Drugs Affecting Uterine Contraction ผศ. พญ. มาลียา มโนรถ.

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Presentation transcript:

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 Nonapeptide supraoptic + paraventricular neurone (hypothalamus) posterior pituitary gland

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

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

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

Clinical Uses Induction of labor Therapeutic abortion During lactation

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

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

2. Amino Acid Alkaloids Ergotamine Ergosine Ergostine Bromocriptine Ergotoxine

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

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

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

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

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

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

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

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

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