Use of antibiotic and analgesic drugs during lactation.

During lactation, multiple situations can arise that require maternal pharmacological treatment. Because of the many health advantages of human milk to infants, breast feeding should be interrupted only when the needed drug might be harmful to the nursing child and exposure via the breast milk will be sufficient to pose a risk. Since the majority of drugs have not been shown to cause adverse effects when used during lactation, and even temporary interruption of breast feeding can be difficult for the nursing dyad, decisions regarding maternal medication use during breast feeding should be based on accurate and up-to-date information. This article reviews available data on the most commonly used antibiotics and analgesics. The use of most antibiotics is considered compatible with breast feeding. Penicillins, aminopenicillins, clavulanic acid, cephalosporins, macrolides and metronidazole at dosages at the low end of the recommended dosage range are considered appropriate for use for lactating women. Fluoroquinolones should not be administered as first-line treatment, but if they are indicated, breast feeding should not be interrupted because the risk of adverse effects is low and the risks are justified. Paracetamol (acetaminophen), low-dose aspirin (acetylsalicylic acid) [up to 100 mg/day] and short-term treatment with NSAIDs, codeine, morphine and propoxyphene are considered compatible with breast feeding. Safer alternatives should be considered instead of dipyrone, aspirin at a dosage >100 mg/day and pethidine (meperidine). In the light of the many safe alternatives for pain control, breast-feeding mothers should not be allowed to experience pain or be made to feel that they must choose between analgesia and breast feeding.     

Pharmacokinetics of arginine butyrate in patients with hemoglobinopathy

Recent reports have demonstrated improvement in the clinical status and hemoglobin levels with use of intravenous arginine butyrate in patients with homozygous β-thalassemia and sickle cell disease.

To allow optimalization of therapy, we conducted pharmacokinetic studies in nine patients, five with sickle cell disease and four with β-thalassemia, treated with continuous intravenous infusion of arginine butyrate.

The disappearance of the drug after discontinuation was characterized by a biphasic elimination with an initial rapid phase followed by a slower phase. Redistribution was noted in five of the patients after 11.2 ± 4.0 min. The short half life was the result of both rapid clearance rate of 93.6 ± 31.9 ml/kg/min and small Vc (0.21 ± 0.26 l/kg) and Vss (0.31 ± 0.37 l/kg).

While preliminary results of the effectiveness of arginine butyrate are encouraging with a rise of γ-globin mRNA and F reticulocytes in some patients, the rapid elimination of this agent will probably limit its current use to administration by continuous infusion.     

Pregnancy outcome after gestational exposure to the new macrolides: a prospective multi-center observational study

Objectives

To determine whether the use of the new macrolides (azithromycin, clarithromycin, roxithromycin) during the first trimester of pregnancy is associated with an increased risk of major malformations.

Study design

In a prospective multi-center study, pregnancy outcome was compared between pregnant women exposed to one of the new macrolides during the first trimester of pregnancy and two comparison groups one exposed to other antibiotics and the other to other non-teratogenic medications. All women enrolled in the study called one of the three participating teratogen information services (TIS). Group 1 macrolides (n = 161), group 2 other antibiotics (n = 213) and group 3 non-teratogens (n = 740).

Results

A total of 161 women exposed to the new macrolides (118 were exposed in the first trimester of pregnancy) and 953 from a comparison groups were followed up. The rate of major malformations in the study group was 4.1% compared to 2.1% in the other antibiotics exposed group (OR = 1.41, 95% CI 0.47–4.23) and 3.0% in the non-teratogens exposed group. The rate of elective terminations of pregnancy was significantly higher in the exposed group in compare to both comparison groups.

Conclusion

Our study, although relatively small sized, suggests that the use of the new macrolides during the first trimester of pregnancy does not represent an increased risk for congenital malformations strong enough for an induced abortion after such an exposure. Elective terminations of pregnancy because of early exposure to these medications should be reconsidered.     

Oral N-acetylcysteine has a deleterious effect in acute iron intoxication in rats

Acute iron intoxication is associated with depletion of reduced glutathione in hepatocytes and changes in the glutathione system enzymes. We hypothesized that treatment with N-acetylcysteine (NAC), a glutathione reducing agent and an antioxidant, would reduce mortality in acute iron intoxication. We used a rat model to test this hypothesis. Male rats were assigned to 4 groups. Group 1 received 400 mg/kg elemental iron by oral gavage, group 2 received the same dose of iron followed by NAC, group 3 received NAC only, whereas group 4 received distilled water. Iron and liver transaminases in the blood, and glutathione system enzymes in the liver and erythrocytes were measured. Mortality in group 2 was significantly higher after 2, 6, and 24 hours compared with group 1 (P < .001). No deaths were observed in groups 3 and 4. Serum iron levels were significantly higher in group 2 rats compared to group 1 rats (P < .001). Hepatic and erythrocyte glutathione system enzymes were significantly lower among rats in group 2 compared to rats in group 1. The administration of NAC probably increased the absorption of iron through the gastrointestinal tract, causing higher serum iron levels with significant hepatic damage. These results indicate that in a rat model of acute iron intoxication, orally administered NAC may increase mortality.     

Intranasal midazolam as a treatment of autonomic crisis in patients with familial dysautonomia

To evaluate the efficacy and safety of intranasal midazolam in the treatment of autonomic crises in children with familial dysautonomia, intranasal midazolam was administered at the hospital to six patients during nine episodes of autonomic crisis. Treatment was successful in seven of nine episodes of autonomic crisis in five of six patients, with a mean interval to response of 9.25 +/- 1.25 minutes. The parents of five patients in whom the treatment was successful were instructed to use midazolam at home. At home, 16 additional episodes were treated by the parents, with successful control achieved in 14 (87%). The mean interval to response was 12.8 +/- 2 minutes. No significant side effects were observed at the hospital or at home after intranasal administration of midazolam. Midazolam, given intranasally, is effective and safe in the management of autonomic crises in patients with familial dysautonomia, either in the hospital or at home by the parents after appropriate instruction.     

First trimester exposure to cefuroxime: a prospective cohort study

AIMS: There are no published studies on the safety of cefuroxime use during pregnancy. We therefore investigated prospectively the possible teratogenic effect of intrauterine exposure to cefuroxime. METHODS: One hundred and six women who received cefuroxime during the first trimester of pregnancy were recruited from three teratogen information centres in Israel. Exposed women were paired for age, smoking habits and alcohol consumption with references being exposed to nonteratogenic antibiotics administered for the same indications. RESULTS: Maternal history, birthweight, gestational age at delivery, rates of live births, spontaneous abortions and fetal distress were comparable among the two groups. Rates of major malformations in the cefuroxime group (3.2%) did not differ from references (2%) (P = 0. 61, relative risk = 1.56, 95% confidence interval 0.27-9.15). There was a significantly higher rate of induced abortions among the cefuroxime exposed women as compared to the references (P = 0.04, relative risk = 3.33, 95% confidence interval 0.94-11.77). CONCLUSIONS: Our data may suggest that exposure to cefuroxime during the first trimester is probably not associated with an increased risk for malformations or spontaneous abortions; however, in light of the small sample size and the broad confidence limits, larger studies are needed to confirm these findings.     

Pediatric poisoning from trimedoxime (TMB4) and atropine automatic injectors

OBJECTIVE: To describe the effects of combined trimedoxime (TMB4) and atropine poisoning from automatic injectors (AI) in children. STUDY DESIGN: Data was collected from two sources: calls to the Israel Poison Information Center (IPIC) during a 1-year period and a cohort of children who presented to pediatric emergency departments (EDs) after unintentional injection of an AI. Demographic data and data regarding the type of AI, site and time of injection, and the clinical manifestations were abstracted. RESULTS: Data were available for 142 patients. The median age was 8.5 years (range 1.25-18 years). The dose of atropine and TMB4 was higher than the recommended dose for age in 22 (15.5%) cases. There were few side effects attributable to atropine: dilated pupils (26.7%), dryness of mucous membranes (24.6%), and tachycardia (22.5%). Compared with children injected with an age-appropriate dose, children injected with an AI that contained a dose that exceeds the recommended one were more likely to be symptomatic ( P = .029). There were no side effects characteristic to oximes, and no specific medical intervention was required. CONCLUSIONS: Unintentional pediatric atropine and TMB4 injection, even an adult dose in a small child, does not cause significant side effects.     

Neuroleptic malignant syndrome in a child treated with an atypical antipsychotic

Neuroleptic malignant syndrome (NMS) is an uncommon potentially fatal side effect of neuroleptic drugs, characterized by movement disorder, altered mental status and autonomic instability. A single dose of clotiapine was administered to an 11-year old male with acute psychosis. The previously healthy child had signs consistent with NMS including hyperthermia, hypertension, motor and mental changes. Repeat examination performed two weeks later, demonstrated that while his hyperthermia subsided, his mental status deteriorated. Olanzapine was administered, after which the child had hyperthermia, dystonia and more pronounced restlessness, once again consistent with NMS. He developed respiratory failure and was intubated and mechanically ventilated. Lorazepam, dantrolene and bromocriptine were administered as treatment of possible NMS. His mental condition, movement disorder and autonomic dysfunction improved significantly. Two weeks later, the patient was discharged in good general condition without the need for any ongoing medical treatment. There are only few case reports of NMS in children treated with olanzapine, an atypical antipsychotic. In children, caution must be exercised when prescribing antipsychotics, particularly atypical antipsychotics as these drugs may cause NMS. Because of the low incidence of NMS, a high index of suspicion is needed to identify cases so prompt treatment can be undertaken.