Safety and Efficacy of Tocolytics for the Treatment of Spontaneous Preterm Labour

Background: Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Attempts to reduce the burden may be proactive using biochemical or biophysical prediction and preventative measures. If these efforts fail, then the approach may have to be reactive using tocolytics to inhibit spontaneous preterm labour. Objective: We have reviewed the evidence concerning the safety and efficacy of various classes of tocolytic agents. Results: The evidence to support the use of magnesium sulfate or nitric oxide donors as a tocolytic is poor. Compared to placebo or no treatment, there is evidence to support the efficacy of calcium channel blockers (mainly nifedipine), prostaglandin synthetase inhibitors (mainly indomethacin and sulindac), oxytocin receptor antagonists (mainly atosiban) and β2-agonists (mainly ritodrine, terbutaline, salbutamol and fenoterol). Maternal safety concerns have reduced the use of β2-agonists. Fetal safety and gestational age restrictions have largely condemned prostaglandin synthetase inhibitors to second-line therapy. First-line therapy in Europe and other parts of the world outside the USA and Australia is limited to calcium channel blockers and oxytocin receptor antagonists. With respect to efficacy, atosiban and nifedipine are similar, but the robustness of the evidence favours atosiban. With respect to safety, atosiban is clearly the safest tocolytic as there are fetomaternal concerns with nifedipine, particularly in high daily doses. Conclusion: The perfect tocolytic that is uniformly effective and safe does not exist. Cost, licensing and informed consent are considerations involved in the choice. Efforts continue to develop and introduce other or better agents, including novel compounds such as progesterone, PGF2α antagonists and statins.

Acetaminophen-induced fulminant liver failure (clinical case presentation and a review of the literature)

Acetaminophen (AAP) is one of the most common and widely used antipyretic drugs, but its overdose is the leading cause of fulminant hepatic insufficiency in the world. Mechanisms of liver damage at the use of toxic doses of AAP are caused by the transformation of the isoform of cytochrome P450 (CYP2E1, CYP2A6) into a reactive metabolite, N-acetyl-parabenzoquinonimine (NAPQI), which plays a major role in hepatotoxicity. Another mechanism of hepatotoxicity includes the formation of peroxynitrite – a toxic free radical produced in the mitochondria, which causes oxidative damage. In addition to liver damage in case of acetaminophen poisoning, nephrotoxic effect can occur. Potential mechanisms of nephrotoxicity in overdose of AAP are presented, caused by cytochrome P450, as well as prostaglandin synthetase and enzyme N-deacetylase are described. In the clinical case described by us, the development of fulminant hepatic insufficiency against the background of acetaminophen administration led to the development of a coma along with the kidney damage, however, a stable positive dynamics, was achieved during treatment. In the catamnesis 2.5 years later, there were no signs of fibrosis or cirrhosis of the liver.