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1-DRUGS 1-DRUGS AFFECTING AFFECTING
UTERINE MUSCLE UTERINE MUSCLE CONTRACTILITYCONTRACTILITY
DRUGS PRODUCING UTERINEDRUGS PRODUCING UTERINE CONTRACTIONS( Oxytocic Drugs ) CONTRACTIONS( Oxytocic Drugs )
OXYTOCINOXYTOCIN((SyntocinonSyntocinonRR))
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.
Oxytocin causes
contraction of the fundus
only.
Pharmacokinetics of oxytocinPharmacokinetics of oxytocin
Absorption, Metabolism and Excretion
Not effective orallyAdministered intravenously* Also as nasal spray (to improve milk
ejection, 2-3 minutes before breast feeding)
Not bound to plasma proteins Catabolized by liver & kidneysHalf life = 5 minutes*S.C or IM difficult to
monitor
Role of oxytocinRole 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)
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
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
oxytocin is not given to induce abortion because the cervix is not dilated (too early)
Mechanism of actionMechanism of action
Myometrial cell
Ca++ Receptor
Oxytocin stimulates
Ca++ to interact with its receptor
Oxytocin Intracellular fluid
Extracellular fluid
N.B. Oxytocin also causes the release of Ca++ from the sacroplasmic reticulum
Contraction occurs
Therapeutic Uses of Oxytocin1. 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
Therapeutic Uses of Oxytocin (continue)
2. Postpartum uterine hemorrhage (IV drip) (ergometrine is often used
nowadays)
3. Impaired milk ejection One puff in each nostril 2-3 min before
nursing
Cephalopelvic disproportionCephalopelvic disproportionFetus’s head is much
larger than the pelvic
outlet.
*to avoid rupture of the
uterus
Effects on the UterusAlkaloid 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.
Sites of ergot
contraction
Ergot alkaloids (pharmacokinetics)Ergot alkaloids (pharmacokinetics)
Absorption fate and excretion
Absorbed orally from the GIT (tablets) Usually given IMNOT given IV because it causes
severe vasoconstriction Extensively metabolized in the liver 90% of metabolites are excreted in bileUterus responds to Ergots more than
Oxytocin
Clinical usesClinical uses
Postpartum hemorrhage (used only at the 3rd stage of labor, when the baby’s head or shoulder start to appear)
PreparationsPreparations
If used I.V ↑↑↑↑ blood pressure
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.
Side effectsSide effects
Nausea, vomiting, diarrheaHypertension because contraction
of blood vesselsVasoconstriction of peripheral blood
vessels ( toes & fingers) which can lead
Gangrene
Contraindications:1.Induction of labour2.1st and 2nd stage of labor3.vascular disease4.Severe hepatic and renal impairment5.Severe hypertension
PROSTAGLANDINS (PGE2 & PGF2α)
Therapeutic uses1. 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
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
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.
Contraindications:Mechanical obstruction of deliveryFetal distress (due to umbilical cord vessels’
vasocontriction)
Predisposition to uterine rupture
Precautions:AsthmaMultiple pregnancyGlaucomaUterine rupture
Difference B/W Oxytocin and ProstaglandinsDifference B/W Oxytocin and Prostaglandins
CharacterOxytocinProstaglandins
ContractionOnly at termContraction through out pregnancy
Cervix Does not soften the cervix
soften the cervix
Cont’dCont’d
Character OxytocinProstaglandins
Duration of action
ShorterLonger
usesInduce and augment labour and post partum hemorrhage
Induce abortion in 2nd trimester of pregnancy.
Used as vaginal suppository (PGE2) for induction of labor
Difference b/w Oxytocin and ErgometrineDifference b/w Oxytocin and Ergometrine
CharacterOxytocinErgometrine
ContractionsResembles normal physiological contractions
Tetanic contraction ; doesn't resemble normal physiological contractions
UsesTo induce &augment labor.
*Post partum hemorrhage
Only in postpartum hemorrhage
Onset and Duration
Rapid onset
Shorter duration of action
Moderate onset
Long duration of action
2-UTERINE RELAXANTS
DRUGS PRODUCING UTERINE DRUGS PRODUCING UTERINE RELAXATION (Tocolytic Drugs)RELAXATION (Tocolytic Drugs)
Action and Uses Relax the uterus and arrest threatened abortion or delay premature labor.
1. β-ADRENOCEPTOR AGONISTS**
Ritodrine, i.v. dripSelective β2 receptor agonist used
specifically as a uterine relaxant.
Tocolytic drugs: drugs that cause inhibition of premature labor.
ββ- adrenoceptor agonists - adrenoceptor agonists e.g. e.g. ββ2 2 selective agonists: ritodrineselective 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 β β22 receptors. This is an attempt to increase ββ2 2 responsiveness to its agonist, an important role for the stability of fetal growth.
Side effects: Tremor Nausea , vomiting Flushing Sweating Tachycardia (high dose) Hypotension Hyperglycemia Hypokalaemia
2.CALCIUM CHANNEL BLOCKERS 2.CALCIUM CHANNEL BLOCKERS Nifedipine Nifedipine
Causes relaxation of the myometrium
Markedly inhibits the amplitude of spontaneous and oxytocin-induced contractions.
Unwanted effects
Headache, dizziness Hypotension FlushingConstipation Ankle edema Coughing Wheezing Reflex tachycardia
3. Prostaglandin synthetase inhibitors 3. Prostaglandin synthetase inhibitors
The depletion of prostaglandins prevents stimulation of uterus
NSAID,s e.g. Indomethacin Aspirin
Ibuprofen
Adverse effectsUlcerationPremature closure of ductus
arterious.
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