatment
High dietary fiber intake
Adequate oral fluid intake, and
Use of sitz baths
 If conservative treatment fails use
 Laxatives and stool softeners

GI Tract
Hemorrhoids
 Anal irritation and pain
 Topical anesthetics
 Skin protectants, and
 astringents
 Hydrocortisone
Gastroesophageal reflux disease
 Occurs in 40% to 80% of pregnant women
 Treatment
 Non pharmacologic
o lifestyle and dietary modifications

• Small, frequent meals
• Alcohol and tobacco avoidance
• Food avoidance before bedtime
• Elevation of the head of the bed
 Gastroesophageal reflux disease
 Pharmacologic
 Antacids (aluminum, calcium, or magnesium preparations)

o Avoid
• Sodium bicarbonate and magnesium trisilicate
 Sucralfate
 Histamine-2 (H2) receptor blockers
o Ranitidine and cimetidine
 PPIs for women who do not respond to H2 antagonists
Nausea and vomiting
 Affect up to 90% of pregnant women
 Begins during the fifth week of gestation
 Lasts through week 20
 Peak symptoms occur between weeks 10 and 16

Hyperemesis gravidarum
 Occurs in 0.3% to 2.3% of women
 Unrelenting vomiting causing
 Weight loss of more than 5% pre-pregnancy weight
 Dehydration
 Electrolyte imbalance, and
 Ketonuria
 Treatment
Dietary modifications
 Eating frequent, small, bland meals
 Avoiding fatty foods
 Applying pressure at acupressure point P6 on the volar

aspect of the wrist
 Ginger
 Treatment
 Pharmacotherapy
o Pyridoxine (vitamin B6)
o Antihistamines (including doxylamine)
o Phenothiazines and metoclopramide
• sedation and extrapyramidal effects, including dystonia
o ondansetron
• Reports of oral clefts
o Corticosteroids: for HG
• a small increase in the risk of oral clefts when used
during the first trimester
Gestational Diabetes
 Glucose intolerance of any degree identified during pregnancy
 New onset or first recognition
 Diagnosed in the second or third trimester that is not overt
diabetes
 Global prevalence 14.0% (95% confidence interval: 13.97-
14.04%)
 Gestational Diabetes
 Risks of GDM
 Fetal loss
 major malformations, and
 Fetal macrosomia
 Gestational Diabetes
 Screen pregnant women not previously diagnosed with diabetes
 First prenatal visit
 Screen all women considered high-risk for diabetes for overt
diabetes
o Obesity
o Glycosuria
o Strong family history of diabetes

 Screening
 Overt diabetes
o A1C ≥ 6.5% (0.065; 48 mmol/mol Hgb)
o FPG ≥ 126 mg/dL (7.0 mmol/L)
o RPG ≥ 200 mg/dL (11.1 mmol/L; requires confirmation

with A1C or FPG)
 Screen for GDM at weeks 24 to 28
 Using a 75-g oral glucose tolerance test (OGTT)

Screen for GDM at weeks 24 to 28
 Gestational diabetes
 Management
o Dietary modification
o Daily self-monitoring of blood glucose

 Gestational diabetes
 Drug therapy recommended if the following levels are not
achieved with dietary modification
o FPG ≤ 95 mg/dL (5.3 mmol/L)
o Plasma glucose concentration
• 1-hour postprandial ≤ 140 mg/dL (7.8 mmol/L), or
• 2-hour postprandial ≤ 120 (6.7 mmol/L)

 Gestational diabetes
 Pharmacologic therapy
o Insulin
• DOC
• does not cross the placenta
o Metformin
• Minimally crosses the placenta
• lack teratogenicity
o Glyburide (glibenclamide)
• Minimally crosses the placenta
 Screen the mother with a 2-hour OGTT at 6 weeks postpartum
for type 2 DM
 Hypertensive Disorders of Pregnancy (HDP)
 Complicate approximately 10% of pregnancies
 Categories of HDP :
 Chronic hypertension: preexisting hypertension or

developing before 20 weeks’ gestation
 Gestational hypertension: hypertension without
proteinuria developing after 20 weeks’ gestation
 Hypertensive Disorders of Pregnancy (HDP)
 Categories of HDP :
 Preeclampsia: hypertension with proteinuria developing
after 20 weeks’ gestation

 Preeclampsia superimposed on chronic
hypertension: proteinuria developing after 20 weeks’
gestation on chronic hypertension
 Eclampsia: Convulsion in the presence of hypertension
 Hypertensive Disorders of Pregnancy (HDP)
 Management
o Activity restriction
• Prolonged bed rest: increase the risk ofVTE
o Stress reduction
o Exercise
o Management
• Calcium 1 to 2 g/day
• Decreases the RR of
• Hypertension by 30% (range, 14% to 43%)
• Preeclampsia by 48% (range, 31% to 67%)
o 1 g/day of supplemental calcium is appropriate for all

pregnant women: when taken for a duration less than 18 weeks
 Preeclampsia
 A multisystem syndrome
 Complicates 2% to 8% of pregnancies
 Cause poorer outcomes including
 Renal failure
 Maternal morbidity/mortality
 Preterm delivery and
 Intrauterine growth restriction

 Preeclampsia
 Risk factors
 Maternal age over 40 years
 Primiparity
 Previous preeclampsia
 Pre-pregnancy body mass index above 30 kg/m2
 Tobacco use
 Underlying medical conditions (e.g., diabetes,
antiphospholipid antibodies, autoimmune disease, renal
disease)
 Multiple gestations
 Preeclampsia
 Signs and symptoms
 BP elevation and proteinuria (300 [or more] mg/24 h)
 Persistent severe headache, new epigastric pain
 Visual changes, vomiting
 Hyperreflexia
 Sudden and severe swelling of hands, face, or feet
 HELLP (hemolysis, elevated liver enzymes, low platelets)
 Increased serum creatinine
 Preeclampsia: treatment to reduce the development of severe
preeclampsia
 For women at risk for preeclampsia
o Low-dose aspirin: 60 to 81 mg/day

o Beginning between 12 and 28 weeks (preferably before 16 weeks)
 The only cure for preeclampsia is delivery of the placenta

 Eclampsia
 Occurrence of seizures superimposed on preeclampsia
 A medical emergency
 Progression to eclampsia decreased to 60% by
 Magnesium sulfate: 4 to 6 g IV over 15 to 20 minutes

followed by a 2 g/h continuous infusion
o The usual duration is 24 hours throughout active labor and 12 to 24
hours postpartum
 Avoid: Diazepam and phenytoin
 Thyroid Abnormalities
 Overt hyperthyroidism: methimazole and PTU
 Overt hypothyroidism: levothyroxine
 Gestational transient thyrotoxicosis (GTT): 1% to 3% of
pregnancies
o HCG structurally similar to TSH
o Resolves by 20 weeks’ gestation as HCG declines
o Treatment with antithyroid medication is not needed
 Postpartum thyroiditis (PPT)
 Result from a destructive inflammation process
o Characterized by
• Transient hyperthyroidism during the first 6 months
postpartum
• A period of transient hypothyroidism
• Permanent hypothyroidism: 2% to 21%
• Finally euthyroidism within 1 year
 Treatment
 Initial hyperthyroid phase
o Does not require treatment with anti-thyroid drugs

o Symptomatic relief
• Propranolol : 10 to 20 mg daily as needed
 Hypothyroid phase
o Levothyroxine:
• For 6 to 12 months
 recommended for
 Severe hypothyroid symptoms
 Duration of hypothyroidism greater than 6 months
 Breast -feeding women, or if another pregnancy is attempted

Venous thromboembolism
 Risk of VTE in pregnant women: five- to ten fold over non-
pregnant women
 Treatment
 LMWH Vs UFH
 Continued throughout pregnancy and for 6 weeks after
delivery
 Minimum total duration of therapy should not be less than 3
months
 Avoid
 Fondaparinux
 Direct thrombin inhibitors: lepirudin, bivalirudin
o Unless in HIT
 Novel oral anticoagulants (eg, dabigatran, rivaroxaban,
apixaban, and edoxaban)
 Warfarin: Especially b/n 6 and 12 weeks’ gestation
o causes
• Nasal hypoplasia, Stippled epiphyses, Limb hypoplasia,
Eye abnormalities
• CNS anomalies: Second- and third-trimester exposure
Recurrent VTE
 Low risk
 A single episode ofVTE
 One transient risk factor
 Surgery
 Injury
 lengthy travel
 Immobility
 Antepartum monitoring is recommended
Recurrent VTE
 Intermediate risk
 Hormone-related
 Pregnancy-related, or
 Unprovoked VTE
 High risk
 More than one unprovoked VTE
 Continuous risk factors
 Antepartum prophylaxis with LMWH plus 6-week postpartum
prophylaxis with either LMWH or warfarin
 Women with mechanical heart valves should receive warfarin
during pregnancy despite the teratogenic risk: dose < 5 mg
 Or LMWH or UFH every 12 hours
 + low-dose aspirin (81–100mg/daily)
 Women with prosthetic heart valves: prophylaxis with LMWH
or UFH during pregnancy
 Use
 LMWH or UFH until week 13 of gestation
 Warfarin until the middle of the third trimester
 Resume LMWH or UFH till birth: Around 36 weeks
 High-risk women with prosthetic heart valves may also receive
low-dose aspirin (75 to 100 mg/day)
Acute Care Issues In Pregnancy
Urinary Tract Infection
 Characterized as
 Asymptomatic: asymptomatic bacteriuria
 Accounts for 2% to 10% of infection
 If untreated can progress to pyelonephritis
 Symptomatic: lower [cystitis] or upper [pyelonephritis]
 Signs and symptoms of cystitis
o Urgency, frequency, hematuria, pyuria, and dysuria

 Causative agents
 Escherichia coli: 75% to 90%
 Gram negative rods:
o Proteus, Klebsiella, Group B Streptococcus (GBS)

 A urine culture should be obtained at the first prenatal visit
 Treatment
 asymptomatic bacteriuria and cystitis
 Duration of therapy: 7-14 days
 β- lactams: penicillins and cephalosporins
o Amoxicillin, Ampicillin: Increasing resistance by E.Coli
 Nitrofurantoin
o Not active against Proteus species

o should not be used after week 37
• Glucose-6-phosphate dehydrogenase deficiency
• Theoretical risk for hemolytic anemia in the neonate
 Treatment
 Sulfa-containing drugs
o newborn kernicterus
o Avoid use during the last weeks of gestation
 Trimethoprim
o contraindicated during the first trimester
o cardiovascular malformations
 Fluoroquinolones: impair cartilage development
 Tetracyclines: Cause deciduous teeth discoloration (if
given after 5 months’ gestation)
 Pyelonephritis
 Signs and symptoms
o Bacteriuria
o Costovertebral angle tenderness
o Dysuria
o Fever
o Flank pain
o Nausea and vomiting
 Pyelonephritis
o Parenteral therapy
• Cephalosporins: cefazolin, ceftriaxone
• Ampicillin + gentamicin or
• Ampicillin–sulbactam
o Switching to oral antibiotics: if afebrile for 48 hours
o Duration of antibiotic therapy:10 to 14 days

Sexually Transmitted Infections
 Includes infections
 Transmitted across the placenta and infect the infant
prenatally: syphilis
 Transmitted during birth and cause neonatal infection:
 Chlamydia trachomatis, Neisseria gonorrhoeae, or
herpes simplex virus
 That pose a threat for preterm labor: bacterial vaginosis
 Screen during the first prenatal visit for
 HIV, C. trachomatis, syphilis. Gonorrhea and
hepatitis B & C
Syphilis
 Caused by Treponema pallidum
 Complications includes
o Mucocutaneous lesions
o Altered mental status
o Visual and auditory abnormalities
o Gumma
o Cranial nerve palsies
Syphilis
o Treatment
• DOC: benzathine penicillin G
• Neurosyphilis: aqueous penicillin G
• Treatment during the second half of pregnancy
• Increase the risk for preterm labor and fetal distress
• Jarisch-Herxheimer reaction
Chlamydia and Gonorrhea
 Chlamydia
 Caused by C. trachomatis
 Complications to the mother includes
 Pelvic inflammatory disease (PID)
 Ectopic pregnancy and
 Infertility
Chlamydia
 C. trachomatis infects the newborn
 Through exposure to the infected cervix during delivery
 Complications to the infant includes
 conjunctivitis 5 to 12 days postpartum
 Afebrile pneumonia at ages 1 to 3 months

Chlamydia
 Treatment
 Gonorrhea
 Caused by N. gonorrhoeae
 Recognizable symptoms may be absent initially
 Can cause PID, a known risk for infertility
 Perinatal gonococcal infection

 Gonorrhea
 Perinatal gonococcal infection
o Symptoms manifest within 2 to 5 days after delivery
o Milder manifestations: rhinitis, vaginitis, and urethritis
o More severe presentations: ophthalmia neonatorum

and sepsis
• Permanent sequelae: blindness
 Coinfection with C. trachomatis is common

 Gonorrhea
 Treatment
Bacterial Vaginosis and Trichomoniasis
 STIs characterized by vaginal discharge
 Bacterial Vaginosis:
 Results from lack of normal vaginal flora (Lactobacillus species)
 Replacement with anaerobic bacteria, mycoplasmas, and
Gardnerella vaginalis
 Risk factor for: premature rupture of membranes, preterm
labor, preterm birth, intraamniotic infection, and postpartum

endometritis
Bacterial Vaginosis
Trichomoniasis
 Caused by the protozoa, Trichomonas vaginalis
 Associated with: premature rupture of membranes, preterm
delivery, and low birth weight

 Treatment may prevent respiratory or genital infection in the
neonate
Genital Herpes
 Caused by herpes simplex virus-2 (HSV-2)
 Recurrent herpes: the cause for most cases of neonatal
transmission
 Prevention strategies
 Avoiding intercourse during the third trimester with partners
having known or suspected genital herpes infection

 Evidence of an infection: cesarean section
 Treatment: Acyclovir,Valacyclovir
Headache
 Primary headaches (e.g., tension, migraine):common
 Secondary headaches: eclampsia, stroke, postdural puncture,
cerebral angiopathy, and cerebral venous thrombosis

 Migraine headaches: associated with estrogen fluctuations
 Pregnant women with a history of migraine headache
 60% and 70%: experience symptom improvement
 20%: complete cessation
 Non-pharmacologic treatment should be tried

Headache
Pharmacological management
 Tension headache: acetaminophen or ibuprofen
 Ibuprofen: considered safe
 All NSAIDs: contraindicated in the third trimester
o Premature closure of the ductus arteriosus

 Aspirin
o effects on ductus arteriosis + maternal and fetal bleeding

o Decrease uterine contractility
Headache
 Migraine
 Analgesics: acetaminophen, ibuprofen
 Opioids: Nausea, vomiting, neonatal withdrawal
 Triptans: sumatriptan
 Ergotamine and dihydroergotamine: contraindicated

Headache
 Migraine-associated nausea: Promethazine, prochlorperazine, and
metoclopramide
 Prophylactic therapy: propranolol
 Alternatives: tricyclic antidepressants (Amitriptyline and

nortriptyline (each dosed 10 to 25 mg by mouth daily)
Chronic Illnesses In Pregnancy
Asthma
 Use medications to achieve and maintain control
 Quick relief of symptoms: albuterol
 persistent asthma: low, medium, high dose of inhaled
corticosteroids
 Budesonide is preferred during pregnancy
 Long acting β2-agonists
 Alternatives: Cromolyn, leukotriene receptor antagonists,
and theophylline
 Allergic rhinitis
o Treatment
o Intranasal corticosteroids: beclomethasone and budesonide
o Nasal cromolyn, and
o First-generation antihistamines: chlorpheniramine, hydroxyzine

Human Immunodeficiency Virus Infection
 Treat HIV infected Pregnant women
 Use 3TC/TDF/EFV
 Nevirapine: severe rash, fatal hepatotoxicity
 Cesarean section before the onset of labor (usually at 39 weeks’
gestation) is recommended
 Reduce the risk of perinatal HIV transmission
Hypertension
 Chronic hypertension
 Hypertension occurring
 Before 20 weeks’ gestation

 Use of antihypertensive medications before pregnancy or
 Persistence of hypertension beyond 12 weeks postpartum
Hypertension
 Chronic hypertension
 Classified as
 Mild/non-severe
 SBP: 140 to 159 mm Hg or
 DBP: 90 to 109 mm Hg
 Severe
 SBP: ≥ 160 mm Hg or
 DBP: ≥ 110 mm Hg
 Hypertension
 Emergency drug therapy: indicated for women with severe
hypertension
 Initial drug choice:
 Parenteral labetalol and hydralazine

 Oral nifedipine
 Magnesium sulfate: limited evidence
 Refractory hypertension
 Nitroprusside, diazoxide, and nitroglycerin

 Treatment of mild hypertension controversial
 Hypertension
 Drugs used during pregnancy
 Labetalol
 Methyldopa
 Calcium channel blockers
 β-adrenoreceptor antagonists: except atenolol (IUGR)
 Thiazide diuretics
 ACEIs, ARBs: contraindicated throughout pregnancy

 Mental Health Conditions
 Depression
 Occurs in 10% to 16% of pregnant women
 Bipolar disorders
 Lithium
o Neonatal side effects: nephrogenic DI , hypoglycemia, cardiac
arrhythmias, thyroid dysfunction,and premature delivery
o If breast-feeding: monitor infant’s lithium levels, TFT and
CBC
 Lamotrigine, carbamazepine, and valproic acid
 Schizophrenia
 Occurs in 1% to 2% of women
 Atypical antipsychotics: first-line treatment
 Favorable side-effect profiles
 Increased efficacy for treating negative symptoms
 Olanzapine, clozapine and quetiapine

o Weight gain and metabolic syndrome
 Typical antipsychotics: minimal toxic or teratogenic potential
 Chlorpromazine, haloperidol, and perphenazine

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.
 The SSRIs are widely used by pregnant women.
 About one or two babies per 1,000 exposed to SSRIs in utero
develop persistent pulmonary hypertension.

 The risk was 6x greater in infants born to women who took
SSRIs after wk 20 of pregnancy.

Labor and Delivery
PRETERM LABOR
 Preterm labor is labor that occurs before 37 wks of gestation
 Changes in cervical dilation and/or effacement happen along
with regular uterine contractions
Tocolytic Therapy
 The goal of tocolytic therapy is to postpone delivery long
enough to allow for:
 administration of antenatal corticosteroids to improve
pulmonary maturity
 Transportation of the mother to a facility equipped to deal with
high-risk deliveries.
 Initiated when there is regular uterine contractions with cervical
change
TocolyticTherapy
 Drugs most commonly used for acute tocolysis include
magnesium sulfate, β-adrenergic agonists, NSAIDs, and

calcium channel blockers.
 Prolong pregnancy between 48 hours to 1week
 Recommended doses of terbutaline are 250 to 500 mcg

subcutaneously every 3 to 4 hrs.
 Maternal side effects (e.g., hyperkalemia, arrhythmias,
hyperglycemia, hypotension, and pulmonary edema) than the
other drugs.
TocolyticTherapy
 Nifedipine is associated with fewer side effects than magnesium or β-
agonist therapy.
 5 to 10 mg nifedipine may be administered sublingually every 15 to
20 minutes for three doses.
 Once stabilized, 10 to 20 mg may be administered by mouth every 4
to 6 hours for preterm contractions.
 NSAIDs…….indomethacin
 Oral or rectal doses of 50 to 100 mg initially, followed by an oral

dose of 25 to 50 mg every 6 hours for 48 hours
 Major side effect: premature constriction of the ductus arteriosus
Preterm labor prevention: other drug therapies
 PPROM before 34 weeks
 A 7-day course of broad spectrum antibiotics
 Ampicillin (2 g IV every 6 hours) plus erythromycin (250 mg IV
every 6 hours) for 48 hours, followed by amoxicillin (250

mg orally three times daily) and erythromycin base (333 mg
orally every 8 hours)
Preterm labor prevention: other drug therapies
 Prior preterm birth
 Progesterone
 Diminish cervical ripening (softening of the cervix necessary
for cervical dilation before birth) ,reduce uterine wall

contractility, and modulate inflammation.
 IM 17-a-hydroxyprogesterone weekly (250mg) starting
between weeks 16 and 24 continued through week 36
Antenatal Glucocorticoids
 Used for fetal lung maturation to prevent respiratory distress
syndrome, intraventricular hemorrhage, and death in infants delivered
prematurely.
 Current recommendations are to administer
 betamethasone, 12 mg IM every 24 hrs for two doses, or
 dexamethasone, 6 mg IM every 12 hrs for four doses, to

pregnant women between 26 and 34 wks’ gestation who are at risk
for preterm delivery within the next 7 days.
 Benefits begins within 24 hrs.
 Repeated use does not improve fetal outcomes

Cervical ripening and labor induction
 PG E2 analogs (e.g., dinoprostone) are the most commonly
used pharmacologic agents for cervical ripening.

 500mcg intracervical and may be repeated after 6 hours to a
maximum of three doses in 24 hours
 Misoprostol, PGE1 analog: effective and inexpensive drug
 25mcg intravaginal/oral given every 3 to 6 hours
 Associated with uterine rupture.
 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.
 Compared to epidural analgesia, parenteral opioids are associated
with lower rates of oxytocin augmentation, shorter stages of labor,

and fewer instrumental deliveries.
 Epidural analgesia involves administering an opioid and/or an
anesthetic (e.g., fentanyl and/or bupivacaine) through a catheter

into the epidural space to provide pain relief.
 Epidural analgesia is associated with longer stages of labor and
more instrumental deliveries than parenteral narcotic analgesia.
 Other options for labor analgesia include spinal analgesia and
nerve blocks
Post partum hemorrhage
 PPH a cumulated blood loss of more than 1,000 mL or blood loss
accompanied with signs and symptoms of hypovolemia within 24

hours after delivery
 Administration of oxytocin should be initiated before placental
delivery
 Second line agents: Methylergonovine, carboprost, and rectal,
sublingual, or oral misoprostol

 Tranexamicacid (TXA), given within 3 hours of delivery
Postpartum issues
DRUG USE DURING LACTATION
 Medications enter breast milk via passive diffusion of nonionized
and non–protein-bound medication.
 Drugs with high molecular weights, lower lipid solubility, and
higher protein binding are less likely to cross into breast milk or
transfer more slowly or in smaller amounts
Mastitis
 Mastitis is usually caused by Staphylococcus aureus, E. coli, and
Streptococcus.
 Treatment includes 10 to 14 days of antibiotic therapy for the
mother
 (cloxacillin, dicloxacillin, oxacillin, or cephalexin),
 bedrest,
 Adequate oral fluid intake,
 Analgesia, and
 frequent evacuation of breast milk.
Postpartum depression
 Nondrug therapies include emotional support from family and friends,
education about the condition, and psychotherapy.
 Drug therapies include TCA and SSRIs.
 Treatment should be continued for at least 29 weeks.
 Nortriptyline, amitriptyline, clomipramine, desipramine,

fluvoxamine, and bupropion have been used successfully.
RELACTATION
 Recommended pharmacologic therapy for relactation is

metoclopramide, 10 mg three times daily for 7 to 14 days.
 It should be used only if nondrug therapy is ineffective.

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Pregnancy and Lactation: Therapeutic

 Approximately only 50% of embryos survive after fertilization

losses occur early: in the first 2 weeks after fertilization

 Spontaneous loss of pregnancy later in gestation (after 12

 Occurs in the fallopian tube

 The attached sperm releases enzymes

 Allow the sperm to fully penetrate the zona pellucida and

 Occurs at approximately 6 days after fertilization

 Begins with the blastocyst sloughing the zona pellucida

 Rest directly on the endometrium

 allowing initiation of growth into the endometrial wall

 By day 10 post fertilization

 The blastocyst receives nutrition from maternal blood

 The embryonic period: b/n weeks 2 and 8 post fertilization

 Formation of most body structures

 The fetal period: from the 8th week until term

 Formed body structures continue to grow and mature

 Gravidity: the number of times that a woman is pregnant

 A multiple birth is counted as a single pregnancy

 Parity: the number of pregnancies exceeding 20 weeks’

 a: number of times that a woman is pregnant

lasts approximately 280 days (about 40 weeks or 9 months)

 measured from the first day of the last menstrual period to

o Due date: add 7 days to the first day of the last

 Increased frequency of urination

 Change in cervical mucus consistency

 Bluish discoloration of the vaginal mucosa

 Increased skin pigmentation, and

 Anatomic breast changes

 Nausea and vomiting

 Commonly called morning sickness

 can happen at any time of the day

 resolve at 12 to 18 weeks’ gestation

A pregnant woman can feel fetal movement in the lower abdomen

 Lipophilic drugs cross the placenta more easily than do water-soluble

 Fetal difference with the mother

 Fetal albumin increases while maternal albumin decreases

 Fetal pH is slightly more acidic than maternal pH

 Effect on weak bases????

 Unknown causes: 65% to 75%

 Genetic causes:15% to 25%

 Environmental issues: 10%

 Medication exposure: <1% of all birth defects

 The stage of pregnancy during exposure

 Route of administration, and

 Risk associated with medication estimated

 By studies other than RCT

 Most commonly cohort or case control studies

 Pregnancy registries by pharmaceutical companies

 Voluntary reporting systems

 tertiary compendia and

 A considered safe and X considered teratogenic

 Maternal health status

 History prior to conception

 Important to prevent adverse pregnancy outcome

Antiepileptic drugs  Known teratogens, • Use lowest possible dose

Alcohol misuse  Fetal alcohol syndrome • Cease alcohol intake

 Neural tube defects (NTDs)

 Lip and cardiac anomalies

 Neural tube defects (NTDs)

 Occur within the first month of conception

 Folic acid: 0.4 - 0.9 mg daily is recommended throughout a

 affect 25% to 40% of women

 Contribute to the development or exacerbation of