Codeine for Acute Pain Related to Caesarean Section

Caesarean section rates have increased over the past 3 decades. Caesarean section is often associated with acute post-operative abdominal pain and medications containing codeine have been used for pain management. There are concerns related to the use of codeine for this purpose, particularly regarding the potential for neonatal toxicity and opioid-related adverse events for the postpartum patient. There is limited evidence regarding the clinical effectiveness of codeine, with or without acetaminophen or nonsteroidal anti-inflammatory drugs, in patients who have undergone Caesarean section. One randomized controlled trial found that codeine in combination with paracetamol (i.e., acetaminophen) provided better pain relief compared to paracetamol only or placebo in patients with high levels of post-Caesarean section pain. However, no difference in pain relief was observed between codeine in combination with paracetamol, paracetamol only, or placebo in patients with moderate levels of post-Caesarean section pain. No evidence was found regarding the clinical effectiveness of codeine alone for acute pain in this specific population.

Neonatal Toxicity From Escitalopram Use In Utero: A Case Report

Selective serotonin reuptake inhibitor (SSRI) exposure during pregnancy can result in symptoms of serotonin syndrome or serotonin withdrawal. In contrast to other SSRIs, reports of serotonin behavioral syndrome following in utero exposure to escitalopram and citalopram are limited. We describe a case of suspected toxicity following in utero exposure to 20 mg escitalopram throughout pregnancy. The infant was transferred to our neonatal intensive unit at 9 hours of life for further evaluation of lethargy, weak cry, bradycardia, and non-reactive pupils. Hypoxic ischemic encephalopathy was suspected upon presentation, despite APGAR scores of 8 and 9. Upon admission, symptoms progressed to signs of hypertonia, irritability, high-pitched cry, and posturing. The patient was loaded with phenobarbital for empiric management of suspected seizures versus drug withdrawal. Both electroencephalogram and computed tomography scan results were normal; however, an electrocardiogram revealed a prolonged QTc interval of 531 milliseconds. Signs of irritability and QTc prolongation continued through day of life (DOL) 5. The infant was discharged on DOL 10 with no further symptoms. We hypothesize that this represented a case of serotonin toxicity due to in utero exposure to escitalopram and recommend close monitoring for neonatal behavioral syndrome symptoms and QTc prolongation in infants exposed to escitalopram during pregnancy.

Two-Generation Reproductive Toxicity Study of Inhaled Acrylonitrile Vapors in Crl:CD(SD) Rats

To assess the effects of acrylonitrile (AN) exposure on reproduction, Sprague-Dawley rats (25/sex/group) were exposed to vapor atmospheres of AN via whole-body inhalation at concentrations of 0, 5, 15, 45 (two offspring generations) and 90 ppm (one offspring generation), 6 h daily, 1 litter/generation, through F2 weanlings on postnatal day 28. After approximately 3 weeks of direct exposure following weaning, exposure of the F1 animals at 90 ppm was terminated due to excessive systemic toxicity in the males. There were no exposure-related mortalities in adult animals, no functional effects on reproduction or effects on reproductive organs, and no evidence of cumulative toxicity or of enhanced toxicity in pregnant and lactating dams or in developing animals. Adult systemic toxicity was limited to body weight and/or food consumption deficits in both sexes and generations (greater in males) at 45 and 90 ppm and increased liver weights in the 90 ppm F0 males and females and 45 ppm F1 males. Neonatal toxicity was expressed by F1 offspring weight decrements at 90 ppm. Clinical signs of local irritation during and immediately following exposure were observed at 90 ppm. Microscopic lesions of the rostral nasal epithelium, representing local site-of-contact irritation, were observed in some animals at 5 to 45 ppm. The no-observed-adverse-effect level (NOAEL) for reproductive toxicity over two generations and neonatal toxicity of AN administered to rats via whole-body inhalation was 45 ppm. The NOAEL for reproduction was 90 ppm for the first generation. The NOAEL for parental systemic toxicity was 15 ppm.

Ontogenetic development of the distribution of constitutive and 3-methylcholanthrene-induced CYP1A1 and CYP1A2 in rabbit liver.

We investigated the expression, distribution, and inducibility of 3-methylcholanthrene (MC)-inducible P450 enzymes, CYP1A1 and 1A2, in livers of rabbits at different stages of development, ranging from 4 days before birth (-4 days of age) to adulthood. These enzymes were identified by immunoblotting and immunocytochemistry and quantified by dot-blotting, utilizing previously characterized monoclonal antibodies, 107 and 3/4/2, specific for CYP1A2 and both CYP1A1 and 1A2, respectively, and a polyclonal antibody that recognizes both enzymes. Expression of CYP1A2 is always greater than that of CYP1A1 in livers of untreated rabbits, regardless of age. Moreover, immunocytochemistry showed that CYP1A1 is evenly distributed throughout the liver at all ages, whereas CYP1A2 is highly localized to only a few scattered cells at 1 day before birth. More hepatocytes express this enzyme perinatally. By 6 days of age, expression of CYP1A2 is confined to a narrow band of centrilobular cells, but with increasing age the enzyme is expressed in more hepatocytes until weaning, when all hepatocytes are positive. Although CYP1A1 is induced by MC treatment at most ages, there is no change in its distribution. In contrast, induction of CYP1A2 was shown immunocytochemically to occur in only a limited number of hepatocytes in fetal rabbits. There is a progressive increase with age in the number of hepatocytes that are inducible for CYP1A2. The greatest fold-induction of hepatic CYP1A2 by MC in the rabbit is a 9-11 days of age, when, for MC-treated rabbits, CYP1A2 represents > 60% of the total P450 pool. The modulation of enzyme expression caused by MC treatment of fetuses/neonates leads to developmentally advanced livers with respect to P450 and could have a significant impact on the fetal and neonatal toxicity of some foreign compounds. These data demonstrate, for the first time, that the ontogenetic expression and localization of CYP1A1 and 1A2 within the liver are differentially regulated at the level of the individual cell.