This document summarizes the effects of pregnancy on pharmacokinetics and the use of various medications in obstetrics. It discusses how pregnancy affects absorption, distribution, metabolism and elimination of drugs. It then covers the effects of medications during pregnancy, labour, and the puerperium. Various drug classes used in obstetrics like oxytocics, tocolytics, anticonvulsants and diuretics are described along with their indications, dosages, side effects and contraindications. The placental transfer of drugs and their potential teratogenic effects on the fetus are also summarized.

1. PHARMACOTHERAPEUTICS
IN OBSTETRICS

2. Pregnancy & its effects on Pharmacokinetics
• The remarkable physiological changes occurring in pregnancy have an
impact on the absorption, distribution, metabolism & elimination.

3. Absorption
• Decreased gastrointestinal motility in pregnancy: although a
major effect on drugs is not observed, reduced gastric emptying
delays the appearance of orally administered drugs in the
plasma. This is observed during labour process.
• Vasodilation in pregnancy: this helps in efficient absorption of
drugs administered through intramuscular injection as the tissue
perfusion is increased because of vasodilation.

4. Distribution
• Increase in body fluid (water): a larger space is created as a
result of increase in total body water up to 8L. This enhances
better distribution of water-soluble drugs.
• Haemodilution in pregnancy: plasma albumin declines by
10g/L from a normal range of 33-55g/L. This results in
increased free concentration of drugs binding to albumin.
Unbound drugs are free to distribute, metabolize and excrete.

5. Metabolism
• Increased hepatic metabolism: Although the blood flow to the
liver does not increase significantly in pregnancy, there is an
increase in the hepatic metabolism. This increase in metabolism
results in increased clearance of drugs like phenytoin. Drugs
like pethidine which are rapidly metabolized have unaltered
clearance because of dependence on hepatic blood flow which
interferes in the elimination rate.

6. Elimination
• Increased renal plasma flow in pregnancy: the renal plasma low
doubles in pregnancy. This causes rapid loss of drugs through
kidney excretion.

7. Effects of drugs on pregnancy, labour &
puerperium

8. 1.Effects of medication during pregnancy
• Effects of consuming drugs in pregnancy depend on factor like following
– Dose of drugs consumed
– Period of pregnancy when the drug was consumed
– Existing health ailments the woman has
– Drug interactions
– Self treatment and consuming over-the-counter drugs without consultation with a
health care provider which is harmful
– Harmful drugs which have teratogenic effects on the unborn fetus resulting on
birth defects
– Pregnant women having already existing conditions like asthma & epilepsy, in
which case they should adhere to the treatment to keep the condition under
control.

9. 2.Effects of medication during Labour
• Common medications used in labour are analgesics as well as
anesthetics. Anesthetics like opioids cause nausea & vomiting in the
women and have effects on the breathing of the fetus causing
drowsiness. Sometimes they cause respiratory distress. Some analgesics
& anesthetics need to be tested with a test dose before administration.

10. 3.Effects of medication in Puerperium
• Drugs, even if they are herbal supplements, consumed during
puerperium should be taken with caution after consultation with a doctor
as they have a tendency to pass through breast milk.

11. Drugs & breast feeding
• Any medication consumed by the mother may be present in the breast
milk. Drug concentration in the breast milk is lesser compared with the
plasma levels in the mother.
• Drugs that are low molecular weight, nonionized and lipid soluble are
usually passed through breast milk.

12. Drugs affecting Lactation
• Oral pill (combined): Lactation suppression
• Ergot derivatives: Lactation suppression
• Bromocriptine: Lactation suppression

13. Drugs affecting Neonate
• Antithyroid drugs: hypothyroidism, goiter & agranulocytes
• Metronidazole: Blood dyscrasias, irritability & anorexia
• Sedatives: anticonvulsants and narcotics: poor sucking reflex
• Tetracycline: tooth staining & delayed bone growth
• Warfarin & heparin: safe
• Corticosteroids: Safe

14. Effects of maternal medication on fetus &
neonate
• Drug transfer through placenta
– Most drugs cross the placental barrier except heparin & insulin which have large
ions. Drug exposures cause human developmental defects. Paternal exposures to
drugs can result in gene mutation and chromosomal abnormalities in sperm,
resulting in defected fetus.
– Simple diffusion is the method through which most medications cross the
placenta.

15. The identified factors for placental transfer
are as follows.
• Molecular weight: drugs having molecular weight more than 1000 do not
cross the placenta
• Drug concentration
• Lipid solubility
• Uteroplacental blood flow
• Surface area of the placenta
There is an increase in the rate of drug transfer, especially in the third
trimester, the reasons being thinning of the placental membranes, large
placental surface area, increase in blood flow from uterus to the placenta &
availability of unbound drug for transfer.

16. Fetal Circulation
The fetal circulation which is established in the third week of conception causes the drugs consumed
by a pregnant woman to reach the fetus.
Permeability
A very thin layer of membrane in the placenta allows permeability of medications from the
maternal blood to the fetal blood which then reach the fetus
Drug binding
In the fetus, these medications remain pharmacologically active as the fetal serum has
decreased levels of albumin & hence less drug binding
Drug metabolism
Drug particles reach the fetal liver where they ate metabolized. The metabolism is slow as the
liver is immature
Drug excretion
Metabolized drugs are excreted through kidney. The excretion os slow as the fetal kidneys are
immature
Overcoming blood-
brain barrier
Few drug molecules reach the heart and get distributed to brain and coronary arteries. Entry
into the fetal brain is quick because of poor development of blood-brain barriers.
Reentry into
maternal circulation
The umbilical arteries carry back half of the blood mixed with drugs to the placenta, enabling
reentry into maternal circulation. The mother metabolizes and excretes on behalf of the fetus.

18. Drug Teratogenicity
• This is seen in 1st trimester exactly between
the 1st day and the 71st day as this is the
crucial period for organogenesis. As the
drugs reach the fetus, the effects of
teratogen begin, resulting in anatomic
malformations or other effects. Drugs
consumed during the second & third
trimesters usually manifest their effects on
the neonate (birth to 28 days) as growth
retardation, respiratory problems or
bleeding. The gestational clock well
explains the classic period of teratogenicity.

19. Food & drug association classification of
drugs
• The US FDA classifies medications under five categories: A, B,
C, D & X.
Classification of Drugs
Category Drug (Proven by Research)
A No risk to patient – safe; derived results from controlled studies
B Animal studies have shown no risk
C Benefits rule out the risk of the foetus
D Proven by evidence to have fetal risks
E Unsafe in pregnancy; the proven fetal risks outweigh the potential benefits

20. Risk category D drugs
Antibacterials:
Aminoglycosides,
tetracyclines,
tigecycline &
trimethoprim
Antiepileptics:
Carbamazepine,
phenytoin & valproic
acid
Antifungal:
Voriconazole
Antiviral: Efavirenz
Antithyroid agent:
Propylthiouracil
Antineoplastics:
Idarubicin & Imatinib
Angiotensin-
converting enzyme
(ACE) inhibitors:
Captopril (in 2nd & 3rd
trimester)
Angiotensin II
receptor blockers
(ARBs like losartan)
Benzodiazepines:
Alprazolam, diazepam
& lorazepam
Biphosphonate:
Zoledronic acid
Mood stabilizer:
Lithium
Opioid analgesics (if
using high dose at
term

21. Risk category X drugs
Antineoplastic: Methotrexate
Antiviral: Ribavirin
Anticoagulant: Warfarin
Benzodiazepine sedative/hypnotic: Flurazepam
Statin cholesterol-lowering drug: Atorvastatin
Antirheumatoid arthritis drug: Leflunomide

22. Drugs Used In Obstetrics

23. Oxytocic
• Oxytocic: these are a group of drugs having varying chemical
nature & have the potential to excite uterine contractions.
Commonly used drugs under this category are oxytocin, ergot
derivatives & prostaglandin.

24. Oxytocin
• It is a natural hormone causing uterine contraction. This is
prepared synthetically & available in different forms of medical
uses.
• Brand name:
– It is Pitocin or Syntocinon

25. Oxytocin - Indications
Antepartum
• Early pregnancy
• To excel retained products of
abortion
• To expel the vesicle in
Hydatidiform mole
• To arrest bleeding after
uterine evacuation by
dilatation & curettage
• Used along with abortifacient
agents to induce the process.
• Late pregnancy
• In Induction of Labor (IOL)
• To aid in cervical ripening
Intrapartum
• To augment the labour process
• In uterine inertia
• Active management of third
stage: used in combination with
ergometrine
• Aids in placental expulsion
Postpartum
• Minimizing hemorrhage
• Preventing postpartum
hemorrhage

26. Oxytocin-method of administration
• Intravenous infusion: commonly preferred method
• IV or IM: used as an alternative to ergometrine for
administering after the delivery of the anterior shoulder
• IM injections: Syntometrine being the commonly used
preparation by this method
• Buccal tablets and nasal sprays

27. Oxytocin-method of administration
• Dosage: the convenient regime is followed while administering
oxytocin for Induction of Labor, augmentation of labor and
uterine inertia. Controlled IV infusion (10 units of oxytocin
in1L of Ringers Lactate or 5% dextrose) is given.
• Action: It increases uterine contraction.
• Side effects:
– Seizures
– Anxiety
– Coma because of complications

28. Oxytocin-method of administration
Contraindications
• Cephalopelvic
disproportion
• Previous CS
• Fetal distress
• Multiple pregnancy
• Previous surgeries
on the uterus
Complications
• PPH
• Abruptio placentae
• Tetanic
contractions
• Infection
• DIC
In fetus
• Hypoxia
• Asphyxia
• Prematurity

29. Ergot Derivatives
• Two commonly used ergot derivatives are ergometrine and
Methergin
• Available forms
– Ergometrine: Ampoules (0.25 or 0.5 mg) & tablets (0.5-1 mg)
– Methergine: Ampoules (0.2mg) & tablets (0.5-1mg)
– Syntometrine: Ampoules (0.5 mg of ergometrine plus 5 units of
Syntocinon)
• Action
– Ergometrine has the potential to decrease bleeding by stimulating
contractions

30. Ergot Derivatives
• Indications
– Main indication: Arrest of excessive bleeding occuring because of
their atonic uterus
– Administered as a prophylaxis against bleeding
• Timing of administration:
Since the drug causes uterine contractions, the best time to administer is
after the delivery of the anterior shoulders or following the delivery of
the baby
• Route:
– it is administered preferably through deep IM injection

31. Ergot Derivatives
• Contraindications
– Multiple pregnancy
– Cardiac diseases
– Severe preeclampsia and eclampsia
– Rh isoimmunization: A small chance of microtransfusion between the
mother and the fetus
• Side effects
– Rise in blood pressure
– Affects lactation on prolonged use

32. Prostaglandin
• The sources of prostaglandins in the body from where it is
synthesized are essential fatty acids , arachidonic acid,
menstrual fluid, endometrium, decidua and amniotic membrane.
• Available forms: it is available as tablets, vaginal suppository
and pessary, ampules and vials.
– Dinoprostone – PGE2
– Misoprostol – PGE1
– Dinoprost tromethamine

33. Prostaglandin
• Actions: Dinoprost tromethamine mainly acts on the
myometrium making it sensitive to oxytocin, whereas dinoprost
acts mainly on the cervix
• Dosage
– Tablets: 0.5 mg dinoprostone
– Vaginal suppository: 20mg PGE2 or 50 mg dinoprost tromethamine
– Ampoules or vials: 1mg/mL PGE2 or 5mg/mL dinoprost
tromethamine
– PGE1 (misoprostol) 50mg is placed four hourly for induction of labor.

34. Prostaglandin
Contraindications
• Hypersensitivity
• Fibroid uterus’
• Pelvis surgery
• PID
• Respiratory disease

35. TOCOLYTIC AGENTS

36. TOCOLYTIC AGENTS
• These drugs perform an action opposite to the oxytocics group
of drugs. They inhibit the uterine contractions if occurred like
in the case of premature contractions. The most commonly used
drugs under this group are magnesium sulphate, ritodine
hydrochloride and isoxsuprine.

37. Magnesium Sulphate
• Magnesium sulphate is used in obstetrics for treating different
conditions like decreasing uterine activity and controlling
seizures in the case of pregnancy – induced hypertension.
• Hence, it is used as a ‘tocolytic’ as well as an ‘anticonvulsant’.
• Action
– Reduces neuromuscular irritability
– Diuretic effect: by decreasing intracranial edema
– Improves uterine blood flow
– Antidepressant action on the uterine muscles

38. Magnesium Sulphate
• Dosage:
– Tocolytic effect: 4g IV slowly over 10minutes, followed by 2g/h, and
then 1g/h in drip of 5% dextrose.
– Antiseizure effect: 20mL of 20% solution IV over 3-4minutes,
followed by 10mL of 50% solution IM & continued four hourly till 24
hours
• Indications
– Preterm labour
– Preeclampsia and eclampsia

39. Magnesium Sulphate
Side effects
• CNS depression
• Muscular paresis
• Fetal tachycardia
• Fetal hypoglycemia
Complications
• Magnesium sulphate toxicity
• S/S of magnesium toxicity
• Muscle weakness
• Lethargy
• Irregular heartbeat
• Urinary retention
• Respiratory distress
• Cardiac arrest
• Low blood pressure
The best antidote for
magnesium sulphate
toxicity is calcium
gluconate 10% 10mL IV

40. Anticonvulsants

41. Anticonvulsants
• The commonly used anticonvulsants are diazepam, phenytoin
and phenobarbitone.

42. Anticonvulsants-Diazepam
• Action: it has anticonvulsant properties and antianxiety
properties
• Dose: it is given 2-10mg TID per oral, 5-10mg bolus IV
followed by 2mg/min, may repeat if needed.
• The dose should not exceed 60mg. Mostly diazepam is
contraindicated while pregnant unless it is mandatory to help
the pregnant woman. In such case the fetal risk is overweighed.

43. Anticonvulsants-Phenytoin
• Action: it cuts off the spread of seizure activity
• Dose:
– Eclampsia: 10mg/kg IV at a rate not to exceed 50mg/min followed 2
hours later by 5mg/kg
– Epilepsy: 300-400mg daily in divided doses.

44. Anticonvulsants-Phenobarbitone
• Action: it reduces impulse transmission, thereby increasing the
seizure threshold
• Dose: it is given 120-140mg in divided doses
• Common side effects for anticonvulsaants are as follows
In mother
• Hypotension
• Drowsiness
• Cardiac arrhythmias (phenytoin)
• Sedation
• Hangover headache (phenobarbitone)
In fetus
• Withdrawal syndrome
(phenobarbitone)
• Respiratory depression
• Craniofacial abnormalities (on
prolonged use)
• Mental retardation (on prolonged use)

45. Diuretics

46. Diuretics
• The use of diuretics arises in the case of presence of oedema
during pregnancy as in the following conditions:
– PIH
– Eclampsia with pulmonary oedema
– Sever anemia
– Used in combination with antihypertensives
• Commonly used diuretic: it is frusemide (Lasix) – loop diuretic
• Action: it increases the excretion of sodium and chloride
• Dose: in case of oral administration, 40mg tablet is given for 5days after
breakfast. It can be used parenterally in acute conditions in doses of 40-
120mg

47. Diuretics
• Contraindications:
– Hypovolemia
– Hypersensitivity to sulphonamides
• Side effects
In mother
• Muscle cramps
• Postural hypotension
• Hypokalemia
• hypocalcemia
In fetus
• Fetal compromise
• Thrombocytopenia
• hyponatremia

48. Antihypertensives
Drug Action Indication Contraindication Dose Side effects
Methyldopa Stimulates central
alpha-adrenergic
receptors
HTN Hepatic disease, CCF,
psychiatric disorders
250mg to 1g BD/TID
po
250-500mg IV
In mother
• Nausea
• Vomiting
• Orthostatic
hypotension
• Dizziness
• Drowsiness
• Headaches
• Lethargy
• thrombocytopenia
• Sodium retention
• Bradycardia
In fetus
• Bradycardia
• Hypoxia
• Neonatal
hypoglycemia
Labetalol Non selective beta
blocker
HTN Hepatic disorders
Bronchial asthma
Sinus bradycardia
100-800mg po. Tid
1-2mg/min IV in
hypertensive crisis
Propranolol Beta adrenergic
blocker
HTN DN, Brochial asthma, renal
insufficiency, CCF
80-240mg divided
dose
Hydralazine Vasodilation Essential HTN CAD, RHD 100mg/day in 4divided
doses po
20-40mg every 4-6
hours IV/IM bolus
Nifedipine Calcium channel
blocker
HTN Heart blocks simultaneous
use with magnesium
sulphate
5-10mg po tid
Diazoxide Vasodilator Hypertensive
crisis
DM heart disease 30-50mg IV may be
repeated every 10-
15minutes
Sodium nitroprusside Vasodilator
(peripheral)
Hypertensive
crisis
Possibility of compensatory
HTN

49. Role of nurse in drug administration
• Patient identification
• Drug identification
• Thorough assessment
• Right technique
• Post administration evaluation
• Education
• Documentation