1. Drugs Affecting Uterine Contraction ผศ. พญ. มาลียา มโนรถ

2. Uterine-Stimulating Agents (Oxytocic) Oxytocin Prostaglandins Ergot Alkaloids

3. Uterine-Relaxing Agents (Tocolytic) beta2-adrenergic agonists Magnesium sulfate Ethanol

4. Oxytocin Oxytocin = quick birth Nonapeptide supraoptic + paraventricular neurone (hypothalamus) posterior pituitary gland

5. Pharmacological Properties 1. Uterus Nonpregnacy : Preganancy : frequency, force (tetanic contraction) 2. Mamary gland ฎ milk ejection 3. CVS : vasodilatation 4. Antidiuretic effect

6. Mechanism of action –Specific receptor Pharmacokinetics –Route : parenteral (IM, IV), intranasal, buccal lozenges –Half-life : 5 min –Excretion : kidney, liver

7. Adverse Reactions CVS –rapid IV infusion marked, transient relaxation of vascular smooth muscle Antidiuretic effect (weak)

8. Clinical Uses Induction of labor Therapeutic abortion During lactation

9. Ergot Alkaloids Ergot : fungus : Claviceps purpurea Ergot alkaloids : derivative of tetracyclic compound 6- methylergoline

10. 1. Amine Alkaloids Ergonivine (ergometrine) Methylergonovine Methysergide Lysergic acid diethylamine (LSD)

11. 2. Amino Acid Alkaloids Ergotamine Ergosine Ergostine Bromocriptine Ergotoxine

12. Pharmacological Properties 1. Uterus : ญ motor activity (ergonovine, methylergonovine) 2. CVS : vasoconstriction (ergotamine) 3. CNS : high dose กระตุ้นสมอง หายใจเร็ว ตื่นเต้น กระวนกระวาย ชัก

13. Pharmacokinetics 1. Amine alkaloids –Ergonovine PO : rapidly, completely IM : slow, reliable Metabolized in the liver bile Half-life of methyergonovine in plasma 0.5-2 hr

14. Pharmacokinetics 2. Amino acid alkaloids –Ergotamine extensive first-pass metabolism (90% of the metabolites bile) –Bromocriptine PO complete

15. Ergot Poisoning 1. Acute poisoning –High dose : ergotamine –(ergonovine < ergotamine 4 fold) 2. Chronic poisoning (ergotism) –Vasoconstriction ฎ Damage capillary endothelium ฎ Thrombosis ฎ Gangrene

16. Clinical Uses 1. Obstetric : Post partum hemorrhage –ergonovine, methylergonovine 2. Migraine : –ergotamine + caffeine ( ญ absorption) –methysergide : prophylaxis 3. Hyperprolactinemia : –bromocriptine

17. Prostaglandins 1. Myometrium : –PGE, PGF : contract 2. Cervix : ripening

18. Adverse Reactions 1. GI : nausea, vomiting, diarrhea 2. Transient pyrexia 3. Bronchoconstriction

19. Tocolytic Agents 1. Beta2-mimetic agents (SE : maternal & fetal tachycardia) 2. Magnesium sulfate (SE : respiratory depression) 3. Ethanol (SE : restlessness, coma) 4. NSAIDs (SE : closure ductus arteriosus) 5. Calcium antagonist

20. Ritodrine PO : rapidly, incompletely absorbed 90% drug ฎ urine (inactivate conjugate) IV 50% drug ฎ urine (unchanged)