1. Pharmacology of Uterotonics

2. Uterotonics Oxytocin Tocolytics Prostaglandin Ergot alkaloid
Progesterone antagonist
Tocolytics
-adrenergist agonist
Ca2+-channel blocker
PG-synthase inhibitors
Magnesium Sulfate
Ethanol

3. Oxytocin Biosynthesis
a cyclic non peptic, structurally similar to vasopressin
synthesized as a larger precursor molecul
rapidly broken down to the active hormone
packaged into secretory granules as and oxytocin-neurophysin complexs
secreted from nerve ending primarily in the posterior pituitary gland (neurohypophyses)

4. Physiologycal Roles Uterus
Stimulates contraction : frequency and force
highly dependent on estrogen
immature uterus : resistance
Responsiveness : paralel to spontaneous activity
Exogenous oxytocin : enhance rythmic contraction high dose for early pregnancy
Breast
milk ejection

5. MOA Oxytocin 1,4,5 triphosphate • mobilization Ca2+ intracellular
• activation voltage-sensitive Ca2+ channels
Local prostaglandin production

6. Clinical Use Induction of labor (selected) risk of continued pregnancy
isoimmunization
intrauterine growth retardation
placental insufficiency

7. Augmentation of labor
should not be used : progressing normally
hypotonic contraction in disfunctional labor
complication : trauma of the mother / fetoes
uterine rupture compromized fetal oxygenation
very prolong latent phase of cervical dilation
arrest / descent of dilation
epidural anesthesia

8. Third stage of labor and puerperium
after delivery or following therapeutic abortion
Oxytocin challenge test
pregnancy hold increased risk for maternal or fectal complication
Oxytocin receptor antagonists
competitively inhibit the interaction of oxytocin with its membran receptor
potential use in the treatment of preterm labor

9. Prostaglandin
HPETEs

10. Inhibitors of Eicosanoid Biosynthesis
Calcium reducer
Glucocorticoids
NSAIDs
Analogs of the natural fatty acid precursores

11. Pharmacological Properties
Cardiovascular system
prostaglandin
tromboxan A2
leukotriens
Blood
Smooth muscle
bronchial and tracheal
uterus

12. Non pregnant : contractile > before menstruation
continued
PGFs
TXA
PGEs : relaxes
Non pregnant : contractile > before menstruation
relaxation > midcycle
Pregnant :
low concentration PGE2
high concentration PGE2
PGI2
iv PGE2
PGF2
contracted
contracted
relaxed
Tone, frequency & intensity of rhytmic contraction >

13. Gastric and intestinal secretion Kidney and Urine Formation
continued
Gastric and intestinal secretion
Kidney and Urine Formation
Central Nervous System
Endocrine
Metabolic effects

14. Therapeutic uses Therapeutic abortion
abortifacients when given early in pregnancy
dinoprostone (PGE2)
misoprostol (PGE1) + mifepristone or methotrexate
Gastric Cytoprotection
Impotence
Maintenance of Patent Ductus Arteriosus

15. The Ergot Alkaloids Pharmacokinetic
Absorption : variably from GI tract
Oral dose of ergotamine 10x > im dose
speed of absorption and peak blood level can be improved with caffeine
Also absorbed from buccal cavity, rectum and after aerosol inhaler
Metabolism : extensive

16. Pharmacodynamics
A MOA : agonist partial agonist antagonist agonist at dopamine CNS receptor uterus : agonist / partial agonist at 5-HT2R B Organ system effects CNS Vascular smooth muscle Uterine smooth muscle Other smooth muscle
at -adrenoceptor & serotonin receptor

18. Clinical Uses : A. Migraine B. Hyperprolactinemia
C. Postpartum hemorrhage
D. Diagnosis of Variant Angina
E. Senile Cerebral Insufficiency

19. * periodic drug holidays (methysergide) Contraindication :
Toxicity :
- gastrointestinal
- medullary vomiting centre
- prolong vasospasm
* large doses of nitroprusside
- fibroblastic changes
* periodic drug holidays (methysergide)
Contraindication :
- obstructive vascular diseases
- collagen disease
- (pregnancy)

20. Antiprogestins Mifepristone (RU486)
derivate of the 19-norprogestin norethindrone
competitive antagonist of glucocorticoid and
progesterone
Pharmacological actions :
- antagonist progesterone
- mifepristone - antagonist invivo
- agonist invitro
- onapristone - antagonist invivo & invitro

21. MOA : Mifepristone
Early stage of pregnancy Decidual breakdown Detachment of the blastocyst h CG < Progesterone < PG > Contraction

22. Pharmacokinetics :
- orally active
- good bioavailability
- peak plasma : several hours
- H.L. : hours
- Binding 1 – acid glycoprotein
- Liver metabolism & enterohepatic circulation
- Excretion : > faeces

23. Therapeutic Uses : + misoprostol + prostaglandin
- Mifepristone termination early pregnancy
+ misoprostol
- Mifepristone (48 hours) medical abortion T 1
+ prostaglandin
- Postcoital contraceptive

24. TOCOLYTICS
treatment of Preterm Labor * bedrest * hydration * sedation (+ tocolytics)

25.  - Adrenergic Agonists
Ritodrine
Terbutaline
Tachycardia
Hypotension Pulmonary edema
Hypo kalemia Palpitation, tremor,
Hyperglycemia angina

26. Therapeutic Uses
iv. to arrest premature labor
can prolong pregnancy

27. ETHANOL Inhibit preterm labor Overt inebriation
iv : impaired gag reflex
Carbohydrate metabolism
more serious in diabetic
Crosses placenta
Overt:lahir inebrition :pemabuk impaired : merusak

28. Prostaglandin Synthase Inhibitor
Inhibit labor
Oral / rectal endomethacin
effective in the treatment of preterm labor
Serious potential ADR in the fetoes

29. Calcium Channel Blockers
Verapamil and nifedipine
Inhibition of premature labor
Nifedipine :
- decreasing uterine contraction
- severe dysmenorrhea
- PG – induced abortion

30. Magnesium Sulfate Inhibiting premature labor antagonizes Ca 2+
Agent of choice in diabetic patients
Crosses placenta // maternal level
Respiratory depression in the mother :
10 ml of 10% calcium gluconate

31. Suggested for the Treatment of Preterm Labor
Diazoxide
Aminophylline
Progesterone

32. Terimakasih