Pharmacology of drugs acting on uterus

1. Drugs
acting on
Uterus.
Patki.
IMS

2. After attending this session,
student will be able to
• Define oxytocic and give at least two examples.
• Discuss the pharmacological actions and clinical uses of
Oxytocin.
• Differentiate pharmacological activities of oxytocin,
Ergometrine and Prostaglandins.
• Name indications of Ergometrine and Prostaglandins.
• Define Tocolytic agents and describe their clinical status.
• Define abortifacients with two examples.
• Enumerate drug therapy of PPH.

3. Drugs & Uterus-Introduction
Primarily effects
• Endometrium -Estrogen, progesterone
and their antagonists
• Myometrium – sympathetic &
parasympathetic
• Pharmacological response varies at
different stages of menstrual cycle &
during pregnancy

5. Uterine Stimulants
• Oxytocics or Ecbolics
• Oxytocin
• Ergmetrine (ergot alkaloid)
• Prostaglandins (PGE2 PGF2α , Misoprostol,
Dinoprostone, carboprost)
• Ethacridine
• induce/augment labor, minimize post
partum hemorrhage, induce abortion

6. Oxytocin
• Polypeptide secreted in hypothalamic
nuclei in Post. Pituitary
• Released by: haemorrhage, dilatation
of cervix & uterus, coitus, parturition,
suckling ( letdown or milk ejection
reflex)

7. Oxytocin-dynamics
• Acts through G-protein coupled receptor &
phosphoinositide-calcium second
messenger system & releases calcium
• Stimulates release of utero-dynamic PG &
LT
• Small dose – increases force & frequency
• Large dose – sustained contraction

8. Milk letdown reflex
• Oxytocin –
contraction of
myoepithilial cells-
milk ejection

9. Pharmacological actions
• Uterus: actions depend on – dose,
species, stage of estrous cycle, pregnancy
( gestational stage) –& inhibited by
progesterone
• Estrogen priming –sensitivity to oxytocin
increases in the 3rd
trimester of pregnancy
as estrogen is secreted.

10. • Mammary Gland: milk ejection facilitated
• CVS : bolus injection – vasodilator –
hypotension
• Kidneys: inconsequential anti-diuretic
activity
ADRs-Water retention – water intoxication
– nausea, vomiting, anorexia, weight gain,
lethargy. Uterine rupture, fetal distress,
maternal injury – always slow infusion

11. Pharmacokinetics
• Not absorbed orally , admin by i.m,
i.v, intranasal routes, sublingual.
• Inactivated in the liver, kidney &
circulating placental oxytocinase
• Short half life – 10-15 mins

12. Therapeutic uses
• Induction & augmentation of term labor:
• Hypotonic uterine dysfunction:
• Post partum hemorrhage: i.m after
delivery of placenta
• Missed abortion: to expel uterine contents
• Oxytocin challenge test – to assess
placental insufficiency
• to promote milk ejection

13. Induction & augmentation
• Oxytocin
• Given i.v infusion 5 units in 500ml of 5%
dextrose solution- to start with 0.1 – 0.2
ml / min; gradually increase the infusion
rate. Monitor – mother & fetus
continuously – mandatory.

14. Therapeutic Uses of Oxytocin
1. Induction & augmentation of labor**
(slow I.V infusion)
a) Mild preeclampsia
b) Uterine inertia
c) Incomplete abortion
d) Post maturity
e) Maternal diabetes

15. Therapeutic Uses of Oxytocin (continue)
2. Post partum uterine hemorrhage
(I.V drip)
3. Impaired milk ejection
One puff in each nostril 2-3 min before nursing

16. Side Effects:
a) Hypertension
b) Uterine rupture
c) Fetal death(ischaemia)
d) Water intoxication
e) Neonatal jaundice

17. Contraindications
a) Hypersensitivity
b) Prematurity
c) Abnormal fetal position
d) Evidence of fetal distress
e) Cephalopelvic disproportion
Precautions
a) Multiple pregnancy
b) Previous c- section
c) Hypertension

18. Ergot Alkaloids
• Ergometrine (Ergonovine)
• Methylergonovine

19. Effects on the Uterus
• Alkaloid derivatives induce TETANIC
CONTRACTION of uterus without
relaxation in between. These does not
resemble the normal physiological
contractions
• It causes contractions of uterus as a whole
i.e. fundus and cervix(tend to compress
rather than to expel the fetus)
Difference between oxytocin & ergots??

20. Ergot alkaloids
• Rapidly & completely absorbed
• Ecbolic effect seen within 10-15 min on
oral, 3-5 min on s.c., 1-2 min on i.v.
• Metabolized – liver & excreted – kidney
• ADR – nausea, vomiting, miosis, anginal
pain.
• ADRs seen mainly due to vasoconstriction
– thrombosis, gangrene.
.

21. Therapeutic uses-ergometrine
• PPH : for prophylaxis & treatment
• Uterine involution
Route of Admin.
PO & i.m.

22. Clinical uses
• Post partum hemorrhage (3rd
stage of labor)**
When to give it?
Preparations
Syntometrine(ergometrine 0.5 mg
+ oxytocin 5.0 I.U), I.M.

23. Side effects
a) Nausea, vomiting, diarrhea
b) Hypertension
b) Vasoconstriction of peripheral blood
vessels
( toes & fingers)
c) Gangrene

24. * Contraindications:
a) 1st
and 2nd
stage of labor
b) vascular disease
c) impaired hepatic and renal functions
* Precautions:
a) Cardiac diseases
b) Hypertension
c) Multiple pregnancy

25. Prostaglandins
• uterine smooth muscle stimulant, cervical
primers
• PGE2 (Dinoprostone)
• PGE1(Misoprostol) -
• Dinoprost
• Carboprost – longer duration of action
ADR – on repeated uses – nausea, vomiting, headache, diarrhea, fever,
vasodilatation

26. PROSTAGLANDINS
(PGE2 & PGF2α)
• MECHANISM OF ACTION:
• Contract uterine smooth muscle
Difference between PGS and Oxytocin:
• PGS contract uterine smooth muscle not only at
term(as with oxytocin), but throughout pregnancy.
• PGS soften the cervix; whereas oxytocin does not.
• PGS have longer duration of action than oxytocin.

27. • Therapeutic uses
1. Induction of abortion (pathological)**
2. Induction of labor (fetal death in utero)
3. Postpartum hemorrhage

28. • Side Effects
a) Nausea , vomiting
b) Abdominal pain
c) Diarrhea
d) Bronchospasm (PGF2α)
e) Flushing (PGE2)

29. • Contraindications:
a) Mechanical obstruction of delivery
b) Fetal distress
c) Predisposition to uterine rupture
• Precautions:
a) Asthma
b) Multiple pregnancy
c) Glaucoma
d) Uterine rupture

30. Difference B/w Oxytocin and Prostaglandins
Character Oxytocin Prostaglandins
Contraction Only at term Contraction
through out
pregnancy
Cervix Does not soften the
cervix
soften the cervix

31. Difference (cont’d)
Character Oxytocin Prostaglandins
Duration of
action
Shorter Longer
uses Not used for abortion
Used for induction and
augmentation of labor
and post partum
hemorrhage
Used for abortion in
2nd
trimester of
pregnancy.
Used as vaginal
suppository for
induction of labor

32. Difference b/w Oxytocin and Ergometrine
Character Oxytocin Ergometrine
Contractions Resembles normal
physiological
contractions
Tetanic contraction ;
doesn't resemble
normal physiological
contractions
Uses *To induce &augment
labor.
*Post partum
hemorrhage
Only in P.partum
hemorrhage
Onset and
Duration
Rapid onset
Shorter duration of
action
Moderate onset
Long duration of
action

33. Therapeutic uses
• Therapeutic abortion: not in 1st
trimester,
but widely used in the 2nd
.
• Cervical priming:
• PPH:
• With oxytocin, augmentation of labor.

34. Tocolytics
• Drugs used to arrest delivery -
premature labor
Types of Tocolytics
• Beta-2 receptor agonist: ritodrine,
salbutamol, terbutaline
• Calcium channel blockers: nifedipine
• Magnesium sulphate
• Oxytocin receptor antagonist: atosiban

36. Tocolytics
• Atosiban: inhibits uncomplicated preterm
labor ( 24-33 wks), dose 6-7mg for 1 min.
followed by i.v inf, for 4-8 hrs. ADR –
nausea, vomiting, headache,
hyperglycemia, irritation at site of injection.
• Ritodrine: 50 mcg/min i.v. infuson, until
uterine contraction controlled.
• Mag sulf.; 4-6 g i.v. followed by 2-4 g hrly
by inf., for 24hrs.
• Nifedipine: sublingually, repeat after
20mts.

37. Tocolytics ……CONTD
• Indication for tocolytic: arrest preterm
labor
• Contraindication: > 37 weeks gestation,
fetus >2500 g, fetal distress, cervix
dilatation >4cm, ruptured membrane,
toxemia, PPH

38. 2.CALCIUM CHANNEL BLOCKERS
e.g., Nifedipine
• Causes relaxation of myometrium
• Markedly inhibits the amplitude of
spontaneous and oxytocin-induced
contractions

39. • Unwanted effects
• Headache, dizziness
• Hypotension
• Flushing
• Constipation
• Ankle edema
• Coughing
• Wheezing
• Tachycardia

40. 3. Prostaglandin synthetase inhibitors
• The depletion of prostaglandins prevents
stimulation of uterus
NSAID,
s e.g. Aspirin
Indomethacin
Ibuprofen

41. Adverse effects
ulceration
• premature closure of ductus arterious.

43. Post partum Haemorrhage
• Is the loss > 500 ml of blood following
vaginal delivery, or 1000 ml of blood
following cesarean section.
• Causes: tone, trauma, tissue, thrombin
• Management: misoprostol / oxytocin

44. Preterm Labor
• Defined as labor that begins prior to 37
weeks gestation
• Signs: cramps, > 5 in 1 hr, bright red blood
from vagina; pain during urination; sudden
gush of clear; watery fluid from vagina;
low, dull backache; intense pelvic
pressure.

45. Management
• Hydration (Oral or IV)
• Bed rest, usually left side lying
• Pharmacotherapy to stop labor
Magnesium sulfate, atosiban, ritodrine
• Medication to help prevent infection
• Evaluation of baby

46. Abortifacients
• Mifepristone
• Methotrexate
• Ethacridine lactate
• Hypertonic saline
• Misoprostol
• Dinoprostone- synthetic analogue of
PGE2
• Carboprost- PGF2α

47. Differentiate Oxytocics and
Tocolytics.
• Oxytocics- Contraction of
• Tocolytics
• Oxytocics are used in ------
• Tocolytics are used in -----------

48. Following are the examples of
Oxytocics
• 1. Oxytocin
• 2…………..
• 3. ------------.
• Examples of Tocolytics are
• 1. -----------
• 2. ------------