Classification by Mechanism of Action
In clinical practice, various pharmacological agents are used to achieve uterine relaxation. They share a common goal—tocolysis—while their mechanisms of action differ significantly:
- Beta-2 agonists: hexoprenaline, salbutamol, terbutaline, fenoterol.
- Progestins (progesterone formulations): hydroxyprogesterone caproate, ethinyl estradiol/acetomepregenol combinations.
- Oxytocin receptor antagonists: atosiban.
- Myotropic antispasmodics: magnesium sulfate.
- Central nervous system depressants: general anesthetics (enflurane) and anxiolytics (diazepam).
Beta-Agonists — The Backbone of Tocolysis
These are the primary medications used to suppress preterm labor. The main representative in obstetrics is hexoprenaline. It is a selective beta-2 adrenergic receptor agonist that markedly and persistently reduces the frequency and amplitude of uterine contractions.
Hexoprenaline is used for preterm contractions, uterine immobilization prior to Cesarean delivery or forceps application, and in emergency situations (umbilical cord prolapse, acute fetal hypoxia, version from transverse lie).
Other agents in this group include:
- Salbutamol: used for threatened abortion in the third trimester. In therapeutic doses, it has minimal effect on cardiac beta-1 receptors and bladder tone.
- Terbutaline: used to suppress preterm contractions starting from 16 weeks of gestation. Administered as an intravenous infusion (lasting up to 8 hours); the solution requires protection from light.
- Fenoterol: stimulates both beta-2 and beta-1 receptors. Indicated for uterine dyscoordination and excessive uterine tension.
Adverse effects stem from systemic receptor stimulation: muscle tremor, headache, vasodilation, palpitations, decreased urinary output, and transient hypokalemia during the first days of therapy. These drugs are strictly contraindicated in severe cardiovascular disease, hepatic and renal impairment, and angle-closure glaucoma.
Oxytocin Antagonists and Other Groups
In addition to beta-agonists, several other agents are utilized to maintain pregnancy:
- Atosiban: a competitive oxytocin receptor antagonist. It effectively halts labor between 24 and 33 completed weeks of gestation. Potential side effects include hypotension, tachycardia, and uterine atony leading to hemorrhage.
- Magnesium sulfate: a parenteral myotropic antispasmodic. In obstetrics, its primary roles are lowering blood pressure and arresting (as well as preventing) seizures in eclampsia.
- Progestins (hydroxyprogesterone): hormonal agents that reduce overall uterine excitability.
Differential Pharmacology: Tocolytics vs. Uterotonics
It is crucial to clearly distinguish tocolytics from uterotonics (uterine stimulants). Misadministration can lead to severe complications.
- Oxytocin induces physiological rhythmic contractions to facilitate labor and delivery.
- Dinoprost (prostaglandin F2-alpha) also stimulates the uterus, with myometrial sensitivity increasing as pregnancy progresses.
- Ergometrine (an ergot alkaloid) causes tonic (continuous) myometrial contraction. This mechanically compresses blood vessels, stopping uterine hemorrhage. The drug does not affect coagulation factors.
- Methylergometrine is a uterine stimulant and is not a tocolytic agent.