1. 1-DRUGS AFFECTING UTERINE MUSCLE CONTRACTILITY

2. DRUGS PRODUCING UTERINE CONTRACTIONS( Oxytocic Drugs )
Oxytocin
Syntocinon
Ergot Alkaloids
Ergometrine (Ergonometrine)
Prostaglandins
PGE2
PGF2α

3. OXYTOCIN (SyntocinonR)
Synthesis
It is a posterior pituitary hormone secreted by the posterior pituitary gland, which is originally synthesized by the hypothalamus.
Oxytocin secretion occurs by sensory stimulation from areas of the cervix ,vagina , and by suckling at the breast.

5. Oxytocin causes contraction of the fundus only.

6. Pharmacokinetics of oxytocin
Absorption, Metabolism and Excretion
Not effective orally
Administered intravenously*
Also as nasal spray (to improve milk ejection, minutes before breast feeding)
Not bound to plasma proteins
Catabolized by liver & kidneys
Half life = 5 minutes
*S.C or IM  difficult to monitor

7. Role of oxytocin Uterus
Stimulates both the frequency and force of uterine contractility particularly of the fundus segment of the uterus.
These contractions resemble the normal physiological contractions of uterus (contractions followed by relaxation)

8. Immature uterus is resistant to oxytocin.
Causes the contraction of at-term uterine smooth muscles only.
Sensitivity increases to 8 fold in the last 9 weeks and 30 times in early labor.
Clinically oxytocin is given only when uterine cervix is soft and dilated. see next slide

9. Oxytocin isn’t used at this stage
oxytocin is not given to induce abortion because the cervix is not dilated (too early)
before labor the cervix is closed
Oxytocin isn’t used at this stage
At term  the cervix is fully dilated
Oxytocin is used at this stage

10. Oxytocin stimulates Ca++ to interact with its receptor
Mechanism of action
Intracellular fluid
Extracellular fluid
Oxytocin
Oxytocin stimulates Ca++ to interact with its receptor
Myometrial cell
Contraction occurs
Ca++ Receptor
N.B. Oxytocin also causes the release of Ca++ from the sacroplasmic reticulum

11. Therapeutic Uses of Oxytocin
Induction & augmentation of labor
(remember only slow IV infusion)
Mild preeclampsia (a serious condition developing in late pregnancy, characterized by sudden hypertension, proteinuria, and edema)
Uterine inertia (Uterine atony)
Incomplete abortion
Post maturity (post-term fetus)
Maternal diabetes

12. Therapeutic Uses of Oxytocin (continue)
Postpartum uterine hemorrhage
(IV drip)
(ergometrine is often used nowadays)
Impaired milk ejection
One puff in each nostril 2-3 min before nursing

13. Uterine rupture (occurs at high doses) Hypertension
Side effect
Maternal death due to
Uterine rupture (occurs at high doses)
Hypertension
Water intoxication B/C it is a weak antidiuretic
Fetal death due to
Constiction of placental blood vessels  Ischemia

14. Contraindications Hypersensitivity to oxytocin
Prematurity
Evidence of fetal distress
Abnormal fetal position  horizontal
Cephalopelvic disproportion

15. Cephalopelvic disproportion
Fetus’s head is much larger than the pelvic outlet.

16. *to avoid rupture of the uterus
precaution
Multiple pregnancy
Hypertension
Previous cesarean section*
*to avoid rupture of the uterus

17. Ergometrine (Ergonovine)
Ergot alkaloids
Ergometrine (Ergonovine)
Methylergonovine
(synthetic)

18. Effects on the Uterus
Alkaloid derivatives induce TETANIC CONTRACTION of uterus without relaxation in between (unlike the normal physiologic contractions)
It causes contractions of the uterus as a whole i.e. fundus and cervix (tends to compress rather than actually expelling the fetus)
Not used anymore for labor augmentation.

19. Sites of ergot contraction

20. Ergot alkaloids (pharmacokinetics)
Absorption fate and excretion
Absorbed orally from the GIT (tablets)
Usually given IM
NOT given IV  because it causes severe vasoconstriction
Extensively metabolized in the liver
90% of metabolites are excreted in bile
Uterus responds to Ergots more than Oxytocin

21. Clinical uses
Postpartum hemorrhage (used only at the 3rd stage of labor, when the baby’s head or shoulder start to appear)

22. Preparations If used I.V ↑↑↑↑ blood pressure ergometrine 0.5 mg
oxytocin 5.0
Syntometrine
I.M
If used I.V ↑↑↑↑ blood pressure

23. Why should we use this combination ?
Ergots have slow onset of action (7min) but have a long half-life.
Yet, oxytocin has a fast onset of action, 1-2 minutes, with a short half-life.

24. Side effects Nausea, vomiting, diarrhea
Hypertension because  contraction of blood vessels
Vasoconstriction of peripheral blood vessels ( toes & fingers) which can lead 
Gangrene

25. Contraindications: Induction of labour 1st and 2nd stage of labor
vascular disease
Severe hepatic and renal impairment
Severe hypertension

26. PROSTAGLANDINS (PGE2 & PGF2α) Therapeutic uses
1. Induction of abortion (pathological)**
(used because the uterus is sensitive to PGs in early stages).
2. Induction of labor (fetal death in utero)
3. Postpartum hemorrhage

27. 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.
N.B. PGs at low doses  physiologic contraction
at high doses  Tetanic contraction

28. Side Effects Nausea , vomiting Abdominal pain Diarrhea
Bronchospasm (PGF2α)
Flushing (PGE2).
P.S. PGE2 causes vasodilation of the mother’s vessels thus leading to cutaneous flushing. Yet, there is vasoconstriction of the umbilical cord’s vessels.
PGE2 is used as a vaginal suppository for cervical dilation and softening.

29. Contraindications:
Mechanical obstruction of delivery
Fetal distress (due to umbilical cord vessels’ vasocontriction)
Predisposition to uterine rupture
Precautions:
Asthma
Multiple pregnancy
Glaucoma
Uterine rupture

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

31. Cont’d Prostaglandins Oxytocin Character Longer Shorter
Duration of action
Induce abortion in 2nd trimester of pregnancy.
Used as vaginal suppository (PGE2) for induction of labor
Induce and augment labour and post partum hemorrhage
uses

32. Difference b/w Oxytocin and Ergometrine
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

33. 2-UTERINE RELAXANTS

34. DRUGS PRODUCING UTERINE RELAXATION (Tocolytic Drugs)
Action and Uses
Relax the uterus and arrest threatened abortion or delay premature labor.
1. β-ADRENOCEPTOR AGONISTS**
Ritodrine, i.v. drip
Selective β2 receptor agonist used specifically as a uterine relaxant.
Tocolytic drugs: drugs that cause inhibition of premature labor.

35. β- adrenoceptor agonists e.g. β2 selective agonists: ritodrine
Mechanism of action
Bind to β-adrenoceptors activating the enzyme adenylate cyclase increasing the level of cAMP reducing intracellular calcium level.
As the pregnancy progresses there is gradual increase of uterine β2 receptors. This is an attempt to increase β2 responsiveness to its agonist, an important role for the stability of fetal growth.

36. Side effects:
Tremor
Nausea , vomiting
Flushing
Sweating
Tachycardia (high dose)
Hypotension
Hyperglycemia
Hypokalaemia

37. 2.CALCIUM CHANNEL BLOCKERS Nifedipine
Causes relaxation of the myometrium
Markedly inhibits the amplitude of spontaneous and oxytocin-induced contractions.

38. Unwanted effects
Headache, dizziness
Hypotension
Flushing
Constipation
Ankle edema
Coughing
Wheezing
Reflex tachycardia

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

40. Adverse effects
Ulceration
Premature closure of ductus arterious.