DRUGS USED IN

PREGNANCY
Prepared by;
MOHAMAD NAZRIN BIN AB LATIB
NADRA HASIEF FARZANA BINTI AZNIL
MUHAMMAD NUZUL ALIMI BIN MOHD DAUD
PLACENTAL CIRCULATION
MECHANISMS OF DRUG TRANSFER
MECHANISM EXPLANATION
SIMPLE DIFFUSION • Most drugs (especially type 1 drugs) cross the placenta by this
mechanism.
• Transfer is either transcellularly through the syncytiotrophoblast layer
or paracellularly through water channels incorporated into the
membrane
FACILITATED DIFFUSION • Will be inhibited if the carrier molecules become saturated by both
drug and endogenous substrates competing for their use.
ACTIVE TRANSPORT • against concentration gradient, energy ATPase–mediated
• E.g: p-glycoprotein (involved in the transfer of drugs including digoxin,
dexamethasone, cyclosporin A, and chemotherapeutic agents like
vincristine and vinblastine), and the multidrug resistance proteins 1–3
(involved in the transfer of drugs such as methotrexate and HIV
protease inhibitors
PINOCYTOSIS Endocystosis and exosytosis
FACTORS AFFECTING PLACENTAL TRANSFER
FACTOR REASONS

Physical • Placental surface area

• Placental thickness
• pH of maternal and fetal blood
• Placental metabolism
• Uteroplacental blood flow
• Presence of placental drug transporters

Pharmacological • Molecular weight of drug

• Lipid solubility
• pKa
• Protein binding
• Concentration gradient across placenta
FDA PREGNANCY DRUGS CLASSES
 PHARMACOKINETICS IN PREGNANCY
• Drug absorption:
– high circulating levels of progesterone slow the gastric emptying as well as
gut motility resulting in slower drug absorption.
– Parenteral drug administration is preferred in order to obtain a quick
response.
– Drug compliance may be poor because of nausea and fear of adverse effect.
• Drug metabolism:
– hepatic drug metabolizing enzymes are induced during pregnancy probably
by high concentration of circulating progesterone.
– This can lead to more rapid metabolic degradation especially of highly lipid
soluble drugs.
• Drug excretion:
– During pregnancy the renal plasma flow increases by 100% and glomerular
filtration rate by 70%.
– Hence, drugs which depend for their elimination mainly on kidney are
eliminated more rapidly than in non-pregnant stage, e.g. ampicillin, gentamicin
and cephalosporin.
• Increase total blood volume:
– There is increased total blood volume, because of increased fluid retention.
– This leads to change in cardiac output, blood pressure and glomerular filtration
rate.
– This results in change in volume of distribution of drug, change in metabolism,
change in absorption, change in excretion of drug, change in protein binding of
drugs and passage of drug through placenta.
TERATOGENS AND FETAL
DEVELOPMENT
THE PRINCIPLES OF TERATOGENECITY INCLUDING
GESTATIONAL TIMING, DOSE AND DURATION
• substances that may produce physical or functional
Teratogens defects in the embryonic life or fetal after the
pregnant woman is exposed to the substances

• determines what structures of the fetus are

Gestational timing developing at what time, exposure to teratogens at
specific times could damage specify systems/ organs

• amount of teratogen also affects the

Dose severity and the appearance of defect

Duration • continued exposure are more detrimental.

FACTORS THAT AFFECT THE TERATOGENICTY OF
THE SUBSTANCES

Nature of Route of Gestational

Dose
agent administration timing

Concurrent Genetic
Toxicity
exposures susceptibility
EFFECTS ON FETAL AGE
• May have and all or nothing
1) Before the 20th day after
• But teratogenesis is unlikely to happen during this
fertilization stage.

• Teratogenesis is most likely to happen at this stage.

2) During organogenesis • May result in spontaneous abortion , sub-lethal
(between 20-56 days after gross anatomic defect and covert embryopathy
fertilization) (where permanent metabolic or functional defect
that manifest later in life)

• Teratogenesis is unlikely but drugs may alter growth and

3) After organogenesis function of normally formed foetal organs and tissues.
(2nd and 3rd trimester) • But as placental metabolism increases, doses must be
higher for fetal toxicity to occur.
PREVENTION OF BIRTH DEFECT ASSOCIATED WITH
TERATOGENIC EXPOSURES
Educate the pregnant Counsel about
women about alcohols, smoking , Change medication
teratogens that will uncontrolled DM and (dosage, type)
affect the conception also uncontrolled HTN

Folic acid
Maintain good diet
supplementation
COMMON DRUGS IN
PREGNANCY
 1.
ANTI-EMETICS
 ANTI EMETICS
•  Use to treat nausea and vomiting( morning sickness)
1) Metoclopramide (Dopamine receptor antagonists)
• Category: B
• Dosage: 5-10mg tds
• Side effects:
i. Extrapyramidal symptoms: dystonia, akathisia, parkinsonism, bradykinesia,
tremor, and tardive dyskinesia
ii. Gastrointestinal upset (diarrhoea)
MOA - acts both centrally (blocking the chemoreceptor zone) and peripherally
(stimulating the motility of upper GI tract)

Early detection and discontinuing metoclopramide is important to prevent

permanent tardive dyskinesia
2) Oral Vitamin B6 (pyridoxine)
• Category: A
• Dosage: 10-25mg tds or qid
• As a single agent the maximum dose in
pregnancy is 200 mg/day; however, a
cumulative dose up to 500 mg/day is found to
be safe
• Overdose may lead to: clumsiness, numbness,
tingling sensation in the hands and feet
3) Promethazine
• Category: C
• Not only act as anti-emetic but also belonged to anti-histamine group.
• Dosage: 25 mg orally OD
• SE: blurred vision, dry mouth, dizziness, drowsiness

MOA : These agents block the histaminic receptors in both

vestibular-system and chemoreceptor trigger zone receptors.
4) Dimenhydrinate
• Category: B
• Dosage: 50-100mg 4-6 hours up to max 400mg/day
• side effects:
• Blurred vision
• Drowsiness
• Ringing of the ears
• Headache
• Incoordination
• Dryness of the mouth
 2.
ANTI-COAGULANT
 3.
THYROID DRUGS IN
PREGNANCY
THYROID DRUG IN PREGNANCY

• Preferably treated with prophylthiouracil (PTU) to

carbimazole
Hyperthyroid • PTU side effect – hepatotoxicity
• Use smallest dose possible to maintain
euthyroidism state

• Levothyroxine
• Side effect – weight and appetite changes
Hypothyroid
 4.
ANTI-HYPERTENSIVES
CLASSIFICATION OF HYPERTENSION IN PREGNANCY
✘ Preeclampsia-eclampsia
✘ Gestational hypertension
✘ Chronic hypertension
✘ Preeclampsia superimposed on chronic hypertension

BP persistently ≥150 mmHg systolic or

WHEN TO
≥100 mmHg diastolic.
AIM: prevent rise of BP & reduce

GIVE?
gradually to <150 mmHg systolic and
90-100 mmHg diastolic
 WHAT TO
GIVE? 1ST LINE 2ND LINE 3RD LINE

DRUG OF CHOICE METHYLDOPA LABETALOL NIFEDIPINE

DOSE Oral 250mg TDS, Oral 100mg BD, Oral 10mg TDS,
Max dose 1g TDS Max dose 400mg BD Max dose 20mg TDS
FDA CATEGORY B C C
(C if IV)
ACTION Centrally acting Reduce sympathetic Calcium channel blocker
stimulation
SIDE EFFECTS Sudden fall of BP Bradycardia Headache
Anxiety Postural hypotension Fatigue
Dry mouth Bronchospasm Pedal edema
Vasoconstriction Shortness of breath
CONTRAINDICATIONS Depression Cardiac failure Severe heart failure
Severe bradycardia Allergies
Severe hypotension
Obstructive airway disease
 WHAT TO
GIVE? FOR SEVERE PREECLAMPSIA

FOR HYPERTENSIVE CRISIS

CONTRAINDICATED
• ACE inhibitor
• ARB
• Propanolol
• Diuretics
 5.
ANTI-DIABETICS
- Oral diabetic agents
- Insulin
 WHEN TO
GIVE?
ORAL DIABETIC AGENT
(METFORMIN)
✘ GDM: blood glucose targets are
not met by modification in diet
and exercise within 1-2 weeks.
✘ Should be continued if already on
treatment before pregnancy
INSULIN
✘ Blood glucose targets are not met after
MNT and metformin therapy
✘ Metformin is contraindicated
✘ FPG ≥7.0 mmol/L at diagnosis (with or
without metformin)
✘ FPG of 6.0-6.9 mmol/L with complications
(macrosomia/polyhydramnios)
 WHAT TO
GIVE?
✘ Initial dose 500mg OD
✘ Usual dose 1500mg OD
✘ Maximum dose 1000mg TDS
- METFORMIN -
✘ Action: ↓ blood glucose production &
↑ insulin sensitivity
✘ Side effects: diarrhea, nausea, abdominal pain.
✘ High blood lactic acid level if prescribed
inappropriately or in overly large doses.
✘ Contraindications: significant liver or kidney diseases

✘ FDA CATEGORY B
✘ Associated with less
maternal weight gain, higher
premature birth as
compared to insulin
 WHAT TO - INSULIN -
GIVE? Human insulin

Estimated total daily - Generally considered safe and effective.

insulin requirement - Sufficient data on the use of human insulin in
pregnant women allows them to be considered
✘ 1st trimester: 0.7 units/kg/day
as low risk in pregnancy.
✘ 2nd trimester: 0.8 units/kg/day
- FDA CATEGORY B
✘ 3rd trimester: 0.9 units/kg/day
- The preferred choice of insulin in view of its cost
and availability.
✘ The preferred choice of insulin
regime in diabetes in pregnancy is
multiple daily injections.
✘ Insulin analogues should be
continued during pregnancy in
women with pre-existing diabetes
who are already on the treatment.
 6.
TOCOLYTICS &
UTEROTONICS
 WHEN TO
GIVE?
TOCOLYTICS
(↓ UTERINE CONTRACTION)
✘ to delay preterm delivery for 48
hours to reduce perinatal
morbidity and mortality.
✘ to allow transfer to tertiary
hospital
✘ to complete dexamethasone for
lung maturity
UTEROTONICS
(↑ UTERINE CONTRACTION)
✘ Accelerate abortion
✘ Induction of labour
✘ Augmentation of labour
✘ Following expulsion of placenta
✘ To minimize bleeding
✘ Treat postpartum hemorrhage
Tocolytic drugs descriptions
Calcium channel Dose: oral 10-30mg TDS
blocker Max dose : 120-180mg per
- Nifedipine day,
NSAID Prostagladin inhibitor
-Indomethacin Doses: 100mg loading
suppository and 25mg TDS
Magnesium sulphate Doses: loading dose 4-6g IV
over 20-30 minutes.
Follow by infusion of 1-
2g/hour.
Beta mimetics Doses: Initiate at 2.5-5
-terbutaline mcg/min IV. Increase gradually
as tolerated at 20-30 minute
intervals. Typical
effective dose ranges between
17.5-30 mcg/min IV
contraindication Side effects
- Maternal cardiac - Hypotension
disease - headache
- hypotension - Flushing
hepatic disease, active - Maternal Peptic ulcer, GI
peptic ulcer, coagulation bleed
disorders - Oligohydromnions.
myasthenia gravis - flushing, sweating,
headache, muscle
weakness
- lethargy, hypotonia,
respiratory distress.
Maternal heart disease - Maternal headache,
Hypotension palpitation, tachycardia,
thyrotoxicosis cardiac failure
- Fetal tachycardia, heart
failure, hypoglycaemia
Uterotonic drugs description
oxytocin started at low dose IV (1-2 mIU/min) and
(syntocinon) increased gradually 20-30minutes
according to response.
(uterine contraction sustained for about 45
seconds and 3 contractions per 10 minutes)
continue until 30-60 minutes after delivery.
Side effects
- Uterine hyperstimulation
(>6 per 10minutes, >60 seconds per contraction)
- Uterine rupture
- Water intoxication due to its antidiuretic
function in high dose
- Hypotension
- Fetal distress, hypoxia or death

For augmentation : high dose oxytocin

(4mIU/min) and increases 4mIU/min at
every 20/30min interval

Ergometrine • dose 0.2mg IM or slow IV - nausea and vomiting.

• repeat 0.2mg after 15min - rise of blood pressure, myocardial
• maximum 5 doses (1mg) infarction, stroke and bronchospasm.
Synthometrine IM 0.5mg of ergometrine with 5 units of
oxytocin.

Prostaglandin Ripening the cervix

 7.
ANTI-ASTHMATIC
 8.
ANTIHISTAMINES
 WHEN TO
GIVE? WHAT TO
✘ Dermatological problems (pruritus)
GIVE?
✘ Relief of allergic rhinitis, allergic conjunctivitis,
URTI FDA 1ST GENERATION 2ND GENERATION
CATEGORY
✘ Treatment of pregnancy symptoms
( nausea, vomiting, motion sickness, dizziness) A Cyproheptadine -

B Chlorpheniramine Cetirizine
✘ Action: prevent histamine-receptor interaction Diphenhydramine Loratadine
through competition with histamine at H1 Dexchlorpheniramine Levocetirizine
receptor (competitive inhibition) Clemastine
✘ Side effects: Tripelennamine
○ 1st gen: CNS depression (sedation,
dizziness, tinnitus, blurred vision, C Promethazine Fexofenadine
tremors) Hydroxyzine Desloratadine
○ 2nd gen: photosensitivity, tachycardia,
prolonged QT interval (rare)
 Pregnancy Risk Categories (FDA)

✘ Category |A|
Safety has been established using human studies, no fetal risk.
✘ Category |B|
Presumed safety based on animal studies, but no well-controlled human
studies.
✘ Category |C|
Uncertain safety. Animal studies show an adverse effect, no human studies.
✘ Category |D|
Evidence of fetal risk, but benefits outweigh risks.
✘ Category |X|
Highly unsafe. Risk outweighs any possible benefit.
 9.
ANTIMICROBIALS
 ANTI MICROBIAL
✘ Perinatal infections account for 2%-3% of birth defects which arise
form a spectrum of organisms and have varying modes of
transmission. (TORCH)
✘ They can be treated with:
-antibiotic
-anti fungal
-anti viral
-anti parasites
✘ Not all anti microbials are safe for pregnancy!!!!!.
 ANTIBIOTICS
✘ Infections in pregnancy include urinary tract infections, pyelonephritits
(kidney infection), bladder infection, pneumonia, cold, bronchitis,
sinusitis, are commanly encountered among pregnant ladies.
✘ These are antibiotics that are considered safe in pregnancy:
-penicillin (amoxicillin,ampicillin)
-Clindamycin
-erythromycin
-Nitrofurantoin
-Cephalosporin
-Metronidazole
 CATEGORY B
Presumed safety based on animal studies, but no well-controlled
human studies.

• Penicillin
• Cephalosporin
• Macrolides
• Nitrofurantoin
• Metronidazole
• Vancomycin (oral)
 Penicilin
✘ Beta lactam group
✘ All trimester are safe
✘ No teratogenic
✘ It was one of the first medicines to treat syphilis
✘ Pass the placenta
✘ Inhibit cell wall synthesis
✘ Dose : Amoxicilin 500mg three times daily orally
Or iv / im
✘ Ask the patient if she has allergy to penicilin!
✘ Side effect: Vomiting,Severe watery diarrhea and
abdominal cramps, Allergic reaction (shortness of breath,
hives, swelling of lips, face, or tongue,
fainting),Rash.Vaginal itching or discharge.,White patches
on the tongue.
Penicilin
 Cephalosporin

✘ Beta lactam group

✘ One of the safest antibiotics in pregnancy
✘ 1st generation cephalosporin (staphylococci & most streptococci, not
enterococci)
-cefazolin, cephalexin (IV 1g six hourly/500mg six hourly)
✘ 2nd generation cephalosporin (gram negative)
- cefaxlor (250mg TID)
- cefuroxime
✘ 3rd generation cephalosporin (gram negative)
- cefexime (400mg daily)
✘ Work by inhibiting cell wall synthesis, bactericidal effect
 Macrolides

✘ Eg : erythromycin& azithromycin can be used (not cross placenta in

appreciable quantity)
✘ Alternative for penicillin-allergy patients
✘ Dose 500mg /BD or QD
✘ Side effect:nausea, vomiting, diarrhea, and ringing or buzzing in
the ears (tinnitus)
✘ Nitrofurantoin : Commonly used in pregnancy to treat UTI, should not
be given to women in late pregnancy due to the potential risk of
hemolytic anemia (breakdown RBC) in the newborn
✘ Metronidazole : not recommended for lactation
✘ Vancomycin (oral): possible fetal ototoxic effect cause deafness to
fetus
CATEGORY C
• Aminoglycosides
• Quinolones
• Trimethoprim
• Chloramphenicol
✘ Aminoglycoside (neomycin – tobramycin)

✘ Quinolones (ciprofloxacin – levofloxacin) : There are safety concerns

of fluoroquinolone use during pregnancy and, as a result, are
contraindicated except for when no other safe alternative antibiotic
exists (possibility of joint abnormalities)

✘ Trimethoprim : can affect folate metabolism, so relatively

contraindicated during pregnancy, especially during 1st trimester

✘ Chloramphenicol :
-Gray Baby Syndrome
-In women/fetuses with (G6PD),cause RBC breakdown
CATEGORY D
• Tetracycline
• Aminoglycoside
✘ Tetracycline : use during tooth development can cause permanent
discoloration & enamel hypoplasia

✘ Aminoglycosides (streptomycin – gentamicin) : cause hearing

deficit & 8th cranial nerve damage (sensoryneural deafness)
 Anti Viral
✘ CATEGORY B
Acyclovir : recommended for treatment of Varicella during pregnancy, especially
during the 2nd and 3rd trimesters

✘ CATEGORY C
Amantadine : CHD - tetralogy of Fallot / single ventricle with pulmonary atresia

✘ ANTI RETROVIRAL (CATEGORY B)

Didanosine – Etravirine – Ritonavir – Enfuviritide – Maraviroc

✘ ANTI RETROVIRAL (CATEGORY C)

Lamivudine – Delaviridine – Indinavir
 Anti Fungal
Category (B)

✘ Amphotericin : remains the drug of choice for systemic fungal

infections in pregnancy despite its serious side effects i.e. renal
toxicity

✘ Terbinafine : approved for the treatment of onychomycosis (fungal

infection of the nail)
Category c
Ketoconazole : inhibits placental microsomal aromatase & cytochrome P-450

Category (C/D)

Fluconazole : depends on doses & duration of use

(teratogenicity side effect)

Category (X)

Griseofulvin : contraindicated during pregnancy & pregnancy should be avoided for 1

month after treatment (increased risk of spontaneous abortion)
 Anti Parasitic

✘ Commonly prescribed anti parasitics are metronidazole and

nitromidazole

✘ Chloroquine
- Drug of choice for the prophylaxis and treatment of sensitive
malaria species during pregnancy
- First line antimalarial agent
- There is no increased risk of congenital with its use

✘ Quinine is the prototype antimalarial agent and used to treat

chloroquine resistant plasmodium
 10.
LAXATIVES
 ✘ Causes of constipation:
1. fetus compression on colon;
2. reduction in intestinal muscle tone;
3. prenatal multivitamin supplements (Ca, Fe etc)
✘ Only bulk-forming, lactulose or emollient laxatives should be used.
WHY?
There are few possible risks?
✘ Mineral oil: decreased/loss of vitamin absorption
✘ Castor oil: premature labour
✘ Osmotic agents: dangerous electrolyte imbalance
✘ saline laxatives: appreciable GI absorption in the mother/ toxicity (e.g.
Mg) muscle weakness, ECG changes, hypotension
1. Bulk-forming laxatives
✘ Agents of choice as initial therapy for most forms of constipation WHY?
- Natural and semisynthetic hydrophilic polysaccharides & cellulose
derivatives that dissolve or swell in the intestinal fluid, forming
emollient gels that facilitate passage of intestinal contents
- Usually effective in hours but may require 3 days in some individuals
- Not absorbed systematically
- Because they most closely approximate the physiologic mechanism in
promoting evacuation
✘ Side effects:
 Diarrhea, abdominal discomfort, flatulence or excessive fluid loss may
occur
 Hypersensitivity reactions (e.g. swollen, watery eyes, & skin rash)
Examples:
✘ Polysaccharides & cellulose derivatives e.g. psyllium (plantago) seed,
agar, alginates, guar gum; methylcellulose, carboxymethyl cellulose
sodium
✘ Calcium polycarbophil: often used in IBS & diverticular disease
✘ Malt soup extract (12-64g)
✘ 1st line treatment : psyllium & calcium polycarbophil
2. Emollient Laxatives “stool softeners”

✘ Docusate sodium, docusate potassium, docusate calcium

✘ In many cases of fecal impaction, a solution of docusate is added to
the enema fluid
✘ Onset of action same as bulk laxatives (except docusate K= 2-15 mins)
✘ Fluid intake should be increased to facilitate softening of stool
✘ Side effects:
-skin rashes
-decrease absorption of fat soluble vitAmin A,D,E,K
3. Lactulose
✘ It is a semi-synthetic disaccharide which is not be absorbed from the
GIT.
✘ Hydrolysed by the gut bacteria, draw fluid
✘ Mechanism : Lactulose, a disaccharide, is a sugar like Hyperosmotic
Laxative . Lactulose produces an osmotic effect in the colon as
bacterial flora breaks down the lactose into lactic, formic and acetic
acids. Fluids that accumulate distend the abdomen, promoting
peristalsis and bowel evacuation.
✘ Results usually occur in hours lasting no longer than 24 hours.
✘ SIDE EFFECTS:
-ABDOMINAL BLOATING
 11.
HEARTBURN
✘ Calcium- or magnesium-containing antacids is 1st line treatment
✘ If antacids fail to improve symptoms, ranitidine can be recommended
(best safety data among the H2 blockers).
✘ Omeprazole, sucralfate, and metoclopramide =safe in pregnancy.
✘ Use of PPI should be reserved for women who do not respond to H2
antagonists.
✘ All the drugs used for heartburn during pregnancy are acceptable during
lactation.
 12.
VACCINATION
✘ The administration of vaccines during pregnancy poses a number of
concerns about the risk of transmitting a virus to a developing fetus
✘ Routine vaccines that generally are safe during pregnancy include:
1. Diphtheria
2. Meningococcal
3. Tetanus
4. Rabies.
5. Influenza
6. Hepatitis B
 Who needs the Tetanus and Diphtheria vaccine?

✘ Previously vaccinated pregnant women who have not received a Td

vaccination within the past 10 years should receive a booster dose.
✘ According to CDC guidelines :
1ST dose between 16 -20 weeks
2nd dose after 4 – 6 weeks .
✘ O.5 ml Intramuscular in upper arm
 thanks!
Any questions?