oxytocin methergin prostaglandin spinal anaesthesia.ppt

Drugs acting on uterus used during pregnancy

1. OXYTOCIN , METHERGIN and
PROSTAGLANDINS
MODERATOR – DR NANISH SHARMA
PRESENTED BY - DR ABHISHEK THAKUR

2. OXYTOCIN Syntocinon
•Group – Oxytocic
•History - Discovered by Henry Dale and synthesized by Vincent Du Vigneaud
in 1953. It was the first polypeptide hormone to be synthesised,
•Chemical Structure - A naturally occuring polypeptide from the posterior lobe
of the pituitary gland
•Formulation and Administration - Colourless clear solution
•Loses its effectiveness unless preserved at the correct temperature (between
2°C and 8°C)
•IV- Oxytocin (5 IU/ml and 10 U/ml)
•Oral - Des amino oxytocin, 50-100 times more effective than oxytocin.
(Tablets 50 IU)
•Nasal solution 40 IU/ml

3. Mechanism of Action
Oxytocin binds to a G-
protein on the surface of the
uterine myocyte, resulting in
the generation of 1,2
Diacylglecerol and Inositol
1,4,5-Tri phosphate (IP3)
via the action of
Phospholipase C.
IP3 triggers Ca" release
from Sarcoplasmic
reticulum.
Oxytocin also increases
Ca² intracellular entry via L-
type Ca" channels and
decreases Ca" efflux.

4. Pharmacokinetics
•Onset :
•IV 30 secs ,
•IM-two and a half min
•Half-life: 8 min (IV),
• 2hrs (intra nasal)
•Protein binding: 20-50%
•Duration of Action: 20 min
•Metabolism: rapidiy removed from the plasma by
hydrolysis in the liver and kidney (by the action of
oxytocinase)

5. Pharmacodynamics
•CVS - Bolus IV administration - Decrease in the blood pressure that occurs
within 30 seconds and lasts up to 10 minutes (Bolus dose should not be
given)
•Reflex tachycardia and an increase in the cardiac output by up to 1.5 l/min
•ECG changes, prolonged QT interval and T-wave flattening, reflect poor
coronary artery filling
•GIT-No effect on the lower oesophageal sphincter pressure during
pregnancy .
•Antidiuretic effect (exerted by a direct action on the renal tubules) which
may, in high doses lead to water Intoxication
•Causes milk ejection by causing contraction of modified smooth muscle
within the mammary glands

6. Uses and Dosage
To accelerate abortion -inevitable or missed and to expedite expulsion of
hydatidiform mole
Adjunct to induction of abortion along with other abortifacient agents (PGE1
or PGE2)
To induce labour -To ripen cervix prior to induction Labour
Augmentation of labour Uterine inertia
In active management of third stage of labour
Puerperium- To minimize blood loss and to control postpartum haemorrhage
To stop bleeding following evacuation of the uterus

7. •Augmentation of labour -
•10 IU in 500 ml of Sodium Chloride 0.9% (20 milli unit / ml) ;
•Started @ 3ml/hr = 1 milli-unit Per minute
• -increased every 30 min by 1-2 milli units/min upto maximum 20-40 milli
units / min
•Control of postpartum bleeding- immediately after umbilical cord
clamping at caesarean delivery / placental delivery at vaginal delivery.
•Infusion prepared with 10 U of oxytocin diluted in 500ml of normal saline or
ringer lactate. Rate of infusion is adjusted according to uterine tone; Max 54
Units/hr
•Minimizing risk of PPH by-reducing blood loss at delivery
•For women without risk factors for PPH delivering via vaginal delivery,
oxytocin (10 IU IM) is the agent of choice for prophylaxis in the third stage of
labor

8. •For women delivering by caesarean section, oxytocin (3-5
IU by slow intravenous injection over 3-5 minutes) should
be used to encourage contraction of the uterus and to
decrease blood loss.
•When uterine atony is perceived, then oxytocin 5 IU by
slow Intravenous injection (may have to repeat dose)
followed by oxytocin infusion (40 IU in 500 ml isotonic
crystalloids at 125 ml/hour)

9. •Adverse Effects
•MATERNAL
•Uterine hyperstimulation (overactivity) - excessive duration of uterine
contraction (hypertonia) or increased frequency ( >6 in 10 min
time’;polysystole) [Normal < 60 sec happening 2-3 minutes apart]
•Uterine rupture - may be seen with violent uterine contractions
•High risk cases are grand multipara, malpresentation, contracted pelvis, prior
uterine scar (hysterotomy) and excessive oxytocin use.
•Water intoxication is due to its antidiuretic function when used in high dose
(30-40 mIU/min). Water intoxications manifested by hyponatremia, confusion,
coma, convulsions, congestive cardiac failure and death.
• It is prevented by strict, fluid intake and output record, use of salt solution and
by avoiding high dose oxytocin for a longtime.
•

10. •Hypotension: Bolus IV injections or large doses of oxytocin cause
hypotension by decreasing both systolic and diastolic blood pressure via
direct relaxant action on vascular smooth muscles. (More in hypovolemic
patients)
•Antidiuresis: Antidiuretic effect is observed when oxytocin infusion rate is
high (40-50mIU/min) and continued for a long time.
FOETAL
•Foetal distress
•Foetal hypoxia or even Foetal death may occur due to uterine
hyperstimulation
•Uterine hypertonia or polysystole causes reduced placental blood flow

11. •Indications of stopping the infusion
•Abnormal uterine contractions – hypertonia and polytsystole
•Evidence of Fetal distress
•Should not be infused through the same intravenous line as
blood and plasma, as rapid inactivation of the polypeptide by
plasma oxytocinase occurs
•Infusions of oxytocin alter the action of co-administered SCH -
increased SCH dose requirements

12. METHYLERGOMETRINE
•
(METHERGIN)
•Group - Oxytocic ,
•Ergot alkaloid
•History : used by mid-wives for quickening childbirth. The
isolation of pharmacologically useful alkaloids started in 1906
with the discovery of Ergotoxine. Stoll isolated Ergotamine
•Chemical Structure : d-lysergic acid 1-butanolamide
• Semi synthetic analogue of ergometrine

13. •Formulation and Administration
•Colourless clear solution, Rapidly deteriorates with exposure to light, heat,
and humidity
•Ampoule of 1 ml containing 200 mcg for Intramuscular use
•Tablet-0.2 mg-Oral
•Methergin should not be given intravenously except in cases of severe,
life-threatening haemorrhage. In such cases, the drug is to be given slowly
and monitor the maternal blood pressure
Mechanism of Action : Ergometrine acts directly on the myometrium. It
excites uterine contractions which come so frequently that the uterus
passes into a state of spasm without any relaxation in between

14. •Pharmacokinetics-
•Onset :
•IV-1 min 30 sec ,
•IM-7 min ,
•Oral- 10 min
•Duration of action: PO-3 h, IM-3 hr, IV- 45 min (although
rhythmic contractions may persist for up to 3 h)
•Primarily hepatic biotransformation and renal excretion

15. Pharmacodynamics:
•Stimulates contraction of uterine and vascular
smooth muscles Produces vasoconstriction primarily of
capacitance vessels, increase in CVP and elevated blood
pressure .
•Ergots interact with adrenergic, dopaminergic, and
tryptaminergic receptors. Stimulation of a- adrenergic and
serotonin receptors leads to vasoconstriction.
•Central nervous system (CNS) effects are mediated by
interaction with serotonin and dopamine receptors.

16. •Uses and Dosage–
•Control of uterine haemorrhage in the second stage of labour following delivery
of the anterior shoulder - 200 mcg IM/IV Postpartum
•Hemorrhage : 0.2 mg IM/IV every 2-4 hr; not to exceed 5 doses, Then 0.2-0.4 mg PO
every q6-8hr for 2-7 days
•Adverse Effects
•Common side effects are nausea and vomiting .
•Because of its vasoconstrictive action, it may precipitate rise of blood pressure,
myocardial infarction, stroke and bronchospasm
•Prolonged use may lead to gangrene of the toes due to its vasoconstrictive effect
•Prolonged use in puerperium may interfere with lactation by lowering prolactin
level
•

17. Contraindications
•PIH- Severe preeclampsia and eclampsia: Sudden rise of blood pressure or
development of fits (eclampsia).
•PVD
•Severe stenotic valvular heart disease,
•Suspected plural pregnancy: If given accidentally with the delivery of the first
baby, the second baby is compromised by the tetanic contractions of the uterus.
•Organic cardiac diseases: Results in sudden squeezing of blood from the uterine
circulation into the systemic circulation causing overloading of the right heart and failure.
•Rh-negative mother: More risk of feto maternal micro transfusion
•Heart disease or severe hypertensive disorders - Oxytocin is a better substitute in
such cases

18. Prostaglandins (PGs):
1. PGE2 (Dinoprostone): It is commonly used vaginally – Induction of
labour; Induction of abortion; For softening the cervix at term
PGE2 directly affects collagenase of cervix that breaks down the collagen
network and softens it.
2. PGE1 analogue (Gemeprost) :
- used as vaginal suppository to induce early medical abortion during
first term of pregnancy or late abortion ( effect enhanced by previous
administration of anti-progestin mifepristone ).
Misoprostol; PGE1 analogue, oral or vaginal supp. may also be used

19. 3. PGF
2α (Dinoprost) : less commonly used
May be given vaginally, intra- amniotically, or IV
for induction of abortion in second trimester.
IM carboprost tromethamine (Carboprost is
15-methyl PGF
2α) may be used to control PPH, when
combined oxytocin and methylergonovine has failed .

20. CARBOPROST
•Group Oxytocic
•Chemical Structure : 15-methyl analogue of naturally occurring
prostaglandin PGF
2α

•Formulation and Administration :
•Each ml of sterile solution contains carboprost tromethamine equivalent
to 250 mcg of carboprost, 83 mcg tromethamine, 9 mg sodium chloride,
and 9.45 mg benzyl alcohol added as preservative
•Mechanism of Action :
•Mimicking endogenous Prostaglandin PGF
2α
, Carboprost activates
Prostaglandin F receptor, a G- protein coupled receptor, on myometrial
smooth muscle cells resulting in uterine smooth muscle contractions.

21. •Pharmacokinetics
•Onset :
•Within 5 min;
•Peak Action 10-15 min
•Plasma Half Life: 8 minutes
•Absorption: Rapidly absorbed from IM site. Peak plasma conc. in 20-30 min
•Metabolism: Metabolised principally via beta-oxidation in liver. Metabolised
more slowly than naturally occurring PGF
2α Excreted in urine (83%)
•Pharmacodynamics - Increase in frequency and amplitude of
uterine contractions in pregnancy , the resultant myometrial contractions
provide haemostasis at the site of placentation .
•Contraction of vascular smooth muscles may result in increased BP .

22. •Uses and Dosage
•Refractory postpartum uterine bleeding :
•IM dosing, initial: 250 mcg;
• if needed, may repeat at 15-to-90-minute intervals;
maximum total dose, 2 mg (upto 8 doses)
•Abortion: IM dosing: 250 mcg, then 250 mcg at 1.5- to
3.5-hour intervals, depending on uterine response

23. •Adverse Effects
•Severe Nausea and vomiting
•Hypertension ,
•Endometritis ,
•Retained placental fragments, and excessive uterine bleeding ,
•Diarrhoea,
•Temperature elevation and flushing
•Contraindications–
•Hypersensitivity
•Patients with active cardiac, pulmonary, renal or hepatic disease

24. • THANK YOU.