Dept.Farmakologi & Therapeutik Fak.Kedokteran USU Medan

Stimulants 1. Oxytocin 2. Prostaglandins (uterotonic):



3. Ergot alkaloids.

II.Inhibitors = (Tocolytics)

1. Beta-mimetics Ritodrine, terbutaline 2. Magnesium Sulfate 3. Indocin 4. Nifedipine (CCBs)

Oxytocin (pitocin)
 Oxytocin adalah hormon yang sering digunakan pada masa akhir kehamilan untuk merangsang kontraksi uterus untuk induksi partus;misalnya pada:  -partus tak maju;  -ada penyulit seperti: = preeclampsia, eclampsia, diabetes).  to remove placenta  and to control bleeding of the womb (uterus) after childbirth.

Oxytocin Synthesised in hypothalamus and released from the posterior pituitary Administered by IV infusion Indications: 1. Initiates contractions of the pregnant uterus 2. Prevention and treatment of postpartum haemorrhage

vomiting. seizures. lightheadedness. and stomach pain may occur. . severe bleeding (after childbirth). seizures. yellowing eyes or skin. headache.  Serious side effects: irregular heartbeat. swelling.  Serious side effects in the newborn: irregular heartbeat. dizziness. cramping. bleeding in the eyes. blurred vision.Side Effects  Nausea.  An allergic reaction to this drug is unlikely but may occur.

and menstrual fluid. Causes softening of the cervix late in the first trimester of pregnancy (3) Toxicity a. c. PGF2α . Stimulatory action on the smooth muscle of the alimentary tract.2. d. In contrast to oxytocin. .hypertension. b. b. PGE2 or PGF2α causes strong uterine contractions and can induce delivery of the fetus. myometrium. prostaglandins are much more effective than oxytocin in the earlier months of pregnancy. Prostaglandins 1) General Informations (1) Found in ovary. Ripening of cervix at doses that do not affect uterine motility b. During the last two trimesters of pregnancy. (2) Cervix: a.vasodilatation. Transient pyrexia (due to actions on thermoregulatory centers in the hypothalamus). PGE2 . (2) Rise in amniotic fluid during labor 2) Pharmacological Properties (1) Myometrium a.

and 15-methyl PGF2α. . (3) Potential use as cervical ripening agents to facilitate normal or induced labor. (2) Used for the performance of mid trimester abortions.3) Therapeutic Uses (1) Major drugs --.PGE2. (4) Potential use to soften the cervix prior to performance of first-trimester abortions by the method of dilatation and evacuation. PGF2α.

Prostaglandin Misoprostol (PGE1 analogue. given intravaginally) Soften and dilate the cervix Stimulate uterine contraction Termination of pregnancy in second trimester Second or third trimester stillbirth .

first alpha blocker (2) Ergotamine (Gynergen) (3) Methysergide (Sansert) (4) Ergonovine Major effects of ergot alkaloids = Serotonin receptor blockade = Direct stimulation of vascular and nonvascular smooth muscle . Ergot Alkaloids. berasal dari Claviceps purpurea .3.Strucural similarity to lysergic acid (LSD) Example (1) Ergotoxine (mixture of 3 alkaloids) .

Methysergide .Clinical uses of ergot alkaloids = Uterine smooth muscle stimulant for treatment of postpartum uterine atony or hemorrhaging (ergonovine. Patients with vasospastic disorders.gangerene Contraindications a.retroperitoneal fibrosis b. Ergotamine . pregnant woman . methylergonovine) = migraine Side-effects: a. b.

4. SYNTOCINON) . trained personnel must be present.IV Infusion (10 milliunits/mL) . . .If too much activity. placental insufficiency) in which the continuation of pregnancy is considered to be a greater risk to the mother or the fetus than the risks of delivery or pharmacological induction.Uterine activity should be carefully monitored. the infusion should be immediately discontinued . Drug of choice: Oxytocin (PITOCIN. hypertensive states.During the entire procedure. The Clinical Use of Drugs That Stimulate Uterine Motility (UTEROTONIC) 1) Induction of Labor: = Indicated inductions include those situations (diabetes.

2) Augmentation of Labor: (1) In most circumstances.. (2) There are occasions. oxytocin should not be used for the augmentation of labor if labor is progressing normally. when oxytocin can be used advantageously by the experienced obstetrician to manage dysfunctional labor. (3) Oxytocin is usually effective in patients with a very prolonged latent phase of cervical dilatation as well as in those cases where there is a significant arrest of dilatation or descent. . however.

ergonovine or methylergonovine may be used in nonhypertensive patient.2 mg) or IV (0. (4) Alternatively. (3) If oxytocin is not effective.2 mg) for immediate action. (2) Oxytocin is given to aid in maintaining uterine tone after delivery. . IM (0.3) Third Stage of Labor and Puerperium: (1) Uterine-stimulating agents are usually given after delivery of the placenta.25 mg) of 15-methyl PGF2α (carboprost) may be used. IM (0.

Vaginal suppositories of PGE2(dinoprostone. HEMABATE) is used. IM (0. Intraamniotic injection of a hypertonic (20%) solution of sodium chloride. prostin E2). a synthetic 19-norsteroid (mifepristone). a. . b.25 mg) 15-metyl PGF2. (2) RU486. (3) Prostaglandin plus mifepristone  99% success (4) During the second trimester. c. is a progesterone antagonist that inhibits the effect of progesterone on the uterus.4) Therapeutic Abortion (1) Abortion during the first trimester most commonly is accomplished by means of suction curettage.

.The Clinical Use of Drugs That Inhibit Uterine Motility (Tocolytic agents) .Indications are: (1) to delay or prevent premature in selected individuals and (2) to slow or arrest delivery for brief periods in order to undertake other therapeutic measures. .

. and 50% or more of patients who present with regular uterine contractions will respond to bed rest and hydration.Premature Labor: (1) Premature births account for a large fraction of perinatal mortality. (2) It is often difficult to determine whether premature birth is imminent. (3) In general the use of tocolytic agents is reserved for those pregnancies where the gestational age is greater that 20 weeks and less than 34 to 36 weeks.

Tocolysis Only evidence showing acute tocolysis is beneficial for short term PTL management. and not for PTD No evidence that maintenance tocolysis is beneficial fro PTL or PTD at this time in large studies .

Tocolysis  Criteria: -Assure maternal/fetal well being first  no contraindication to rx  no contraindication to prolonging pregnancy  Diagnosis clear  Cervix <4cm  24-34 weeks .

Tocolysis  General Contraindications  Acute fetal distress  Chorioamnionitis  Severe preeclampsia/eclampsia  Fetal demise  Fetal maturity  Maternal hemodynamic instability .

Tocolytic Agents  Beta-mimetics  Ritodrine. terbutaline  Magnesium Sulfate  Indocin  Nifedipine (CCBs) .

but studies done prior to steroid use .Beta-mimetics  Function:  Stimulate beta2 receptors in uterus and lung. decrease contractility  Cross react with beta2 in heart  Efficacy: shown to prolong labor 24-48 hours to allow transfer and steroid benefits  Ritodrine (FDA approved) and Terbutaline  Neither beneficial to neonatal mortality.

titrate down & stop 12 hours after contractions stopped (max 0.35 mg/min) .  0.1 mg/min.25 mg q 1-4 hours  IV 0. 0.005 mg/min to maximum of 0. increase by 0.025 mg/min  Oral dose not effective in PTL (ok for PTCx) Ritodrine: iv only.Beta-mimetics Terbutaline  IV and multiple SC dosing effective in temporarily stopping contractions  SC 0.01 mg/min.05 mg/min q 30 minutes.

anxiety. chest pain • Hyperglycemia. nervousness. palpitations.Maternal Side Effects: Beta-mimetics • Tremor. arrhythmias. hyperkinesias • Hypertension. pulmonary edema. electrolyte abnormalities • Fluid retention. MI. tachyphylaxis . . N/V.

heart failure. hypotension  Hyper/hypoglycemia.Fetal Side Effects of Beta-mimetics  Tachyarrhythmia. hyperbilirubinemia  Death . MI.

hypertension. eclampsia. migraines. diabetes • Relative:  Diabetes. severe pre-eclampsia.Contraindications: Beta-mimetics • Absolute: Maternal cardiac disease. hemorrhage. sepsis  . uncontrolled hyperthyroid.

no wean  Oral dose not effective . then 1-4 gm/hour. but studies show less gross motor dysfunction in infants  ? Works by calcium antagonist activity  Load 4-6 gm IV.Magnesium Sulfate  Widespread use  No clear evidence showing efficacy in delaying/preventing PTD  Controversy: ?may increase infant mortality.

Magnesium Sulfate  Side effects:  N/V. cardiac arrest (rare)  Pulmonary edema worse when used with terbutaline  Crosses placenta. respiratory arrest (toxic levels). pulmonary edema. flushing. hypotension. tetany. no adverse fetal effects (may have less reactivity) . muscular paralysis. . sweating. palpitations. warmth. hypocalcemia.

toxic >15  Antidote: calcium gluconate . VS.5-7. mental status hourly  Pulmonary examination  Reflexes (loss when level >8)  Therapeutic level: 5.Magnesium Sulfate  Contraindications:  Myasthenia Gravis.5 mg/dl. hypocalcemia  Exam:  Fluid I/O. renal failure.

<32 weeks  Dosing:  100mg rectal dose. repeat x1 in 1-2 hours if contractions persist  25-50 mg orally q4-6 hours <48 hours for cessation of contractions .Indocin  Inhibits prostaglandins/cytokines that trigger labor  Well studied. use limited by side effects  Can inhibit PTL for 48 hrs in <37 weeks  Use in cases w/ good dating.

oligohydramnios . causing usual NSAID side effects  Does not decrease neonatal mortality  Can cause PPH. constrict fetal ductus arteriosis.Indocin  Well tolerated by mom.

Nifedipine  Inhibit contraction of smooth muscle  Very efficacious  Nifedipine most widely studied CCB  Some studies show as efficacious or better than beta- mimetics with less side effects  Gaining popularity as tocolytics of choice .

cardiac disease or hemorrhage .Nifedipine  Fetal effects:  No adverse fetal effects  No increase congenital anomalies  Maternal effects:  Flushing dizziness. nausea. hypotension  Contraindicated if hypotensive.

Nifedipine  Dosing:  30 mg oral dose load  10-20 mg po q 4-6 hours .

if needed . .Conclusions Various strategies that have been used to prevent or treat preterm labor. Tocolysis should be considered only for 2 days. or in utero transfer to a tertiary center .for corticosteroids thereby . haven't proven effective.

delay of PTD  Ampicillin 2 gms iv q 6 hours (macrolides also effective) often used if unclear GBS/possible infection  USE IN PPROM. but decrease transmission to infant)  Empiric antibiotics in PTL w/ intact membranes:  Conflicting results: no short/long term benefits.beneficial . treat (no benefit PTL. treat  If known GBS+.Antibiotics  If have specific infection.

(HMD) .PTL: Steroids  Reduces RDS. infant mortality  Only treatment shown to improve fetal survival in PTL  Criteria:  Delivery likely within 7 days  fetus 24-34 weeks  Able to delay delivery 24-48 hr respiratory distress syndrome (RDS) intraventricular hemorrhage Hyaline membrane disease. NEC. IVH.

q 12 hr . q 24 hr -Dexamethasone 6 mg IM.may no benefit RDS but may benefit IVH up to 34 weeks • Regimens: -Betamethasone 12 mg IM. 4 doses. 2 doses.PTL: Steroids • Use between 32-34 weeks arguable.

infection  Long term: no adverse effects  Fetal Adverse Effects  No long term effects of single course  Multiple course associated w/ infection.PTL: Steroids  Maternal Adverse Effects  Short term: glucose control. pulmonary edema. abnormal development .

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