OVARIAN

STIMULANTS
AND OXYTOCICS
Dr Solith Senanayake
Senior registrar in cardiology/Lecturer
Department of Pharmacology
FMS/ USJP
A group of drugs that are used to

• Hasten child birth

• Induce or augment labour

• Induce abortion
• Drugs which stimulate uterine contractions

a) Oxytocin

b) Ergometrine

c) Prostaglandins
 Oxytocin
Peptide hormone of the posterior pituitary gland
Synthesized by supraoptic and paraventricular
nuclei

Physiological role
1. Initiation and maintenance of labour
Sensory stimulation of cervix and vagina lead
to secretion of oxytocin
2. Contraction of myoepithelial cells of breast

• In non pregnant uterus – effect of oxytocin insignificant

• In pregnant uterus – effect minimal in 1st & 2nd trimesters

• Maximal effect in 3rd trimester, increasing in labour & delivery

Good to know (MCQ……..)
 Pharmacological action
Stimulates frequency and force of contraction of
uterine muscles
Cause rhythmic contractions
(relaxation in between contractions)which will not compromise
placental blood circulation
Act on estrogen dependant oxytocin receptors in
myometrium
(myometrial oxytocin receptor concentrations increase
approximately 100- to 200-fold during pregnancy)
 Administration

 Given parenterally – IV infusion

 Plasma t ½ - 6 minutes

 Inactivated in the liver and kidneys by

placental oxytocinase

 IV – onset of action – immediate

 IM – contraction – 2 ½ minutes
 15 – 20 minutes

 Prep. – synthetic oxytocin injection

 Uses…….

1. Induction of labour at or near term – vaginal

delivery
Slow IV infusion
Start with low dose in 5% Dextrose infusion.

Caesarean section
• Other uses of oxytocin
• Post partum hemorrhage(PPH) -when ergometrine
is contraindicated
IM 10U after delivery of the placenta
• Promote lactation (intra nasal spray)

• Adjunctive treatment of abortion:

 IV: Incomplete, inevitable, or elective abortion:
10 units as an IV infusion after suction or a sharp curettage
(used to help contract the uterus)

• Mid trimester elective abortion

Adverse effects

• Uterine rupture

• Amniotic fluid embolism

• Neonatal jaundice – increase erythrocyte fragility

• Water intoxication – structurally similar to ADH &
infusion of large volumes
• BP , HR, ECG abnormalities

• Nausea ,vomiting
• No dose adjustments recommended in renal or hepatic
impairment

• Contra indicated in

• Hypersensitivity to oxytocin
• Uterine hyperactivity
• Any contraindication to vaginal delivery
• Such as
• Significant cephalo-pelvic disproportion
• Unfavourable foetal positions
 Monitoring

• Maternal pulse and BP – hourly

• Frequency , intensity and duration of uterine

contractions – ½ hourly

• Foetal heart rate – ½ hourly

 Ergometrine

• Alkaloid of ergot

Pharmacological action
• Insignificant action on non pregnant uterus

• Pregnant uterus – Stimulation of  adrenoceptors

and serotonin (5HT) receptors
• Effect increases during pregnancy

• Causes sustained contractions with no relaxation in

between (tetanic contractions)
 Clinical use

• Prevention and treatment of PPH

• Usual dose – 0.5 mg IM

0.25 mg IV

• Ergometrine + oxytocin injection: “Syntometrine”

• Ergometrine 0.5 mg, oxytocin 5 units

• combination of quick action + prolonged effect
 Adverse effects

 Hypertension
 Peripheral ischemia
 Vomiting (D2 receptors)- activation of medullary
vomiting center
Avoid ergometrine in patients with
• Hypertension
• toxemia of pregnancy,
• rheumatic heart disease
• peripheral vascular disease
• For induction of labour
• 1st and 2nd stages of labour
 Prostaglandins

 Induction of labour
 Induction of abortion
 Treatment of hemorrhage (PPH)

•Induction of labour
 Uterine muscle contraction
 Relaxation of cervix
  uterine tone
• Misoprostol is a synthetic prostaglandin E1 analog has
been shown to induce uterine contractions

• In women with unfavorable cervixes, prostaglandins are

a proven method of cervical ripening and may initiate
labor as a result of their uterotonic effects
 Pharmacological properties
• Absorption: Rapid and extensive; extensive; food
decreases absorption of misoprostol acid

• Protein binding: Misoprostol acid: <90%

• Metabolism: Hepatic; rapid de-esterification to

misoprostol acid (active)

• Half-life elimination: Misoprostol acid: 20 to 40 minutes

• Excretion: Urine (80%)

 Adverse effects

 Vomiting

 Diarrhea

 Headache

 Pyrexia

 Local tissue reaction

 Bronchospasm
 Uterine relaxants

• Tocolytic agents used for inhibition of premature labour

 Salbutamol
 Terbutaline
 Isoxsuprine
 Ritodrine
Should be cautious

• In patients with pre existing cardiac diseases

• Multiple pregnancies

S/E
• Tachycardia
• Elevated BP
 OVARIAN STIMULANTS
• Ovulatory disorders can be identified in 18 to 25
percent of couples presenting with infertility

• Most of these women have oligomenorrhea

• clinical approach to ovulation induction requires an

understanding of the causes of anovulation
Goals of treatment
• Induce mono follicular rather than multi follicular
development and subsequent ovulation and,
ultimately, a singleton pregnancy and birth of a healthy
newborn
• Start with the least invasive, simplest, and cheapest
treatment option
• Maximize the rate of singleton pregnancies, minimize
multiple gestation rates
• Minimize the risk of OHSS in women undergoing
gonadotropin therapy, particularly those with
polycystic ovary syndrome (PCOS), who are at higher
risk
 Hypogonadotropic hypogonadism

•  Hypothalamic causes of hypogonadotropic hypogonadism

include functional hypothalamic amenorrhea (FHA) and
isolated gonadotropin-releasing hormone (GnRH) deficiency

• Multiple factors may contribute to the pathogenesis of FHA,

including eating disorders (such as anorexia nervosa),
exercise, and stress.

• Women in this group, which accounts for 5 to 10 percent of

anovulatory women, usually have amenorrhea
 Drug therapy

Clomiphene

Used for treatment of infertility associated with

failure of ovulation

These drugs are competitive inhibitors of estrogen

binding to estrogen receptors and have mixed
agonist and antagonist activity
Anti estrogen effect
 Endogenous gonadotrophin secretion by
blocking negative feed back to the pituitary
• Clinical use

Treatment of infertility
females with potentially functional pituitary and ovaries
infertility following oral contraceptives

Dose and administration

Start on day 2 or 5 of the menstrual cycle, start with
50 mg daily
If no response higher dose

Can go up to 6 cycles if no response

Ovulation confirmed by
Measurement of serum progesterone
Adverse effects
• >10%: Endocrine & metabolic: Ovary enlargement

• Central nervous system: Headache

• Endocrine & metabolic: Hot flash

• Ovarian hyperstimulation syndrome

(OHSS)Gastrointestinal: Abdominal distention
abdominal distress, bloating, nausea, vomiting
• Genitourinary: Breast disease (discomfort), abnormal
uterine bleeding

• Ophthalmic: Visual disturbance

• Worsening dyslipidaemia – risk of pancreatitis

• Contra indicated in pregnancy

Prior to therapy:
• Rule out primary pituitary or ovarian failure,
endometriosis/endometrial carcinoma, adrenal
disorders, thyroid disorders, hyperprolactinemia, and
male infertility. Serum triglycerides

• Pelvic exam prior to each course of therapy; pregnancy

test prior to repeat courses; ovulation

• OHSS: Monitoring of hospitalized patients should

include abdominal circumference, albumin,
cardiorespiratory status, electrolytes, fluid balance,
haematocrit, haemoglobin, serum creatinine, urine
output, urine specific gravity, vital signs, weight
Letrozole

An aromatase inhibitor, blocks the conversion of

testosterone and androstenedione to estradiol and
estrone, respectively
(unlike clomiphene which blocks estrogen action)
thereby reducing negative estrogenic feedback at the
pituitary and thus increasing follicle-stimulating
hormone (FSH) output

Less adverse effects on endometrial and cervical mucus

attributed to clomiphene citrate
 Other drugs

Metformin

Polycystic ovary syndrome (PCOS)

In PCOS impaired glucose resistance

Metformin

 Improves menstrual regularity

 Reduce insulin resistance
 Lower serum free testosterone
 Induce ovulation
PULSATILE GnRH THERAPY
• Pulsatile GnRH administration is indicated for women
with hypogonadotropic hypogonadism (hypothalamic
amenorrhea [HA]) who have normal pituitary function

Pulsatile GnRH therapy maintains normal feedback

mechanisms
• most cycles result in a single dominant follicle
• Low rates of multiple gestations
• Low risk of ovarian hyperstimulation syndrome (OHSS)
Gonadotrophins
Follicular stimulating hormone (FSH) & Human
chorionic gonadotrophin (HCG)
• Infertility due to hypothalamic or pituitary dysfunction
Human menopausal gonadotrophin (HMG) - FSH &
LH activity

Gonadotrophins
 Development of ovarian follicles
 Secretion of estrogen
 Ovulation and corpus luteum formation
In summary

• Different oxytocic drugs have different roles during

labour and post partum period
• Induction of labour should be a smooth process
• Use of drugs to prevention of post partum
haemorrhage is extremely important

• Evaluation of hypogonadism thoroughly and choosing

the best method of induction is important