Drugs acting on the uterine smooth muscle 1

Drugs acting on the uterine smooth muscle 1

Drugs acting on the uterine smooth muscle s ug Dr (sagittal plane) (coronal plane) 2

★for birth or abortion e. g. oxytocin dinoprostone (PGE 2) dinoprost (PGF 2α) Stimulants ★ for hemostasia & uterus restoration after labor e. g. oxytocin ergonovine Inhibitors ● for methlergometrine guard against miscarriage or alleviation of dysmenorrhea salbutamol, nifedipine, Mg. SO 4 3

І. Oxytocin ●Synthesis: the paraventricular and supraoptic nuclei of the hypothalamus ● storage and release: posterior lobe of the pituitary gland Brain, ovaries and testes also release little 4

Physiological Effects ★Stimulation of milk ejection (milk letdown) mammary alveoli ★ Stimulation of uterine smooth muscle contraction during birth ★ Establishment of maternal behavior 5

Pharmacologic Effects ★ Stimulation of uterine contraction Characteristics ①Frequency and force all enhanced ②Affected by sexual hormone levels in blood plasma: estrogen sensitizes, and progesterone oppresses it ③Different dosages lead to different contractions low dosage: rhythmic contraction uterine fundus contracts while cervix relaxes high dosage: sustained contraction in whole uterus ★ Milk letdown effect & weak antidiuretic effect ★ Dilation of vessels at High dosage 6

Mechanism of stimulation of uterine smooth muscle contraction Oxytocin G protein-coupled membrane receptor IP 3 generation intracellular Ca 2+ release from SR extracellular Ca 2+ entry via VDCC Ca 2+ in cytoplasm increased Contraction IP 3: inositol triphosphate SR: sarcoplasmic reticulum 7

pharmacokinetics • Null swallowed • im or iv usually used, ivd for parturition • Not bound to plasma protein • Catabolized by kidney & liver • T 1/2: 5 min 8

Clinical use • Induction (abortion) or Augmentation (birth) ivd 1 m. U/min initially and increased to 5 -20 m. U/min gradually contraindications: � malposition � cephalopelvic disproportion � birth canal abnormality • postpartum hemostasia &uterus restoration im 5 -10 U each time 9

Ⅱ. Ergot alkaloids • Ergot: an epiphyte parasitizes in rye • Drugs Ergotamine ergotoxine Ergometrine (ergonovine) Pharmacodynamics ●stimulation of uterus smooth muscle contraction Characteristics ①pregnant uterus more sensitive to them ②fiercer and more sustained than oxytocin 10

● stimulation of blood vessel constriction Drug- and vessel-dependent In a predictable, prolonged, and potent manner ● blockade of α-adrenoceptor Clinical use ★uterus hemorrhage ★postpartum uterus restoration ergometrine po 0. 2 -0. 5 mg, im or iv 0. 1 -0. 3 mg, 1 -2/d ★migraine ergotamine po 1 -2 mg, im 0. 25 -0. 5 mg, <10 mg/w 11

Ⅲ. prostaglandins • Drugs dinoprostone (PGE 2) dinoprost (PGF 2α) • Effects Stimulation of rhythmic uterine contraction • Clinical use For inducing abortion • contraindications � Similar to oxytocin � PGF 2α is banned for patient with asthma � PGE 2 is banned for patient with glaucoma 12

Brief summary 1. Oxytocin low dosage: rhythmic contraction of uterus; fundus contracts while cervix relaxes; used via ivd for induction or augmentation. high dosage: sustained contraction in whole uterus; used via im or iv for hemostasia or restoration of postpartum uterus. 2. Ergot alkaloids stimulation of sustained contraction in whole uterus, ergometrine used via po, im or iv for hemostasia or restoration of postpartum uterus; stimulation of blood vessel constriction, ergotamine used via po or im for migraine. 3. Prostaglandins PGE 2 & PGF 2α stimulation of rhythmic uterine contraction, used via ivd for induction (abortion) 13

Thank you 14