1-DRUGS AFFECTING UTERINE MUSCLE CONTRACTILITY

1
1-DRUGS AFFECTING UTERINE MUSCLE CONTRACTILITY
2
DRUGS PRODUCING UTERINE CONTRACTIONS( Oxytocic
Drugs )
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.

4
(No Transcript)
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,
  2-3 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 is not given to induce abortion because
the cervix is not dilated (too early)
before labor ?the cervix is closed Oxytocin
isnt used at this stage
At term ? the cervix is fully dilated Oxytocin
is used at this stage
10
Mechanism of action
Oxytocin
Intracellular fluid
Extracellular fluid
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
(No Transcript)
14
(No Transcript)
15
Cephalopelvic disproportion
Fetuss head is much larger than the pelvic
outlet.
16
to avoid rupture of the uterus
17
(No Transcript)
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 babys head or shoulder
  start to appear)

22
Preparations
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 PGF2a)
• 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 (PGF2a)
• Flushing (PGE2).
• P.S. PGE2 causes vasodilation of the mothers
  vessels thus leading to cutaneous flushing. Yet,
  there is vasoconstriction of the umbilical cords
  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
Prostaglandins Oxytocin Character
Contraction through out pregnancy Only at term Contraction

soften the cervix Does not soften the cervix Cervix
31
Contd
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
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
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. ß-ADRENOCEPTOR AGONISTS
• Ritodrine, i.v. drip
• Selective ß2 receptor agonist used specifically
  as a uterine relaxant.
• Tocolytic drugs drugs that cause inhibition of
  premature labor.

35
ß- adrenoceptor agonists e.g. ß2 selective
agonists ritodrine

• Mechanism of action
• Bind to ß-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 ß2 receptors. This is an
  attempt to increase ß2 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.