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1-DRUGS

AFFECTING

UTERINE MUSCLE

CONTRACTILITY

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DRUGS PRODUCING UTERINE

CONTRACTIONS( Oxytocic Drugs )

Oxytocin

Syntocinon

Ergot Alkaloids

Ergometrine(Ergonometrine)

Prostaglandins

PGE2

PGF2

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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.

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Oxytocin

causes

contraction

of the

fundus only.

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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

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Role of oxytocin

Uterus Stimulates both the frequency and force of uterine

contractility particularly of the fundus segment of theuterus.

These contractions resemble the normal physiologicalcontractions of uterus (contractions followed by

relaxation)

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Immature uterus is resistant to oxytocin.

Causes the contraction of at-term uterinesmooth muscles only.

Sensitivity increases to 8 fold in the last 9weeks and 30 times in early labor.

Clinically oxytocin is given only when uterinecervix is soft and dilated. see next slide

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before laborthe cervix is closed

Oxytocin isnt used at this stage

At term the cervix is fully dilated

Oxytocin is used at this stage

oxytocin is not given

to induce abortionbecause the cervix isnot dilated (too early)

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Mechanism of action

Myometrial cell

Ca++

Receptor

Oxytocin

stimulates

Ca++ to

interact with

its receptor

OxytocinIntracellular fluid Extracellular fluid

N.B. Oxytocin also causes

the release of Ca++

fromthe sacroplasmic reticulum

Contraction

occurs

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Therapeutic Uses of Oxytocin

1. Induction & augmentation of labor(remember only slow IV infusion)

Mild preeclampsia (a serious condition developing inlate pregnancy, characterized by sudden hypertension,

proteinuria, and edema)

Uterine inertia (Uterine atony)

Incomplete abortion Post maturity (post-term fetus)

Maternal diabetes

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Therapeutic Uses of Oxytocin (continue)

2. Postpartum uterine hemorrhage

(IV drip)

(ergometrine is often used nowadays)

3. Impaired milk ejectionOne puff in each nostril 2-3 min before nursing

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Side effect

Maternal deathdue to

Uterine rupture(occurs at high

doses)Hypertension

Waterintoxication B/C

it is a weakantidiuretic

Fetal death dueto

Constiction ofplacental blood

vesselsIschemia

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Contraindications

Hypersensitivityto oxytocin

Prematurity

Evidence offetal distress

Abnormalfetal position horizontal

Cephalopelvicdisproportion

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Cephalopelvic disproportion

Fetuss head is

much largerthan the pelvic

outlet.

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precaution

Multiple

pregnancy

HypertensionPreviouscesareansection*

*to avoid rupture of

the uterus

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Ergotalkaloids

Ergometrine(Ergonovine)

Methylergonovine

(synthetic)

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Effects on the Uterus Alkaloid derivatives induceTETANIC

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.

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Sites ofergotcontraction

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Ergot alkaloids (pharmacokinetics)

Absorption fate and excretion

Absorbed orally from the GIT (tablets)

Usually given IM

NOT given IV because it causes severevasoconstriction

Extensively metabolized in the liver 90% of metabolites are excreted in bile

Uterus responds to Ergots more than Oxytocin

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Clinical uses

Postpartum hemorrhage (used only at the 3rd

stage of labor, when the babys head or shoulder

start to appear)

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Preparations

ergometrine0.5 mg

oxytocin 5.0

Syntometrine

I.M

If used I.V blood pressure

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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, 1-2minutes, with a short half-life.

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Side effects

Nausea, vomiting, diarrhea

Hypertensionbecause contraction of bloodvessels

Vasoconstriction of peripheral bloodvessels ( toes & fingers) which can lead

Gangrene

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Contraindications:

1. Induction of labour

2. 1st and 2nd stage of labor

3.vascular disease

4. Severe hepatic and renal impairment

5. Severe hypertension

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PROSTAGLANDINS

(PGE2 & PGF2)Therapeutic uses

1. Induction of abortion (pathological)**

(used because the uterus is sensitive to PGs in earlystages).

2. Induction of labor (fetal death in utero)

3. Postpartum hemorrhage

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Difference between PGS and Oxytocin:

PGs contract uterine smooth muscle not only atterm(as with oxytocin), but throughout pregnancy.

PGs soften the cervix; whereas oxytocin does not.

PGs have longer duration of action than oxytocin.

N.B. PGsat low doses physiologic contraction

at high doses Tetanic contraction

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Side Effects

Nausea , vomiting

Abdominal pain

Diarrhea

Bronchospasm (PGF2) Flushing (PGE2).

P.S. PGE2 causes vasodilation of the mothers vesselsthus leading to cutaneous flushing. Yet, there is

vasoconstriction of the umbilical cords vessels.

PGE2 is used as a vaginal suppository for cervicaldilation and softening.

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Contraindications:

Mechanical obstruction of delivery

Fetal distress (due to umbilical cord vessels vasocontriction)

Predisposition to uterine rupture

Precautions:

Asthma

Multiple pregnancy

Glaucoma

Uterine rupture

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Difference B/W Oxytocin and Prostaglandins

ProstaglandinsOxytocinCharacter

Contraction

through out

pregnancy

Only at termContraction

soften the cervixDoes not soften the

cervix

Cervix

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Contd

ProstaglandinsOxytocinCharacter

LongerShorterDuration of

action

Induce abortion in 2nd

trimester ofpregnancy.

Used as vaginal

suppository (PGE2)for induction of labor

Induce and augment

labour and post partumhemorrhage

uses

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Difference b/w Oxytocin and Ergometrine

ErgometrineOxytocinCharacter

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

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2-UTERINE RELAXANTS

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DRUGS PRODUCING UTERINE

RELAXATION (Tocolytic Drugs)

Action and UsesRelax the uterus and arrest threatenedabortion or delay premature labor.

1.-ADRENOCEPTOR AGONISTS**Ritodrine, i.v. drip

Selective 2 receptor agonist used specificallyas a uterine relaxant.

Tocolytic drugs: drugs that cause inhibition of premature labor.

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- adrenoceptor agonists

e.g. 2 selective agonists: ritodrine

Mechanism of action

Bind to -adrenoceptors activating the

enzyme adenylate cyclase increasing the level ofcAMP reducing intracellular calcium level.

As the pregnancy progresses there is gradual

increase of uterine2 receptors. This is an attempt

to increase 2 responsiveness to its agonist, animportant role for the stability of fetal growth.

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Side effects:

Tremor

Nausea , vomiting Flushing

Sweating

Tachycardia (high dose)

Hypotension

Hyperglycemia

Hypokalaemia

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2.CALCIUM CHANNEL BLOCKERS

Nifedipine

Causes relaxation of the myometrium

Markedly inhibits the amplitude of spontaneousand oxytocin-induced contractions.

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Unwanted effects

Headache, dizziness Hypotension

Flushing

Constipation

Ankle edema

Coughing

Wheezing

Reflex tachycardia

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3. Prostaglandin synthetase inhibitors

The depletion of prostaglandins prevents

stimulation of uterus

NSAID,s e.g. Indomethacin

Aspirin

Ibuprofen

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Adverse effects

Ulceration

Premature closure of ductus arterious.