INTRODUCTION

Pharmacology is the science of drugs (Greek: Pharmacon - drug; logos - discourse in). In a
broad sense, it deals with interaction of exogenously administered chemical molecules with
living systems, or any single chemical substance which can produce a biological response is a
drug. It encompasses all aspects of knowledge about drugs, but most importantly those that are
relevant to effective and safe use for medicinal purposes.

pharmacodynamics:-
( Greek: dynamics - power)

What the drug does to the body. This includes physiological and biochemical effects of
drugs and their mechanism of action at organ /system /subcellular/ macromolecular levels.

pharmacokinetics :-
(Greek: kinesis - movement) - what the body does to the drug. this refers to
movement of the drug in and alteration of the drug by the body; includes absorption, distribution,
binding/ localization/ storage, biotransformation and excretion of the drug. Example-
Paracetamol is rapidly and almost completely absorbed orally attaining peak blood level at 30 to
60 min; 25% Bond to plasma protein, widely and almost uniformly distributed in the body
(volume of distribution – 1 L/ kg ) ;extensively metabolized in the liver.

DRUG
(French: Drogue – a dry herb ). It is the single active chemical entity present in
the medicine that is used for diagnosis, prevention, treatment/ cure of a disease. This disease
oriented definition of drug does not include contraceptives or use of drug for improvement of
health. The WHO (1966) has given a more comprehensive definition - “Drug is any substance or
product that is used or is intended to be used to modify or explore physiological systems or
pathological States for the benefit of the recipient”.

The term ‘drugs’ is being also used to mean addictive /abused/ illicit/ substances.

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pharmacotherapeutics :-
It is the application of pharmacological information together with knowledge of
the disease for its prevention, mitigation or cure. Selection of the most appropriate drug, dosage
and duration of treatment taking into account the specific features of a patient are a part of
pharmacotherapeutics.

clinical Pharmacology :-
It is the scientific study of drugs (both old and new) in man. It includes
pharmacodynamic and pharmacokinetic investigation in healthy volunteers and in patients ;
evaluation of efficacy and safety of drugs and comparative trials with other forms of treatment;
surveillance of pattern of drug use, adverse effect, etc.

Chemotherapy:-
It is the treatment of systemic infection/ malignancy with specific drugs that have
selective toxicity for the infecting organism /malignant cell with no /minimal effects on the host
cells.

Drugs in general, can be divided into :

Pharmacodynamic agents – these are designed to have pharmacodynamic effects in the

recipient.

chemotherapeutic agents - these are designed to inhibit /kill invading parasite /malignant cell
and have no/ minimal pharmacodynamic effects in the recipient.

Toxicology:-
It is the study to poisonous effect of drugs and other chemicals (household
,environmental pollutant ,industrial, agricultural ,homicidal) with emphasis on detection,
prevention and treatment of poisonings. It also includes the study of adverse effect of drugs,
since the same substance can be a drug or a poison, depending on the dose.

Essential medicines (Drugs) concept:-

The WHO has defined Essential Medicines (Drug) as “ those that satisfy the priority
health care needs of the population”. They are selected with due regard to public health
relevance, evidence on efficacy and safety, and comparative cost effectiveness.

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 ROUTES OF DRUG ADMINISTRATION
Most drugs can be administered by a variety of routes. The choice of appropriate
route in a given situation depends both on drug as well as patient related factors. Mostly common
sense considerations, feasibility and convenience dictate the route to be used.

routes can be broadly divided into those for ( a) local action and (b) systematic action.

LOCAL ROUTES :-
These roads can only be used for localized lesions at accessible sites and for drugs
whose systemic absorption from these sites is minimal or absent. Thus, high concentrations are
attained at the desire site without exposing the rest of the body. Systemic side effects or
toxicity are consequently absent or minimal. For drugs that are absorbed from these sites/
routes ,the same can serve as systemic route of administration.

The local routes are:

1. Topical :-
This refers to external application of the drug to the surface for
localized action. It is often more convenient as well as encouraging to the patient. Drugs can
be efficiently delivered to the localized lesions on skin, oropharyngeal/ nasal mucosa,
eyes, ear canal, anal canal,or vagina in the form of lotion, ointment, cream, powder, rinse,
paints, drops, spray, lozenges, suppositories or pesseries.
2. Deeper tissues:-
Certain deep areas can be approached by using a syringe and needle, but
the drugs should be in such a form that systemic absorption is slow, e.g. Intra-articular
injection (hydrocortisone acetate in knee joint), infiltration around a nerve or intrathecal
injection( lidocain), retrobulbar injection ( hydrocortisone acetate behind the eyeball).
3 arterial supply :-
Closed intra -arterial injection is used for contrast media in angiography;
anticancer drugs can be infused in femoral or brachial artery to localise the effect for limb
malignancies.

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SYSTEMIC ROUTES:-
The drug administered through systemic routes is intended to be absorbed into the
blood stream and distributed all over, including the site of action, through circulation.

1. oral :-
Oral ingestion is the oldest and Commonest mode of drug administration. It is safer,
more convenient, does not need assistance, noninvasive, often painless, the medicament
need not to be sterile . Both solid dosage forms (powders, tablets, capsules , spansules,
dragees, moulded tablets, gastrointestinal therapeutic systems- and liquid dosage forms
can be given orally.
2. Sublingual or buccal:-
The tablet for pellet containing the drug is placed under the tongue or
crashed in the mouth and spread over the buccal mucosa. Only liquid soluble and non –
irritating drugs can be so administered. Absorption is relatively repid- action can be
produced in minutes. Though it is somewhat inconvenient, one can spit the drug after the
desired effect has been obtained. The chief advantage is that liver is bypassed and drugs
with high first pass metabolism can be absorbed directly into systemic circulation.
Drugs given sublingually are - gtn, buprenorphin, desamino-oxytocin.
3. Rectal:-
Certain irritant and unpleasant drugs can be put into rectum as suppositories
or retention enema for system effect. This route can also be used when the patient is
having recurrent vomiting or is unconscious. However, it is rather inconvenient and
embarrassing; absorption its lower, irregular and often unpredictable, though diazepam
solution and Paracetamol suppository are rapidly and dependably absorbed from the
rectum in children.
4. Cutaneous:-
Highly lipid soluble drugs can be applied over the skin for slow and prolonged
absorption. The liver is also bypassed. The drug can be incorporated in an ointment and applied
over specified area of skin. Absorption of the drug can be enhanced by rubbing the preparation,
by using an oily base an occlusive dressing.

5. Inhalation :-
Volatile liquids and gases are given by inhalation for systematic action, e.g.
General anesthetics . Absorption takes place from the vast surface of alveoli- action is
very Rapid . When Administration is discontinued the drug diffuses back and is rapidly
eliminated in expired air. Thus, controlled Administration is possible with moment to
moment adjustment . Irritant vapours (Ether) cause inflammation of respiratory tract and
increase secretion.

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 6. Nasal :-
The mucous membrane of the nose can readily absorb many drugs; digestive juices
and liver are bypassed. However, only certain drugs like gnrh agonist and desmopressin
applied as a spray or nebulized solution have been used by this route . This route is being tried
for some other peptide drugs like insulin , as well as to bypass the blood brain barrier.

7. Parenteral :-
(par-beyond, enteral –intestinal)
Conventionally, parenteral refers to administration by injection which takes
the drug directly into the tissue fluid or blood without having to cross the enteral mucosa.
The limitations of oral administration are circumvented.

Drug action is faster and surer ( valuable in emergencies). Gastric irritation and
vomiting are not provoked. Parenteral route can be employed even in unconscious,
uncooperative or vomiting patient. There are no chances of interference by food or digestive
juices. Liver is bypassed.

Disadvantages of parenteral routes are- the preparation has to be sterilized and is

costlier, the technique is invasive and painful, assistance of another person is mostly needed
(through self injection is possible, e.g. Insulin by diabetics), there are chances of local tissue
injury and in general, parenteral route is more risky then oral. The important parenteral route
are :

i. Subcutaneous ( S.C):-
The drug is deposited in the loose subcutaneous tissue which is richly
supplied by nerves (irritant drugs cannot be injected) but is Les vascular (absorption is
slower than intramuscular ). Only small volumes can be injected s.c . Self injection is
possible because deep penetration is not needed. This route should be avoided in
shock patients who are vasoconstricted - absorption will be delayed. Respiratory
(depot) preparations that are Aqueous suspensions can be injected for prolonged
action.
ii. Intramuscular (i.m):-
The drug is injected in one of the large skeletal muscles - deltoid, triceps,
gluteus Maximus, rectus femoris , etc. Muscle is less richly supplied with sensory
nerves ( mild irritant can be injected) and is more vascular ( absorption of drugs is
aqueous solution is faster). It is less painful , but self injection is often impracticable
because deep penetration is needed. Deport preparations (oily solutions, aqueous
suspensions ) can be injected by this route . Intramuscular injections should be avoided
in anticoagulant treated patients, because it can produce local hematoma.

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 iii. Intravascular (i.v) :-
The drug is injected as a bolus ( greek: bolos- lamp) or infused
slowly over hours in one of the superficial veins. The drug reaches directly into the
blood stream and effects are produced immediately (great value in emergency). The
intima of veins is insensitive and drug gets diluted with blood, therefore, even highly
irritant drug can be injected i.v. But hazards are – thrombophlebitis of the injected
vein and necrosis of adjoining tissue if extravasation occurs. These complications can
be minimized by diluting the drug or injecting it into a running i.v. Line. Only
aqueous solution( not suspensions, because drug particles can cause embolism) are to
be injected i.v. And there are no depot preparations for this route.
iv. Intradermal injection:-
The drug is injected into the skin rising a bleb (e.g. Bcg vaccine, sensitivity
testing) or scarring/ multiple puncture of the epidermis through a drop of the drug is
done . This route is employed for specific purposes only.

ABSORPTION
Absorption is movement of the drug from its site of administration into the circulation.
Not only the fraction of the administered dose that gets absorbed. But also the rate of absorption
in important . Except when given i.v. The drug has to cross biological membranes ; absorption
is governed by the above described principles. Other factors affecting absorption are:

aquifers solubility , concentration, area of absorbing surface, vascularity of the absorbing

surface , route of administration etc.

Bioavailability :-
Bioavailability refers to the rate and extent of absorption of a drug from a dosage
from as determined by its concentration- time curve in blood or by its excretion in urine. It is a
measure of the fraction of administered dose of a drug that reaches the systemic circulation in
the unchanged form. Bioavailability of drug injection i.v. Is 100% , but is frequently lower after
oral ingestion because –

a. The drug maybe incompletely absorbed .

b. The absorbed drug may undergo first pass metabolism in the intestinal well/liver or be
excreted in bile.

Incomplete bioavilability after s.c or i.m injection is less common, but may occur due to local
binding of the drug.

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 DISTRIBUTION
once a drug has gained access to the blood stream, it gets distributed to other
tissues that initially had no drug , concentration gradient being in the direction of plasma to
tissues. The extent and pattern of distribution of a drug depends on its:

 Lipid solubility.
 Ionization at physiological ph (a function of its pka)
 Extent of binding to plasma and tissue proteins.
 Presence of tissue -specific transports.
 Difference in regional blood flow.
Movement of drug proceeds until an equilibrium is established between unbound drug
in the plasma and the tissue fluids. Subsequently, there is a parallel decline in both due to
elimination.

12 RIGHTS OF DRUG ADMINISTRATION

1. RIGHT CLIENT

2.RIGHT DRUG

3.RIGHT DOSE

4.RIGHT ROUTE

5.RIGHT TIME

6.RIGHT ASSESSMENT

7.RIGHT MOTIVATION/ APPROACH

 
8.RIGHT OF THE CLIENT TO REFUSE

9.RIGHT OF THE CLIENT TO KNOW THE REASONFOR THE DRUG

 10.RIGHT EVALUATION

 11.RIGHT DOCUMENTATION

12.RIGHT DRUG PREPARATION

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 DRUG USED IN OBSTETRICS :-

There are many physiologic changes occurring in the to the fetus female during
pregnancy. These changes can cause an alteration in the pharmacokinetics of drugs , which can
alter their effectiveness in the female. In addition, during pregnancy there is developing fetus ,
which can incur permanent damage from some drug . This damage may not be apparent for
many years. For example, the reported incidence of vaginal adenocarcinoma in young women
who were exposed to diethylstilbestrol during the first trimester of gestation is well documented.
Pharmacokinetic variables , effectiveness of the drug, and concern for teratogenicity effects on
the fetus all influence drug usages during pregnancy . Before any drug therapy is began , any
women of child bearing age is always assed for pregnancy and asked about plans for a future
pregnancy.

Today, the majority of physicians limit the number of prescription medicines that are
given to pregnant women and counsel them to refrain from taking any over the-counter
medications. Since many women do take medication during pregnancy, education regarding their
use is important . When prescribed drugs are necessary for the mother, the dosage is adjusted to
ensure that the drug is effective but not harmful to the fetus. Dosages may be different from
those utilized for a non-pregnant female.

EFFECTS OF PREGNANCY ON DRUG PHARMACOKINECTS:-

All the pharmacokinetic varibles are affected by the physiologic changes that occur during
pregnancy. These variables include absorption , distribution, biotransformation, and excretion
.The pharmacokinetic variables provide a rationale for the attention of drug dosages during
pregnancy. The hormones of pregnancy also alter the effectiveness of some drugs. For example ,
the insulin dependent diabetic usually requires an increased insulin dosage during the second
half of pregnancy because of the insulin –antagonistic effect of human placental lactogen(HPL),
which in also called human chorionic somatotropin(HCS). HPL acts to stimulates lipolysis and
exerts an antagonistic effect on insulin actions on carbohydrate metabolism . This tends to raise
the plasma glucose in order to maintain the continuous flow of glucose to the fetus. Blood
glucose levels and insulin dosages need to be monitored closely during pregnancy to maintain
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close controle of the blood glucose levels. After delivery the blood glucose level is monitored to
determine insulin dosage because the antagonistic hormones are not present .

ABSORPTION :

The stomach empting time is longer during pregnancy, and there is decreased gastrointestinal
motility due to the influence of high levels of progesterone. While this would suggest a
prolonged rate and decreased amount of drug absorption , clinical evidence does not support this
conclution, expert possibly with digoxin.

DISTRIBUTION :

During pregnancy there is a large increase in total body water. The greatest percentage *of the
increase isin the extracellular fluid. Plasma volume increases while the concentration of plasma
albumin falls. Because most drugs are bound to plasma protein, the decrease of plasma protein
results in an increase of unbound drug fraction to cause pharmacologic effects. The effects can
cause a difference in the volume of distribution and plasma drug concentration. The drugs
affected most are those of relatively low lipid solubility, which are highly bound to plasma
protein. This increased distribution volume results in a reduction in the peak plasma drug
concentration after a dose. This would cause a longer half-life if not for an increase in clearance
by biotransformation or excretion.

Decrease in plasma protein binding results in a larger amount of unbound drug in position to
leave the blood stream, to be widely distributed, to cause pharmacologic effects, and to be bio
transformed or excreted.

Elimination is increased during pregnancy ; therefore there is not an increase in tissue

concentration. The results during pregnancy are lower total drug concentrations in the pregnant
woman plasma. Plasma drug concentrations should be monitored closely to maintain therapeutic
blood levels. For examples phenytoin levels need to be monitored during pregnancy because of
the possible need to increase dosage to prevent scisure activity. After delivery, return to the
patient’s prepregnant dose probably will be necessary.

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 BIOTRANSFORMATION : -

During pregnancy, it is believed that drug metabolism in the liver is stimulated, primarily by
progesterone. There is also increased excretion of drug metabolizing enzymes and microscopic
evidence of hyperplasia of some of the endoplasmic retention in the liver cells.

A small amount of drug metabolism also occurs during pregnancy in the placenta
and the fetal liver. The feto-plcental unit contribution to drug metabolism is very small.

EXCRETION:-

If the stimulation of drug metabolism causes a measurable increase in liver clearance,

elimination of drugs is accelerated, and half-life is shorter. The flow of blood through the liver is
not appreciably changed during pregnancy; therefore drugs that are dependent only on liver
blood flow to be cleared from the body are cleared at the same rate as in the non-pregnant
women unless the volume of distribution is higher.

The renal plasma blood flow during pregnancy is almost twice that of the pre-
pregnant state, and there is a substantial increase in the glomerular filtration rate and creatinine
clearance. Drugs that are excreted unchanged as for example Gentamycin and Digoxin are
cleared in proportion to the creatinine clearance. Therefore, these drugs would need to be closely
monitored during pregnancy to maintain an effective dosage.

It seems obvious that because of changes in the pharmacokinetic variables related

to pregnancy, there may be changes needed administration to the pregnant women. However, this
information is available for only a few drugs. More study is required to determine the effective
dosage of all drugs for usage during pregnancy

The ethical difficulty of studies during pregnancy is a limitation on drug doses for
the pregnant female. Before any drug is prescribed during pregnancy, the pharmacokinetic
variables should be conserved and researched.

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 FETAL AND MATERNAL DRUG EFFECT :---

Placental transfer of drug effects : The effect of drugs on the fetus is dependent on
whether a drug is distributed throughout the body or distributed selectively. This distribution is
significant in determining whether the drug can pass through the placental barrier.

The placenta has the important function of allowing the transfer of substances between
the mother and the fetus. The significant variables that determine the transfer of drugs across the
placenta are physicochemical characteristics of the compound, physiologic properties of the
placental tissue, the maternal and fetal placental blood flow. The physiochemical characteristics
that determine placental transfer are molecular weight, molecular configuration, degree of
ionization, lipid solubility and tissue binding protein properties . If the molecular weight of a
substance is less than as for example warfarin sodium ) , it crosses the placenta with ease. A
substance with a molecular weight between

Crosses more slowly, while compounds with a molecular weight of greater than
as for example heparin meet a relatively impermeable placental barrier. The more highly ionized
a drug molecule is, the more highly ionized a drug molecule is, the lower the chance that it will
cross the placenta. If a drug is highly bound to maternal plasma protein, it will not readily cross
the placenta. Since only unbound drugs transfer back across the placenta, the drugs that are
highly bound to fetal plasma protein concentrate in the fetus.

Maternal and fetal acid-base balance also affects the transfer of drugs across the
placenta. In maternal acidosis the fetus becomes more acidotic. Maternal alkalosis, which results
from hyperventilation, causes the oxyhemoglobin curve to move left, resulting in fetus hypoxia
and acidosis. These changes cause an accumulation of drugs that have an alkaline ph in the fetus.

The placenta also functions as an organ of metabolism. Metabolism the placenta

can result in metabolites of increased or decreased potency. The significance of the effects of the
metabolic change is dependent on whether the desired effect is in the fetus or the mother. If the
metabolites from placental metabolism are more potent, a toxic level may occur in the fetus.

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The rate of transfer of a drug across the placenta is also dependent upon the uteroplacental blood
flow. This blood flow will decrease because of certain conditions, such as pre-eclampsia,
hypertention, and diabetes. Maternal position also affects the uteroplacental blood flow. Blood
flow decreases when the female is in a supine or semi recumbent position because of pressure
from the uterus on the aorta and the vena cava. The blood flow will increase when she is a side
line position, particularly on her left side . The rate of transfer of drugs is decreased at times of
decreased blood flow and continues to be lowered in labour because of the contraction of the
uterus. During uterine contraction, there is decreased blood flow to the uterus. This decrease
blood flow may result in an accumulation of drug in the fetus because they are unable to transfer
back across the placenta in to the maternal blood stream.

Effects of drugs on fetus

Whether or not a drug will cause adverse effects on the fetus depends on certain factors : the type
of drug , the amount of drug rate of elimination, distribution in the fetal tissue , gestational age ,
and specific receptor function in the fetus . During the first trimester, drug may produce major
effects. The degree of teratogenicity is different at various times during gestation. From
fertilization until after implantation, the effects range from damage that can be repaired by the
developing embryo to demise resulting in abortion. The 18th day through approximately the 60th
day or the period or organogenesis is the developmental period when the greatest damage can
occur with regard to malformations. The genitourinary system and palate are the most
vulnerable after the 36th day of gestation. In the fetal period teratogenic agents affect the cell
population by causing cell death and cell growth retardation or by inhibiting cell differentiation.
After the 8th week of gestation, the fetal brain is developing very rapidly and is very susceptible
to damage from teratogens. After the first trimester, drugs do not produce gross structural
abnormalities, but they can affect the growth and fuctional development of the fetus. They can
also have toxic effects on the fetus.

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The Federal Drug Administration ( FDA ) has developed and published a classification system
for risk factors of systemic drug usage during pregnancy . The classification is based on the level
of known risk the drug presents to the fetus . These classification is based on the level of known
risk the drug presents to the fetus . These classifications are A , B , C , D and X. An A ranking
indicates that studies in women have not indicate a risk to the fetus ; therefore , the chance of
harm to the fetus is remote . The B category indicates that human studies have not been
completed to support animal studies that indicated on adverse effect . Category C drug should be
utilized by a pregnant woman only if the potential benefit outweighs the risk to the fetus as
indicated by studies with animals . The D category identifies a drug for which there is
documented evidence of human fetal risk . These drugs may be used in life threatening situations
or pathology that is not treatable with a safer drug . Category X drugs should not be used by
women any time there is the possibility of pregnancy ( e.g. Diethylstilbestrol and isotretinoin ) .
It should be remembered that studies cannot rule out any possibility of harm to a fetus ; therefore
, drugs should not be utilized during pregnancy unless absolutely necessary and after
implications for the fetus have been determined .

Because of the ethical nature of research into the effects of drugs on the fetus ,
most reported teratogenic effects have been based on retrospective reports . Table – 3 lists some
of the common agents known to teratogenic effects on fetal development .

Neonatal drugs: The neonate is not commonly given as variety of drugs . The
neonate liver and kidney are immature and therefore may be slow in metabolizing and excreting
drugs that the neonate receives from the mother before birth or those given after birth.

No later than one hour after birth the neonate receives the legally required silver
nitrate solution or erythromycin ointment in its eyes to prevent gonococcal opthalmia ointment in
its eyes to prevent gonococcal opthalmia neonatorum , which is caused by Neisseria gonorrhea in
the maternal vaginal tract . Erythromycin ointment will also prevent neonatal chlamydial
conjunctivitis contracted during delivery , while silver nitrate will not .

Silver nitrate is administered by instilling one drop of 1% solution in each eye. It

causes protein denaturation , which prevents gonorrheal ophthalmia neonatorum The silver
nitrate solution may cause periorbital edema , temporary staining of the lids and surrounding

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tissues and conjunctivitis . The eyes are not irrigated following instillation. Because of the
possibility of the adverse reactions , instillation may be delayed up to one hour to enable mother-
neonatal bonding . The parents are reassured regarding the reactions and told that the reactions
should subside in 24 hours .

LIST OF DRUGS USED IN OBSTETRICS

A. Hypertensive disorders and heart diseases

1. Drugs for prevention of pre-eclampsia
 Aspirin
 Calcium
 Anti-oxidants - Vitamin-C , E.
2 Drugs to be used for treatment of pre-eclamptsia.

 Nefedipine
 Hydralazine
 Magnesium sulphate
2. Drugs to be used for controlling eclamptic fit.
 Magnesium sulphate
 Phenytoin
3. Antihypertensive for essential hypertension during pregnancy
 Methyldopa
 Labetalol
4. Drugs used for heart diseases.
 Atenolol
 Digoxin
 Diuretics

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  Antibiotics
 Verapamil
 Anticoagulant
 Adenosine
B. Diseases of respiratory system.
1. Therapy for common cold and cough during pregnancy.
 Paracetamol
 Antibiotic
 Chlorpheneramine maleate
 Phenyl epinephrine
 Karvolplas inhalant
 Strepsils lozenge
 Expectorant Bromhexine
 Xylometazolin nasal drop
 Choice of antibiotic for upper respiratory tract infection and pneumonia.
 Erythromycin
 Amoxicillin
 Ampicillin Ceftriaxone
 Azithromycin
 Amoxicillin and clavulanate combination
 Anti-tubercular drugs regime during pregnancy
 WHO recommends four ( 4 ) drug therapy for six month
 Pregnant asthmatic.
 Salbutamol
 Deriphyllin
 Beclomethasone inhaler
 Aminophylline Salbutamol aerosol Sodium cromoglycate inhaler.
 Hydrocortisone injection
 Prednisolone tablet

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  Oxygen
 Antibiotics
 Expectorant
C. Diseases of gastrointestinal system
 Safe drugs of nausea and vomiting of pregnancy.
 Doxylamine
 Metoclopramide
 Pyridoxine
 Prochlorperazine
 Drugs for hyperemesis graqvidrum.
 Metoclopramides injection
 Ondansteron injection
 Thiamine
 Pyridoxine
 Drugs used in acidity , Heartburn , Dyspepsia
 Antacid
 H2 RECEPTOR ANTAGONISTS
 Digestive enzyme
 Safe medicine for peptic ulcers in pregnancy.
 H2 receptor blocker
 Sucralfate
 Omeprazole
 Constipation in pregnancy, labor, puerperium and bowel preparation for USG.
 Proctoclysis enema
 Milk of magnesia
 Suppository
 Drugs for piles and fissure during pregnancy and postpartum
 Proctoclys enema
 Heparin containing ointment

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 Suitable drugs for amoebiasis, giardiasis and intestinal helminthiasis
 Metronidazole
 Quinolochlor
 Mebendazole
 Choosing drug for typhoid during pregnancy
 Ceftriaxone
 Azithromycin
 Drugs for prevention of Mendel son syndrome
 Antacid
 Ranitidine Metoclopramides
D. Diseases of genitourinary system
 Urinary tract infection

1st line 2nd line 3rd line

 Amoxicillin  Nitrofurantoin  Aminoglycosides
 Cephalosporin  Combination of  Ceftriaxone
amoxicillin and
clavulanate

 Recommended drugs for VDRL po0sitive cases/ for syphilis during pregnancy
 Benzedrine penicillin G
 Erythromycin
 Azithromycin
 Cephalosporin
 Drugs for vulvovaginitis in pregnancy
 Ointment with steroid
 Ointment without steroid
 Metronidazole
 Tinidazole

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 Drugs for chlamydial cervitis during pregnancy
 Erythromycin
 Amoxicillin
 Azithromycin
 HIV infection during pregnancy : Treatment, prevention of mother to child transmission and
post exposure prophylaxis for doctors and other health worker
 Zidovudine
 Neviparine
 Lamivudine
 Recommended drugs for gonorrhea during pregnancy.
 Ceftriaxone
 Cefixime
 Spectinomyci

E. Endocrine disorder during pregnancy.

 Therapy for hypothyroidism during pregnancy .
Thyroxine

 Thyrotoxicosis and antithyroid drugs .

 Carbimazole
 Propylthiouracil
 Thyroxine
 Aquous Lodine solution
 Diabetes in pregnancy.
Insulin – Human Actrapid

Human Mixtard

 Sexhormones, Antihormones and gonadotropins

1. OCP ( Oral contraceptive pil )

2. Danazole

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 3. Clomephene
4. Bromocriptine
5. Cyproterone acetate
6. Derivatives of progesterone
7. Depoprovera injection

F. Dermatology lesions during pregnancy

 Drugs for idiopathic generalized pruritus during pregnancy.
o Antihistaminic
o Dexamethasone
o Calamine lotion
 Hyperpigmentation of pregnancy.
 Hydoxyquinone ointment
 Tretinoin topical gel
 Sunocrun lotions and creams
 Common skin infection--- Ring worm Pityriasis Scabies and Pediculosis
 Clotrimazole
 Permethrin
 Miconazole
 Drugs to be used for herpes gestations
 Topical steroid
 Systemic steroid
 Drugs to be used for impetigo herpetiformis
1. Amoxicillin

33.Treatment of herpes genetalis and libialis and herpes zoster during pregnancy.

 Acyclovir ointment / oral

 Paracetamol

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  Topical anaesthetic
34.Antileprotic drugs in pregnancy.

 Rifampicin
 Dapsone
 Clofazimine
F .Disorders of coagulation during pregnancy

35.Anticoagulation for antenatal deep venous thrombosis.

 He3parin
 Protamin sulphate
 Low molecular weight heparin
36. For postnatal deep vein thrombosis

 Warferin sodium
 Phenindione
 Vit- K
37. Pulmonary embolism

 Streptokinase
 Aprotinin
38. Thrombo- prophylaxis during pregnancy

 Heparin
 Low dose aspirin
 Warferin
 Low molecular weight heparin

39Thrombophlebitis

 Thrombphobe ointment
 Ibuprophen

~ 20 ~
40. Diseminated intravascular coagulopathy

 Ringer lactate solution

 Fresh blood tranfution
 Fresh frozen plasma

41. Drugs to be used for amniotic fluid embolism.

 Dopamine drip
 Sodium bi-carbonate
 Methyl prednisolone

G. Drugs used in problems of CNS

43. Sleep disturbance in pregnancy.

 Alprazolum
 Diazepam

44. Anti-epileptic drugs in pregnancy.

 Phenoburbitone
 Phenytoin
 Carbamazepine
 Diazepam

45. Psychiatric disorders during pregnancy and puerperium.

 Chlordiazepoxide
 Chlorpromzine
 Trifluperazine

~ 21 ~
  Haloperidol

H. Autoimmune diseases during pregnancy.

46. Drug therapy for positive anti phospholipid antibodies during pregnancy

 Low dose aspirin

 Prednisolone
 Immunoglobulin

47. Drug therapy for SLE during pregnancy.

 Azathioprine
 Ibuprofen
 Cyclophosphamide
 Prednisolone
 Aspirine

48. Drug used for rheumatoid arthritis during pregnancy.

 Paracetamol
 Ibuprofen
 Gold
 Cyclosporin
 Azathioprin

I. Drugs for two common blood and tissue parasitic infection during pregnancy
49. Anti-malarial drugs for the pregnant

 Chloroquine
 Pyrimethamine-sulphadoxin
 Quinine

~ 22 ~
  Mefloquin

50. Anti-toxop[lasmosis therapy during pregnancy

 Spiramycin
 Pyramethamine sulphadoxin
 ]Leucovorin/ polinic acid

J. Some typical pregnancy related problems of antenatal period.

51. Drugs used in threatened and recurrent abortion

 Natural progesterone
 Synthetic progesterone
 HCG injection
 Sedative
 Folic acid

52. Drugs for MTP and missed abortion

 Mifepristo
 Misoprostol
 Prostodine injection
 Priprost tablets
 Cerviprime gel

53. Drugs for IUGR

 Vitamines
 Zinc
 Protein supplements

~ 23 ~
  Beta mimetic
 Low dose aspirin
 Energy supplements

54. Drugs for sever painful night cramps

 Diazepam
 Paracetamol
 Topical analgesic gel

55. Drugs for cholestasis of pregnancy

 Antihistaminic
 Dexamethasone
 Cholestyramine
 Naltrexone

K. O ytocics and tocolytics

56. Formula for oxytocin usage

57. Recommendation for ergometrine usage.

58.Recommendation for prostaglandin usage

 Dinoprostone
 Misoprostol
 Carboprost

~ 24 ~
 59. Practical tocolysis

 Ritodine
 Terbulalin
 Isoxsuprine

L. Drugs for ripening of cervix

60. Drugs for ripening the cervix in any trimester

 Misoprostol
 Oxytocin infution
 Dinoprostone gel
 Cervical tent

M. Drugs for labor analgesia

61. Choice of analgesia for labor pain

 Tramadol
 Pethidine
 Entonox gas
 Bupivacaine
 Pentazocine
 Promethzine HCL

N. Drugs for some typical problems of puerperium

62. Drugs for care of perineal wound

 Ointment--- Providone iodine, Framycetine

 Hip bnath-chemicals—Cetrimide,Chloroxylenol, Common salt
 Analgesic, anti-inflammatory cum enzyme

~ 25 ~
  Recommended suture materials---Polygalactin suture

63. Drugs for stimulation or suppression of lactation

 For stimulation---Metoclorpramide, Oxytocin, Lnolin cream, Allantion

 For suppression---Cbagolin, Diuretics, Pyridoxine, Bromocriptine

64. Drugs for mastitis and breast abscess

 Ampiliox
 Erythromycin
 Anti-inflammatory analgesics
 Cephalexin

65. Drugs for treatment of subinvolution of uterus

 Methyl ergometrine
 Antibiotics
 Haematinic

66. Contraceptives for post-partum women

 Combined pill
 Progesteron pill only
 Long acting implant
 I.U.C.D.S.

O Some commonly prescribed drugs during pregnancy and lactation

 Minerals --- Oral iron, Parenteral iron, Calcium.

 Vitamins – Folic acid, B 12, Vitamin C,D,E,A.

~ 26 ~
  Trace elements – Zinc, Iodine, Magnesium, Manganese ,Copper,
Selenium.
 Antibiotics for the pregnant.
 Systemic steroids in pregnancy – Hydrocortisone, Dexamethasone,
Prednisolon, Betamethasone.
 Topical steroids.
 Antihistamine – Promethazine, Chlorpheniramine.
 Diuretic in pregnancy – Frusemide, Thiazides.
 Analgesics and anti-inflammatory – Paracetamol , Aspirin, Ibuprofen
 Antipyretics during pregnancy – Paracetamol standard.
 Plasma volume expander---
 Crystaloids – Normal saline, Dextrose saline,
Ringer lactate,
 Colloids – Degraded polygelatin.
 Natural colloids –Fresh frozen plasma
P. Immunization during pregnancy

Tetanus toxoid , Tetanus immunoglobulin , Hepatitis A vaccine , Hepatitis B vaccine ,

Typhoid vaccine,

Gas gangrene , Antitoxin , Antirabis vaccine.

Immunitherapy for prevention of rhesus iso immunization

Q. Drug for resuscitation of new born.

Naloxone , 10% Dextrose solution , Adrenalin , Ringer lactate, Sodi-bi –carb.

R. General guidelines about the use of drugs during pregnancy and lactation.

Risk categories of drugs for use in pregnancy.

 Drugs OK to use during pregnancy.

~ 27 ~
  Drugs that may be used during pregnancy with caution.
 Highly risky drugs for the pregnant state.
 Drugs those may be avoided during breast feeding
 Common drugs that may be used during breast feeding.

PHARMACOTHERAPEUTICS IN OBSTETRICS

OXYTOCICS IN OBSTETRICS

DEFINITION : Oxytocics are the drugs of varying chemical nature that have the power to
excite contractions of the uterine muscles. Among a large number of drugs belonging to this
group, the following are the important ones and are extensively used in clinical practice.

 Oxytocin
 Ergot derivatives
 Prostaglandins

OXYTOCIN

PHARMACOLOGY : Oxytocin is a nonapeptide. In 1950, de Vigneaud and coworkers did the

Nobel prize winning work on structure of oxytocin. It is synthesized in the supraoptic and
paraventricular nuclei of the hypothalamus. By nerve axons it is transported from the
hypothalamus to the posterior pituitary where it is stored and eventually released.

~ 28 ~
 Oxytocin has a half life of 3-4 minutes and a duration of action of approximately 20
minutes. It is rapidly metabolized and degraded by oxytocinase.

MODE OF ACTION : Myometril oxytocin receptor concentratioincreases maximum (100-200

fold) during labour. Oxytocin acts through receptor and voltage mediated calcium channels to
initiate myometrial contractions. It stimulates amniotic and decidual prostaglandin production.
Bound intracellular calcium is eventually mobilized fro the sarcoplasmic recticulum to activate
the contractile protein. The uterine contractions are physiological i.e. causing fundal contraction
with relaxation of the cervix.

PRESPARATIONS USED :

i) Synthetic oxytocin (Syntocinon-Sandoz or Pitocin-Parke-Davis) is widely used. It has

only got oxytocic effect without nay vasopressor action. The Syntocinonis available
in ampoules containing 5 IU/ml : Pitocin 5 IU/ml
ii) Syntometrine (Sandoz) – A combination of syntocinon 5 units and ergometrine 0.5mg
iii) Desamino oxytocin – It is not inactivated by oxytocinase and is 50 – 100 per cet more
effective than oxytocin. It is used as buccal tablets containing 50 IU
iv) Oxytocin nasal solution contains 40 units/ml.

EFFECTIVENESS : In the first trimester, the uterus is almost refractory to oxytocin. In the
second trimester, relative refractoriness persists and as such, oxytocin can only supplement other
abortifacient agents in induction of abortion. In later months or pregnancy and during labour in
particular, it is highly sensitive to oxytocin evening small doses. Oxytocin loses its effectiveness
unless preserved at the correct temperature (between 2 and 80 C).

INDICATIONS : Oxytocin may be conveniently used in pregnancy, labour or puerperium. The

indication is are groped as follows :

~ 29 ~
  Therapeutic
 Diagnostic

THERAPEUTIC :

 Pregnancy
 Labour
 Puerperium

Pregnancy :

Early :

 To accelerate abortion – inevitable or missed and to expedite expulsion of hydatidiform

mole
 To stop bleeding following evacuation of the uterus
 Used as an adjunct to induction of abortion along with other abortifacient agents (PGE1
or PGE2).

Late :

 To induce labour
 To ripen the cervix before induction

Labour

 Augmentation of labour
 Uterine inertia

~ 30 ~
  Inactive management of third stage of labour
 Following expulsion of placenta as an alternative to ergometrine.

CONTRAINDICATIONS OF OXYTOCIN

PREGNANCY LABUR ANY TIME

 Grand mulitipara  All the  Hypovolaemic state

contraindication in
pregnancy
 Contracted pelvis  Obstructed labour  Cardiac disease
 History of Caesarean  Incoordinate uterine
section or hysterotomy contraction
 Malpresentation  Fetal distress

Puerperium : To minimize blood loss and to control postpartum hemorrhage.

DIAGNOSTIC :

 Contraction stress test (CST)

 Oxytocin sensitivitytest (OsT)

DANGERS OF OXYTOCIN

~ 31 ~
  Maternal
 Fetal

MATERNAL :

Uterine hyperstimulation (over activity) – Is a frequently observed side effect. There may be
excessive durationof uterine contraction (hypertonia) or increased frequency (> 6 in 10 min
time) of contractions (polysystole). It is often associated with abnormal FHR pattern.

Uterine rupture – may be seen with violent uterine contractions common. High risk cases are :
grand multipara, malpresentation, contracted pelvis, prior uterine scar (hysterotomy) and
excessive oxytocin use.

Water intoxication is due to its antidiuretic function when used in high dose (30-40 mIU/min).
Water intoxication is manifested by hyponatremia, confusion, coma, convulsions, congestive
cardiac failure and death. It is prevented by strict fluid intake and output record, use of salt
solution and by avoiding high dose oxytocin for a long time.

Hypotension : Bolus IV injections of oxytocin causes hypotension specially when patient is

hypovolaemic or with a heart disease. Occasionally oxytocin may produce anginal pain.

Antidiuresis : Antidiuretic effect is observed when oxytocin infusionrate is high (40-50)

mIU)/min) and continued for a long time.

~ 32 ~
Fetal : Fetal distress, fetal hypoxia or even fetal death may occur due to uterine
hyperstimulation. Uterine hypertonia or polysystole causes reduced placental blood flow.

ROUTES OF ADMINISTRATION

 Controlled intravenous infusionisthewidely used method

 Bolus IV or IM – 5-10 units after the birth of the baby as an alternative to ergometrine
 Intramuscular – the preparation used I syntomerine
 Buccaltablets or nasal spray – Limited use on trial basis

METHODS OF ADMINISTRATION OF OXYTOCIN

 Controlled intravenous infusion

 Intramuscular

CONTROLLED INTRAVENOUS INFUSION : Oxytocin infusion should be ideally by

infusion pump. Fluid load should be minimum. It s started at low dose rates (1-2) mIU/min) and
increased gradually.

 For induction of labour

 For augmentation of labour

For induction of labour

Principles :

1. Because of safety, the oxytocin should be started with a low dose and is escalated at an
interval of 20 0 30 minutes where there is no response. When the optimal response is
achieved (uterne contraction sustained for about 45 seconds and numbering 3
contractions in 10 minutes), the administration of the particular concentration in mU/per
minute is to be continues. This is called oxytocin titration technique.

~ 33 ~
 2. The objective of oxytocin administration is not only to initiate effective uterine
contractions but also to maintain the normal pattern of uterine activity till delivery and at
lest 30 – 60 minutes beyond that.

Calculation of the infused dose : Nowadays the infusion is expressed in term of mill units per
minute. This can give an accurate idea about the exact amount administered per minute
irrespective of the concentration of the solution.

Regulation of the drip : The drip is regulated by –

1. Manyally, counting the drops per minute commonly practiced

2. Oxytocin infusion pump which automatically controls the amount of fluid to be infused.

Convenient regime : Because of wide variation in response, it is a sound practice to start with
a low dose (1-2 mU/min) and to escalate by 1-2 mIU/min at every 20 min, intervals up to 8
mU/min. The patient should preferably lie on one side or in semi-Fowler’s position to minimize
venacaval compression.

High dose oxytocin begins with 3mU/min and increased 4 mU/min at every 20-30 min. interval.
It is mainly used for augmentation of labour and in active management of labour. Risks of
uterine hyperstimulation and fetal heart irregularities are more with high dose regime.

In majority of cases, a dose of less than 16 milliunits per minute (2 units in 500 ml
Ringer solution with drop rate of 60/minute) is enough to achieve the objective. Conditions
where fluid overload is to be avoided, infusion with high concentration and reduced drop
rate is preferred.

~ 34 ~
For augmentation of labour

Oxytocin infusion is used during labour in uterine inertia or for augmentation of labour or in the
active management of albour. The procedure consists of low rupture of the membranes followed
by oxytocin infusion when the liquor is clear. Feto-pelvic disproportion must be ruled out before
hand.

Observation during oxytocin infusion

 Rate of flow of infusion by counting the drops per minute or monitoring the pump.
 Uterine contractions – number of contractions
per 10 min duration of contraction and period of
relaxation are noted. ‘Finger tip’ palpation for
the tonus of the uterus in between contraction
may be done where gadgets are not available.
 Peak intrauterine pressure of 50-60 mmHg
with a resting toe 10 – 15 mm Hg is optimum
when intrauterine pressure monitoring is used.
 FHR monitoring is done by auscultation at
every 15 min interval or by continuous EFM.
 Assessment of progress of labour (descent of
the head and rate of cervical dilatation)

Indications of stopping the infusion

1. Nature of uterine contractions – (a) Abnormal uterine contractions occurring frequently

(every 2 minutes or less) or lasting more than 60 sec (hyperstimulation) or polysystole.
(b) Increased tonus in between contractions.
2. Evidences of fetal distress.
3. Appearance of untoward maternal symptoms.

~ 35 ~
DIAGNOSTIC USE OF OXYTOCIN

 Contraction Stress Test (CST)

 Oxytocin Sensitivity Test (OST)

CONTRACTION STRESS TEST (CST) (Syn : Oxytocin challenge test)

It is an invasive method to assess the fetal well being during pregnancy. When there is alteration
in FHR in response to uterine contractions, it suggests fetal hypoxia.

Principles : The test is based on determination of the respiratory function of the feto-placental
unit during induced contractions when the blood flow through the unit is curtailed. The objective
is to detect the degree of fetal compromise so that a suitable time can be selected to terminate the
pregnancy.

Candidates for CST :

1. Intrauterine growth restriction

2. Postmaturity
3. hypertensive disorders of pregnancy
4. diabetes.

Contraindication :

i) Compromised fetus
ii) Previous history of caesarean section
iii) Complications likely to produce preterm labour
iv) APH
v) Multiple pregnancy.

~ 36 ~
Procedure : The oyxtocin infusion is started n the same manner as mentioned earlier. The initial
rate of infusion is 1 mU/minute which is stepped up at intervals of 20 minutes until the effective
uterine contractions are established (vide supra). The alteration of the FHR during contractions is
recorded by electronic monitoring. Alternatively, clinical monitoring can effectively be
performed using hand to palpate the hardening of the uterus during contraction and auscultation
of FHR during contraction and for one minute thereafter. It takes at least 1-2 hours to perform
the test.

INTERPRETATION OF CST

 Positive – Persistent ate deceleration of FHR with 50% o ore of uterine contractions
 Negative – No late deceleration or significant variable deceleration
 Suspicious – Inconsistent but definite declarations do not persist with most uterine
contractions
 Unsatisfactory – Poor quality of recording or adequate uterine contraction not
achieved
 Hyper stimulation – Declarations of FHR with uterine contraction lasting > 90 seconds
or occurring more frequently than every tow minutes or 5 contractions in 10 minutes.

~ 37 ~
Importance : A negative test is associated with good fetal outcome. Whereas a positive CST is
associated with increased incidence of IUD, fetal distress in labour and low Apagar score. But
there is 50% chance of false positive results and as such positive test cases are subjected to
other methods of evaluation for the well being of the fetus. Suspicious CST should have a repeat
test in 24 hours.

Nipple stimulation test : The woman induces uterine contractions for CST by massaging the
nipple through her clothes for 10 minutes. It takes less time compared to CST.

ERGOT DERIVATIVES

Out of many ergot derivatives, two are used extensively as oxytocices. These are :

 Ergometrine (Ergonovine in USA)

 Methergin (Mythyl 1 ergonovine in USA.
CHEMISTRY : Engometrine is an alkaloid isolated by Dubley and Moir in 1953 from Ergot,
a fungus Claviceps purpurea that develop commonly in cereals like rye, wheat, ctc. The
alkaloisa are detoxified in the liver and eliminated in the urine. Methergin is a semisynthetic
product derived from Iysergic acid.

MODE OF ACTION : Ergometrine acts directly on the myometrium. It excites uterine

contractions which come to frequently one after the other with increasing intensity that the uterus
passes into a state of spasm without any relaxation in between.

Composition of different ergot preparations

Preparations Ampoules Tablet

Ergometrine (Ergonovine) 0.25-0.5mg 0.5-2 mg.

Methergin (Methyl-ergonovine) 0.125-0.250mg 0.125 - 0.5 mg

~ 38 ~
Syntometrine (Sandoz) 0.5 mg – Ergometrine

5 units Syntocinon

EFFECTIVENESS : Keeping the physiological function in mind, it should not be used in the
induction of abortion or labour. On the contrary, it is highly effective in haemostasis – to keep
bleeding from the uterine sinuses, either following delivery or abortion. Methergin is somewhat
slower in producing uterine response taking 96 seconds, in contrast to 55 seconds by ergometrine
when administered intravenously.

MODE OF ADMINISTRATION : Ergometrine and methergin can be used parenterally or

orally. As it produces titanic uterine contractions, the preparation should only be used either in
the late second stage of labour (after the delivery of the anterior shoulder) or following delivery
of the baby. Syntometrine should always be administered intramuscularly.

Comparative study of onset and duration of action of different oxytocics

Routes Ergometrine Methergin Syntometrine Syntocinon on puerperal

uterus

IV 45-60 sec. 1½ min. Not to be used 30 sec.

IM 6-7 min. 7 min. 2½ min. 2½ min.

Oral 10 min. 10 min. -- --

Duration of time

~ 39 ~
 3 hours 3 hours 3 hours 8 min.

USES OF ERGOMETRINE/METHERGIN

Indications Contraindications

A. Prophylactic A. Prophylactic

Active management of third stage of labour (1) suspected pleural pregnancy. If given
as prophylaxis to excess bleeding following accidentally with the delivery of the first
delivery. baby, the second baby is compromised by the
titanic contractions of the uterus.

(2) Organic cardiac diseases : results in

sudden squeezing of blood from the uterine
circulation into the systemic, circulation
causing overloading of the right heart and
failure.

(3) Severe pre-eclampsia and eclampsia :

sudden rise of blood pressure or development
of fits (eclampsia)

Rh-negative mother (more risk of the feto-

maternal micro-transfusion.

B. Therapeutic B. Therapeutic

To stop the atonic uterine bleeding, Heart disease or severe hypertensive

following delivery, abortion or expulsion of disorders – because of its vasoconstrictive
hydatidiform mole. effect, it may cause transient hypertension or
cardiac failure specially when given

~ 40 ~
 Indications Contraindications

intravenously. Oxytocin is a better substitute

in such cases

HAZARDS :

1. Common side effects are nausea and vomiting.

2. Because of its vasoconstrictive action, it may precipitate rise of blood pressure,
myocardial infraction, stroke and bronchospasm.
3. Prolonged use may lead to gangrene of the toes due to its vasoconstrictive effect.
4. Prolonged use in puerperium may interfere with lactation by lowering prolactin level.

CAUTIONS : As a haemostatic inuterine haemorrhage following explusion of the fetus

irrespective of duration of pregnancy, ergometrine or methergin is the drug of choice. On the
contrary, oxytocin is predominantly used to initiate uterine contractions (induction) and to
accelerate uterine contractions in labour.

Comparative study of ergot derivatives and oxytocin

Ergot derivatives Oxytocin

Mode of action Acts directly on the Acts on the physiological

myometrium producing uterine contractile system.
titanic contraction with Law of polarity is
complete loss of polarity. maintained.

Onset of action Comparatively slower Faster in action

Duration Long sustained Short lived.

Clinical uses  To stop haemorrhage In the induction of labour.

following delivery,

~ 41 ~
 abortion or expulsion of To augment uterine
H. mole. contraction during labour.
 Prophylactic use in late
To stop postpartum or post-
second or in third stage,
abortal haemorrhage along
to hasten separation of
with ergometrine or in
placenta and to minimize
isolation.
blood loss.

Hazards Nausea and vomiting Uterine hyperstimulation.

Rise in blood pressure, stroke Antidiuretic effect, uterine

rupture.
Rarely gangrene of the toe.
Anginal pain or rarely
hypotension.

Contraindication

Prostaglandins (PGs)

Prostaglandins are the derivatives of prostanoic acid from which they derive their names. They
have the property of acting as "local hormones". Prostaglandins were first described and named
by Von Euler in 1938.

Chemistry : Prostaglandins are 20-carbon carboxylic acids with a cyclopentane ring which are
formed from polyunsaturated fatty acids. Of the many varieties of prostaglandins, PGE 2, and
PGF2a are exclusively used in clinical practice. The subscript numeral after the letter indicates the
degree of unsaturation. Inactivation is done in lungs and liver.

Source : Prostaglandins are synthesizes from one of the essential fatty acids, archidonic acid,
which is widely distributed throughout the body. In the female, these are identified in menstrual
fluid, endometrium, decidus and amniotic membrane.

~ 42 ~
Prostaglandins (PGs) : Increased biosynthesis of PGs of E and F series in the uterus is a
prerequisite for labour both term and preterm. PGs are paracrine/autocrine hormones as they act
on locally at their site of production. Their half life in the peripheral circulation is about 1-2
minutes. Decidua is the main source of PGF2a, fetal membrances (amnion) produce PGE2 and the
myometrium mainly produce PGI2. In vivo, PGF2a promotes myometrial contractility, PGE2
helps cervical ripening. PGs promote myometrial contraction irrespective of the duration of
gestation, whereas oxytocin acts predominantly on the uterus at term or in labour. This has
helped the widespread use of PGs to effect first trimester medical termination of pregnancy and
also for induction of labour at term. Side effects of PGs are less when used vaginally. Local
application of PGE2 gel is the gold standard for cervical ripening.

USE IN OBSTETREICS

 Induction of abortion (MTP and missed abortion)

 Termination of molar pregnancy.
 Induction of labour.
 Cervical ripening prior to induction of abortion or labour.
 Augmentation (acceleration) of labour.
 Management of atonic postpartum haemorrhage.
 Medical management of tubal ectopic pregnancy.

Contraindications :

 Hypersensitivity to the compound

 Uterine scar.
 Active cardiac, pulmonary, renal or hepatic disease, hypotension (PGE2)
 Bronchial asthma (PGP2a).

~ 43 ~
Mechanism of Action :

Both PGE2 and PGF2a have got an oxytocic effect on the pregnant uterus when used in
appropriate dose. The probable mechanism of action is change in myometrical cell membrane
permeability and/or alteration of membrane-bound Ca++. PGs also sensitive the myometrium to
oxytocin. PGE2 is at least 5 times more potent than PGF 2a acts predominantly on the
myometrium, while PGE2 acts mainly on the cervix due to its collagenolytic property.

Prostaglandins in Obstetrics

Advantages Disadvantages and side effects

 Powerful oxytocic effect, irrespective of  It is costly compared to oxytocin.

duration of gestation.  Nausea, vomiting, diarrhoea, pyrexia,
 Induction of labour (PGE2, PGE1) : In bronchospasm, tachycardia and chills.
cases with (a) low preinduction score (b)  Cervical laceration may occur (PGF20)
IUFD. when used as an abortifacient.
 Used in induction of abortion (PGE1)  Tachysystole (Hyperstimulation) of the
with success. uterus, may occur during induction and
 It has got no antidiuretic effect (cf may continue for a variable period.
oxytocin)  Risk of uterine rupture in cases with
 PGE, (Misoprostal) can be used for uterine scar.
augmentation of labour.

Preparations :

~ 44 ~
Prostaglandin E2 is widely used because it is less toxic and more effective than PGF 2a. It is
however more costly.

Vaginal tables – Contains 3 mg dinoprostone (Prostin E2). In the posterior fornix followed by
3 mg after 6-8 hour maximum 6 mg.

Vaginal pessary (with retrival device) releasing dinoprostone approximately 10 mg over 24

hours. It is removed when cervical ripening is adequate.

Prostin E2 (Dinoprostone) gel – 500 g into the cervical canal, below the level of internal os
or 1-2 mg in the posterior fornix.

Parenteral :(a) PGE2 (I.V.) – Prostin E2 containing 1 mg /ml (b) PGF20 – Prostin F20
(Dinoprost tromethamine) containing 5mg/ml (c) Methyl analogue of PGF 2a
(Carboprost – containing 250 

Methyl ester of PGE1 (Misoprostol). It is rapidly absorbed and is more effective than
oxytocin or dinoprostone for induction of labour.

Misoprostol (PGE1) has been used for cervical ripening. Primarily it has been used for peptic
ulcer disease. Transvaginal misoprostol is used for induction of labour. A dose of 50g
every 4 hours has been used. Misoprostol has been found to be as effective as PGE 2 for
Cerfical ripening and induction of labour. The optimum dose of misoprostol is yet to be
determined. To date no evidence of teratogenic or carcinogenic effects has been
observed.

~ 45 ~
 Advantages of PGE1 over PGE2 : Misoprostol is cheap, stable at room temperature, long
self life, easily administered (oral or vaginal or rectal) and has less side effect.
Induction delivery interval is short. Need of oxytocin augmentation is less. Failure of
induction is less.

Risks : Incidence of tachysystole (hyperstimulation) meconium passage are high. Rupture of

uterus though rare, has also been observed. It should not be used for cases with
previous caesarean birth because the risk of rupture is high. Misoprostol is not yet
approved for use in preganancy by PDA. Use of misoprostol for induction of abortion
has been discussed.

(a) Hyperstimulation : Contractions >5 in 10 min time and lasting for at least 2
minutes. Fetal heart rate (FHR) change may or may not be present.
(b) Tachysystole is the hyperstimulation without FHR changes.
(c) Hyperstimulationsyndrome is the hyperstimulation or tachysystole with FHR
abnormalities (ACOG-2003).

REMARKS ABOUT OXYTOCICS : All the oxytocics have got their places in obstetrics

 To arrest hemorrhage following delivery (PPH) or abortion, ergot preparation

(methergin, ergometrne) is the life saving drug. In refractory cases of atonic PPH, PGF 2α
(IM/intra-myometrial) or PGE1 (misoprostol) 1000 μg (rectal) is an effective choice.

 For induction of labour – either prostaglandins or oxytocin can be used. With

favourable preinduction cervical score, there is very little to choose between oxytocin
and prostaglandin, but when the score is unfavourable as in IUD, shorter period of
gestationor inelerly primigravida, prostaglandins have got a distinct advantage over
oxytocin. Misoprostol has certain advantages over PGE2.

 In augmentation or acceleration of labour, oxytocin still enjoys its popularity

although prostaglandins are equally effective.

~ 46 ~
  For induction of abortion – Prostaglandins (misoprostol – PGE1) has got a distinct
advantage over oxytocin. Oxytocin may supplement the effects of PGs in the process.

ANTHIHYPERTENSIVE THERAPY

Antihypertensive drugs are essential when the BP is 160/110 mm of Hg to protect the mother
from eclampsia, cerebral hemorrhage, cardiac failure and placental abruption. Aim is to reduce
BP to a mean < 125 mm Hg. Their benefit in mild or moderate hypertension is not yet known. If
there is any risk of target organ damage (kidney) anthihypertensives are given to maintain BP ≤
140 mm of Hg. First line therapy is either methyldopa or labetalol. Second line drug is
nifedipine. ACE inhibitors are avoided in pregnancy. The following are the drugs with their
pharmacological property and clinical use :

 IN pre-eclampsia and eclampsia.

 Chronic hypertension.
The commonly used drugs are grouped into :

I. Sympatholytics II. Andrenergic III. Vasodilators IV. calcium V. Ace

receptor blocking channel inhibitors /ARB
agents blocker

 Methyl-dopa  Labetalol  Hydralazi  Nifedipine  Captopril

 Recerpine  Propranolol ne  Nicardipine  Telmisartan
 Nitroglyce
rin
 Sodium
nitroprusside
Table 2 : Antihypertensive Drugs

~ 47 ~
Drugs Mechanism of Dose Side effects Contraindications
action and precautions

 
DOPA METHYL

Drug of first choice. Orally -250 Maternal – Hepatic disorders,

Central and mg bid – may be Postural psychic patients,
peripheral increased to 1 g hypotension, congestive cardiac
antiadrenergic qid depending haemolytic failure. Postpartum
  Maternal
AZINE HYDRAL

Acts by peripheral Oraly – 100 Because of variable

vasodilatation as it mg/day in four hypotension, sodium retention,
relaxes the arterial divided doses. tachycardia, diuretics should be
smooth muscle.  IV 5 – 10 mg arrhythmia, used. To control
  Tremors,  Hepatic disorders.
OL LABETAL

Combined α and β Orally – 100

adrenergic blocking mg tid may be headache,  Asthma, congestive
agent. increased. asthma, cardiac failure.
 IV infusion congestive
arteriolar   Flushing
NE NIFEDIPI

Direct Orally – 5 – Stimulataneous use of

vasodilatation by 10 mg tid hypotension, magnesium sulphate
inhibition of slow maximum dose headache, could be hazardous
inward calcium 60 – 120 mg/day. tachycardia, due to synergistic
 Maternal :
NITROGL SODIUMN

Direct vasodilator IV infusion 0.25 Drug of last resort

(arterial and venous). – 8 μg/kg/min. Nausea, for acute hypertension.
vomiting, Should be used in
severe critical care unit for
Relaxes mainly the Given as IV infusion Tachycardia, Used in hypertensive
venous but also 5 μg/min to be headache, crisis for short time
YCRINEITROPRU

arterialsmooth increased at every 3 Methaemoglobina only. Contraindicated

muscle – 5 min. up to 100 emia in hypertensive
 Captopril  Maternal :
– II receptor blockers ACE inhibitrs/Antiotensin

ACE inhibitors : Oraly Should be avoided in

Inhibit formation of 6.25 mg bid Hypotension, pregnancy. Suitable
angiotension II from  Telmisartan orally headache, for chronic
angiotensin I. 20 – 40 mg a day asthenia, hypertension in non
arrhythmias. pregnant state or
ARB – Blocks postpartum.
 Fetal :
angiotensin – II
oligohydramnio
receptors
us, IUGR, fetal
renal tubular

~ 48 ~
DIURETICS

The diuretics are used in the following conditions during pregnancy :

 Pregnancy induced hypertension with pathological oedema

 Severe anemia in pregnancy with heart failure
 As an adjunct to certain antihypertensive drugs such as hydralazine or diazodxide.
 Eclampsia with pulmonary oedema
 Prior to blood transfusion in severe anemia.

COMMON PREPARATIONS USED : Frusemide (Lop diuretic) Dose – 40 mg tab daily

following breakfast for 5 days a week. In acute conditions, the drug is administered parenterally
in doses of 40 – 120 mg daily. Mode of action – It directly prevents reasbsorption of sodium and
potassium mainly from the loop of Henle.

Hazards -

a) Maternal complications include – weakness, fatigue, muscle cramps, hypokalaemia

and postural hypotension. These canbe corrected by potassium supplement during
therapy
b) Fetal – IN pre-eclampsia, its routine use shouldbe restricted, as it is likelyto cause
further reduction of maternal plasma volume, which is already lowered. This may result
in diminished placental perfusion leading to fetal compromise. Other hazards include
thrombocytopenia and hyponatraemia.

~ 49 ~
 Thiazide diuretic is often used in conjunction with other antihypertensive. It is safe in
pregnancy. Dose : 125 mg twice daily maximum up to 50 mg daily may be used. Side effects
are : Maternal and fetalhyponatraemia, acute pancreatitis, rise in uric acid levels, and neonatal
thrombocytopenia. Ina diabetic patient, it may cause hyperglycaemia.

Spironolactone potentiates thiazide or loop diuretics by antagonizing aldosterone. It is a

potassium sparing diuretic. It is contraindicated in hyperkalaemia. Drospirenone is an analog of
spironolactone. It has antiandrogenic and antimineralocorticoid properties. The dose used in
COCs is usually not associated with hyperkalaemia.

TOCOLYTIC AGENTS

Preterm labour and delivery can be delayed by drugs in order to improve the
perinataloutcome. ?Short term delay of 48 hours allows the use of corticosteroids that can reduce
the perinatal mortality and serious morbidity significantly. Tehcommonly use drugs are :
Betamimetics, Prostaglandin synthetase inhibitors, Magnesium sulphate, Calcium channel
blockers, Oxytocin receptor antagonists, Nitric oxide donors and progesterone.

Drugs : The commonly used drugs are given in the Table 33.7.

Table 33.7 : Tocolytic agents

Drugs Mechanism of action Doses Side effects and precautions

Calcium Nifedipine blocks the Oral (not Maternal : Hypotension,

channel entry of calcium inside sublingual) 10 headache, flushing and
blockers the cell. It is equally – 20 mg every 3 nausea. Combined therapy
Nifedipine effective to MgSO4 – 6 hours. with β mimetics or MgSO4

~ 50 ~
 Drugs Mechanism of action Doses Side effects and precautions

Nicadipine should be avoided.

Verapamil

Magnesium It acts by competitive Loading dose MgSO4 is relatively safe.

sulphate inhibition to calcium 4-6 g IV (10 Common maternal side
ion either at the motor -20% solution) effects are flushing,
and plate at the cell over 20 – 30 perspiration headache and
membrane reducing min followed muscle weakness, rarely
calcium influx. by an infusion pulmonary oedema. Neonatal
Decreases of 1-2 g/hr – to side effects are lethargy,
acetylcholine release continue hypotonia, rarely respiratory
and its sensitivity at tocolysis for 12 depression. Monitoring : See
the motor end plate. hrs after the p. 509.
Direct depressant contractions
Contraindication : Patients
action on the uterine have stopped.
with myasthenia gravis and
muscle. Tocolytic effect
impaired renal function.
is poor.

(Indomethacin) Reduces sythesis of Loading dose Maternal : Heart burn, sthma

(Cyclo- PGs, thereby reduces 50 mg PO or GI bleding,
oxygenase intracellular free Ca++, PR followed by thrombocytopenia,
inhibitor) activation of MLCK 25mg every 6 renalinjury.
[sulinadac (p. 115) and uterine hrs for 48
Contraindications : Hepatic
another NSAID contractions. hours.
disease, active peptic ulcer,
is also used as it
coagulation disorders. Fetal
has les placental
and Neonatalside effects : i)
transfer] (Pgs cause ↑ in free
Constriction of the ductus
intracellular Ca++ and
arteriosus (due to inhibiton of
activation of MLCK).
synthesis of PGI2and PGE2)

ii) Oligohydramnios

iii) Neonatal pulmonary

hypertension

~ 51 ~
 Drugs Mechanism of action Doses Side effects and precautions

iv) IUGR.

Betamimetics Activation of the Ritodrine is Side effects of β mimetics

intracellular enzymes given by IV are more when used
 Terbutaline
(adenylate cyclase, infusion, 50 parenteraly
 Ritodrine CAMP, Protein kinse), μg/min and is
 Isoxsuprine Maternal: Headache,
reuces intracellular increased by 50
(Effective for free calcium (Ca++↓↓) palpitation, tachycardia,
μg every 10
48 hours to and inhibits activation pulmonaryoedema,
min until
allow time for of MLCK (↓↓) – hypotension, cardiac failure,
contractions
steroids and hyperglycaemia, ARDS,
cease.
antibiotics to hyper insulinaemia, lactic
Infusionis
work) acidaemia, hypokalaema and
Reduced interaction of continued for
even death.
actin and myosin – about 12 hours
smooth muscle after the Fetal : Tachycardia, heart
relaxation (see p. 120) contractions failure,
cease.
β (β2) receptor IUFD. Neonatal :
stimulation causes Terbutaline Hypoglycaemia and
smooth muscle has longer half intraventricular hemorrhage.
relaxation. life and has
fewer side-
effects.
subcutaneous
injection of
0.25 mg every 3
to 4 hours is
given.

Oxytocin Oxytocin analogue IV infusion Nausea, vomiting, chest pain

Antagopnists (antagonist_ that 300 μg/min. (rarely).
Atosiban blocks myometrial Initial bolus
oxytocin receptors. It may be needed.
inhibits intracellular
calcium release,

~ 52 ~
 Drugs Mechanism of action Doses Side effects and precautions

release of PGs and

thereby inhibits
myometrial
contractions.

Nitric oxide Smooth muscle Patches May cause cervical ripening

(NO) Donors relaxant
 Headache See p. 507.
Glyceryl
trinitrate (GTN)

ANTICONVULSANTS

Convulsion in pregnancy’s largely due to eclampsia. Other causes are – epilepsy, meningitis,
cerebral malaria and cerebral humors. Eclampsia should be considered first unless proved
otherwise by history, examination and investigations.

The commonly used drugs are given in the tabulated form

Drugs Mechanism of action Doses Side effects and

precautions
UM MAGNESI

It decreases the acetylcholine IM – Loading dose “ 4 g IV MgSO4 is relatively safe and

release from the nerve (20% solution) over 3-4 min. is the drug of choice.
endings and reduces the To follow 10 g (50% Muscular paresis (diminished
M DIAZEPA

Central muscle
motor end relaxant and
plate sensitivity to Initially
solution)20 – 40
deep mg5 gIVinto be
IM, Mother – Hypotension
knee jerks), respiratory
anticonvulsant followed by an infusion
Fetus – Reparatory
containing 500 ml of
depressant effect which may
dextrose with 40 mg of

~ 53 ~
Drugs Mechanism of action Doses Side effects and
precautions
IN PHENYTO

Centrally acting Eclampsia : 10 mg/kg IV – Maternal – Hypotension,

anticonvulsant (for other at te rate not more than 50 cardiac arrhythmias, and
anticonvulsant drugs see p. mg/min followed 2 hours phlebitis at the injection site.
291) later by 5 mg/kg.

ANTICOAGULANTS

Anticoagulants are not commonly used in pregnancy. Cardiac disease, venous thrombosis,
antiphospholipid syndrome are some of the indications. The commonly used drugs are discussed
here.

Drugs Mode of action Doses Side effects

Herpin Inhibits action of 5000 – 10000 I.U. to e Maternal – Hemorrhage,

(unfractionnated thrombin, it also administered urticaria with long term use
heparin) enhances the activity parenterally. DVT and thrombocytopenia and
of antithrombin III pulmonary embolism : osteopenia, hyperkalaemia.
loading dose 5000 units
Fetal : It does not cross the
Low molecular IV followed by
placenta.
weight heparin continuous infusion of
18 units/kg/hour. Low molecular weight
heparins – as effective and
Pregnancy : 5000-1000
safe as unfractionated
SC every 12 hours (with
heparin. Longer half life
monitoring).
and once daily dose is
Deltaparin sodium convenient. Standard dose
(Fragmin) : 2500 units does not require
Sc every 24 hours. monitoring.

Warfarin Interferes with 10 mg orally daily for Maternal – Hemorrhage.

~ 54 ~
 Drugs Mode of action Doses Side effects

synthesis of vit K initial 2 days then 3-9

dependent factors (II, mg daily (taken at the
Fetal – Contradi’s
VII, IX, X) same time each day)
syndrome (skeletal & facila
depending upon the
anomalies), optic atrophy,
prothrombin time (INR)
microcephaly,
chondrodysplasia punctata.

MATERNAL DRUG INTAKE AND REAST FEEDING

Maternal drug intake during nursing may have adverse effect not only on lactation but also on
the baby through the ingested breast milk. Any drug ingested by a nursing other may be present
in her breast milk, but its concentrations are usually low compared to blood levels in the mother.
Usually such low levels are not of any clinical significance to the infant.

However, milk concentrations of some drugs (e.g. iodides) may exceed those in the
maternal plasma so that therapeutic doses in the mother may cause toxicity to the infant (table
3.9). common side effects from maternal medication on breast fed infants are : diarrhea
(antibiotics), irritability (antihistaminics), drowsiness 9sedatives, antidepressants,
antiepileptics).

Factors Involved in Drug transfer into Guidelines for Medication During Lactation
Milk

• Chemical properties of the drug • Benefits of medication must outweigh the

risks
• Molecular weight
•Select drugs that are most widely tested and
• Degree of protein binding
with short half life

~ 55 ~
• Ionic dissociation •Monitor the infant during the course of
therapy.
• Lipid solubility
Nonionised, low molecular weight, lipid
• Tissue pH soluble compounds are usually excreted

• Drug concentration in maternal blood through breast milk.

• Duration of exposure time

Benefits of breast feeding are well known. The risk of drug exposure to the neonate must be
weighed against these benefits. If the drug amount is 1 to 2% of the mother, usually no adverse
effects are noted.

Table :

Maternal medication Effects on lactation and the neonate

Oral pill (combined) Suppression of lactation

Bromocriptine - do –

Ergot Vomiting, diarrhea, convulsions in infant

Progesterone (only pill) It is ideal for breast-feeding mother

Metronidazole (single dose regimen) No adverse effects have been reported

Anti-thyroid drugs, radioactive iodine Temporary cessation of lactation (12 – 24

hours) is advised

Hypothyroidism,goiter, agrranulocytosis
Warfarin
Safe in therapeutic doses. Prophylactic
Cytotoxic agents
vitamin K to the infant (p. 481)

Risk of immune suppression. Risks may

Lithium outweigh the benefits depending on

~ 56 ~
 Maternal medication Effects on lactation and the neonate

individual drug.

Lethargy, hypotonia, lithium toxicity

Narcotics, sedatives and anticonvulsants Sedation with poor sucking reflex

Tetracycline Tooth staining, delayed bone growth

Corticosteroids No significant effect. Up to maternal dose of

40 mg daily
Heparin
Does not cross into milk

Not known to be harmful

Acyclovir

FETALHAZARDS ON MATERNAL MEDICATION DURING PREGNANCY

TERATOLOGY AND PRESCRIBING IN PREGNANCY

Teratogen causes permanent alteration in the structure and/or function of an organ, acting during
the embryonic or fetal life. The tertatogens may be chemical agents (drugs) or physicalagents
(radiation, heat). The dose (amount) and duration of teratogen exposure may cause variable
response from on effect level to lethal level. Final results of an abnormal development are :
death, malformation, growth restriction and functional disorder.

The term ‘placental barrier’ is a contradiction as many drugs cross the barrier with
the excepton of large organic ions such as heparin and insulin. Approximately 25% of human
development defects are genetic in origin, 2-3% are due to drug exposure and about 65% ar
either unknown or from combination of genetic and environmental factors.

~ 57 ~
Mechanism of Teratogenecity : The actual mechanism is unknown. Teratogens may affect
through the following ways :

1. Folic acid deficiency leads to deficient methionine production and RNA, DNA synthesis.
Folic acid is essential for normal meiosis and mitosis. Periconceptional folate deficiency
leads to neural tube defects, cleft lips and palate.

2. Expoxids orarena oxides are the oxidative inter metabolites ofmany drugs like hydration
and carbamazepine. These intermediary metabolities have carcinogenic and teratogenic
effects unless they are detoxified by fetal epoxide hydrolase.

3. Environment and Genes. Abnormalities that are multi factorial depends on the ultimate
interaction between the environment and fetal gene mutation. Genotype of the embryo
and their susceptibility to teratogens are the important determinants. Homozygous gene
mutations are associated with more anomalies.

4. Maternal disease and drugs 9epilepsy and anticonvulsants) have an increased risk of
fetal anomalies. Patrnal exposure to drugs or mutagens (polycyclic hydrocarbons) can
cause gene mutation and chromosomal abnormality in sperm.

5. Hormeobox genes are groups of regulatory genes that control the expression of other
genes involved in the normal development of growth and differentiation. Teratogens like
retinoic acid can dysregulate these genes to cause abnormal gene expression.

TIMING OF TERATOGEN EXPOSURE

AND THEE HAZARDS

 Before D 31 : Teratogen produces an all

or none effect. The conceptus either does
not survive or survives without

~ 58 ~
 anomalies. In early conception only few cells are there. So any damage at that phase, is
irreparable and is lethal.
 D 31 – D 71 is the critical period for organ formation. Effects or teratogen depend on the
following factors : i) Amount of the drug reaching the fetus ii) Gestational age at the time
of exposure iii) Duration of exposure.
 After D 71 development of other organs continues. Diethyl stilboesterol (DES) related
uterine anomalies occur with exposure around 20 weeks.

Brain continues to develop throughout pregnancy and neonatal period. Fetal alcohol syndrome
occurs in late pregnancy.

Placental transfer of drugs : Most cross the placental barrier by simple diffusion. The factors
responsible for transfer are –

i) Molecular weight (molecular weight > 1000 Da do not cross the placenta)
ii) Concentration of free drug
iii) Lipid solubility
iv) Utero placental blood flow and
v) Placental surface area.
The rate of drug transfer across the placenta is increased in late pregnancy.

This is due to :

i) Increased unbound drug available for transfer

ii) Increased utero placental blood flow
iii) Increased placental surface area
iv) Decreased thickness of the placental membranes.

FDA RISK CATEGORIES FOR DRUGS AND MEDICATIONS :

FDA Drug Bulletin (1994)

~ 59 ~
Category Definitions

A Well controlled studies in pregnant women havee failed to demonstrate a fetal

risk.

B No evidence of risk in humans : well controlled studies in pregnant women

have not shown any increased risk of fetal malformation despite adverse findings
in animals. The chance of fetal harm is remote but remains a possibility.

C Risk cannot be ruled out. Adequate, well controlled human studies are lacking.
Animal studies have shown a risk to the fetus or are lacking as well. Potential
benefit may outweigh the risk.

D Positive evidence of risk : Studies in human have demonstrated fetal risk.

Potential benefits from use of the drug (life threatening situation) may out weight
the potential risk.

X Contraindicated in pregnancy : Proven fetal risks ccelarly outweight any

possible benefit. Drugs in this group are : alcohol, ACE inhibitors, Lithium,
Methotrexate, Valproic acid, Mifepristone, Danazol, Isotretinoin, Radioactive
iodine and others.

Teratogen information data bases :

Organization of Teratology Information Services (OTIS) : http:## www.otispregnancy org.

Keeping these in mind, the following guidelines are formulated :

 If the benefit outweighs the potential risks, only then can the particular drug be used with
prior counseling.
 Only, well tested and reputed drugs are to be prescribed and that too using the minimum
therapeutic dosage for the shortest possible duration.

Table :

~ 60 ~
Maternal medication Fetal or neonatal affection and comment

 Cytotoxic drugs - Multiple fetal malformations and abortion

 Diethylstilboesterol - Vaginal adenosis, cervical hoods, uterne hypoplasia of the
female offspring
- Masculinisation of the female offspring
 Androgenic steroids
- Cardiovascular (EBstein’s) anomalies, fetal diabetes inspidus,
 Lithium
polyhydramnios, neonatal goiter, hypotonia and cyanosis.
- Benefits of treatment outweigh the risks to the fetus.
Polytherapy should be avoided.

 Anticonvulsants
- phenytoin - Increase risk of neural tube defects, neonatal bleeding
- valproate - High doses in the last few weeks cause premature closure of

 Paractamol ductus arteriosus, persistent pulmonary hypertension and

 Antimalarials kernicterus in newborn. Risk of prolonged pregnancy and

maternal bleeding due to platelet dysfunction is there
- Amount too small to be harmful
- Chloroquine, Quinine – no evidence of fetal toxicity
intherapeutic doses; benefits outweigh the risk
- High doses (>10 mg prednisolone daily) may produce fetal and
neonatal adrenal suppression. Prolonged systemic use may
 Corticosteroids cause IUGR
 Aminoglycosides

- Nephrotoxicity, ototoxicity in preterm infants

 Chloramphenicol - “Gray baby” Syndrome (peripheral vascular collapse)

- Dental discoloration (yellowish) and deformity
Inhibition of bony growth – should be avoided

- Arthropathy n animal studies. No malformation was noted

 Tetracycline
- Neonatal haemolysis, Jaundice and kernicterus
 Quinolones
- Haemolysis in newborn with G 6 PD deficiency, if used a term.

~ 61 ~
Maternal medication Fetal or neonatal affection and comment

 Long acting No congenital defects noted

sulphonamides - No known teratogenic risk
 Nitrofurantoin - No increased risk of teratogenicity reported
- Known to be eratogenic
- No increased risk of malformation
 Metronidazole
- Mentioned earlier
 Ranitidine
- May be teratogenic
- Potentially dangerous to the fetus
 Omeprazole - Depression of CNS – apnoea, bradycardia and hypothermia
 Zidovudine (ZDV)
 Efavirenz
 Acyclovir
 ACE inhibitors
 Vitamin A (large dose)
 All live viralvaccines
 Narcotics

 Anticoagulants, antihypertensives, diuretics and beta-blockers, oral contraceptives are

mentioned earlier.

ALCOHOL : Heavy drinkers have major risk to the fetus. Fetal alcohol Syndrome (FAS) is
defined as the presence of at least one characteristics from each of the following 3 categories :

1. Growth restriction before and/or after birth.

2. Fetal anomalies : Small palpebral fissures, indistinct or absent helium, epicanthic folds,
flattened nasal bridge, short length of nose, thin upper lip, low set and unparallel ears and
retarded midfacial development.
3. CNS dysfunction : Microcephaly, mental retardation, abnormal neurobehavioural
development (attention deficit with hyperactivity).

~ 62 ~
PATERNALLY MEDICATED DRUGS AFFECTING HUMAN PROGENY :

Adverse effects on human progeny has been observed in the form of abortion, congenital
malformations, low birth weight and increased perinatal loss when the father has been exposed to
lead, anaesthetic agents, smoking or caffeine ingestion. These agents probably alter the
morphlogy of the spermatozoa or cause some change in the composition of the semen.

ANALGESIA AND ANASTHESIA IN OBSTETRICS

Relief of pain during labour and delivery is an essential part in good obstetric care. Choice of
anaesthesia depends upon the pateint’s conditions and the associate disorders. Anaesthetic
complications may cause maternal death. Anaesthesia following full meal may cause maternal
death due to vomiting and aspiration of gastric contents. Maternal risk factors for anaesthesia
are : Short stature, short neck, marked obesity, severe pre-eclampsia, bleeding disorders,
placenta praevia, medical disorder, placenta praevia, medical disorders, like cardiac, respiratory
and neurological disease.

ANATOMICAL AND PHYSIOLOGICAL CONSIDERATIONS

NERVE SUPPLY OF THE GENITAL TRACT : Uterus is under both nervous and hormonal
control; Hypothalamus controls the uterine activity through the reticular formation which
balances the effects of the two autonomic divisions.

~ 63 ~
Motor nerve supply : The uterus receives boty sympathetic and parasympathetic nerve fibres.
The sympathetic nerve fibres arise frm lower
thoracic and upper lumbar segments of the
spinal cord. The parasympathetic fibres
arise from sacral 2, 3 and 4 segments of the
spinal cord.

The pre-ganlionic fibres of the sympathetic

nerves arising from the spinal cord pas
through the ganglia of the sympathetic trunk
to aortico-renal plexus where they synapse.
The aortico-renal plexus continues as the
superior hyprogastric plexus or presacral nerve and passes over the bifurcation of aorta and
divides into right and left hypogastric nerves. Each hypogastric nerve joins the pelvic
parasympathetic nerve of the coresponsding side and forms the pelvic plexus (right and left) or
inferior hypogastric plexus. The pelvic plexus then continues along the course of the uterine
artery as paracervical plexus on each side of the cervix.

Sensory pathway : Sensory stimuli from the uterine body are transmitted through the pelvic,
superior hypogastric and aortico-renal plexus to the 10 th, 11th ad 12th dorsal and the first lumbar
segments of the spinal cord. Sensory stimuli from cervix pas through the pelvic plexus along the
pelvic parasympathetic nerves to sacral segments 2, 3 and 4 of the spinal cord. Sensory stimuli
from upper vagina pass to 2, 3 and 4 sacral parasympathetic segments and from lower vagina
pass through the pudendal nerve. The perineum receives both motor and sensory innervations fro
sacral roots 2, 3 and 4 through the pudendal nerve. The branches of illio-inguinal and genital
branch of genitor-femoral nerves supply the labia majora and also carry the impulses from the
perineum.

~ 64 ~
NERVOUS CONTROL OF UTERINE ACTIVITY : Regarding motor innvervation of the
uterus, the sympathetic nerves rather than the parasympathetic have the influences over the
uterine activity.

HORMONAL CONTROL : It is generally agreed that intact nerve supply is not essential
for the initiation and progress of a labor. Total spinal block does not inhibit uterine activity,
provided blood pressure s not allowed to fall, and normal vaginal delivery can occur in the
paraplegic patent. It is believed that some hormones are essential for the control of uterine
activity. Oxytocin, a hormone derived from posterior pituitary maintains the uterine activity
during labour. Progesterone is the pregnancy – stabilizing hormone. Labour commences when it
is withdrawn. Adrenaline with its beta activity inhibits the contraction o uterus, while its
alpha activity excites it.

ANALGESIA DURING LABOUR AND DELIVERY

The pain during labour results from a combination of uterine contractions and cervical dilatation.
During caesarean delivery incision is usually made around the T12 dermatome anaesthesia is
required from the level of T4 to block the peritoneal discomfort. Labour pain is experienced by
most women with satisfaction at the end of a successful labour. Antenatal (mothercraft) classes,
sympathetic care and encouraging environment during a labour can reduce the need of analgesia.
Drugs have an important part to play in the relief of pain in labour but it must not be supposed
that they are of greater importance than proper preparation and training for child birth. The
intensity of labour pain depends on the intensity and duration of uterine contractions, degree of
dilatation of cervix, distension of perineal tissue, parity and the pain threshold of the subject. The
most distressing time during the whole labour is just prior to full dilation of the cervix.

METHODS OF PAIN COMMOLY USED SEDATIVES AND ANALGESICS IN

~ 65 ~
 RELIEF LABUR

1. Psychoprophylaxis Drug Usual dose Frequency Neonatal

2. Sedatives and Half-life
analgesics (Approx.)
3. Inhalation agents
4. Patient controlled Pethidine 50 – 100 mg IM 4 hr 13 – 20 hr.
analgesia (PCA)
5. Transcutaneous Fentanyl 50 – 100 μg IV 1 hr. 5 hr.
electric nerve
stimulation (TENS)
Nabuphine 10 mg (IV/IM) 3 hr. 4 hr.
6. Regional analgesia
7. General anaesthesi
Morphine 10 mg IM 4 hr. 7 hr.

The ideal procedure should produce efficient relief of pain but should neither depress the
respiration of the fetus nor depress the uterine activity causing prolonged labour. The drug must
be non-toxic and safe for both the mother and the fetus. But it is regretted that no such agent is
available at present that fulfills all these conditions. Every case of labour does not require
analgesia and only sympathetic explanation may be al that is required.

SEDATIVES AND ANALGESICS

The following factors are important to control the dose of sedative and analgesics :

1. Pain threshold : the threshold of pain varies from patient to patient. Some patients
experience severe pain through the uterine contractions are relatively weak. In such cases,
it is preferable to control the pain adequately.
2. Parity : The multiparous women need less analgesia due to added relaxation of the birth
canal and rapid delivery.
3. Maturity of the fetus – Minimal doses of drugs are indicated while the fetus is thought
to be premature to avoid neonatal asphyxia.

For the purpose of selecting a general analgesic drug, labour has been divided arbitrarily into
two phases. The first phase corresponds up to 8 cm dilation of the cervix in primigravidae

~ 66 ~
and 6 cm in case of multipar. The second phase corresponds to dilation of the cervix beyond
the above limits up to deliver. The first phase is controlled by sedatives and analgesics and
the second phase is controlled by inhalation agents. The idea is to avoid the risk of delivery
of a depressed baby.

OPIOID ANALGESICS – Pethidine : For long time pethidine has been used as an
analgesic in labour. It has got strong sedative but less analgesic efficacy. Pathidine is
generally used ii the first phase of labour and indicated when the discomfort of labour merges
into regular, frequent and painful contractions. The initial dose is 100 mg (1.5 mg/kg body
wt) IM and repeated as the effect of the first dose begins to wane, without waiting for the re-
establishment of labour pain.

The side effects of pethidine to the mother are nauses, vomiting, delayed gastric
emptying. Ranitidine should be given to inhibit gastric acid production and emetic effect
is counteracted by metoclopramide (10 mg IM). Pethiidine crosses the placenta and
accumulates in fetal tissues. Pethidine depresses respiration and suckling of the new born
when administered before delivery.

Fentanyl is a short synthetic opioid and is equipotent to pethidine. It has less neonatal effects
and less maternal nausea and vomiting. It needs frequent dosing.

Phenothiazines : Promethazine (phenargan) is commonly used I nlabour in combination

with an opioid. It does not cause manjor neonatal depression. Promethazine is a weak
antiemetic drug and causes sedation in the mother.

Narcotic antagonists are used to reverse the respiratory depression induced by opioid
narcotics. Naloxone is given to the mother 0.4 mg IV in labour. It may have to be repeated. It
is given to the newborn 10 μg/kg IM or IV and is repeated if necessary when the infant is

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born with narcotic depression. Naloxone is given to a new born of a narcotic addicted
mother, with proper ventilation arrangement only otherwise withdrawal symptoms are
precipitated.

Benzodiazepines (Diazepam) : It is well tolerated by the patient. It does not produce

vomiting and helps in the dilation of cervix. It is metabolized in the liver. The usual dose is 5
– 10 mg. It may be used in larger doses in the management of pre-eclampsia. However,
diazepam is avoided in labour.

Major disadvantages are : Loss of beat to beat variability in labour, neonatal hypotonia and
hypothermia. Flumazenil is a specific benzodiazepine antagonist. It can reverse the
respiratory depression effect of benzodiazepines.

Combination of narcotics and antiemetics : Narcotics may be used in combination with

promethazine, metoclopramide or ondansetron. The advantages claimed that the combination
potentiates the action of narcotic, produces les respiratory depression ad prevents vomiting.
But there are also disadvantages like hypotension and delay of second stage of labour.

INHALATION METHODS

Premixed nitrous oxide and oxygen : Cylinders contain 50 percent nitrous oxide and 50
percent oxygen mixture. Entonox apparatus has been approved for use by midwives. This
agent is used in the second phase (from 8 cm dilation of cervix to deliver). It can be self
administered. Entonox is most commonly used inhalation agent during labour in UK.
Hyperventilation, dizziness, hypocapnia are the side effects. The woman is to take slow and
deep breaths before the contractions and to stop when the contractions are over. The woman
should be monitored with pulse oximetry.

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 COMMONLY USED LOCAL ANAESTHETIC AGENTS IN OBSTETRICS

Drug Usual Onset Duration Use in obstetrics

dose (Min)

Lignocai 7 mg/kg Rapid 60-90 min Local or pudenea block and also for
ne epidural or spinal for caesarean delivery

Bupivac 3 m/kg Slow 90 – 150 Epidural or spinal for caesarean delivery

cine min

Toxicity – Cental Nervous system : Depression, dizziness, tinnitus, metallic taste,

numbness of tongue, slurred speech, muscle fasciculation. Rarely generalized
convulsions and loss of consciousness. Cardiovascular toxicity : Hypotension, cardiac
arrhythmias and fetal distress due to impaired placental circulation.

REGIONAL ANAESTHESIA

The methods so far considered cannot ensure a painless delivery nor can the make labour
tolerable when the pain is very severe. When complete relief of pain is needed throughout
labour, epidural analgesia is the safest and simplest method for procuring it. But
anesthetists/obstetrician have to be trained properly to make use of this very valuable method in
normal and abnormal labour.

Advantages of regional anesthesia

 The patient is awake and can enjoy the birth time

 New born Apgar score generally good
 Lowered risk of maternal aspiration
 Post operative pain control is better

Continous lumbar epidural block : A lumbar puncture is made between L2 and L3 with the
epidural needle (Tuohy needle). With the patent on her left sie, the back of the patient is cleansed
with antiseptics before injection. When the epidural space is ensure, a plastic catheter is passed
through the epidural needle for continuous epidural analgesia. A local anaesthetic agent is

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injected into the epidural space. Full dose is given after a test dose when there is no toxicity. For
complete analgesia a block from T10 to the S5 dermatomes is needed. For caesarean delivery a
block for T4 to S1 is needed. Repeated doses (top ups) of 4 to 5 ml of 0.5 percent bupivacaine or
1 percent lignocaine are used to maintain analgesia. Epidural analgesia, as a general rule should
be even when labour is well established. Maternalhydration should be a adequate with normal
saline or Hartmann’s solution (Crystalloid) infusion prior commencing the blockade. The
patient’s blood pressure, pulse and the fetal heart rate should be recorded at 15 minutes interval
following the induction of analgesia and hypotension, if occurs, should be treated immediately.
The women is kept in semi-lateral position to avoid aorto-caval compression.

Epidural analgesia is specially beneficial in cases like pregnancy induced hypertension, breech
presentation, twin pregnancy and preterm labour. Previous caesarean section is not a
contraindication epidural analgesia when used there is no change in duration of first sate of labur.
But second stage of labour appears to be prolonged. This might lead to frequent need of
instrumental delivery like forceps or ventouse.

CONTRAINDICATIONS OF COMPLICATIONS OF EPIDURAL

EPIDURAL ANALGESIA ANALGESIA

 Maternal coagulopathy or anticoagulant  Hypotension due to sympathetic

therapy blockade. Parturient should be well
 Supine hypotensinoi hydrated with (IL) crystalloid solution
 Hypovoaemia before hand.

 Neurological diseases  Pain at the insertion site. Back pain.

 Spinal deformity or chronic low back  Post spinal headache due to leakage of
pain cerebrospinal fluid through the needle

 Skin infection at the injection site hole in the dura

 Total spinal due to inadvertent
administration of the drug in the
subarachnoid space
 Injury to nerves, convulsions, pyrexia

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  Ineffective analgesia

Paracervical nerve block : Is useful for pain relief during the first state of labour. Following the
usual antiseptic safe guards, a long needle (15 cm or more) is passed into he lateral formic, at the
three and nine o’clock positions. 5-10 ml of 1 percent lignocaine with adrenaline are injected at
the site of the cervix and the procedure is repeated on the other side. This dose is quite sufficient
to relieve pain for about an hour or two, and injections can be given more than once if necessary.
Bupivaciaine is avoided due to its cardiotoxicity. Paracervical block should not be sued where
placental insufficiency is present. In order to avoid complications, a specially construct4ed guard
tube is used. A needle is inserted through the tube and is of such a length that it protrudes not
more than 7 mm beyond its tip.

Although paracervical block may be used from 5 cm dilatation of the cervix, it is most
useful towards the end of the first stage of labour to remove the desire to bear down earlier.
Paracervical block can only relieve the pain of uterine contraction and the perineal discomfort is
removed by pudendal nerve block. Fetal bradycardia is a known complication. This iw due to
dereased placental perfusion resulting from uterine artery vasoconstriction or its direct
depressant effect on the fetus following transplacental transfer.

Pudendal nerve block : It is a safe and

simple method of analgesia during
delivery. Pudendal nerve block does not
relieve the pain of labour but affords
perineal analgesia and relaxation.
Pudendal nerve block is mostly used for
forceps and vaginal breech delivery.
Simultaneous perineal and vulval
infiltration is needed to block the perineal
branch of the posterior cutaneous nerve of

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the thigh and the labial branches of the ilio-inguinal and genitor-femoral nerves (vide supra).
This method of analgesia is associated with less danger, both for the mother and for the baby
than general anesthesia.

Technique : The pudendal nerve may be blocked by either the transvaginal or the transperineal
route.

Transvaginal route : Transvginal route is commonly preferred. A 20 ml syringe, one 15 cm (6”)

22 gauge spinal needle and about 20 ml of 1% lignocaine hydrochloride are required. The index
and middle fingers of one hand are introduced into the vagina, the finger tips are placed on the
tip of the ischial spine of one side. The needle is passed along the groove of the fingers and
guided to pierce the vaginal wall on the apex of ischial spine and thereafter to push a little o
pierce the sacrospinous ligament just above the ischial spine tip. After aspirating to exclude
blood, about 10 ml of the solution is injected. The similar procedure is adopted to block the
nerve of the other side by changing the hands.

Complications : Haematoma formation, infection and rarely intravascular injection.

Spinal anesthesia : spinal anaesthesia is obtained by injection of local anesthetic agent into the
subarachnoid space. It has less procedure time and high success ate. Spinal anesthesia can be
employed to alleviate the pain of delivery and during the third stage of labour. For normal
delivery or for outlet forceps with episiotomy, ventouse delivery, block should extend from T10
(umbilicus) to S1. For caesarean delivery l4vel of sensory block should be up to T4 dermatome.
Hyperbaric bupivacaine (10 – 12 mg) or lignocaine (50-70 mg) is used. Addition of fentanyl (to
enhance the onset of block) or morphine (to improve pain control) may be done. Brief or
minimal spinal anesthesia is far safer than prolonged spinal anesthesia. The advantages of

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spinal anesthesia are : a) less fetal hypoxia unless there is hypotension and (b) minimal blood
loss. The technique is not difficult and no inhalation anesthesia is required, but post spinal
headache occurs in 5 – 10 per cent o patients.

Spinal anaesthesia can be obtained by injecting the drug into the subarachnoid space of
the third or fourth lumbar inter space with the patient lying on her side with a slight head uptilt.
The blood pressure and respiratory rate should be recorded every 3 minutes for the first 10
minutes and every 5 minutes thereafter. Oxygen should be given for respiratory depression and
hypotension. Sometimes vasopressor drugs may be required if a marked fall in blood pressure
occurs. It is used during vaginal delivery, forceps, ventouse and caesarean delivery.

Combined spinal – epidural analgesia : An introducer needle is first placed in the

epidural space. A small gauge spinal needle is introduced through the epidural needle into the
subarachnoid space (needle through needle technique). A single bolus of 1 ml 0.25%
bupivacaine with 25 μg fentanil is injected into the sub-arachnoid space. The spinal needle is
then withdrawn. An epidural catheter is thus sited for repeated doses of anaesthetic drug. The
method gives rapid and effective analgesia during labour and caesarean delivery.

INFILTRATION ANALGESIA

Perineal infiltration : For episiotomy – Perineal infiltration anesthesia is extensively used prior
to epidiotomy. A 10 ml syringe, with a fine needle and about 8-10 ml 1% lignocaine
hydrochloride (Xylocaine) are required. The perineum on the proposed episiotomy site is
infiltrated in a fan-wise manner starting from the middle of the fourchette. Each time prior to
infiltration, aspiration to exclude blood is mandatory. Episiotomy is to be done about 2-5
minutes following infiltration.

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 For outlet forceps or ventouse – (Perineal and labial infiltration) : The combined perineal
and labial infiltration is effective in outlet forceps operation or ventouse traction. A 20 ml
syringe, a long fine needle and about 20 ml of 1% lignocaine hydrochloride are required. The
needle is inserted just posterior to the introitus. About 10 ml of the solution is infiltrated in a fan
wise manner on both sides of the midline (as for episiotomy). The needle is then directed
anteriorly along each side of the vulva as far as the anterior-third to block the genital branch of
the genitor-femoral and ilio-inguinal nerve. 5 ml is required to block each side.

Local abdominal for caesarea delivery : This method is rarely used where regional block is
patchy or inadequate. Technique : The skin is infiltrated along the line of incision with diluted
solution of lignocaine (2%) with normal saline. The subcutaneous fatty layer, muscle, rectus
sheath layers are infiltrated as the layers are seen during operation. The operation should be done
slowly for the drug to become effective.

PATIENT CONTROLLED ANALGESIA (PCA) :Narcotics are administered by the mother

herself from a pump t continuous or intermittent demand rate through intravenous route. Total
dose is limited as there is a lockout interval. This offers better pain control than high doses given
at a long interval by the midwife. Maternal satisfaction is high with this method. Drugs
commonly used are pethidine, meperidine or Fentanyl.

PSYHOPROPHYLAXIS (Syn : Natural child birth) : It is psychological method of antenatal

preparation designed to prevent or at least to minimize pain and difficulty during labour. For
most women, labour is a time of apprehension, fear and agony. As a result of suitable antenatal
preparation, majority of women have labour that is easy and painless.

Relaxation and motivation can reduce the fear and apprehension to a great extent. Patient
is taught about the physiology of pregnancy ad labour in antenatal (mothercraft) classes.

~ 74 ~
Relaxation exercises are practiced. Husband or the partner is also involved in the management.
His presence in labour would encourage the bearing down efforts. Need of analgesia would be
less.

TRANSCUTANEUS ELECTRIC NERVE STIMULATION (TENS) : It is a noninvasive

procedure and is preferred by many women during labor. Electrodes are placed over the level of
T10 – L1 and S2 – 4. current strength can e adjusted according to pain. It works by inhibiting
transmitter release through inter neurone level. However, no change in pain score was observed
when TENS was switched on.

GENERAL ANAESTHESIA CAESAREAN SECTION

The following are the important considerations of general anaesthesia for caesarean section
:

 Caesarean section may have to be done either as an elective or emergency procedure.

 A fasting of 6-8 hours is preferable for an elective surgery
 The mother may have a full stomach raising the probability of aspiration
 A large number of drugs pas through the placental barrier and may depress the baby
 Uterine contractility may be diminished by volatile anaesthetic agents like ether,
halothane
 Lateral tilt of the women during operation. Halothane, isoflurane cause cardiac
depression, hepatic necrosis and hypotension
 Hypoxia and hypercapnia may occur
 Time interval from uterine incision to delivery is related directly to fetal acidosis and
hypoxia
 Longer the exposure to general anaesthetic before delivery the more depressed is the
Apgar score.

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General anaesthesia : Preoperative medication with sedatives or narcotics is not required as
they may cause respiratory depression of the fetus.

100% oxygen is administered by ight mask fit for more than 3 minutes. Induction of
anaesthesia is done iwith the injection of thiopentone sodium 200 to 250 mg (4 mg/kg) as a 2.5
percent solution intravenously, followed by refrigerated syxanetgonium 100 mg. The assistant
applies cricoid pressure as consciousness is lost. The patient is intubated with a cuffed
endotracheal tube and the cuff is inflated. Anaesthesia is maintained with 50 percent nitrous
oxide, 50 per cent oxygen and a trace (0.5%) of halothane. Rlaxation is maintained with
nondepolarising muscle relaxant (vecuronium bromide 4 mg or atracuyrium 25 mg). After
delivery of the bay, the nitrous oxide concentration should be increased to 70% and narcotics are
injected intravenously to supplement anaesthesia.

Complications of general anaesthesia : Aspiration of gastric contents (Mendelson’s

syndronme) is a serous and life threatening one. Delayed gastric emptying due to high level of
serum progesterone, decreased motilinand maternal apprehension during labour is the
predisposing factor. The complication is due to aspiration fo gstci acid contents (pH<2.5) with
the development of chemical pneumonitis, atelectsis and bronchopneumonia. Right lower lobe is
commonly involved as the aspirated food material reach the lung parenchyma through the right
bronchus. Clinical presentation : tachycardia, tachypnoea, bronchospasm, ronchi, rales, cynosis
and hypotension. X-ray chest reveals right lower lobe involvement.

Prevention : The following safety measures should be taken to prevent this complication :

 Patient should not be allowed to eat during labour.

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  H2-blocker (Ranitidine 150 mg orally) should be given night before (elective procedure)
and to be repeated (50 mg IM.IV) one hour before the administration of general
anaesthetic, to raise thegastric pH.
 Metoclopramide (10 mg IV) isgiven after minimum 3 minutes of pre-oxygenation to
decrease gastric volume and to increase the tone follower oesophageal sphincter.
 Non-particulate antacid (0.3 molar sodium citrate 30 ml) is given orally before
transferring the patient to theatre to neutralize the existing gastric acid.
 Intubations with adequate cricoid pressure following induction should be done.
 Awake extubation should be a routine.

Management :

Immediate suctioning of oropharynx and nasopharynx is done to remove the inhaled

fluid. Bronchoscopy may be needed if there is any large particulate matter. Continuous positive
pressure ventilation to maintain arterial oxygen saturation of 95% is done. Pulse oximeter is a
useful guide. Antibiotics are administered when infection is evident. Role of corticosteroid is
doubtful.

Other complications of general anesthesia are : (i) Failure in intubation and ventilation
(ii) Nausea, vomiting and sore throat.

KEY POINTS

 Oxytocics are drugs used to stimulate uterine contractions (p. 416).

 Oxytocin can be used in pregnancy, labour and puerperium (p. 498). Contraindications (p.
499) and dangers (p. 499) of oxytocin use must be carefully assessed.
 Oxytocin is given by controlled intravenous infusion (p. 499) During infusion, the woman
must be observed carefully (p. 500).
 Methergin (ergot derivative) can be used orally r parenterally (p. 502).It differs with oxytocin
in its action (Table. 33.5). Indications (p. 502), contraindications (p. 503) of ergot derivaties
must be assessed.

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 Prostaglandins are widely used in obstetrics (p. 504). They have many advantages (p. 504).
Of the different preparations, PGE2, PGF2α and PG1 are commonly used (. 505).
Prostaglandins have some advantages over oxytocin in medical induction of labour (p. 523).
 Commonly used antihypertensives in pregnancy are : Methyldopa, Labetalol, Hydralazine
and Nifedipine (p. 506). Nitroglycerine and sodium nitroprusside are used for hypertensive
crisis (p. 507). ACE inhibitors or ARB should be avoided in pregnancy.
 Commonly used to colytics are – Betamimetics (Terbutaline, Ritodrine, Isoxsuprine),
Indomethacin, Calcium channel blockers, Magnesium sulphate, Oytocin antagonists and
Nitric odxide donors (p. 509) MgSO4 is the drug of choice.
 While breast feeding, the benefits of breas6 milk must be weighed against the risk drug
exposure to the neonate (p. 510). Information as regard some commonly used drugs are
available (Table. 33.9).
 Teratogens exert their effects through different mechanisms (p. 511). The hazares of drugs
depend upon the placental transfer of drugs and the period of gestation (p. 515) Information
as regard some commonly used drugs are available (Table. 33.10).
 Opoid analgesics are commonly used in labour (p. 515). F the inhalation methods, premixed
nitros oxie and oxygen is commonly seed (p. 516).
 Epidural analgesia is the safest and simplest method of regional anaesthesia. One must know
the contraindications and complications of its use (p. 517). In obstetrics, it is specially
beneficial for some cases (p. 517)/
 Pudendal block is good for perinaeal analgesia and is used for forceps and vaginal breech
delivery.
 Spinal anaesthesia has some advantages but is should be used carefully to avoid the side
effects (p.517).
 Mendelson’s syndrome is a serious complication of general anaesthesia. This can be
prevented when the safety measures are taken before hand.

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Drugs that exert a pronounced effect upon the fetus when administered during pregnancy.

Receptive Tissue Specific Drug

1. Heart Digoxion, diphenylhydaitoin
2. Skeleton Tetrancycline, warfrain
3. Red blood cells Sulphonamides
4. Control nervous system Diazepam, ethanol, narcotics.
5. Platelets Aspirin
6. Adrenal gland Sex steroids, diphenyl hydantion.
7. Mullerian duct vagina Diethylstibestrol
8. Otic nerve Streptomycin.

In evaluating the possible harm to the fetus from any substance, the five major
considerations are –

1. The amount of the substance that can be expected to reach the embryo or fetus.
2. The gestational age of the embryo or fetus at the time of administration.
3. The duration of the exposure.
4. The genotypes of the mother and embryo or fetus.
5. The expected effects on the embryo or fetus of this substance when combined with other
agents in the mothers body.

Exposure to some substances during the first 3 weeks after conaptin can be so destructive to the
embryo that spontaneous abortion ocemn. Major malformation are most likely to occur firms the
third to the tenth week of gestation, when the organ are being formed. From the 11 th week after

~ 79 ~
conception through delivery, exposure mostly slows down the growth process of creates
physiologic debieitc, which appear in the fetus or neonate.

ROLE AND RESPOSIBILITY OF NURSE

Midwives-

 Know and comply with the state laws and regulations regarding prescribing of
medications.
 Know and comply with the state Nurse practice act related to medication prescribing
authority.
 Limit access to prescription pads and notify local pharmacies and the drug enforcement
in agency if blank descriptions are stolen.
 Limit telephone refills to one prescription and require the patient to come in and be seen
before providing additional telephone refills.
 Avoid refilling narcotics and pain medication by telephone and outside of regular office
hours.
 Perform peer review of the prescribing practices of licensed Independent practitioners
and obtained additional education and expertise as needed.
 Maintain drugs in a safe area with limited access and it appropriate or required by law,
under lock and key.
 Store drugs at manufacturer’s recommended temperature .
 Store drugs in a separate location away from food or other materials or supplies.
 Avoid storing similar looking Drugs near one another.
 Avoid keeping drugs with similar sounding names and the formulary, but it such our
similarities do occur, provide adequate additional warning on packaging.
 Regularly check drug expiry dates and properly discard/ destroyed expired drugs
prescribing medications.

~ 80 ~
 Know the appropriate indications, dosage range, routes of Administration,
contraindications, side effects, and warnings related to the drugs prescribed and
administered.
 Maintain readily available, current drug reference materials and refer to them whenever
there are questions regarding a drug or when prescribing a drug that is not frequently
prescribed.
 Maintain access to resources that provide clinical information on drug interactions.
 Consult with physicians and pharmacists when appropriate to confirm appropriate drugs
selection, prescription and ordering, and to check for potential drug interaction or
contraindication with patients existing drug therapy.

NURSES RESPONSIBILITY DURUNG DRUG ADMINISTRATION:-

1. The injection should be given in a large muscle. Aspiration should be performed to avoid
infections into a blood vessel which can result in breanchospasm, titanic contractions, and
shock.
2. After administration, monitor uterine contraction and bleeding carefully.
3. Report excess bleeding to the physician/CNM.
4. Check vital signs routinely, observing for an increase in temperature, elevated pulse, and
described blood pressure.
5. Present feeding should be delayed for 24 hours after administration (Wilson et al..; 2006).
6. Assess for presence of contraindications.
7. Monitor maternal vital signs, cervical dilatation, and effacement carefully.
8. Monitor fetus status for presence of reassuring fetal heart rate pattern (baseline 110-160
bpm, presence of short term variability, average variability presence of necelemtions with
fetal movement, absence of late or variable decelerations.
9. Remove vaginal insert if uterine hyperstimulation, sustained uterine contractions, non
reassuring fetal status or any other maternal adverse action occur.
10. Monitor the blood pressure closely during administration.
11. Monitor maternal serum magnesium levels as ordered (usually every 6-8 hours).
Therapeutic levels are in the range of 4 -8 mg/dl. Reflexes often disappear at serum

~ 81 ~
 magnesium levels of 9-13 mg/dl; respiratory depression may occur at levels of 14 mg/dl.
cardiac arrest occurs at levels above 30mg/dl (Rideoust 2005).
12. Monitor respirations closely. If the rate is less than 12/minute magnesium toxicity may be
developing and further assessments are indicated. Many protocols require stopping the
medication if the respiratory rate falls below 12/min.
13. Assess Knee Jerk (Patellon tendon reflex) for evidence of diminished or absent reflexes.
Lose of reflexes is often the first sign of developing toxicity. Also note marked lethargy
or decreased level of consciousness and hypotension.
14. Determine urinary output. Output less than 30 ml/hour may results in the accumulation of
toxic levels of magnesium.
15. If the respirations or urinary output fall below. Specified levels or if the reflexes are
diminished or absent no further mangnesium should be administered until these factors
return to normal.
16. The antagonist of magnesium sulfate is calcium. Consequently, an ampute of calcium
gluconate should be available of the bedside. The usual dose is 1gm give I.V. over a
period of about 3 minutes.
17. Monitor fetal heart tones continuously with I.V. administration.
18. Continue magnesium sulfate infusion for approximately 24 hours after birth as
prophyloxis against postpartum scizures if given for pre-eclampsia.
19. If the mother has received magnesium sulfate close to birth the newborn should be
closely observed for signs of magnesium toxicity for 24 – 478 hours.
20. Monitor fundal height and consistency and the amount and character of the lochia.
21. Notify provider if uterus remains boggs despite Methergine administration.
22. Assess the blood pressure before and routinely throughout dry administration.
23. Observe for adverse effects or symptoms of ergot toxicity (ergolism) such as nausea and
vomiting headache muscle pain, cold or numb fingers an dtoes, chest pain and general
weakness.
24. Provide client / family teaching regarding importance of not smoking during methergine
administration (nicotine form cigarattes, lead to dilate vessels and may lead to
hypertension) singe of toxicity.

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CONCLUSION :-
Most women are exposed to drugs of one type or another during pregnancy. These may be
prescribed drugs or those brought over-the-counter. They may be given as part of the
management of the pregnancy itself or that of coincidental medical problem. However, when
considering the use of any drugs in a pregnant or breastfeeding women, it is important to
consider the effects of drug not only on the women itself, but also on the foetus or neonate.

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