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Drugs Affecting Uterine Contraction

Drugs Affecting Uterine Contraction. ผศ. พญ. มาลียา มโนรถ. Uterine-Stimulating Agents (Oxytocic). Oxytocin Prostaglandins Ergot Alkaloids. Uterine-Relaxing Agents (Tocolytic). beta2-adrenergic agonists Magnesium sulfate Ethanol. Oxytocin. Oxytocin = quick birth N onapeptide.

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Drugs Affecting Uterine Contraction

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  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. 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 Tocolytic Agents

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

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