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Chapter: Modern Medical Toxicology: Miscellaneous Drugs and Poisons: Gastrointestinal and Endocrinal Drugs

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Drugs Acting on the Uterus

– Classification – Oxytocin – Prostaglandins

DRUGS ACTING ON THE UTERUS

Classification

·      Drugs which cause contraction of uterine muscle:

o     Oxytocin

o     Prostaglandins

o     Ergot alkaloids.

·      Drugs which relax uterine muscle:

o     Beta-adrenergic receptor agonists: ritodrine hydrochlo-ride, terbutaline, feneterol, albuterol.

o     Magnesium sulphate

o     Calcium channel blockers

o     Prostaglandin synthetase inhibitors: indomethacin

o     Oxytocin antagonists: atosiban.

Some of these drugs have been discussed elsewhere, and the reader is advised to consult the Index for information on their toxicity. From among the others, the important examples will be discussed in this section.

Oxytocin

Oxytocin is a cyclic nonapeptide produced by the supraoptic and periventricular nuclei in the hypothalamus. It is stored in the posterior pituitary. It is structurally related to vasopressin. The clinical preparation of oxytocin is a synthetic chemical compound.

Uses

·      Induction or stimulation of labour.

·      Control of postpartum uterine bleeding.

·      Treatment of incomplete or inevitable abortion.

Toxicokinetics

Oxytocin is effective after parenteral administration (IM or IV), and can also be given intranasally as a spray. Since oxytocin is absorbed to some extent from oral mucosa, it is sometimes given as buccal lozenge.

The mean apparent volume of distribution is 0.3 L/kg, while the half-life is about 10 minutes. It is removed from the plasma by the liver, kidney, and functioning mammary glands. Oxytocin can cross the human placenta, but the extent is not certain.

Adverse Effects

Routine oxytocin administration has been associated with uterine rupture, antepartum foetal death, and neonatal hyper-bilirubinaemia. Large doses can cause water intoxication with convulsions (due to its antidiuretic effect). Other adverse effects include initial hypotension, followed occasionally by hypertension.

Diagnosis

■■  Plasma oxytocin concentration by radioimmunoassay.

■■High serum hepatic enzyme activity and coagulopathy in foetus (after maternal oxytocin overdose).

Treatment

·      Monitor blood pressure and pulse of both mother and foetus. Monitor also foetal heart, resting uterine tone and frequency, duration and force of contractions. Discontinue immediately in the event of foetal distress. Administer oxygen to the mother. Obtain obstetric advice.

·      Manage water intoxication by restriction of fluids, diuresis, IV hypertonic saline, correction of electrolyte imbalance, and control of convulsions.

Prostaglandins

Prostaglandins can be considered to be local hormones since they exert most of their effects and are inactivated principally in the organs or tissues in which they are synthesised.

Those found most abundantly in the uterus, and in the menstrual and amniotic fluid are of the E and F types. Prostacyclin (PGI2) is mainly confined to the uterine, umbil-ical, and foetal vasculature. Prostaglandins used in current obstetric practice include PGE2, PG2alpha, and its synthetic derivative 15-methyl PGF2alpha. Misoprostol, a PGE1 analogue has recently been introduced as an abortifacient and cervical ripening agent.

Uses

·               Abortifacient (especially PGE and 15-methyl PGF Treatment of postpartum haemorrhage (15-methyl PGF2alpha).

·              Cervical ripening agent (local application of PGE ).

Clinical (Toxic) Features

·              Routine use is associated with vomiting, diarrhoea, and fever.

·              Large doses may cause hypertension (PGF2alpha and 15-methyl PGF2alpha). Misoprostol is associated with fewer side effects.

 

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