OXYTOXIC & TOCOLYTIC

Suharti K Suherman Dept. Pharmacology & Therapeutic Medical Faculty , University of Indonesia

Oxytocin
a cyclic nonapeptide, differs from vasopressin, only by 2 amino acids synthesis & secretion hypothalamus stimulated by : sensory stimuli from dilation of cervix & vagina & suckling of the breast estradiol stimulates oxyt secretion , whereas ovarian polypeptide, relaxin, inhibits release

 factors primarily affect vasopressin secretion have the same effect on oxyt release ( eg. ethanol, dehydration, hemorrhage & hypovolemia stimulate release) role of oxyt : # uterus exogenous stimulates the frequency& force of contractn the responsiveness paralelles the in spontaneous

 the responsiveness paralelles with the in spontaneous activity that constitutes the initiation of labour & is highly dependent on estrogen (= the receptors of oxyt) is more responsive in late pregnancy progest antagonizes the stimulant effect of oxyt in vitro, & a in progest receptors signaling in late pregnancy may contribute

to the normal initiation of human parturation # breast - stimulates the breast through suckling / mechanical manipulation induces oxyt secretion contraction of myoepithelium surrounding alveoli channels in mammary gland forces milk from the alveolar channels into large

 this action forces milk from the alveolar channels into large collecting sinuses, where it is available to the suckling infant

Mechanism of action
In human myometrium , oxyt # activation of voltage-sensitive Ca2+ channels # local PG production further s timulates uterine contractions

indications
1. induction of labor , in which the risk of continued pregnancy to the mother / fetus is to be greater than the risks of delivery or of pharmcological induction (eg. premature membranes rupture, isoimmunization, fetal growth restriction

,& utero placental insufficiency (as in DM, preeclampsia & eclamps) # before labor is induced to verify that the fetal lungs are sufficiently mature & to exclude potential contraindications : abnormal fetal position, evidence of fetal distress, placental abnormalities

previous uterine surgery predispose to uterine rupture route of administration : IV infusion (10mlU/mL) or infusion pump if hyperstimu lation occurs oxyt discont immediately t IV is short, 3min hyperstimulatory effects should dissipate over several minutes after the infusion is stopped

 since the structure is similar to vasopressin, at higher doses activate V2 receptor antidiuretic effects; particularly if hypotonic fluids (eg. dextrose in water) are infused too liberally water intoxication may result causing convulsions, coma, & even death vasodilation also has been noted, particu

 vasodilation has been noted, particularly at high doses may provoke hypotension & reflex tachycardia Deep anesthesia may exaggerate the hypotensive effect of oxyt , by preventing the reflex tachycardia 2. augmentation of dysfunctional labor to augment hypotonic contractions in dysfunctional labor infusion rate > 10mlU/min is rarely necessarily

& doses > 20mlU/min are rarely effective when lower concentr fail

 3. third stage of labor & puerperium

Ritodrine
a 2 agonist originally developed as a uterine relaxant orally rapidly but incompletely (30%) absorbed ; 90% of the drug is excreted in urine as inactive conjugates IV 50% excreted unchanged

 kinetic in pregnant woman are complex & incompletely defined given intravenously in selected women can arrest premature labor & prolong pregnancy however 2-selective agonists may not have clinically significant benefits on perinatal mortality & may actually maternal morbidity

 in one trial comparing nifedipine vs ritodrine, in managing preterm labor, nifep was associated with a longer postponement of delivery, fewer maternal side effects, & fewer adminissons to neonatal ICU

Side effects of ritodrine

the major side effects : excessive activation of receptors tremor, to which tolerance develops & which

Ergot alkaloids

all natural ergot alkaloids markedly the major activity of uterus as dose is contractions become more forceful & prolonged, resting tone is dramatically , & may cause sustained contracture

Ergonovine & methylergonovine orally, rapidly absorbed, Tmax 6090 min 10x > ergotamine in postpartum woman10min after 0.2mg ergonovine orally uterotonic effect + it is metabolized &/or eliminated more rapidly than ergotamine plasma t1/2 methylergonovine : 0.5 2 hrs

 Indications : all natural ergot alkaloids markedly the major activity of uterus small doses, contractions in force & / or frequency followed by a normal degree of relaxation as dose is , contractions become > forceful & prolonged, resting tone is dramatically , & may cause sustained contracture