Drugs for Uterine muscle Contractality

36
DRUGS AFFECTING UTERINE MUSCLE CONTRACTILITY

Transcript of Drugs for Uterine muscle Contractality

Page 1: Drugs for Uterine muscle Contractality

DRUGS AFFECTING UTERINE MUSCLE CONTRACTILITY

Page 2: Drugs for Uterine muscle Contractality

DRUGS PRODUCING UTERINE CONTRACTIONS( OXYTOCIC DRUGS ) 1. OXYTOCIN

2. ERGOT ALKALOIDS Ergometrine (Ergonovine)

3. PROSTAGLANDINS a) PGE2 b) PGF2α

Page 3: Drugs for Uterine muscle Contractality

OXYTOCIN

Synthesis

Is a posterior pituitary hormone secreted by the posterior pituitary gland.

Oxytocin secretion occurs by sensory stimulation from cervix ,vagina , and from suckling at breast.

Page 4: Drugs for Uterine muscle Contractality
Page 5: Drugs for Uterine muscle Contractality
Page 6: Drugs for Uterine muscle Contractality

PHARMACOKINETICS OF OXYTOCIN

Absorption ,Metabolism and Excretion Not effective orallyAdministered intravenously Also as nasal spray Not bound to plasma proteins Catabolized by liver & kidneysHalf life = 5 minutes

Page 7: Drugs for Uterine muscle Contractality

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)

Page 8: Drugs for Uterine muscle Contractality
Page 9: Drugs for Uterine muscle Contractality

Immature uterus is resistant to oxytocin.

Contract uterine smooth muscle only at term.

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

Clinically oxytocin is given only when uterine cervix is soft and dilated.

Page 10: Drugs for Uterine muscle Contractality

MECHANISM OF ACTION The interaction of endogenous or

administered oxytocin , with myometrial cell membrane receptor promotes the influx of ca ++ from extra cellular fluid and from S.R in to the cell , this increase in cytoplasmic calcium ,stimulates uterine contraction .

Page 11: Drugs for Uterine muscle Contractality

Therapeutic Uses of Oxytocin1. Induction & augmentation of labor** (slow I.V infusion)

a) Mild preeclampsia

b) Uterine inertia

c) Incomplete abortion

d) Post maturity

e) Maternal diabetes

Page 12: Drugs for Uterine muscle Contractality

Therapeutic Uses of Oxytocin (continue)

2. Post partum uterine hemorrhage (I.V drip)

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

Page 13: Drugs for Uterine muscle Contractality

Side Effects:

A. HypertensionB. Uterine ruptureC. Fetal death(ischaemia)D. Water intoxication E. Neonatal jaundice

Page 14: Drugs for Uterine muscle Contractality

CONTRAINDICATIONSa) Hypersensitivityb) Prematurity

c) Abnormal fetal position d) Evidence of fetal distress e) Cephalopelvic disproportion

Precautions a) Multiple pregnancy b) Previous c- section c) Hypertension

Page 15: Drugs for Uterine muscle Contractality

ERGOT ALKALOIDS

Ergometrine (Ergonovine)

Methylergonovine

Page 16: Drugs for Uterine muscle Contractality

Effects on the Uterus Alkaloid derivatives induce TETANIC CONTRACTION of

uterus without relaxation in between. These does not resemble the 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??

Page 17: Drugs for Uterine muscle Contractality
Page 18: Drugs for Uterine muscle Contractality

ERGOT ALKALOIDS( PHARMACOKINETICS)

Absorption ,fate and excretion

Absorbed orally from GIT(tablets)

Usually given I.M

Extensively metabolized in liver.

90% of metabolites are excreted in bile

Page 19: Drugs for Uterine muscle Contractality

CLINICAL USESPost partum hemorrhage (3rd stage of labor)**

When to give it? Preparations

(ergometrine 0.5 mg + oxytocin 5.0 I.U), I.M.

Page 20: Drugs for Uterine muscle Contractality

SIDE EFFECTS

1. Nausea, vomiting, diarrhea

2. Hypertension3. Vasoconstriction of

peripheral blood vessels ( toes & fingers)

4. Gangrene

Page 21: Drugs for Uterine muscle Contractality

* Contraindications: a) 1st and 2nd stage of labor b) vascular disease c) impaired hepatic and renal

functions

* Precautions: a) Cardiac diseases

b) Hypertension c) Multiple pregnancy

Page 22: Drugs for Uterine muscle Contractality

PROSTAGLANDINS (PGE2 & PGF2Α) MECHANISM OF ACTION: Contract uterine smooth muscle 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.

Page 23: Drugs for Uterine muscle Contractality

Therapeutic uses1. Induction of abortion (pathological)**

2. Induction of labor (fetal death in utero)

3. Postpartum hemorrhage

Page 24: Drugs for Uterine muscle Contractality

Side Effects

a) Nausea , vomitingb) Abdominal painc) Diarrhead) Bronchospasm (PGF2α)e) Flushing (PGE2)

Page 25: Drugs for Uterine muscle Contractality

Contraindications:a) Mechanical obstruction of deliveryb) Fetal distressc) Predisposition to uterine rupture

Precautions:a) Asthmab) Multiple pregnancyc) Glaucomad) Uterine rupture

Page 26: Drugs for Uterine muscle Contractality

DIFFERENCE B/W OXYTOCIN AND PROSTAGLANDINS

CharacterOxytocinProstaglandins

ContractionOnly at termContraction through out pregnancy

Cervix Does not soften the cervix

soften the cervix

Page 27: Drugs for Uterine muscle Contractality

DIFFERENCE (CONT’D)Character OxytocinProstaglandins

Duration of action

ShorterLonger

usesNot used for abortion

Used for induction and augmentation of labor and post partum hemorrhage

Used for abortion in 2nd trimester of pregnancy.

Used as vaginal suppository for induction of labor

Page 28: Drugs for Uterine muscle Contractality

DIFFERENCE B/W OXYTOCIN AND ERGOMETRINE

CharacterOxytocinErgometrineContractionsResembles normal

physiological contractions

Tetanic contraction ; doesn't resemble normal physiological contractions

Uses*To induce &augment labor.*Post partum hemorrhage

Only in P.partum hemorrhage

Onset and Duration

Rapid onset Shorter duration of action

Moderate onsetLong duration of action

Page 29: Drugs for Uterine muscle Contractality

UTERINE RELAXANTS

Page 30: Drugs for Uterine muscle Contractality

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.

Page 31: Drugs for Uterine muscle Contractality

Β- ADRENOCEPTOR AGONISTS Mechanism of action

Bind to β-adrenoceptors , activate enzyme Adenylate cyclase , increase in the level of cAMP reducing intracellular calcium level and decreasing the sensitivity of actin myosin contractile unit.

Page 32: Drugs for Uterine muscle Contractality

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

Page 33: Drugs for Uterine muscle Contractality

2.CALCIUM CHANNEL BLOCKERS E.G., NIFEDIPINE

Causes relaxation of myometrium

Markedly inhibits the amplitude of spontaneous and oxytocin-induced contractions

Page 34: Drugs for Uterine muscle Contractality

Unwanted effects

Headache, dizziness Hypotension FlushingConstipation Ankle edema Coughing Wheezing Tachycardia

Page 35: Drugs for Uterine muscle Contractality

3. PROSTAGLANDIN SYNTHETASE INHIBITORS

The depletion of prostaglandins prevents stimulation of uterus

NSAID,s e.g. Aspirin Indomethacin Ibuprofen

Page 36: Drugs for Uterine muscle Contractality

Adverse effects ulceration premature closure of ductus arterious.