1. Rozaimah Zain-Hamid & Yazanul Anwar Department of Pharmacology and Therapeutics Faculty of Medicine, Universitas Sumatera Utara

2. OXYTOCIC / UTEROTONIC AGENTS Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

3. OXYTOCIC / UTEROTONIC AGENTS UTERINE CONTRACTION  Induction/augment dysfunctional labor  Control of post partum hemorhage  Incomplete abortion/abortion therapeutic Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara Stimulation

4. OXYTOCIC / UTEROTONIC AGENTS  Oxytocin  Derivate of Ergot Alkaloids  Derivate of Prostaglandin Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

5. Oxytocin Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

6. OXYTOCIC / UTEROTONIC AGENTS Stimulation of prostaglandin synthesis Uterine contraction Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara Direct action on uterus smooth muscle At terminal stage of pregnancy (  oxytocin receptor in myometrium) Cervix dilatation & stretching of vagina

7. Uterine contraction Cervix dilatation & stretching of vagina Stimulation of cervix & vagina  oxytocin secretion Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

8. Pharmacokinetic : * RoA : i.v & buccal absorption * Swallowed  inactive * Not bound to plasma protein * Catabolized by the kidneys & liver * Circulating t 1/2 : 5 minutes OXYTOCIN (Posterior pituitary hormone) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

9. Pharmacodynamic : Alters transmembrane ionic currents in myometrial smooth muscle cells & myoepithelial cells of mammary alveoli Uterine contraction & leads to milk ejection UTEROTONIC (OXYTOCIN) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

10. Clinical pharmacology :  Diagnostic : placental circulatory condition = Preparation available : Syntocinon & pitocin Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara UTEROTONIC (OXYTOCIN)

11.  Therapeutic :  Induce labor  Augment dysfunctional labor for : 1.Conditions requiring early vaginal delivery: Rh problem, maternal DM, preeclampsia 2. Uterine inertia 3. Incomplete abortion Clinical pharmacology : Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara UTEROTONIC (OXYTOCIN)

12. Adverse reaction : * Maternal death  hypertensive episodes * Uterine rupture * Water intoxication * Fetal death * Afibrinogenemia Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara UTEROTONIC (OXYTOCIN)

13. Contraindication :  Fetal distress  Prematurity  Abnormal fetal presentation  Cephalo-pelvic disproportion  Other predispositions for uterine rupture  Using sympathomimetic agents Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara UTEROTONIC (OXYTOCIN)

14. Derivate of Ergot Alkaloids Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

15. ERGOT ALKALOIDS  Adrenoceptors Dopamine receptors 5-HT receptors Produced by Claviceps purpurea Histamine Acetylcholine Tyramine UTEROTONIC (ERGOT ALKALOIDS) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

16. PHARMACOKINETICS: Variably absorbed from g.i.t  Amino acid alkaloids (ergotamine):  oral dose > i.m  Speed of absorption & peak blood level improved by caffeine UTEROTONIC (ERGOT ALKALOIDS) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

17. PHARMACOKINETICS:  Amine alkaloids (ergonovine / ergometrine) :  Also absorbed from rectum, buccal cavity, aerosol inhaler  After i.m : slow absorption (reliable)  Metabolism : liver Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara UTEROTONIC (ERGOT ALKALOIDS)

18. PHARMACODYNAMICS: STIMULANT EFFECTS ON THE UTERUS:  Combine  agonist, 5-HT receptors  Changes dramatically  pregnancy (  dominance  1 receptors as pregn.progresses)  Sensitivity: uterus aterm > earlier pregn. > non pregn. Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara UTEROTONIC (ERGOT ALKALOIDS)

19.  Small doses: rhytmic contr. & relaxation  Higher doses: powerful & prolonged contr.  Ergonovine : more selective  uterus (drug of choice : obstetric application) PHARMACODYNAMICS: STIMULANT EFFECTS ON THE UTERUS: Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara UTEROTONIC (ERGOT ALKALOIDS)

20. CLINICAL APPLICATION:  For control of late uterine bleeding (Post-partum hemorrhage)  Should never be given before delivery  Given at the time of delivery of placenta or immediately afterward if bleeding is significant Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara UTEROTONIC (ERGOT ALKALOIDS)

21. SIDE EFFECTS : Nausea, vomiting,  Blood Pressure Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara UTEROTONIC (ERGOT ALKALOIDS)

22.  Gastrointestinal disturbancies: diarrhea, nausea, vomiting  activation of medullary vomiting center & gastrointestinal serotonin receptors  prolonged vasospasm (gangrene  amputation) Therapy: infusion of large doses of nitroprusid or nitroglycerin Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara TOXICITY: UTEROTONIC (ERGOT ALKALOIDS)

23. CONTRA INDICATION : Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara Obstructive vascular disease & collagen disease UTEROTONIC (ERGOT ALKALOIDS)

24. Derivate of Prostaglandin Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

25. UTEROTONIC ( PGE2 & PGF2  ) Contractile effects Release of calcium ions  the frequency & strength of uterine contraction Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

26. A. ABORTION  PGE 2 & PGF 2   1 st & 2 nd trimester abortion    proteoglycan & changing biophysical properties of collagen  soften the cervix UTEROTONIC ( PGE2 & PGF2  ) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

27. A. ABORTION  PGE 2 & PGF 2  (i.v ) produced abortion in ± 80 % of cases rate  PGF2  (intra-amniotic): success rate ± 100 %  Adverse effects < i.v  Other road of administration : i.m, intravaginal UTEROTONIC ( PGE2 & PGF2  ) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

28.  Success rate  dose, duration of infusion & parity of the woman  Dose-limiting side effects  vomiting, diarrhea, hyperthermia & bronchoconstriction UTEROTONIC ( PGE2 & PGF2  ) A. ABORTION Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

29.  Dinoprost tromethamine ( der. PGF 2  ) : single 40 mg intra-amniotic injection  complete abortion  20 hours Side Effects: cardiovascular collaps/anaphylactic shock, pulmonary hypertension  ultrasonic guidance UTEROTONIC ( PGE2 & PGF2  ) A. ABORTION Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

30.  Carboprost tromethamine (i.m) & multiple dose  Synthetic PGE 2 analogue : vaginal suppositoria direct affects the collagenase UTEROTONIC ( PGE2 & PGF2  ) A. ABORTION Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

31. B. FACILITATION OF LABOR  PGE 2 & PGF 2   PGF 2  > potent than PGE 2  PGF 2  has more g.i.t toxicity than PGE 2  Success rate = oxytocin  G.i.t side effect > oxytocin UTEROTONIC ( PGE2 & PGF2  ) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

32. B. FACILITATION OF LABOR  PGE 2 & PGF 2   pass fetoplacental barrier  fetal toxicity uncommon  Oral PGE 2 superior than oral oxytocin, but = oxytocin i.v UTEROTONIC ( PGE2 & PGF2  ) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

33. B. FACILITATION OF LABOR  PGE 2 & PGF 2  have no antidiuretic effect  induction labor in woman : preeclampsia, cardiac & renal disease  Uterine fetal death  prostglandine alone or + oxytocin UTEROTONIC ( PGE2 & PGF2  ) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

34. TOCOLYTIC AGENTS Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

35. TOCOLYTIC AGENTS Suppress UTERINE CONTRACTION Inhibition, delaying or halting labor Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

36. TOCOLYTIC AGENTS   Adrenergic agents (terbutaline, ritodrine)  Calcium Channel blockers (verapamil, nifedipine)  Prostaglandin synthetase inhibitor (indomethacin) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara  Magnesium sulphate (MgSO 4 )

37. Magnesium sulphate (MgSO 4 ) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

38. Magnesium sulphate (MgSO 4 ) Acts as a calcium antagonist & membrane stabilizer (  the force of contraction)  Prophylaxis for preeclampsia (1 st line therapy)  Prevent seizures continued for 12-24 hours after delivery Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

39.  Route of Administration: oral & i.v  SIDE EFFECTS: Feeling of extreme warmth, perspiration, flushing, nausea, vomiting, blurred vision, lightheadedness, lethargy, nasal stiffness, constipation, affects the reflexes, and slow breathing, chest pain (taking together with other tocolytic) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara Magnesium sulphate (MgSO 4 )

40.  CONTRA INDICATION: Heart block, myocardial infarction, myasthenia gravis, renal impairment Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara Magnesium sulphate (MgSO 4 )  TOXICITY: Hypoxia, respiratory depression, cardiac arrest

41. Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara Magnesium sulphate (MgSO 4 )  EFFECTS TO THE NEWBORN:  Baseline heart rate, drowsy, weak cry,  sucking rate in the early postpartum period  Strict monitoring for mother & newborn

42.  Adrenergic agents (terbutaline, ritodrine) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

43.  Adrenergic agents (terbutaline, ritodrine)  Level of cAMP via adenylate cyclase Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara smooth muscle relaxation  level of free calcium ions

44. Terbutaline & ritodrine  or stop uterine contraction Preterm labor Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

45.  Route of Administration: oral & i.v, subcutaneus controlled infusion pump (to give continuous low dose of terbutaline) Terbutaline & ritodrine Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

46. Terbutaline & ritodrine SIDE EFFECTS: Nervousness, restlessness, insomnia headache, rapid heart rate, nausea, hyperglycemia, hypokalemia, and pulmonary edema, shortness of breath, chest pain Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

47. Terbutaline & ritodrine WARNING: Cardiac dysrhythmia, cardiac disease, hypertension or thyrotoxicosis, shortness of breath, chest pain or contraction still exist during administration of terbutaline & ritodrine Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

48.  EFFECTS TO THE NEWBORN: Fast heart rate, high or low blood sugar after birth Terbutaline  Strict monitoring for mother & newborn Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

49. Calcium Channel blockers (verapamil, nifedipine) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

50.  the force of smooth muscle contraction Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara Calcium Channel blockers (verapamil, nifedipine) Calcium ions Entering smooth muscle cells

51. Calcium Channel blockers (verapamil, nifedipine)  or stop contraction of uterus Delay labor (used for occasional uterus irritability) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

52. Calcium Channel blockers (verapamil, nifedipine)  Route of Administration: oral  SIDE EFFECTS: Facial flushing, headache, nausea, palpitation, lightheadedness Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

53.  EFFECTS TO THE NEWBORN: No serious side effects have been note Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara Calcium Channel blockers (verapamil, nifedipine)

54. Prostaglandin synthetase inhibitor (indomethacin) Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara

55.  the frequency & strength of uterine contraction Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara Prostaglandin synthetase inhibitor (indomethacin) Synthesis of prostaglandin

56. Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara Recommended as a tocolytic in preterm labor at << 32 weeks of gestation Indomethacin

57.  Route of Administration: oral, suppository  SIDE EFFECTS: Abdominal discomfort, nausea, vomiting, depression & dizziness Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara Indomethacin

58. WARNING: Pregnant woman who has a story of bleeding disorders, aspirin sensitivity & kidney problems Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara Indomethacin

59.  EFFECTS TO THE NEWBORN: Have serious side effects on the foetus Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara Indomethacin

60. Zain-Hamid R & Anwar Y, Faculty of Medicine, Universitas Sumatera Utara