Topical Drug Administration

Purpose A eutectic mixture of local anesthetics (EMLA) is commonly used to provide topical anesthesia for intravenous (iv) cannulation. One of its side effects is vasoconstriction, which may render cannulation more difficult. A gel formulation of amethocaine (Ametop™) is now commercially available. The aim of this study was to compare EMLA and Ametop™ with regard to the degree of topical anesthesia afforded, the incidence of vasoconstriction and the ease of iv cannulation. Methods Thirty two ASA 1 adult volunteers had a # 16 gauge iv cannula inserted on two separate occasions using EMLA and Ametop™ applied in a double blind fashion for topical anesthesia. Parameters that were recorded after each cannulation included visual analogue pain scores (VAPS), the presence of vasoconstriction and the ease of cannulation, graded as: 1 = easy, 2 = moderately difficult, 3 = difficult and 4 = failed. Results The mean VAPS ± SD after cannulation with Ametop™ M was 12 ± 9.9 and with EMLA was 25.3 ± 16.6 (P = 0.002). Vasoconstriction occurred after EMLA application on 17 occasions and twice after Ametop™ (P = 0.001). The grade of difficulty of cannulation was 1.44 ± 0.88 following EMLA and 1.06 ± 0.25 with Ametop™ (P = 0.023). Conclusions Intravenous cannulation was less painful following application of Ametop™ than EMLA. In addition, Ametop™ caused less vasoconstriction and facilitated easier cannulation. Its use as a topical anesthetic agent is recommended, especially when iv access may be problematic. Objectif Un mélange eutectique d’anesthésiques locaux (MEAL) est souvent utilisé pour l’anesthésie topique lors d’une canulation intraveineuse (iv). La vasoconstriction, qui est l’un des effets secondaires du MEAL, peut compliquer la mise en place d’une canule. Une présentation en gel d’améthocaïne (Ametop™) est maintenant offerte dans le commerce. Le but de la présente étude était de comparer le MEAL et l’Ametop™ en regard du degré d’anesthésie topique fourni, de l’incidence de la vasoconstriction et de la facilité de la canulation iv. Méthode: On a inséré, en deux occasions séparées chez 32 volontaires adultes d’état physique ASA 1, une canuleiv de calibre 16 en utilisant en double aveugle le MEAL et Ametop™ pour réaliser l’anesthésie topique. Après chaque canulation, on a enregistré les paramètres suivants: les scores de douleur à l’échelle visuelle analogue (EVA), la présence de vasoconstriction et la facilité de canulation notée 1 = facile, 2 = modérément difficile, 3 = difficile et 4 = impossible. Résultats Les scores moyens à l’EVA ± l’écart type ont été de 12 ± 9,9 à la suite de la canulation avec Ametop™ M et de 25,3 ± 16,6 après le MEAL (P = 0,002). La vasoconstriction est survenue en 17 occasions après l’application du MEAL et deux fois plus souvent après Ametop™ (P = 0,001). Le degré de difficulté de canulation a été de 1,44 ± 0,88 après le MEAL et de 1,06 ± 0,25 après Ametop™ (P = 0,023). Conclusion La canulation intraveineuse est moins douloureuse après l’application d’Ametop™ que celle du MEAL. De plus, l’Ametop™ a provoqué moins de vasoconstriction et a facilité l’introduction d’une canule. Son usage comme anesthésique topique est recommandé, surtout lorsqu’une action rapide est nécessaire ou que l’accèsiv peut être problématique.

Mucosal (and in minor extent transcutanous) stimulation can induce local or distant mucosa secretory IgA. Liposomes and other vesicles as mucosal and transcutaneous adjuvants are attractive alternatives to parenteral vaccination. Liposomes can be massively produced under good manufacturing practices and stored for long periods, at high antigen/vesicle mass ratios. However, their uptake by antigen-presenting cells (APC) at the inductive sites remains as a major challenge. As neurotoxicity is a major concern in intranasal delivery, complexes between archaeosomes and calcium as well as cationic liposomes complexed with plasmids encoding for antigenic proteins could safely elicit secretory and systemic antigen-specific immune responses. Oral bilosomes generate intense immune responses that remain to be tested against challenge, but the admixing with toxins or derivatives is mandatory to reduce the amount of antigen. Most of the current experimental designs, however, underestimate the mu...

Clostridiopeptidase A, also called collagenase 1, is derived from fermen-tation of Clostridium histolyticum. Clostridiopeptidase A is a proteolytic enzyme capable of digesting collagen. Preparations containing clostridio-peptidase A are used topically for the debridement of dermal ulcers, ...

Cetirizine dihydrochloride (CTZ) is a second-generation histamine H1 antagonist, effective for the treatment of a wide range of allergic diseases. It has been utilized for managing the symptoms of chronic urticaria and atopic skin conditions. Thus, two novel semisolid formulations, nanoemulsion (NE) and hydrogel (HG) were developed to study their potential utility as vehicles including cetirizine (CTZ) and evaluate the potential use as topical H1-antihistamines agents. The physicochemical and stability properties of both vehicles were tested. Drug release kinetics and human skin permeation studies were performed using Franz cells. The antihistaminic activity was assayed in New Zealand rabbits and compared with two commercial first generation antihistamines. Both formulations were stable and provided a sustained drug release. Amounts of CTZ remaining in the skin were higher for HG, showing the maximum biological effect at 30 min, similar to topical first generation H1-antihistamines ...

The effects of melanocyte-stimulating hormone (alpha-MSH) and related analogs on follicular melanogenesis in the mouse (C57BL/6JA gamma) were studied. [Nle4, D-Phe7]-alpha-MSH and the related fragment analogues Ac-[Nle4, D-Phe7]-alpha-MSH4-11-NH2 and Ac-[Nle4, D-Phe7]-alpha-MSH4-10-NH2, stimulated the conversion of pheomelanogenesis to eumelanogenesis when subcutaneously injected at concentrations 100-fold lower than the native hormone, alpha-MSH. In addition, the melanotropin analogs stimulated follicular eumelanogenesis when applied topically to the skin of mice. The melanotropins were transdermally delivered to the systemic circulation as evidenced by the fact that eumelanogenesis was stimulated in hair follicles in areas distant from the site of topical application. These results demonstrate that peptide hormone analogs can be transported across the skin. The unique actions of the melanotropin analogs may relate to the fact that these peptides are nonbiodegradable and thus exert prolonged actions on melanocytes. These compounds may prove important for studies on normal integumental melanogenesis and for the treatment of hypopigmentary disorders in humans.

To achieve photoprotection indicated on the package of sunscreen products they should be used appropriately. As previously published data documented that people usually applied much less than the recommended dose, the current study was undertaken to assess whether a detailed instruction can improve the use of sunscreens.

Inhaled corticosteroids are widely used in the long-term management of asthma in children. Data on the relationship between inhaled corticosteroid therapy and osteoporotic fracture are inconsistent. We address this issue in a large population-based cohort of children aged 4-17 years in the UK (the General Practice Research Database). The incidence rates of fracture among children aged 4-17 years taking inhaled corticosteroids (n=97,387), taking bronchodilators only (n=70 984) and a reference group (n=345,758) were estimated. Each child with a non-vertebral fracture (n=23,984) was subsequently matched by age, sex, practice, and calendar time to one child without a fracture. Fracture incidence was increased in children using inhaled corticosteroids, as well as in those receiving bronchodilators alone. With an average daily beclomethasone dose of 200 microg or less, the crude fracture risk relative to nonusers was 1.10 [95% confidence interval (CI), 0.96-1.26]; with dosage of 201-400 m...

Many hospital-based studies throughout Europe have shown that a substantial number of children receive off-label prescribed drugs that lack marketing authorisation for paediatric use. Since information about the extent and characteristics of this prescribing pattern in paediatric primary health care is limited, we assessed the proportion of off-label drug prescribing for paediatric outpatients in a reference population of 350,000 children using a computerised prescription database. We also determined the adherence to a treatment guideline provided by the Stockholm county council as a quality of prescribing indicator. All drugs prescribed for children younger than 16 years of age in the Stockholm county in the year 2000 were ranked by the number of prescription items. The retrospective, descriptive analysis was restricted to those drugs that accounted for 90% of total prescribing. We calculated the proportion of off-label drug prescribing for different age and therapeutic groups with...

The murine model of cantharidin-induced ear inflammation was profiled in detail for its alignment with the human model and to explore the mechanism of anti-inflammatory activity of the macrolide antibiotics, clarithromycin and azithromycin. Ear swelling in CD1 mice persisted for 7 days, with peak intensity at 16 h after inflammation induction. As in humans, cantharidin (12.5 μg/ear) generated macrophage-inflammatory protein (MIP)-2, monocyte chemoattractant protein (MCP)-1, keratinocyte-derived chemokine (KC), interleukin (IL)-6, IL-1β, and myeloperoxidase (MPO) production, as well as neutrophil accumulation in mouse ear tissue. The tested macrolides, clarithromycin and azithromycin, administered orally (2 × 150 mg/kg) 0.5 h before and 5 h after cantharidin challenge, reduced MIP-2, MCP-1, KC, and MPO concentrations and thereby decreased ear swelling. Our results suggest that cantharidin-induced acute inflammation represents an excellent model for translational research of novel ant...

Myospherulosis is a unique, inflammatory, granulomatous lesion, which results from the action of lipid substances on extravasated erythrocytes. Petrolatum-based antibiotic ointments are the most frequent etiologic agents of iatrogenically acquired lesions. Six intraoral cases of myospherulosis are presented, including the first reported case in oral soft tissues. The literature of reported cases is summarized and the epidemiology, histopathology, and ultrastructure of the lesions are discussed. Predisposing events and recommendations for future use of petrolatum-based antibiotic ointments are presented.