Drug use during breastfeeding. A survey from the Netherlands.

OBJECTIVE: To survey drug use by breastfeeding women, and to compare this with nonbreastfeeding women. In addition, we were interested whether drug use was of influence on the decision to give breastfeeding, and the other way around. DESIGN AND SETTING: During a 6-week period in 2002, a questionnaire was handed out to all women with a child not older than 6 months, who visited a Well-Baby Clinic in the province of Friesland, the Netherlands, eventually resulting in 549 returned questionnaires (response 43%). RESULTS: In all, 82.1% of the participants breastfed their baby at least at any time during the first 6 months after birth. More than half (65.9%) of all breastfeeding women had used drugs; however, they used drugs less frequently than nonbreastfeeding women (79.6%). The pattern of drug use differed: oral contraceptives, iron preparations, drugs for peptic ulcer, and several psychotropic drugs were more frequently used by nonbreastfeeding women, while vitamins were more frequently used by breastfeeding women. Drugs play an important role in women's decision to start or continue breastfeeding: women frequently hesitated to use drugs during breastfeeding, stopped either breastfeeding or drug use to avoid combining the two, took a measure to minimise exposure to the child, did not use any drug because of breastfeeding, or did not breastfeed because of drug use. CONCLUSIONS: Drugs are frequently though reluctantly used during breastfeeding, and play an important role in the decision to start and stop breastfeeding. Information how to deal with drugs seems therefore indispensable in efforts to promote breastfeeding.

Lack of appropriate formulations of medicines for children in the community.

AIM: Appropriate formulations are essential in pharmacotherapy. This study surveyed the use of different formulations by children in the community, and examined the reported lack of appropriate formulations (oral solutions) in relation to the licensing status of drugs. METHODS: A cross-sectional study based on 68,019 pharmacy dispensing records was performed in The Netherlands. For each prescription the formulation was assessed, and all prescriptions were categorized: unlicensed (no product licence), off-label (licensed drugs used outside the licence terms) and authorized (licensed drugs used according to the licence). The types of formulation used were assessed in relation to age and licensing status. RESULTS: In all age groups, approximately half of all prescriptions were for oral drugs. The only major age-related trend was within oral drugs: younger children were more likely to be prescribed oral solutions. For authorized drugs the proportion of tablet/capsules exceeded oral solutions at the age of 7 y, whereas for off-label drugs this occurred at 3 y of age. For those medicines prepared by the pharmacy, tablets and capsules were more likely to be prescribed from the age of 9 y. CONCLUSION: Many children in the community receive inappropriate oral formulations. Regulatory authorities and the pharmaceutical industry need to ensure that children have access to medicines with appropriate formulations.

Low use of medication in home deliveries in the Netherlands.

OBJECTIVES: In view of the growing concern for de-medicalizing childbirth, the aim of this study is to give detailed figures on the use of medication during home deliveries in the Netherlands. METHODS: A prospective study of medication use by 68 community midwives during 716 home births in the Netherlands. RESULTS: Medication was used in 58.4% of the home deliveries, with an average of 1.4 drugs per delivery. The drugs used were mostly oxytocin (in 35.6% of all deliveries) and local anesthetics (in 32.9%). When medication was used, it was administered before cutting the umbilical cord in 16.7% of the cases. Prophylactic or routine administration of local anesthesia, postpartum hemorrhages, and retained placenta were the most frequent indications for using medication. CONCLUSIONS: The use of medication during home deliveries in the Netherlands is low and newborns are minimally exposed to medication. This illustrates the Dutch birth culture, which tends to minimize the medical aspect of childbirth.

Psychotropic medication in children: a study from the Netherlands.

OBJECTIVE: Although there is a global concern about the increased use of psychotropic agents in children, most research literature originates in the United States and is based on figures from the first half of the 1990s. Also, few studies document the use of various types of psychotropic agents. The objective of this study was to investigate the use of psychotropic medication in children in the Netherlands and to determine whether this corresponds with previously reported figures from the United States. METHODS: A drug utilization study based on computerized pharmacy dispensing records was conducted from 1995 to 1999 for children aged 0 to 19 years in the north of the Netherlands. RESULTS: Stimulants were the most widely used psychotropic agents among 0- to 19-year-olds (prevalence: 7.4/1000 in 1999), followed by hypnotics/anxiolytics (6.9/1000) and antidepressants (4.4/1000). Prevalence rates of stimulants increased from 1.5/1000 in 1995 to 7.4/1000 in 1999. Incidence rates, proportion of girls, and duration of stimulant treatment increased as well. Changes in prevalence rates of other psychotropic agents were much smaller than those of stimulants. Finally, the vast majority of children who were treated with psychotropic agents used only 1 agent at a time. CONCLUSION: The prevalence of stimulant use in the Netherlands is much lower than reported previously (28/1000 children in 1995) from the United States, and differences also existed with regard to the use of other psychotropic agents and combinations of psychotropic agents. However, the increase in Dutch stimulant use agrees with the previously reported 2.5-fold increase in the United States and shows that the increased use of stimulants is not limited to the United States.

Pharmacotherapy in the perinatal period--an exploratory study in midwifery.

OBJECTIVE: To gather information on the adherence to the Dutch national neonatal vitamin K policy and on the administration of prescription medication during labor by community midwives. METHODS: A telephone questionnaire under community midwives in the North of the Netherlands. RESULTS: In the main, the vitamin K practices follow the guidelines with respect to who receives the first dose and maintenance therapy. There is possibly underdosing. Midwives use their license to administer medicines during labor in moderation: 91% report to never use tocolytics, oxytocics or analgesics. CONCLUSION: In general, the national vitamin K policy is followed. Information gathered prospectively is needed on the use of pharmacotherapy by community midwives in the perinatal period.

Drug use of children in the community assessed through pharmacy dispensing data.

AIMS: : To determine the extent of drug use in children and the types of drugs that children use. METHODS Cross-sectional study and cohort study, using computerized pharmacy dispensing records for all children aged 0-16 years in the northern part of The Netherlands in 1998. The main outcome measures were proportion of children that used drugs (per sex and age group), mean number of drugs per child, 10 most widely used drug groups and cumulative proportions of drugs users (per drug group) during the first 2 years of life. RESULTS: Drug use was the highest among infants, decreased till adolescence and increased from there. Overall, approximately 60% of all children used at least one drug in 1998. At younger ages, boys used more drugs than girls and at older ages girls used more drugs than boys. Systemic antibiotics were used by 21% of the children and were by far the most widely used drugs. Other frequently used drugs were analgesics (10%), corticosteroids for dermatologic use (9%), anthistamines (8%) and antiasthmatics (7%). Approximately 10% of the children had used at least one drug at the age of 1 month and at the age of 2 years this proportion was 81%. CONCLUSIONS: The majority of children was exposed to one or more drugs and this exposure started at very young age. This shows the importance of good guidelines for drug use in children and emphasizes the necessity of research of pharmacokinetic and pharmacodynamic properties in children to obtain safety, efficacy and quality evidence of these drugs.

[Deptropine still prescribed for 0-4 year olds]. / Nog steeds deptropinevoorschriften voor o-4-jarigen.

OBJECTIVE: To determine to what extent the negative reporting concerning deptropine and its removal from the professional guidelines for asthma in children was followed by changes in the prescription of deptropine to young children and to determine to what extent the alternatives to deptropine were prescribed in the same period. DESIGN: Retrospective cross-sectional study in 5 calendar years. METHODS: This study was performed using computerised pharmacy data from the InterAction database of public pharmacies in the northern part of the Netherlands. The percentage of 0-4-year-olds who were prescribed deptropine or one of its alternatives was determined per year from 1994-1999. RESULTS: In 1994, 14.9% of the 0-4-year-olds used deptropine, and this proportion decreased to 4.8% in 1999. beta 2 adrenergic agonists and glucocorticosteroids, both by inhalation, were used by 2.4% and 1.8%, respectively, of the 0-4-year-olds in 1994, and these proportions were 6.8% and 7.0%, respectively, in 1999. CONCLUSION: Deptropine was still being prescribed frequently, although there has been a sharp decrease since 1994. beta 2 adrenergic agonists and glucocorticosteroids, both by inhalation, are being prescribed increasingly often.

Involvement of medial septal glutamate and GABAA receptors in behaviour-induced acetylcholine release in the hippocampus: a dual probe microdialysis study.

In the present study, the role of medial septal receptors in behaviour-induced increase in acetylcholine (ACh) release in hippocampus was investigated using dual-probe microdialysis in combination with a simple behavioural procedure. gamma-Aminobutyric acid (GABA) and glutamate receptor agonists and antagonists were administered by retrograde dialysis into the medial septal area, while ACh was measured in the ventral hippocampus. Rats were behaviourally activated by immobilization or handling, but only handling was performed during drug-treatment. The GABAA receptor agonist muscimol did not affect ACh release, but blocked the handling-induced increase in ACh release completely. In addition, muscimol administration induced behavioural activity. Administration of the GABAA receptor antagonist bicuculline increased ACh release more than 2-fold. However, handling-induced increase in ACh release, expressed as percentage of drug-induced release, was similar to that of controls. Administration of the glutamate receptor agonists N-methyl-D-aspartate (NMDA) and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in the septal area increased hippocampal ACh levels, but reduced the handling-induced increase in ACh release. The NMDA antagonist, 3-((R)-2-carboxypiperazin-4-yl) (CPP) increased ACh levels moderately, and reduced handling-induced increase in ACh release. However, similarly to muscimol, CPP administration induced behavioural activity. The AMPA/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) did not affect behaviour or basal ACh levels, but attenuated the handling-evoked ACh release. We conclude that the handling-induced increase in hippocampal ACh levels is mediated via stimulation of septal non-NMDA, and possibly NMDA receptors, whereas GABAA receptors are probably not involved. The feasibility of the experimental design is further discussed.

Effects of neostigmine and atropine on basal and handling-induced acetylcholine output from ventral hippocampus.

The involvement of muscarinic autoreceptors in the regulation of hippocampal acetylcholine levels during acetylcholinesterase inhibition was examined by perfusing the acetylcholinesterase inhibitor neostigmine bromide (10, 100 or 1000 nM) alone and in the presence of the muscarinic receptor antagonist atropine methylnitrate (10 microM), in resting and behaviourally-activated animals. In resting animals, local perfusion of neostigmine caused a dose-dependent increase in acetylcholine levels. Coadministration of atropine did not affect basal levels in the presence of 10 nM neostigmine, but increased acetylcholine levels approximately four and 11-fold in the presence of 100 nM and 1000 nM neostigmine, respectively. In animals which were behaviourally activated by handling, acetylcholine levels increased two- to three-fold in the presence of all neostigmine concentrations. However, the handling-induced increase in acetylcholine levels was somewhat smaller with 1000 nM neostigmine as compared to 10 nM neostigmine. Atropine had no effect on handling-induced acetylcholine output in the presence of 10 nM neostigmine, but caused greater and longer increases in the presence of 100 nM and 1000 nM neostigmine. These data indicate that acetylcholine levels are greatly reduced by autoinhibition at higher levels of acetylcholine esterase inhibition. The handling-evoked increase in acetylcholine levels is only moderately affected by the level of acetylcholinesterase inhibition, despite the participation of autoreceptors in the handling effect at higher levels of acetylcholinesterase inhibition.