Drugs acting on uterus and with their use, adr, and contraindication,

1. DRUGS AFFECTING UTERINE MOTILITY

3. Oxytocics drugs:
(OXYS meaning quick, TOKOS meaning childbirth)
• Drugs stimulate uterine smooth muscles during pregnancy,
produce contraction that promotes rapid labor.
Tocolytics:
• Drugs relax uterine smooth muscles

4. UTERINE STIMULANTS (Oxytocics)
• These drugs increase uterine motility, especially at term.
• 1. Posterior pituitary hormone : Oxytocin, Desamino oxytocin.
• 2. Ergot alkaloids : Ergometrine (Ergonovine),
Methylergometrine.
• 3. Prostaglandins: PGE1 (Misoprostol)
PGE2(Dinoprostone),
PGF2α(carboprost),
15-methyl PGF2α.
• 4. Miscellaneous : Ethacridine, Quinine.

5. OXYTOCIN
Synthesis
• Synthesize with in cell bodies in Supraoptic and Paraventricular nuclei of
hypothalamus.
• Stored in nerve ending within the pituitary gland.
• It is secret by the posterior pituitary gland.
• Oxytocin secretion occurs by sensory stimulation from cervix ,vagina ,
and from suckling at breast.
• Release of oxytocin inhibited by relaxin and alcohol

7. Pharmacokinetics of oxytocin
 Destroyed in GIT by proteolytic enzyme ,Not effective orally
 Given IV, IM
 Nasal spray ( in cases of impaired milk ejection)
 Not bound to plasma proteins
• Metabolized in liver and kidney
• Plasma t½ 6–12 min
• Destroyed by oxytocinase (pregnant ut & placenta)

8. Pharmacodynamics of oxytocin
• Mechanism of action
Acts through GPCR  activation of phospholipase C  production of IP3 
mobilization of calcium from its stores (SR) .
Also, activates voltage sensitive calcium channels causing an increase in
cytoplasmic calcium level that stimulates uterine contraction .

9. Pharmacological actions of oxytocin
Uterus
1. Small doses stimulates both the frequency and force of uterine
contractility particularly of the fundus segment of the uterus.
2. These contractions resemble the normal physiological contractions
of uterus (contractions followed by relaxation)

10. 3. Large doses causes Inc. frequency and incom. Relaxation.
High dose – sustained contraction without relaxation result less blood flow
to fetus, fetal distress and death.
4. Immature uterus is resistant to oxytocin.
5. Contract uterine smooth muscle only at term .
6. Sensitivity increases to 8 fold in last 9 weeks and 30 times in early labor.
7. Clinically oxytocin is given only when uterine cervix is soft and dilated.
8. Oxytocin increases PG synthesis and release by the endometrium which may
contribute to the contractile response.

11. Mammary glands- Oxytocin contracts the myoepithelium of
mammary alveoli produces milk ejection.
Suckling of nipple by infants
Stimulate the mechanoreceptor of nipple
Hypothalamus
PP
Inc. release of Oxytocin
Milk ejection

12. CVS
• Normal doses used in obstetrics have no effect on BP,
• Higher doses cause vasodilatation → brief fall in BP, reflex
tachycardia and flushing.

13. Kidney
• At high doses produced ADH-like action—urine output is decreased
• Pulmonary edema can occur if large amounts of i.v. fluids and
oxytocin are infused together.

14. • CLINICAL USES OF OXYTOCIN

15. 1. Induction of labour Labour
• Needs to be induced in case of
• Toxaemia of pregnancy,
• Diabetic mother,
• Erythroblastosis,
• Ruptured membranes
• Placental insufficiency.
• For this purpose oxytocin is given by slow i.v. infusion: 5 IU is diluted
in 500 ml of glucose or saline solution.

16. • Before starting infusion, confirm that:
• presentation is correct
• foetal lungs are adequately mature
• there is no cephalopelvic disproportion
• no placenta previa
• no foetal distress and no uterine scar (due to previous surgery).
• Uterine contractions are then closely monitored:
• The drug is discontinued when they are strong enough.
• Usually a total of 2–4 IU is needed.

17. Uterine inertia
• When uterine contractions are feeble and labour is not progressing —
oxytocin can be infused i.v. to augment contractions.
• Oxytocin is the drug of choice and is preferred over ergometrine/PGs for
the above two purposes:
• (a) Because of its short t½ and slow i.v. infusion,
• (b) Low concentrations allow normal relaxation inbetween contractions
• (c) Lower segment is not contracted

18. Postpartum haemorrhage
• Oxytocin 5 IU may be injected i.m. or by i.v. infusion for an immediate
response, especially in hypertensive women in whom ergometrine is
contraindicated.
• It acts by forcefully contracting the uterine muscle which compresses
the blood vessels passing through its mesh work to arrest haemorrhage
from the inner surface exposed by placental separation.

19. Impaired milk ejection
• It may occur due to inefficient milk ejection reflex.
• intranasal spray may be given few minutes before suckling.
• It does not increase milk production.

20. Adverse effects
• causing maternal and foetal soft tissue injury,
• rupture of uterus,
• foetal asphyxia and death.
• Water intoxication: This occurs due to ADH like action of large doses
given along with i.v. fluids, especially in toxaemia of pregnancy and
renal insufficiency.

21. Desamino-oxytocin
• it has been developed as a buccal formulation; action is similar to
injected oxytocin, but less consistent.
• its indications are: induction of labour: 50 iu buccal tablet repeated
every 30 min, max 10 tabs.
• uterine inertia: 25 iu every 30 min.
• breast engorgement 25–50 iu just before breast feeding.

22. Carbetocin
• It is a long-acting analogue of oxytocin that

23. ERGOT ALKALOIDS
• Natural
Ergometrine (Ergonovine)
• Synthetic
Methyl ergometrine( Methyl ergonovine)

24. Effects on the Uterus
• Alkaloid derivatives induce TETANIC CONTRACTION of uterus without
relaxation in between(not like 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??

25. Ergot alkaloids( pharmacokinetics)
• Absorbed orally from GIT (tablets)
• Usually given I.M
• Metabolized in liver and
• Excreted in urine.
• Plasma t½ is 1–2 hours.
• Effects of a single dose last 3–4 hours.

26. Clinical uses
1. Post partum hemorrhage
1. involution of the uterus

27. Adverse effects
• Nausea, vomiting and rise in BP occur occasionally.
• They can decrease milk Secretion if higher doses
• avoided in—
• (i) patients with vascular disease, hypertension,
• (ii) presence of sepsis—may cause gangrene.
• (iii) liver and kidney disease.

28. PROSTAGLANDINS
• Dinoprostone ( synthetic PGE2)
• Given intravaginally as a gel or tablet.
• Some absorption directly through cervix & lymphatics into
maternal circulation
• Half-life 2.5- 5 min

29. Effects of dinoprostone
1. Stimulation of G protein coupled PGE2 receptors  contraction of
myometrium
2. Ripening of cervix due to direct effect on cervical collagenase resulting
in softening
3. Has natriuretic effect, Superior to oxytocin for women with pre-
eclampsia , as no fluid retention

30. Therapeutic uses of dinoprostone
1. Facilitation of labor at term
2. Induction of labor
3. Medical Abortifacient
• Used as vaginal suppositories alone or with oral misoprostol

31. Carboprost: 15 methyl PGF2α Analog
• Therapeutic uses
1. Induction of labor
2. To control PPH I.M.
3. For 2nd trimester abortion ,

32. Misoprostol ( synthetic PGE1)
• Given intravaginally as a gel or tablets

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

34. Difference (cont’d)
Prostaglandins
Oxytocin
Character
Longer
Shorter
Duration of
action
Induce abortion in 2nd
trimester of
pregnancy.
Used as vaginal
suppository for
induction of labor
Induce and augment
labor and post partum
hemorrhage
uses

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

36. TOCOLYTIC DRUGS
1. β2 selective stimulants
• Ritodrine, salbutamol,terbutaline,isoxsuprine.
2. Calcium channel blockers
Nifedipine
3 .Oxytocic Antagonist
• Atosiban
4. Magnesium sulphate
5. Other dugs
• General anaesthetics,nitrates
• COX inhibitors ( indomethacin)

37. TOCOLYTIC DRUGS
USES
1. To arrest premature labor .
2. Delay delivery for 48 hrs , this time can be used to administer
glucocorticoids (Injection betamethasone) to mother for
maturation of the fetal lung.

38. Ritodrine (β- adrenoceptor agonist)
• Mechanism of action
Bind to β-adrenoceptors , activate Adenylate cyclase ,
increase in the level of cAMP reducing intracellular
calcium level.

39. ( ATOSIBAN ) OXYTOCIC ANTAGONIST
• Antagonizes the effects of oxytocin at its receptors
• Used as tocolytic in premature labor
• Given by IV infusion for 48 hrs

40. MAGNESIUM SULPHATE
• Infused iv ,for prevention and treatment of seizures in
preeclampsia and eclampsia.
• It directly uncouples excitation –contraction in
myometrial cells.

41. CALCIUM CHANNEL BLOCKERS (Nifedipine)
• Causes relaxation of myometrium
• Markedly inhibits the amplitude of spontaneous and oxytocin-
induced contractions

42. THANK YOU