1. Pharmacotherapy in obstetrics

2. Topics of the lecture Introducton Medications used during pregnancy – hormones and neuro-peptide analogues Medications used in labor Medications used for miscarriage treatment Medications used for fetal hypoxia and gestosis treatment. Medications used for treatment of extra-genital pathology. Medications used for treatment of puerperium diseases.

3. Introduction Neuro-humoral system of woman is aimed for keeping uterus’ muscle relaxed during pregnancy. It’s possible because of increasing of blood levels of steroid hormone pregesterone which is “pregnancy pretector”

4. Both estrogens and proges-terone are increased during pregnancy but proges-terone prevails

5. Influence of steroid hormones Progesterone performs its acton on uterus only in case estrogenes are synthesised enough by corpus luteumand placenta In other case, progesterone looses its relaxing action on uterus’ muscle

6. Progesterone Increases level of adenosinmonophosphate (AMP) which ties Са2+ ions and blocks actine-myosine contractions

7. Progesterone Increases membrane potential of myocyte and particularly blocks impulses between myocytes Myometrium becomes insensitive to irritatons myometrium

8. Progesterone Since placenta is formed, progesterone is synthesized by it. Consequently, placental site is more relaxed than the rest of myometrium

9. Progesterone Keeps its relaxing action even in case of retention of the part of the placenta inside of the uterus in puerperium. It can provoke sub-involution of uterus and post-partum bleeding

10. Influence of steroid hormones Before labor level of progesterone decreases and estrogenes are rised Estrogenes take out myometrium block

11. Influence of steroid hormones Membranes of myocytes become sensitive to: oxitocine, prostaglandines, catheholamines, serotonine.

12. Mechanism of myometrium contractions Depolarization of membtanes Releasing of Ca2+ Interaction of calcium ions with contractive proteins.

13. Mechanism of myometrium contractions Myometrium has alpha and beta-adrenoreceptors. Stimulation of alpha-receptors by catheholamines causes uterus contraction Stimulation of beta-receptors by catheholamines causes uterus relaxation

14. Mechanism of myometrium contractions Uterus body contains alpha and beta catheholamines receptors Lower segment contains choline and serotonine receptors Cervix contains chemo-, baro- and mechanoreceptors

15. Uterotonics and tocolytics drugs Uterotonics increase uterine contractions (oxytocine, prostaglandines, serotonine, kinines, cathecholamines). Tocolytics decrease uterine contracions (spasmolytics, beta-receptor-stimulating medications, anti-oxytocin drugs).

16. Oxitocine It’s a hormone of supra-optic and para-ventricular nuclei of hypothalamus Transported to pituitary by axons Performs its influence on membranous level

17. Prostaglandines Play very big role in preparing to labor and delivery onset. “Tissue hormones” are made from fatty (lipid) acides

18. Prostaglandines Nowadays synthetic analogues of E2 and F2-alpha prostaglantines are popular because of their high activity E2 medications (dinoprostone, prepidil-gel, 1 mg) prepare cervix for labor (makes it “ripe”) F2-alpha medications (dinoprost, enzaprost, i.v. 5 mg/ml) cause regular uterine contractions

19. Prostaglandines Their administration causes termination of pregnancy in any term

20. Pharmacotherapy of miscarriage Spasmolytics: drotaverine (No-spa) 2 ml i.m., papaverine in average doses Homeopatic medication: Viburcol

21. Magnesial treatment MgSO4 25% - 40 ml i.v. soluted in 400 ml of 0.9% NaCl MagneB6 1 pill 4-6 times daily (200-300 mg of Mg daily),

22. Tocolysis (after 16 weeks of pregnancy) Beta-adrenoreceptor agonist: Gynipral (hexoprenalini sulphatis) Pills 0.5 mg each 6-12 hrs I.v. vials 5 mcg Side effects should be treated by calcium antagonists: verapamil (isoptin) 1 pill (40 mg) 3 times daily

23. Tocolysis (after 16 weeks of pregnancy) Calcium-chanel-blocking agents: Corinfar (nifedipine) 10 mg every 20 min until symptoms of threatening of pre-term labor are resolved

24. Key points of hormonal therapy of mascarriage Hormonal medications should be strictly indicated; Risk/benefit should be assessed thoroughly; Individual dosage; Prescription after 8 weeks of pregnancy should be preferred.

25. Gestagens Progesterone 10-25 mg daily; Utrogestane 100 mg p.o. per vaginum 2 times per day (till 27 weeks); Duphastone (didrogesterone) – 40 mg p.o.at once, then 1 pill(10 mg) 2-3 times daily.

26. Treatment of post-partum hemorrage Oxitocine 5-20 IU Methylergometrine— 1 ml i.m. Prostaglandines

27. Thank You!