Tocolytic Drugs.pptx

Used of tocolytic drugs in prevention of preterm birth

1. Tocolytic Drugs Dr Noor Asikin Mohd Sakri

2. Introduction Tocolytics (also called anti-contraction medications or labor suppressants ) are medications used to suppress premature labor. Preterm birth accounts for 70% of neonatal deaths. Therefore, tocolytic therapy is provided when delivery would result in premature birth, postponing delivery long enough for the administration of glucocorticoids, which accelerate fetal lung maturity but may require one to two days to take effect.

3. Indications Generally, from 24 to 34 gestation Spontaneous premature contractions. No evidence of infection. No life threatening.

4. Contraindications Several general factors may contraindicate delaying childbirth with the use of tocolytic medications. Pregnant woman has severe pregnancy-induced hypertension. IUGR fetus Intrauterine infection is present. Lethal congenital or chromosomal abnormalities. Intrauterine fetal demise. Placental insufficiency.

5. Classifications Β2 adrenergic receptor agonist- Terbutaline , Isoxsuprine , Ritodrine Magnesium sulphate Calcium channel blocker Nifedipine and Nicardipine Oxytocin receptor antagonist Atosiban Prostaglandin synthetase inhibitors Indomethacin,Sulindac Nitric oxide Nitroglycerine Halothane

6. 1. Β2 - adrenergic receptor agonist Terbutaline ( Bricanyl ) Isoxsuprine ( DUVADILAN ) Ritodrine hydrochloride ( YUTOPAR )

7. Mechanism of action Mechanism of action :- Activation of intracellular enzymes (adenylate cyclase, cAMP, Protein kinase, decreases intracellular free Ca++ ( Ca++) & inhibits activation of MLCK ( ) Reduced interaction of actin & myosin causing smooth muscle relaxation.

8. Dosage of Terbutaline Recommended dose: 5-20 mcg/min (0.3-1.2 mg/H) Dilution: 2.5 mg (5 ampules) of IV Terbutaline in 50 ml Dextrose 5% Titration: Start at 3 ml/H via infusion pump Increase by 3 ml/H every 15 mins until contraction less than 1:10, then maintain rate for 12-24H After that may reduce infusion rate by 3 ml/H every 30 mins

9. Terbutaline Contraindications: heart conditions or hyperthyroidism, and poorly controlled diabetes. Side effects: increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia Stop and review if: PR >140 bpm BP<90/60 mmHg Palpitation, cough, SOB or symptomatic of APO

10. 2. Magnesium sulphate Magnesium sulphate (MgSO4) has been successfully used to inhibit premature labor. Magnesium sulphate is used mainly for patients who have contraindications to beta-adrenergic agents. Magnesium sulfate used as a second-line tocolysis .

11. Mechanism of action Acts by competitive inhibition of Ca2+ ion either at the motor end place at the cell membrane reducing calcium influx. Reduces acetylcholine release & its sensitivity at motor end plate. Direct depressant action on uterine muscle.

12. Dosage of MgSO4 Initial Loading dose 4-6gm IV (10-20% solution) over 20-30 mins. Maintenance followed by an infusion of 1-2gm/ hr to continue tocolysis for 12 hrs after the contractions have stopped Contraindications: Patient with myasthenia gravis , heart block & impaired renal function. Side effects & precautions: Common maternal side effects are flushing, perspiration, headache, muscle weakness, rarely pulmonary oedema . * Watchout for MgSO4 toxicity. (monitor urine output, BP, RR, and reflexes hourly) Neonatal side effects are lethargy, hypotonia, rarely respiratory depression.

13. 3. Calcium channel blockers Calcium channel blockers such as nifedipine appear to be powerful uterine relaxant. The mechanism of action appears to be derived from blockade of voltage-dependent calcium channels in myometrial cells. E.g. - Nifedipine , Nicadipine , Verapamil

14. Mechanism of action It blocks the entry of calcium inside the cell, thereby reducing the intra cellular calcium, thus reduces the tone of myometrium and opposes the contraction. Nifedipine, which has prominent smooth muscle relaxant action is effective, if used early.

15. Dosage of Nifedipine 20 mg oral STAT and followed by 20 mg orally 6-8 hourly for 48-72 hours as indicated. If contraction persist after the first dosage, a repeat dose of 20 mg should be given after 30mins Maximum dose is 160mg/day After 72H, if maintenance therapy is required, nifedipine should be tapered to lowest effective dose

16. Monitoring and observations 1/2hourly BP and PR for first hour Hourly BP and PR for the first 24 hours Followed by 4 hourly observation Continuos CTG while contracting Tocolysis must be done in labour room/PE room

17. Nifedipine Contraindications: CHF, Hypotension, aortic stenosis Side effect: Hypotension, Headache, Flushing , tachycardia and nausea. Precautions: Combined therapy with Beta mimetic or MgSO4 should be avoided.

18. 4. Prostaglandin inhibitors Indomethacin (Cyclo-oxygenase inhibitor) Suldinac another NSAID is also used as it has less placental transfer. Mechanism of action: Reduces synthesis of PGs thereby reduce intracellular free Ca++, inhibit activation of myosin light chain kinase and thus reducing uterine contractions

19. Indomethacin Dosage and routes: Loading dose 50mg PO or PR followed by 25mg every 6 hrs for 48 hrs. Contra-indications: Hepatic diseases, active peptic ulcer ,coagulation disorders. Side effects: Maternal headache, dizziness, nausea, vomiting, diarrhoea, haematemesis Neonatal-early closure ductus arteriosus, neonatal pulmonary hypertension, oligohydraminos

20. 5. Oxytocin Antagonists E.g. – Atosiban is a peptide analogue of oxytocin, acts as an antagonist at oxytocin receptors. Has been licensed in UK for use in pre-term labour. Mechanism of action blocks myometrial oxytocin receptors. It inhibits intracellular Ca++ release, release of PGs & thereby inhibits myometrial contractions

21. Atosiban Dosage and routes: Administered 6.75mg as a bolus over 1 minute followed by infusion at 18mg/hour for 3 hours and 6mg/hour for up to 45 hours. Total duration of treatment not to exceed 48 hours and total dose not to be exceed 330mg. Contra-indications: Hepatic and Renal diseases. Side effects: Nausea, vomiting, dyspnea, chest pain

22. 6. Nitric Oxide (NO) Donors E.g. – Glyceryl trinitrate ( GTN ) Mechanism of action :- Smooth muscle relaxant. Doses :- Patches Side effects :- May cause cervical ripening, headache

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