[At the end of the lecture, the student should be able to:-]

1. Identify the source of drugs administered to the patients.

2. Discuss the various factors (such as gestational age) involved in
the transfer of drugs to the fetus.
3. Distinguish between a “safe” drug and a teratogen.
4. Define teratogens, and recognize teratogenic drugs and agents
and the significance of avoiding such agents in obstetrics.
5. Understand the classification of drugs and its application to
commonly prescribed drugs.
6. Recognise the common indications for drug administration in
Obstetrics.
7. Appreciate that unusual indications (drug addiction/smoking
etc) are quite important in obstetrics.

8. Discuss the adverse effects of some special drugs on the

mother and the fetus and the need for caution in the use of
such drugs; apply such knowledge to new or unfamiliar
drugs.

9. Understand the basis of drug prescription for the obstetric

patient and the importance of accurate record keeping of all
drugs administered to the obstetric patient.

10.Understand the need to apply appropriate caution ( on the

basis of the effects of drugs in the fetus) in drug usage for the
wide variety of indications in gynaecology.
1. Introduction
2. Case Illustration
3. Drugs in Obstetrics
i. Sources of drugs
ii. Metabolism of Drugs
III. Transfer of drugs to the fetus
• Maternal factors
• The placenta
• The fetus
 iv. Effects of Drugs on the fetus
• Type of Drug
•Teratogens
• Gestational age
• Route of Administration
v. Classification of Drugs
vi. Indication for Drug use in pregnancy
vii. Specific illustrations of Drug usage
in pregnancy

4. Drugs in gynecology
4. Questions
INTRODUCTION:
Drugs indicated in all aspects of Medical
practice

Route of Administration
Dosage Regimes
Indications Already covered
Modes of Action in Pharmacology
Duration of Usage Lectures
Toxic effects
In this lecture, we shall discuss
* Various aspects of drugs in Obstetrics
* Indications for use with emphasis
on gestational age
* Toxic effects (if any) of such drugs on
the fetus and mother
* General indications for drugs in
gynaecology.
 A 30 year old P2+3+2+2 presented in the antenatal
clinic with 8 weeks amenorrhoea. She had a mild
stroke after her last delivery and she was diagnosed as
protein S deficiency and was on treatment with
warfarin. Discuss the management of this case.

Essential points
1. Age - 30yrs
2. Gravida 7 para 5
3. Previous preterm deliveries
4. Protein S deficiency
5. Warfarin Therapy
DRUGS IN OBSTETRICS

Importance of Topic
Maternal effects
* Benefits
* Side / Toxic effects
Effects of drugs on the fetus
Incidence
* Varies world wide
5 - 35%
Sources of Drugs to patients
* Over the counter
* Patient to patient
* General practitioner / other professionals
* Specialists (Obst. / Gyn. / others )
TRANSFER OF DRUGS TO THE FETUS
1. Drugs usually administered to the mother
primarily and then transferred to the fetus
(Physiologically)
- MORE IMPORTANT / FREQUENT ROUTE
OF DRUG TRANSFER TO THE FETUS.
2. Occasionally, drugs may be primarily
administered to the fetus.
Transfer of drugs to the fetus depends on
* Type of drugs administered
* Dosage / Duration of usage / Route
of Drug administration.
Factors affecting transfer:

Maternal Factors
Physiological changes of pregnancy
- Blood volume affect
- Serum albumin variation drug
and drug binding concentration
The role of the placenta
- Transfer of drugs across the placenta
by simple passive diffusion
- drug transfer dependent on molecular weight of
drugs
Virtually all drugs low in molecular weight
cross placenta easily
Few Drugs ( Insulin / Heparin ) high in molecular
weight dont cross placenta
Physical properties of drugs - Lipid solubility
Gestational age ( easier drug transfer near term)
Placental state ( chronic diseases lower
transfer of drugs)
Role of the Fetus
* Circulation of drugs through fetal circulation
to all parts of the fetus
* Tissue specific uptake of drugs by some fetal
tissues
- Teeth ( Tetracycline )
- Mullerian ducts / vagina (Diethylstilboestrol)
- Thyroid gland ( Iodides, Propyl thiouracil)
* Fetal drug metabolism / elimination.
EFFECTS OF DRUGS ON THE FETUS
TERATOGENICITY
Depend on
1. Type of drug
2. Gestational age at intake of drug by mother
3. Duration of intake / route of administration /
dosage of drug administered
4. Status of mother / fetus.
Type of Drug.
Most drugs “safe” in pregnancy.
Some drugs have adverse effects on the fetus:
- destruction of cells / abortion
- Various grades of fetal malformation
- intra-uterine growth retardation/restriction
- cerebral damage / neurological damage
- mental retardation
- death of the fetus
Such drugs with major destructive effects on the fetus are
known as TERATOGENS.
Other agents to which the mother is exposed may also
cause damaging effects on the fetus
Such agents are also called teratogens.
They include infections / chemicals / radiation.
DRUGS AND OTHER AGENTS AS TERATOGENS
Teratogens include
Infections - Rubella : Toxoplasmosis, CMV
Chemicals : Isotretinoin
Radiation - Radioiodine

Drugs
Thalidomide (30th -70th Day of Pregnancy)
Tetracycline
Some other tetratogenic Drugs are:

Diethylstilboestrol ( DES ) Valproic acid

Aminopterin
Cyclophosphamide Androgens
Phenytoin Lithium
Methotrexate Isotretinoin
Alcohol
Danazol
Coumarins
ACE Inhibitors
ACE = Angiotensin- converting enzyme
2. Gestational age at drug intake by mother
Ist Trimester - Maximum damage from drugs
a. Ovum period
fertilization to implantation
b. Embryonic period
2nd - 8th week
c. Fetal period
8th - 12th week
2nd and Third Trimesters
- Fetal period -13th week to term
Effects of Drugs.
* 1st 3 weeks - abortions etc.
* 3rd week - 10th week period of
organogenesis- malformations
Later in pregnancy - various effects
e.g. Tetracycline discolouration of teeth
Effect of drugs may be detected soon after
abortion or delivery or much later in life - e.g.
adolescent effects of diethylstilboestrol.
3. Duration / Route of Administration / dosage of
Drug Administered.
4. Status of mother / Fetus
 IMPORTANCE OF ACCURATE RECORD
KEEPING OF DRUG INTAKE IN PREGNANCY
To document effect of drugs on the mother & fetus.
Data required
* Type of Drug / Dosage
* Gestation of pregnancy at intake of drug
* Duration of Drug usage / route of
Administration
* Indication for drug intake
* Side effects / toxic effects reported by the
mother
* effects of drug on outcome of pregnancy
* any abnormal effects noted in the fetus at
abortion / birth / neonatal period
* Any abnormalities noted in the infant /
adolescent / adult.
CLASSIFICATION OF DRUGS USED IN PREGNANCY
Drugs classified into various groups in the light of
possible adverse fetal effects as recommended by FDA.

Category Description.
A. No fetal risk factors demonstrated from controlled
studies. Drugs proven safe for use during pregnancy.
e.g. prenatal vitamins.

B. Fetal risk not demonstrated in animal or human

studies. Many drugs commonly used fall into this
category e.g. Penicillins.
Acetominophen (Adol, Paracetomol ) Insulin,
*Chloroquine, Nystatin.
C. Fetal risk may be known: No adequate human studies
nor animal studies. In some cases, animal studies
may demonstrate adverse fetal effects but no human data
available e.g. Furosemide, methyl dopa, Aspirin,
Chlorpromazine. Again many drugs commonly used fall in
this category

D. Some evidence of fetal risk known in humans: It may

however be quite necessary to use such drugs, the benefits
of such drugs may thus be viewed as outweighing the risks
of the drugs. e.g. Diazepam, Aspirin, Pethidine, Progestins,
Corticosteroids, Tetracyclines etc.

X. Proven fetal risks. In this group the proven risks of the

drugs outweigh any benefits for the drugs e.g. Isoretinein,
an acne medicine.
INDICATIONS FOR DRUGS IN PREGNANCY.
A. Most Common Indications:
Cardiovascular disease - Hypertension / Cardiac
/ Infections.
(Antibiotics and anti-infective drugs)
G.I.T. Disorders Nausea / Vomiting
Reflux oesophagitis
Diarrhoeas
Respiratory Disorders
Analgesias - Mild / Strong/ Short term / Long term
Anaemias.
Most drugs used for above conditions /disorders
are generally safe Category A/B/C drugs
Cardiovascular drugs used in pregnancy
Drugs Category
#ACE Inhibitors (capoten) C/D
β – Blockers (Tenormin, Propanolol C
*Labetalol)
Calcium antagonists (Nifedipine)
Coumarins D
Digoxin C
Furosemide (Lasix) C
Heparin (Mini – Heparin) C
Heparn (Low molecular weight H: clexane, B
fraxiparine)
Methyl Dopa (Aldomet) C
Thiazides D
Quinidine C

Other Drugs
Diazepam D
# Should not be used in pregnancy
Antimicrobial Agents commonly used in pregnancy
Antimicrobial agent Category of Drugs(FDA)
Aminoglycosides C/D
Cehalosporins B
Erythromycin B
Azithromycin B
Chloroquine C
Imipenem C
Metronidazole B
Nitrofurantion B
Penicillins B
Sulphonamides B
Tetracyclines D
Trimethoprim (Septrin/Bactrim) C
Vancomycin C
Antivirals
Acyclovir C
Ganciclovir B
Zindovudine C
Antiprotozoals
Quinine D
Mebendazole C
Antifungals
Amphotericin B
Fluconazole C
Intraconazole C
Nystatin B
B. Other Indications
CNS - Epilepsy
- Sedatives
- Psychiatric
Haematological - Oral anti-coagulants
Hormone therapy -
Malignancies -

Many drugs used for above indications are

rather unsafe and fall into category D.
C. Unusual Indications - Drugs that cause
addiction
Heroin
Cocaine Dangerous
Amphetamine with-drawal
Methadone effects

Alcohol - Excessive intake definitely

dangerous

D. Smoking
E. The Uterus
Tocolytic Agents - Ritodrine
Stimulants - prostaglandins / syntocinon
Drugs used for above indications usually
safe

F. Drugs and Lactation

Suppression of lactation
Most drugs excreted in small amounts in breast
milk.
No major adverse effects on the fetus.
Indications for Drugs usage in the labour ward
Indications:
A. Hypertension - Acute Hypertension
Severe PIH/ Eclampsia
- Pulmonary Oedema

B. Acute Respiratry distress (Maternal)

- Acute / severe Asthmatic Attack
- Mendelsohn’s Syndrome
- Severe Respiratory Infection
Prevention of Neonatal RDS
C. Induction of Labour
- Augumentation of labour
D. Obstetric Haemorrhage
- Intrapartum
DIC
Postpartum
E. CNS Disorders
- Epilepsy
F. Anaesthesia/Analgesia
- Epidural / General
G. Others
- Diabetes mellitus
- Cardiac disease
- Systemic Infections etc
Drugs Frequently prescribed:
Labetalol Digoxin/Drugs for cardiac Arrythmias
Hydrallazine Furosemide (Lasix)
Magnesium sulphate Heparin (protamine sulphate)
Lasix
Diazepam
Epanutin (phenytain sodium)
Hydrocortisone
Aminophylline
Zantac
Dexamethasone / Bethamethasone
Prostaglandin E2
(Pessaries – 3mg; 1.5mg)
* Postaglandin F2x*
Syntocinin Analgesic Agents
Syntometrine Entonox / Pethdine / Morphine/
(Nalorphine)
Methergin Anaesthetic Agents
Ergometrine
Ritodrine / Tocolytic Agents
Antibiotics
Penicillins
Cephalosporins
Aminoglycosides
Metronidazole
Insulin Injections
Blood products / Intravenous fluids
Others – vitamin K injection
Route of administration
- Intravenous
- Intramuscular
Dosage of Drugs
Side – Effects of Drugs
- Complication / Anaphylaxis
 SPECIAL CASES OF DRUG USE IN PREGNANCY
AND THE EFFECTS ON THE FETUS
1. Anti- Coagulants
a) Heparin - High molecular weight (12,000)
Doses not cross placenta to fetus
Does not cause major fetal effects
Maternal risks over prolonged usage
include
- Osteoporosis
- Thrombocytopaenia
- Vaginal bleeding / placental abruption
(May cause expected fetal risks - SB etc)
Heparin is the preferred anti-coagulant in pregnancy
Indications
Route of administration
Dosage Regime
LOW MOLECULAR WEIGHT HEPARINS
CURRENTLY USED HEPARIN*
Mini-Heparin (Calcium Heparin)
Mol. Wt.: 12,000-15,000 Daltons
Does not cross the placenta
DOSE :-
5,000 - 10,000 UNITS
Subcut 12 hrly (or more
frequently in some cases)
* Unfractionated heparin
RECENTLY INTRODUCED
TO MATERNITY HOSPITAL
CLEXANE ENOXAPARIN
(other brands exist)
Lower molecular weight
Mol.Wt: 5000 Daltons
does not cross the placenta
DOSE :-
20 mg - 40 mg
(pre - loaded syringe)
Subcut (Anterior abdominal
wall)
DAILY
b) Oral Anti- Coagulants
-Warfarin etc.
Low molecular weight
Easy transfer through placenta to fetus
Major adverse effects on fetus
Warfarin is the preferred oral anti-coagulant that should be
prescribed in pregnancy ( if indicated )
BUT - It causes major adverse fetal effects.
Ist trimester.
( Greatest risk 6-9 weeks gestational age )
“Fetal warfarin syndrome”
- Nasal hypoplasia
Deafness
Stippled vertebra and femoral epiphyses
- Spontaneous abortion / Fetal death
- IUGR / Developmental Delay
In 2nd and 3rd Trimester,
Warfarin usage also associated with multiple adverse effects.
- Optic atrophy
- Cataracts
- Mental retardation
- Microcephaly
- Hydrocephaly
- Blindness
- IUGR
Oral anti-coagulant best avoided in pregnancy (especially in
the first trimester)
May be used in very special circumstances with caution
2. Anti-Convulsants: Transferred across placenta.
Two - three fold risk of malformed fetus in
mothers on anti-convulsants compared with
controls
Phenobarbitone - Small risk of fetal anomally
exists
Meprobamate - Risk of fetal defects.

Phenytoin ( Epanutin )
Folic acid antagonist
Megaloblastic anaemia in the
mother. Coagulation defects in the mother
Reports of fetal anomaly exist
“Fetal hydantoin syndrome”
Noted in some reports
- Craniofacial / limb malformations
(hypoplasia of distal phalanges)
- Mental retardation
- Growth retardation

Folic Acid supplementation recommended

before onset of pregnancy ( where possible ) to
reduce adverse effects.
Carbamazepine (Tegretol )
Fetal effects similar to those due to phenytoin
Valproic Acid-
Micro cephaly
Neural tube defects
Use should be avoided
Maternal side effects and
In Epilepsy , inspite of fetal hazards from the
drugs used, medical therapy must be continued
all through pregnancy in the interests of the
mother.
3 a.
Analgesics:
Easily transferred across placenta to fetus
Mild analgesia
- Acetaminophen (Paracetamol - Adol)
safe in pregnancy
No fetal effects.
Mild oral analgesic / antipyretic of choice in
pregnancy.
3 b.
Aspirin: Suggested fetal risk if used in first trimester.
- Prostaglandin synthetase inhibitor
Prolonged usage in 3rd trimester associated with
- Decrease in platelet adhesiveness and
aggregation
- Increased incidence of neonatal bleeding,
especially intracranial bleeding
Prolonged usage in standard or high dosage should
be avoided. Could also cause GIT bleeding in mother .
3 c.
Use in smaller doses (Baby aspirin for PIH and
Recurrent abortions due to Antiphospholipid
syndrome ) not associated with fetal risks.
Ibuprofen - Non -steroidal anti-inflamatory (Brufen) analgesic
Relatively new drug
Risk similar to aspirin; use with caution
Indomethacin - Adverse fetal effects (Indocid )
Aspirin / Indomethacin / Non-steroidal anti inflamatory agents
which inhibit prostaglandin synthesis may cause premature
closure of the fetal ductus arteriosus with adverse fetal
effects

These drugs in high dosage could arrest premature labour,

prevent onset of labour, and prolong the pregnancy. Caution!
Stronger Analgesics: (In labour, etc)
Pethidine Cause depression of respiratory
Morphine system of neonate: Antidote is
Naloxene.
4. Sedatives
Transferred across the placenta to the fetus
Diazepam:
(Valium)
Small incidence of cleft lip / palate reported with first
trimester usage .
In third trimester / labour:
- Sedates the fetus
- Loss of beat to beat variation {NSTα CTG chart }
(depression of fetal medullary centre)
- Neonatal hypotonia, hypothermia / apnoeic attacks
reported.
Monitor neonate carefully.
Use Diazepam with caution
Other sedatives - Be Cautious !
DRUGS IN GYNAECOLOGY
Drugs in gynaecology less complicated.
No adverse fetal effects to contend with
Indications for drugs in gynaecology same as in general Medical
Practice and surgical practice
Special Indications for drug usage in gynaecology
- General Infections
- Hormone therapy
- Infertility / Pelvic and Vaginal infections (Antibiotics,Antifungal
agents etc)
- Contraception
- Oncology (chemotherapy)
- Classification
- Side effects
ALWAYS ASK ABOUT MENSTRUAL HISTORY ( L.M.P ) and thus
EXCLUDE PREGNANCY BEFORE DRUG PRESCRIPTION IN GYNAE.
KEEP RECORDS OF DRUGS USED
QUESTIONS
Write shorts notes on :-
1. Magnesium sulphate
2. Methotrexate
3. Clexane
4. Bromocriptine
5. Methergin
6. Aspirin
7. Epanutin
Short Notes on Format for above
Questions:-
1. Type of drug
- Brief Notes
2. Indications for Drug
3. Dosage / Route / Mode of administration
4. Mode of action
5. Side Effects / Toxic Effects
6. Prevention of Side Effects / Toxic Effects