Adverse effects of sedatives in children

The application of sedation/analgesia in paediatric patients is rapidly expanding as less invasive, non-operative techniques of diagnosis and treatment are applied to the paediatric population. Medical providers who are asked to provide sedation may include radiologists, paediatricians, nurses and emergency physicians, as well as anaesthesiologists and intensive care physicians. At the same time, the range of drugs used in these settings has expanded considerably. As there is no single drug fulfilling the criteria for the ideal sedative (rapid-onset, rapid recovery, no adverse effects, immobility appropriate to procedure being performed), multiple drugs may be used in combination. It is imperative that practitioners using drugs for sedation/analgesia in children be aware of the adverse effect profile(s) of these drugs, both individually and in combination. The purpose of this review is to describe the adverse effects of sedative and reversal agents currently used in paediatric sedation/analgesia.     

New oral H1 antihistamines in children: facts and unmeet needs

Background: Second‐generation antihistamines differ from first‐generation ones because of their elevated specificity and affinity for peripheral H1‐receptors and because of their lower penetration to the central nervous system, having fewer sedative effects as a result. Over the last few years, new compounds with different pharmacokinetic properties have been synthesized. More recent improvements of the molecules, generally in the form of active metabolites, led to the synthesis of new‐generation antihistamines. Methods: Recommendations on the minimum criteria that would have to be met for compounds to be classified as new‐generation antihistamines have been recently established by a consensus statement. In the past, the pharmacokinetics and pharmacodynamics of H1 antihistamines have not been optimally investigated in the pediatric population, especially in infants and young children. Results: The pharmacology of second‐generation H1 antihistamines has been investigated relatively deeper than old antihistamines in children. In the pediatric population, clinical studies with new‐generation antihistamines are still limited in number and, with rare exceptions, of brief duration. Comparative trials on the efficacy and safety between different compounds are also lacking. Conclusions: Properly designed, long‐term trials with new‐generation H1 antihistamines need to be performed in single age groups, in order to better define the effects of these drugs in all pediatric population.     

Patterns of concomitant prescription,over-the-counter and natural sleep aid use over a 12-month period: a population based study

Study ObjectivesConcomitant patterns of sleep aid use may provide insight for understanding the transition to chronic sleep medication use. Therefore, we sought to characterize the trajectories of concomitant natural product (NP), over-the-counter (OTC), and prescribed (Rx) sleep aid use in a population-based sample over 12-months.MethodsSelf-reported data on the use of NP, OTC, and Rx sleep aids were extracted from a Canadian longitudinal study on the natural history of insomnia (N = 3416, M age = 49.7 ± 14.7 years old; 62% women) at baseline, 6-month, and 12-month. Latent class growth modeling was used to identify latent class trajectories using MPlus Version 7. Participants completed a battery of clinical measures: Ford Insomnia Response to Stress Test, abbreviated Dysfunctional Beliefs and Attitudes about Sleep Scale, Beck Depression Inventory, Insomnia Severity Index and, the Pittsburgh Sleep Quality Index. Associations between class membership and baseline covariates were evaluated.ResultsConcurrent sleep aid use fell into six distinct latent class trajectories over a 12-month period: Minimal Use (74.5%), Rx-Dominant (11.3%), NP-Dominant (6.3%), OTC-Dominant (4.3%), Rx-NP-Dominant (2.4%), and Rx-OTC-Dominant (1.1%). The three latent classes with prominent prescribed agent use predicted greater incidence of healthcare professional consultations for their sleep (p < 0.05), poorer sleep quality (p < 0.001), elevated dysfunctional sleep beliefs (p < 0.001), and sleep reactivity (p < 0.001). Compared to the other four latent classes, clinical profiles of Rx-NP-dominant and Rx-OTC-dominant groups endorsed greater severity across measures.ConclusionsPatterns of sleep aid use may provide insight for identifying individuals who may be vulnerable to inappropriate self-medicating practices.     

Blood basophil numbers in chronic ordinary urticaria and healthy controls: diurnal variation, influence of loratadine and prednisolone and relationship to disease activity

BACKGROUND: The basopenia of chronic urticaria relates to histamine releasing autoantibodies in the serum of patients with autoimmune urticaria. This reduction in circulating basophils may be due to active recruitment into weals. If so, it might be expected that numbers in blood would be reduced when urticaria is active and increased after treatment. The primary aim of this study was to look at diurnal variation of basophil numbers in patients with chronic ordinary urticaria (not physical or vasculitic) in relation to disease activity and the effect of treatment with antihistamines and corticosteroids, and to compare the results with healthy controls. A secondary aim was to compare a standard manual counting method with automated basophil counts and to look at numbers of other circulating leucocytes that might be relevant to urticaria pathogenesis. METHODS: Manual basophil counts using a toluidine blue stain and automated 5-part differentials (Coulter Gen. S) were performed at 4-hourly intervals from 08.00 to 20.00 in 10 healthy controls (six women, age 24 to 63 years) and seven chronic urticaria patients (five women, 24 to 50 years). All chronic urticaria patients had severe daily or almost daily urticaria. Only one of six chronic urticaria sera showed in vitro basophil histamine releasing activity. Counts were performed without treatment, after a week of taking loratadine 10 mg daily and after 3 days of adding prednisolone at 0.6 mg/kg/day (maximum 40 mg). Daily urticarial activity scores (UAS) were derived from weal numbers and itch, maximum 7. RESULTS: There was no significant overall diurnal variation of basophil numbers in healthy controls or chronic urticaria patients. Mean (SE) manually counted basophil were higher in healthy controls than chronic urticaria (43.4/ microL (2.1) vs. 4.4 (0.8), P < 0.001). Basophil counts were reduced in healthy controls on steroids (19.2 (1.9), P < 0.001) but increased in chronic urticaria (8.9 (1.9), P < 0.001). Loratadine did not influence them. UAS fell on treatment (3.3 (0.4) baseline, 1.4 (0.5) on loratadine and 0.5 (0.2) on prednisolone with loratadine, P < 0.001). There was a negative linear correlation between basophil numbers and UAS in untreated chronic urticaria patients (P = 0.001, Spearman rank correlation). Manual and automated basophil counts showed poor agreement. Lymphocyte numbers were lower in chronic urticaria than healthy controls. Neutrophils increased whereas lymphocytes and eosinophils decreased in all subjects on prednisolone. They were unaffected by loratadine. CONCLUSION: The results are consistent with the hypothesis that circulating basophils may be recruited from blood into urticarial weals during disease activity. Automated counts are not suitable for assessing basophil numbers in chronic urticaria. The relevance of reduced lymphocyte numbers in chronic urticaria needs to be explored.     

Cimetidine for mucosal warts in an HIV positive adult

An HIV-positive adult presented with recalcitrant mucosal warts which failed to respond to therapies including curettage and cautery, cryocautery and oral etretinate. There was an apparent complete resolution of intra- and perioral warts with the histamine H2 antagonist, cimetidine.     

A comparison of the efficacy of Cetirizine and terfenadine

In a 20-d, double-blind, randomized, parallel study, the efficacy of cetirizine and terfenadine was compared in 30 patients with chronic idiopathic urticaria. Subjects were randomly divided into two 15-patient groups. The first group was given cetirizine (10 mg once daily); the second terfenadine (60 mg twice daily). Cetirizine proved to be more effective than terfenadine in controlling urticaria symptoms. In fact, the score of the investigators' overall assessment was signifieantly lower in the cetirizine-treated group than in the terfenadine-treated group. Moreover, patient evaluation by a visual analog scale and symptoms assessed on a 4-point scale showed a better improvement in the cetirizine group. The number and severity of side-effects were similar in both treatment groups.     

Effect of a non-sedative antihistaminic (loratadine) in moderate asthma

Seventeen patients with perennial asthma, stable on a moderate dose of inhaled steroid, participated in a crossover study comparing the clinical effect of a non-sedative, potent and highly selective H1 antagonist (loratadine 10 mg) with placebo. Each treatment period began with 2 weeks run-in followed by 8 weeks on either antihistamine or placebo. During the 8-week periods inhaled steroid was gradually tapered according to a fixed scheme. One patient was withdrawn from active treatment and three from placebo periods because of decreasing lung function (P greater than 0.1). Among the remaining 13 patients there was a threefold (1.8-4.8) decrease in the bronchial sensitivity to histamine during treatment with antihistamine compared to placebo (P less than 0.01). There was a trend in favour of active treatment with regard to changes in all symptom scores, lung function and use of escape medication, but these differences were not statistically significant. The increase in FEV1 was less than 5% of predicted normal (P less than 0.05). We concluded that the bronchial response to histamine can be attenuated by loratadine, an oral H1 receptor antagonist, but further studies are necessary to assess the clinical usefulness and place of loratadine in the therapy of asthma.     

Peripheral antihistamine and central sedative effects of single and continuous oral doses of cetirizine and hydroxyzine

Summary The peripheral histamine-inhibiting and central sedative effects of single oral doses (SOD) and of repeated administration for one week (steady state, SS), of 20 mg hydroxyzine HCL and 10 mg cetirizine have been assessed in 12 healthy volunteers, in a double-blind placebo-controlled cross-over study. Peripheral H₁-receptor antagonism was estimated as the reduction in the area of the flare and the duration of the itch after intradermal injection of histamine 0.1 and 1.0 g. CNS effects were assessed by a battery of computerized neuropsychological tests and seven visual analogue scales. Drug compliance was ascertained by plasma level determinations.Cetirizine 10 mg (SOD) produced a more pronounced peripheral effect than 20 mg hydroxyzine, whereas hydroxyzine but not cetirizine, showed a significant sedative action in the relevant rating scales. These effects vanished during steady state, suggesting adaptation to the initial sedative effect of hydroxyzine in most of the subjects.No sedative effect of cetirizine was demonstrated. There was no impairment at group level in the neuropsychological tests after the SOD or SS treatment. However, six subjects who showed sedation in the analogue ratings after hydroxyzine, displayed significantly impaired performance after hydroxyzine SOD.The findings are discussed in relation to the individual characteristics of the study groups.     

Effects of topical budesonide and levocabastine on nasal symptoms and plasma exudation responses in seasonal allergic rhinitis

This study compares the effects of two topical nasal treatments for allergic rhinitis, budesonide and levocabastine, on symptom development during seasonal pollen exposure. Additionally, the protective effects of drug treatments on allergen-challenge-induced responses (symptoms and microvascular exudation of plasma) are examined late into the pollen season. Forty-four patients with seasonal allergic rhinitis to birch pollen participated in this single-blind, randomized, and placebo-controlled study. Topical nasal treatment with either levocabastine (200 p.g b.i.d.: n = 16), budesonide (200 μg b.i.d.; n = 16), or placebo (n= 12) was instituted before the start of the pollen season and continued for 5 weeks until the end of the birch pollen season. The participants kept diaries for scores of nasal and ocular symptoms. Nasal allergen challenges with increasing doses of a birch pollen extract (10², 10³ and lC SQ-U) were carried out both before, when patients were asymptomatic and without treatment, and late into the pollen season. A nasal lavage followed each challenge, and the lavage fluid levels of albumin were measured as an index of the acute inflammatory response of the allergic mucosa. The birch pollen season was rather mild, producing only small increases in nasal symptoms. Budesonide treatment reduced the total nasal symptoms compared to placebo (P<0.01) and to levocabastine (P<0.05), while levocabastine treatment did not differ significantly from placebo. Ocular symptoms and use of rescue medication did not differ between placebo and the active treatments. At the end of the pollen season, both treatments reduced allergen-challenge-induced nasal symptoms compared to placebo (P<0.01). Only budesonide reduced allergen-challenge- induced increments of albumin levels in postchallenge nasal lavage fluids (P<0.05, in comparison with placebo). The results suggest that budesonide reduces both seasonal and allergen-challenge-induced nasal symptoms, while levocabastine is effective against allergen-challenge-induced symptoms also during the season. In addition, the topical steroid treatment, but not the antihistamine, inhibits the inflammatory exudation evoked by allergen challenge in patients with active seasonal disease.