Drugs and Medications

in Pregnancy

Presented by: Mikiyas Sharew

Moderator:Dr. Gebresilassie
August 15, 2022
Outline
 Introduction

 Pharmacokinetics and pharmacodynamics in pregnancy

 Teratology

 Medications used in pregnancy

 Known teratogenic drugs

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Introduction
 More than 90% of pregnant women take prescribed or OTC medicines or use social
drugs (alcohol and tobacco) or illicit drugs at some time during pregnancy

 In general drugs should not be used during pregnancy unless absolutely necessary as
many can harm fetus

 About 2-3% of all birth defects result from drug that are taken to treat disorder or
symptoms

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Maternal Physiologic changes
 GI absorption:
  GI motility 2ndry to progesterone
  gastric acid secretion
  gastric mucus secretion
  gastric emptying time

 Lung absorption:
 Cardiac and tidal volume  by 50%
 Hyperventilation and  pulmonary blood flow

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 Transdermal absorption:
  in peripheral vasodilation and  in blood flow to skin
  transdermal absorption

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Metabolism and excretion
 Hepatic drug metabolizing enzymes  induced during pregnancy, probably by high
levels of circulating progesterone

 This leads to rapid metabolic degradation of especially of lipid soluble drugs

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Placental pharmacokinetics
 Physiochemical properties of the drug:
 Lipid solubility
 Molecular size  less than 500D

 Rate at which drugs cross placenta:

 Placental transporters
 Protein binding
 Placental metabolism dealkylation, hydroxylation, demethylation
 Blood flow through placenta  GA
 Surface area of placenta  term max

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Fetal pharmacokinetics
 Plasma binding proteins differ from maternal

 Drugs transferred across placenta undergo 1st pass metabolism through fetal liver

 Liver expresses metabolizing enzymes capacity is not fully developed

 Fetal kidneys are immature

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FDA risk categories

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PLLR

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Teratology
 “Tertatos = monster”

 Teratogenesis structural or functional dysgenesis of fetal organs/somatic tissues

 Teratogen  agent

 To be considered teratogenic:

 Result in characteristic set of malformations

 Exert its effect at particular stage of fetal development

 Show dose dependent incidence

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1959 James Wilson 6 basic principle of teratology:

1. Susceptibility to teratogenesis depends on genotype of the conceptus

and manner in which it interacts with the environmental factors

2. Susceptibility to teratogens varies with developmental stage at time

of exposure

3. Teratogenic agents act in specific ways on developing cells and

tissues to initiate abnormal developmental process

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1959 James Wilson 6 basic principle of teratology:

4. Access to adverse environmental influence to developing tissues

depends on nature of influences

5. Final manifestations of altered development are death,

malformations, growth retardation and functional disorder

6. Manifestations of altered development increase in frequency and in

degree as dosage increases from no effect to 100% in lethality

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Effect of drugs in pregnancy
1. Pre-implantation stage /pre-embryonic
 The first 2 weeks
 All-or-None effect

2. Period of organogenesis/ embryonic

 2nd – 8th weeks
 Abortion
 Sublethal gross anatomic defect
 Permanent metabolic or functional defect

3. Fetal period
 Beyond 8th week
 Retardation of physical or brain growth
 Premature

4. Labor-delivery stage  danger of toxicity in neonatal period

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Teratogenic MOA
 Folate antagonism

 Neural crest cell disruption

 Endocrine disruption

 Oxidative stress

 Vascular disruption

 Specific receptor/ enzyme mediated teratogenesis

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18
Medications during
pregnancy

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Medications during pregnancy
 Drug prescribed for:
 Treatment of common minor aliments
 Nausea and vomiting
 Pain
 Diarrhea
 Dyspepsia
 Constipation
 Common cold
 Cough
 Treatment of pre-existing or pregnancy aggravated medical illness
 Asthma
 HTN
 Cardiac arrhythmias
 Hematologic diseases
 Epilepsy
 DM
 Thyroid disorders

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 Analgesic and antipyretics:  Nausea and vomiting:

 Paracetamol [cat B]; safe in normally  Meclizine and cyclizine [cat B]  safe

recommended doses  Metoclopramide [cat B]  labor

 Aspirin:  Ondansetron [cat B]

 Inhibits prostaglandin synthesis. Uterine  Vitamin B6 (pyridoxine) 25 mg three times a

contractility is decreased  ? day

 closure of the ductus arteriosus in utero  Constipation:

 Neonatal pulmonary HTN  Bulk laxatives [cat B] containing

methylcellulose
 Antidiarrheal:
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 Loperamide [cat B]
Common cold:
 Heartburn/ dyspepsia:
 Antihistamine [cat B]:
 Non absorbable antacids [cat B]
 loratadine(hypospadias)

 diphenhydramine(sedating)  Sucralfate [cat B]

Cough:  H2 blockers [cat B]

 Guaifenesin [cat C]  All PPIs [cat B]

 Dextromethorphan [cat C]  omeprazole [cat C]

 Iodide containing expectorants  fetal
 Lansoprazole is the safest PPI
goiter  respiratory obstruction
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Asthma
 SABA
 Terbutaline [cat B]
 Salbutamol [cat C]

 LABA
 Salmeterol [cat C]

 Glucocorticoids
 Budesonide [cat B]
 Beclomethasone dipropionate [cat C]
 Increase preeclampsia in asthmatic women on oral steroids
 prednisone and prednisolone Vs. betamethasone and dexamethasone

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Hypertension
 Methyldopa [cat B] is the 1st line drug

 Beta blockers [cat C] shouldn’t be preferred during the first 28 weeks

 Fetal bradycardia, hypoglycemia and fetal growth restriction

 HTN emergencies

 Hydralazine 5-10mg IV or labetalol 20mg IV

 ACE inhibitors and ARBs [cat D]

 fetal renal tubular dysplasia  oligohydramnios  fetal limb contractures, craniofacial

deformities, and hypoplastic lung development

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Hypertension
Ca channel blockers [cat C]

nifedipine have been widely used for chronic hypertension in pregnancy without evidence of

teratogenicity

1st trimester phalangeal deformities

2nd-3rd trimester  fetal growth restriction

Diuretics

Furosemide [cat C]

Thiazide [cat D]

Spironolactone [cat B]

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Arrhythmias Anticoagulants

 Heparin:
 Digoxin [Cat C] - maternal atrial flutter or
 Used for management of venous
fibrillation thromboembolism in pregnancy as they
do not cross placenta
 Quinidine [Cat C] - safe during late
 Warfarin [Cat X/D]:
 Amiodarone [Cat D] – when benefit  women with mechanical heart valves
 Warfarin embryopathy
outweighs risk
 nasal hypoplasia, bone stippling,
 ophthalmologic abnormalities including
bilateral optic atrophy
 mental retardation
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Diabetes mellitus Thyroid disorders

 Thyrotoxicosis:
 Diet restriction and insulin therapy
 PTU is preferred to methimazole
 PTU hepatotoxicity
 Metformin [cat B]
 Methimazole -scalp defects, choanal and
esophageal atresia
 Oral hypoglycemics:
 1st trimester Vs. 2nd and 3rd trimester
 causes fetal hyperinsulinemia
 Hypothyroidism:
 Malformation if taken early pregnancy  Thyroid hormones triiodothyronine and
thyroxine cross the placenta poorly
 levothyroxine dose by about 30% as soon
as pregnancy is confirmed
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Antibiotic
 TETRACYCLINES
 chelation to calcium in developing bone and tooth structures.
 brown discoloration of teeth on 2nd and 3rd trimester, hypoplasia of the enamel, and
inhibition of bone growth.
 AMINOGLYCOSIDES
 Ototoxicity and nephrotoxicity

 FLUOROQUINOLONES
 high affinity for bone tissue and cartilage and may cause arthralgia in children

 Sulfonamide:
 Hyperbilirubinemia if used near delivery in preterm infants

 PENICILLINS, CEPHALOSPORINS, ERYTHROMYCIN, and CLARITHROMYCIN are safe in

pregnancy
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 ANTITUBERCULOSIS DRUGS
 no teratogenic effect of isoniazid,
rifampin, or ethambutol
 ANTIFUNGAL AGENTS
 no teratogenic effect of Nystatin,
Clotrimazole or miconazole

 ANTIRETROVIRAL AGENTS
 Zidovudine and lamivudine  No
teratogenicity.
 Efavirenz  NTD.

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Anticonvulsant
 Valproic acid
 spina bifida, ASD, cleft Palate hypospadias,polydactyly,craniosynostosis and Low IQ
 Valproate not first choice drug in women of reproductive age

 carbamazepine
 NTD, CV and urinary abnormality

 Phenytoin
 low IQ, decrease folate absorption-folic acid supplementation given
 affect vitamin K–dependent clotting factors in the newborn

 A high daily dose or a combination of two or three drugs increases the

chance of malformations

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 fetal hydantoin syndrome

 Microcephaly

 growth deficiency

 developmental and mental retardation

 dysmorphic craniofacial feature

 hypoplasia of the nails and distal

phalanges
 Hypertelorism

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Teratogenic drugs

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 Vitamin A Analogues
 Isotretinoin [cat X}

 2 weeks

 Severe birth defects

 Cleft palate

 Cardiac anomalies

 neuropsychological impairment

 Spontaneous abortion

 Premature birth

 Fetal death

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 Thalidomide
 Cat X

 Used for nausea and to alleviate morning sickness

 Causes:

 Meromelia

 CHD

 Eye abnormalities

 Facial palsy

 Intestinal atresia

 Phocomelia

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 Androgenic
 Danazol:

 Synthetic progestin

 When given during the first 14 weeks  masculinization of female fetus’s genitals

 Cat X

 Increased CVS abnormalities

 OCP when taken during early stages of unrecognized pregnancy are shown to be

teratogenic

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 Diethylstilbestrol
 Cat X

 Used in 1940 and 50’s

 Caused:
 Increased incidence of vaginal CA

 Increased incidence of cervical CA

 Increased reproductive dysfunction

 T- shaped constricted uterus

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 Caffeine
 Small amount ( 1 cup of coffee/day pose little or no risk )

 Large amounts of caffeine is associated with: ACOG 

 Still birth

 Preterm deliveries

 Low birth weight

 Spontaneous abortions

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 Lithium
 Causes- hypotonia, lethargy, poor

feeding, goiter, hypothyroidism and

 Polyhydramnios

 Ebstein anomaly

 Ultrasound and fetal

echocardiography

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 Smoking
 CO and nicotine  hypoxia and vasoconstriction 
 Spontaneous abortion
 Fetal growth restriction
 Abruptio placentae
 Placenta previa
 Premature rupture of membrane
 Preterm birth
 Stillbirth
 CHD
 Orofacial cleft
 Sudden infant death syndrome
 Associated with childhood asthma

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 Alcohol
 Increase risk of spontaneous abortion
 Decrease weight by 1-1.3 kg if regular drinking
 Fetal alcohol syndrome
 Dysmorphic facial features
 Small palpebral fissure
 Thin vermilion border
 Smooth philtrum
 Prenatal and postnatal growth impairment
 CNS abnormalities
 Head size < 10th percentile
 Significant brain abnormality on imaging
 Functional, global cognitive or intellectual deficits

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 Amphetamines:
 Cat C
 Causes: oral cleft, CV abnormalities

 Cocaine:
 Vasoconstrictor  hypoxia
 Spontaneous abortion
 Growth retardation
 Microcephaly
 Urogenital anomalies
 Gastroschisis

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 Vaccines
 Killed virus, toxoid or recombinant vaccines may be given during

pregnancy

 Live attenuated vaccines  3 months

 Varicella

 MMR

 Polio

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 principle of prescribing
 Where possible non-drug therapy
 Prescribe drugs only when definitely needed
 Choose drugs having best safety record
 Avoid new drugs
 OTC cannot be assumed safe
 If possible avoid medication in initial 10 weeks
 Use lowest effective dose
 Use drugs for shortest period necessary

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 Drug of choice/ summary
 HTN  methyldopa
 HTN emergencies  labetalol
 Diabetes mellitus  Insulin
 Hypothyroidism  L-thyroxine
 Hyperthyroidism  PTU/methimazole
 Seizure in eclampsia  Mgso4
 Syphilis  pencillin G
 Asthma  terbutaline
 Antiretroviral  Zidovudine

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References
 OBSTETRICS Normal and Problem Pregnancies 7th edition
 Goodman & Gilman’s the pharmacological basis of therapeutics 12th edition
 Williams OBSTETRICS 26th edition
 katzung basic and clinical pharmacology 15th edition
 FDA Human Prescription Drug and Biological Products; Requirements for Pregnancy
and Lactation Labeling
 UpToDate 2022

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