DRUGS USED IN MIDWIFERY

DRUGS USED IN OBSTETRICS

Hyperemisis  gravidarum

Zofran: This is an antiemetic that is effective against vomiting and nausea. Although it's a newer drug, preliminary studies indicate that it causes no harm to either Mother or Baby.

Reglan: Used more often in treating GERD (gastroesophageal reflux disease), this is also effective in many cases and is considered safe for use during pregnancy.

Premature Labor: The aim of medication in preterm labor is to prevent delivery for as long as possible, with a focus on holding off delivery for at least 24 hours to allow time for lung-strengthening steroids to take effect on the baby. Depending on the pregnancy, the patient and the progression of the preterm labor, the following medications may be used:

Terbutaline: Used most commonly to treat asthma, terbutaline is thought to relax the muscles of the uterus.

Procardia: A calcium channel blocker, this treats pregnancy-induced hypertension and inhibits preterm labor.

Indomethacin: Given as a suppository in the short term. Delays premature labor by reducing uterine contractions through inhibition of prostaglandins.

Magnesium sulfate: Used to treat pre-eclampsia, eclampsia and preterm labor.

Glucocorticoids: Administered, often in two doses, to stimulate growth in the lungs of the fetus.

Induction of Labor: This is often done for a variety of medical reasons and rarely just for convenience. A patient who is being induced will be watched carefully for rare side effects that are possible with the following medications:

Cervidil and Cytotec: Both are administered as vaginal suppositories to ripen the cervix prior to delivery. This is the first step in preparing the cervix to respond to contractions. Cytotec, while very effective, has been implicated in some uterine ruptures and should not be used under certain circumstances.

Pitocin: The synthetic form of oxytocin, which is a natural hormone produced by a woman's body, Pitocin is used to start or improve contractions.

Drugs Used for Delivery

By far the most common use of all drugs in active labor are for pain relief. There are some of the medications anesthesiologists and nurse anesthetists use to help patients in labor:

Narcotics: Marketed under various names, narcotics are used early in labor to take the edge off pain. They're generally administered by injection or intravenously. The drawbacks are that they do cross the placenta and should not be given if birth is imminent or if labor is progressing quickly.

Sedatives: Given to ease anxiety, these are usually injected. They do not provide pain relief and are not commonly used unless the patient is in very early labor.

Nitrous oxide: This is used frequently in the United Kingdom, less so in the United States, mostly for reasons having to do with ventilation issues. This is an inhaled gas that can ease pain early in labor.

1.  Prostaglandins and oxytocics

Induction and augmentation of labour

         Dinoprostone vaginal gel 1mg and 2mg

         Oxytocin injection 5units/ml, 10units/ml

         Dinoprostone vaginal pessaries 10mg

Prevention and treatment of haemorrhage

          Carboprost injection 250 microgram/ml

          Ergometrine injection 500 microgram/ml

          Oxytocin with ergometrine (Syntometrine®)

Induction of abortion – Consultant only

           Misoprostol tablets 200micrograms [unlicensed]

 Ductus arteriosus

Maintenance of patency

          Alprostadil intravenous solution 500 microgram/ml

          Dinoprostone 1mg/ml 0.75ml amp [unlicensed]

Closure of ductus arteriosus

          Indometacin injection 1mg

2. Mifepristone

          Mifepristone tablets 200mg

3.  Myometrial relaxants

          Salbutamol solution for intravenous infusion 5mg/5ml

     Nifedipine capsules 5mg, 10mg - Three times daily preparations

                   (only for Raynaud’s, achalasia and pre-term labour [unlicensed])

Drugs used to modify uterine contractions.
These include oxytocic drugs used to stimulate uterine contractions both in induction of labour and to control postpartum haemorrhage and beta₂ -adrenoceptor agonists used to relax the uterus and prevent premature labour.

POSTPARTUM HAEMORRHAGE

  Ergometrine and oxytocin differ in their actions on the uterus. In moderate doses oxytocin produces slow generalized contractions with full relaxation in between; ergometrine produces faster contractions superimposed on a tonic contraction. High doses of both substances produce sustained tonic contractions. Oxytocin is now recommended for routine use in postpartum and  post-abortion haemorrhage since it is more stable than ergometrine. However, ergometrine may be used if oxytocin is not available or in emergency situations.

PREMATURE LABOUR

  Salbutamol is a beta₂ -adrenoceptor agonist which relaxes the uterus and can be used to prevent premature labour in uncomplicated cases between 24 and 33 weeks of gestation. Its main purpose is to permit a delay in delivery of at least 48 hours. The greatest benefit is obtained by using this delay to administer corticosteroid therapy or to implement other measures known to improve perinatal health. Prolonged therapy should be avoided since the risks to the mother increase after 48 hours and the response of the myometrium is reduced.

ECLAMPSIA AND PRE-ECLAMPSIA

 Magnesium sulfate has a major role in eclampsia for the prevention of recurrent seizures. Monitoring of blood pressure, respiratory rate and urinary output is carried out, as is monitoring for clinical signs of overdosage (loss of patellar reflexes, weakness, nausea, sensation of warmth, flushing, double vision and slurred speech—calcium gluconate injection (section 27.2) is used for the management of magnesium toxicity).
  Magnesium sulfate is also used in women with pre-eclampsia who are at risk of developing eclampsia; careful monitoring of the patient (as described above) is necessary.

Ergometrine maleate

Ergometrine is a representative oxytocic drug. Various drugs can serve as alternatives
Tablets, ergometrine maleate 200 micrograms
Injection (Solution for injection), ergometrine maleate 200 micrograms/ml, 1-ml ampoule

NOTE.

Injection requires transport by ‘cold chain’ and refrigerated storage

Uses:
prevention and treatment of postpartum and post-abortion haemorrhage in emergency situations and where oxytocin not available
Contraindications:
induction of labour, first and second stages of labour; vascular disease, severe cardiac disease especially angina pectoris; severe hypertension; severe renal and hepatic impairment; sepsis; eclampsia
Precautions:
cardiac disease, hypertension, hepatic impairment (Appendix 5) and renal failure (Appendix 4), multiple pregnancy, porphyria; interactions: Appendix 1
Dosage:
Prevention and treatment of postpartum haemorrhage, when oxytocin is not available, by intramuscular injection, ADULT and adolescent 200 micrograms when the anterior shoulder is delivered or immediately after birth
Excessive uterine bleeding, by slow intravenous injection, ADULT and adolescent 250–500 micrograms when the anterior shoulder is delivered or immediately after birth
Secondary postpartum haemorrhage, by mouth , ADULT and adolescent 400 micrograms 3 times daily for 3 days
Adverse effects:
nausea, vomiting, headache, dizziness, tinnitus, abdominal pain, chest pain, palpitations, dyspnoea, bradycardia, transient hypertension, vasoconstriction; stroke, myocardial infarction and pulmonary oedema also reported

Magnesium sulfate

Injection (Solution for injection), magnesium sulfate 500 mg/ml, 2-ml ampoule, 10-ml ampoule
Uses:
 prevention of recurrent seizures in eclampsia; prevention of seizures in pre-eclampsia
Precautions:
hepatic impairment (Appendix 5); renal failure (Appendix 4); in severe hypomagnesaemia administer initially via a controlled infusion device; interactions: Appendix 1
Dosage:
Prevention of recurrent seizures in eclampsia, by intravenous injection , ADULT and adolescent initially 4 g over 5–15 minutes followed either by intravenous infusion , 1 g/hour for at least 24 hours after the last seizure or by deep intramuscular injection 5 g into each buttock then 5 g every 4 hours into alternate buttocks for at least 24 hours after the last seizure; recurrence of seizures may require additional intravenous injection of 2 g
Prevention of seizures in pre-eclampsia, by intravenous infusion , adult and adolescent initally 4 g over 5–15 minutes followed either by intravenous infusion , 1 g/hour for 24 hours or by deep intramuscular injection 5 g into each buttock then 5 g every 4 hours into alternate buttocks for 24 hours; if seizure occurs, additional dose by intravenous injection of 2 g

DILUTION AND ADMINISTRATION.

According to manufacturer’s directions For intravenous injection concentration of magnesium sulfate should not exceed 20% (dilute 1 part of magnesium sulfate injection 50% with at least 1.5 parts of water for injection); for intramuscular injection , mix magnesium sulfate injection 50% with 1 ml lidocaine injection 2%

Adverse effects:
generally associated with hypermagnesaemia (see also notes above), nausea, vomiting, thirst, flushing of skin, hypotension, arrhythmias, coma, respiratory depression, drowsiness, confusion, loss of tendon reflexes, muscle weakness; see also Appendix 2

Oxytocin

 Injection (Solution for injection), oxytocin 10 units/ml, 1-ml ampoule
Uses:
routine prevention and treatment of postpartum and post-abortion haemorrhage; induction of labour
Contraindications:
hypertonic uterine contractions, mechanical obstruction to delivery, fetal distress; any condition where spontaneous labour or vaginal delivery inadvisable; avoid prolonged administration in oxytocin-resistant uterine inertia, in severe pre-eclamptic toxaemia or in severe cardiovascular disease
Precautions:
induction or enhancement of labour in presence of borderline cephalopelvic disproportion (avoid if significant); mild to moderate pregnancy-associated hypertension or cardiac disease; age over 35 years; history of low-uterine segment caesarean section; avoid tumultuous labour if fetal death or meconium-stained amniotic fluid (risk of amniotic fluid embolism); water intoxication and hyponatraemia (avoid large volume infusions and restrict fluid intake); caudal block anaesthesia (risk of severe hypertension due to enhanced vasopressor effect of sympathomimetics); interactions: Appendix 1
Dosage:
Induction of labour, by intravenous infusion, ADULT and adolescent , initially 0.001–0.002 units/minute increased in 0.001–0.002 units/minute increments at intervals of 30 minutes until a maximum of 3–4 contractions occur every 10 minutes; maximum recommended rate 0.02 units/minute; no more than 5 units should be administered in 24 hours

NOTE..

The dose shown above is suitable for use in hospital where equipment to control the infusion rate is available; alternative recommendations may be suitable for other settings (consult Managing Complications in Pregnancy and Childbirth : A guide for midwives and doctors 2003 . Geneva: WHO)

IMPORTANT.

Careful monitoring of fetal heart rate and uterine motility essential for dose titration (never give intravenous bolus injection during labour); discontinue immediately in uterine hyperactivity or fetal distress

Prevention of postpartum haemorrhage, by slow intravenous injection , ADULT and adolescent 5 units when the anterior shoulder is delivered or immediately after birth
Prevention of postpartum haemorrhage, by intramuscular injection , adult and adolescent 10 units when the anterior shoulder is delivered or immediately after birth
Treatment of postpartum haemorrhage, by slow intravenous injection , adult and adolescent 5–10 units or by intramuscular injection , 10 units, followed in severe cases by intravenous infusion , a total of 40 units should be infused at a rate of 0.02–0.04 units/minute; this should be started after the placenta is delivered

DILUTION AND ADMINISTRATION.

According to manufacturer’s directions. Prolonged intravenous administration at high doses with large volume of fluid (for example in inevitable or missed abortion or postpartum haemorrhage) may cause water intoxication with hyponatraemia. To avoid: use electrolyte-containing diluent (not glucose), increase oxytocin concentration to reduce fluid, restrict fluid intake by mouth; monitor fluid and electrolytes

Adverse effects:
uterine spasm, uterine hyperstimulation (usually with excessive doses—may cause fetal distress, asphyxia and death, or may lead to hypertonicity, tetanic contractions, soft-tissue damage or uterine rupture); water intoxication and hyponatraemia associated with high doses and large-volume infusions; nausea, vomiting, arrhythmias, rashes and anaphylactoid reactions also reported

Salbutamol

Salbutamol is a representative myometrial relaxant. Various drugs can serve as alternatives
Tablets , salbutamol (as sulfate) 4 mg
Injection (Solution for injection), salbutamol (as sulfate) 50 micrograms/ml, 5-ml ampoule
Uses:
 uncomplicated premature labour between 24–33 weeks gestation; asthma (section 25.1)
Contraindications:
first and second trimester of pregnancy; cardiac disease, eclampsia and pre-eclampsia, intra-uterine infection, intra-uterine fetal death, antepartum haemorrhage, placenta praevia, cord compression, ruptured membranes
Precautions:
monitor pulse and blood pressure and avoid over-hydration; suspected cardiac disease, hypertension, hyperthyroidism, hypokalaemia, diabetes mellitus; if pulmonary oedema suspected, discontinue immediately and institute diuretic therapy; interactions : Appendix 1
Dosage:
Premature labour, by intravenous infusion , ADULT initially 10 micrograms/minute, rate gradually increased according to response at 10-minute intervals until contractions diminish then increase rate (maximum of 45 micrograms/minute) until contractions have ceased, maintain rate for 1 hour then gradually reduce; or by intravenous or intramuscular injection , ADULT 100–250 micrograms repeated according to response, then by mouth , 4 mg every 6–8 hours (use for more than 48 hours not recommended)
Adverse effects:
nausea, vomiting, flushing, sweating, tremor; hypokalaemia, tachycardia, palpitations, and hypotension, increased tendency to uterine bleeding; pulmonary oedema; chest pain or tightness and arrhythmias; hypersensitivity reactions including bronchospasm, urticaria and angioedema reported

Dinoprostone (vaginal gel, vaginal tablets) is the drug of choice for induction of labour.  The two preparations are not bioequivalent, the usual dose of gel being 1 - 2mg, whereas that of the tablets is 3mg.
Dinoprostone 10mg vaginal delivery system (Propess®) is a new pessary formulation available for initiation of cervical ripening in patients at term (from 38th week of gestation). The new pessary formulation releases approximately 10mg dinoprostone over 24 hours and can remain in place for up to 24 hours where necessary.

Gemeprost (pessaries) is used to soften and dilate the cervix before induction of abortion.  In order to ensure that the patient receives maximum benefit from the drug, it is essential that the pessary is inserted as near as possible to 3 hours before the operative procedure is due to be carried out.  Gemeprost is also used in conjunction with mifepristone (see special indications).

Oxytocin (injection) is given by slow intravenous infusion for induction and augmentation of labour.  Guidelines for the use of this product are included in the Aberdeen Maternity Hospital labour ward protocol/Dr. Gray's labour ward protocol.

Syntometrine® (injection) is a combination of oxytocin (5 units) and ergometrine maleate (500 micrograms) in 1mL.  It is given by intramuscular injection for the routine management of the third stage of labour.  It is also the drug of choice in the management and prevention of post-partum haemorrhage, and for the control of bleeding due to incomplete abortion.  Its use is contra-indicated in patients with pre-eclampsia.  It is used in accordance with the guidelines included in the Aberdeen Maternity Hospital labour ward protocol.

Ergometrine maleate (injection) is used for the management of post-partum haemorrhage.

NICE guidance (induction of labour)

The National Institute for Clinical Excellence has recommended that:

·         dinoprostone is preferable to oxytocin for induction of labour in women with intact membranes regardless of parity or cervical favourability.

·         dinoprostone or oxytocin are equally effective for the induction of labour in women with ruptured membranes, regardless of parity or cervical favourability.

·         intravaginal dinoprostone preparations are preferable to intracervical preparations.

·         oxytocin should not be started for 6 hours following administration of vaginal prostaglandins.

·         when used to induce labour, the recommended dose of oxytocin by intravenous infusion is initially 0.001-0.002 units/minute increased at intervals of at least 30 minutes until a maximum of three to four contractions occur every 10 minutes (0.012 units/minute is often adequate); the maximum recommended rate is 0.032 units/minute (licensed max. 0.02 units/minute).

SPECIAL INDICATIONS

Dinoprostone (extra-amniotic solution) is indicated only for rare cases of failed medical termination of pregnancy.

Mifepristone (tablets) is used in conjunction with gemeprost pessaries or misoprostol (tablets) [unlicensed indication] for the medical termination of pregnancy (see protocol).  It is also used to soften and dilate the cervix before mechanical cervical dilation for termination of pregnancy.

Carboprost (injection) is used to treat post-partum haemorrhage in patients who do not respond to Syntometrine®.

Ritodrine (tablets, injection) is a beta2-adrenoceptor stimulant, which causes relaxation of uterine muscle.  It is used in selected cases to inhibit premature delivery.  Care and close monitoring are required, especially when given by infusion.  There is a particular danger of pulmonary oedema developing in patients with a cardiac history or when steroids are used concurrently.  Guidelines for use are included in the Aberdeen Maternity Hospital labour ward protocol/Dr. Gray's labour ward protocol.

Atosiban (injection) may be used under the supervision of a consultant obstetrician to delay imminent birth in uncomplicated pre-term labour.  See prescribing protocol.