Development of monolithic matrix type transdermal patches containing cinnarizine: Physical characterization and permeation studies

To overcome the problems associated with bioavailability and systemic side effects of the drug by oral administration, monolithic matrix type transdermal patches containing cinnarizine (CNZ) were developed. For this purpose, films based on hydroxypropyl methylcellulose and polyvinylpyrrolidone as matrix-forming polymers were designed. Physical characteristics of transdermal films and drug-excipient compatibility were investigated. Factors affecting in vitro drug release and ex vivo skin penetration and permeation of the drug were studied. It was confirmed that films displayed sufficient flexibility and mechanical strength for application onto the skin for a long time period. Ex vivo penetration experiments gave satisfactory results for transdermal drug delivery through rat skin. The parameters determining good skin penetration were also evaluated. The highest drug permeation rate was obtained with incorporation of Transcutol® (0.102 mg/cm2/h) into the base CNZ formulation, followed by propylene glycol (0.063 mg/cm2/h), menthol (0.045 mg/cm2/h), and glycerin (0.021 mg/cm2/h) as penetration enhancers (p < 0.05). As a result, the developed transdermal patches of CNZ may introduce an alternative treatment for various conditions and diseases such as idiopathic urticarial vasculitis, Ménière's disease, motion sickness, nausea, and vertigo. Thus, the risk of systemic side effects caused by the drug can be reduced or eliminated

Molecular Diversity of Anesthetic Actions Is Evident in Electroencephalogram Effects in Humans and Animals.

Anesthetic agents cause unique electroencephalogram (EEG) activity resulting from actions on their diverse molecular targets. Typically to produce balanced anesthesia in the clinical setting, several anesthetic and adjuvant agents are combined. This creates challenges for the clinical use of intraoperative EEG monitoring, because computational approaches are mostly limited to spectral analyses and different agents and combinations produce different EEG responses. Thus, testing of many combinations of agents is needed to generate accurate, protocol independent analyses. Additionally, most studies to develop new computational approaches take place in young, healthy adults and electrophysiological responses to anesthetics vary widely at the extremes of age, due to physiological brain differences. Below, we discuss the challenges associated with EEG biomarker identification for anesthetic depth based on the diversity of molecular targets. We suggest that by focusing on the generalized effects of anesthetic agents on network activity, we can create paths for improved universal analyses.

Retrospective Comparison between the Effects of Propofol and Inhalation Anesthetics on Postoperative Recurrence of Early- and Intermediate-Stage Hepatocellular Carcinoma.

OBJECTIVE: Previous studies have reported that propofol has antitumor, anti-inflammatory, and antioxidant effects in addition to its anesthetic properties. To confirm this, a retrospective investigation was conducted to determine whether different anesthetic agents, particularly propofol and inhalation anesthetics, have an effect on the recurrence of hepatocellular carcinoma (HCC) in patients who were diagnosed with primary HCC and underwent laparoscopic hepatectomy. SUBJECTS AND METHODS: Patients with Barcelona Clinic Liver Cancer stages 0, A, and B HCC, who underwent laparoscopic hepatic resection, were enrolled in this study. Post-operative HCC recurrence, which was determined from postoperative liver CT, was evaluated 24 months postoperatively with respect to the main anesthetic agents. The characteristics of HCC and other patient-related or surgery-related variables were evaluated together. RESULTS AND CONCLUSION: During the 24-month period after hepatic resection, less HCC patients in the propofol group than in the inhalation group recurred (p = 0.046). The mean time to recurrence was 20.8 months (95% CI, 19.7-22.0) and 19.1 months (95% CI, 17.8-20.4) in the propofol group and the inhalation group, respectively. In addition, multivariable Cox proportional regression analysis revealed that the propofol group showed significantly decreased recurrence versus the inhalation group (hazard ratio, 0.57; 95% CI, 0.47-0.69; p = 0.029). When propofol was used as the main general anesthetic agent for laparoscopic hepatic resection, the postoperative 2-year recurrence rate decreased in early- and intermediate-stage HCC.

Opioid Free Anaesthesia and Cancer.

Opioid-free anesthesia is revolutionizing anesthetic practices for its potential benefits in selected patients. Opioid-free anesthesia represents a step forward in anesthetic practice as it has been suggested to provide potential clinical benefits for selected patients. Opioid-free anesthesia spares the use of opioids and involves the administration of multiple adjuvant anesthetics, which may have an impact on cancer progression. All this have added to the growing interest in the immune response to anesthetics, making opioid-free anesthesia a promising avenue for future research. Assessing the role of anesthetics in immunomodulation in the surgical setting is challenging, and results are often contradictory. Indeed, there is a scarcity of data of studies on humans, which hinder the interpretation of results. However, promising evidence has been published that cancer progression can be delayed by the administration of specific anesthetic agents.

Choice of Perioperative Anesthetic Medications in Patients Undergoing Bariatric Surgery.

The prevalence of obesity is increasing globally. Rational perioperative anesthetic drug selection and administration require knowledge of how obesity interacts with those drugs. In this review, we summarize different aspects of the anesthetic agents, including pharmacokinetics (PK), pharmacodynamics (PD) and clinical application of the most commonly used medications with particular focus on the enhanced recovery of the obese patient.

Anestesia en dermatología / Anesthesia in dermatology

En la práctica dermatológica, se realizan diversos procedimientos quirúrgicos y estéticos que pueden causar dolor a los pacientes. Actualmente en el mercado se dispone, de un amplio arsenal de drogas que permiten lograr una anestesia segura y eficaz. Existen diferentes modalidades y técnicas de anestesia, según el tipo de intervención y el segmento corporal en el cual se va a realizar el procedimiento. Los efectos adversos de los diferentes anestésicos están bien definidos y se deben tomar ciertas precauciones en poblaciones especiales donde el riesgo de complicaciones es mayor. Es de fundamental importancia que el clínico posea un acabado conocimiento de los diversos fármacos utilizados en anestesia, para poder minimizar las complicaciones derivadas de su administración.

In dermatological practice, various surgical and cos-metic procedures are performed that can cause pain to patients. A large stock of drugs is now available on the market to provide safe and effective anesthesia. There are different modalities and techniques of anesthesia, depending on the type of intervention and the body segment in which the procedure will be performed. The adverse effects of different anesthe-tics are well defined and certain precautions should be taken in special populations where the risk of complications is greater. It is fundamental that the clinician has a thorough knowledge of the various drugs that can be used in anesthesia, in order to minimize complications arising from its administration

Anestesia regional mandibular con modificación de tacher / Regional anesthesia with tacher modification

La anestesia dental es un tema importante en la práctica cotidiana enlas diversas especialidades odontológicas, motivo por el que nace lanecesidad de hacer una revisión de las técnicas anestésicas actuales. Con base en nuestra experiencia nos dimos cuenta de que la practicidad de utilizar referencias anatómicas confiables nos sirven de guía para obtener una mejor efi cacia al momento de anestesiar el nervio alveolar mandibular. Lo anterior se traduce en menor dolor posterior a la punción, menor dosis anestésica y una profundidad anestésica adecuada en tejidos blandos y duros, del mismo modo nos permite llevar a cabo diversos tratamientos con un margen de seguridad más amplio y disminuir losriesgos de toxicidad. Cabe mencionar que dicha técnica se ha incluido enla práctica clínica cotidiana en nuestra práctica privada en el Postgradode Ortodoncia del Instituto universitario Franco Inglés de México yen el Servicio de Cirugía Oral y Maxilofacial del Centro Médico Lic.Adolfo López Mateos en la ciudad de Toluca, Estado de México.

Dental anesthesia is an important issue in daily practice in the variousdental specialties, which is why the need for a review of the anesthetictechnique arises. Based on our experience, we realized the practicalityof using reliable anatomical references that serve as a guide, to obtaina better effi cacy when anesthetizing the mandibular alveolar nerve,resulting in less pain after puncture, lower anesthetic dose and anadequate anesthetic depth in soft and hard tissues, which allows us tocarry out various treatments with a wider margin of safety and reducethe risks of toxicity. It is worth mentioning that this technique hasbeen included in daily clinical practice in our private practice, in theorthodontic postgraduate course of the Instituto Franco in Mexico andin the oral and maxillofacial surgery service of the Licensed MedicalCenter «Adolfo Lopez Mateos¼ in the City of Toluca, State of Mexico.

Impact of Stroke Therapy Academic Industry Roundtable (STAIR) Guidelines on Peri-Anesthesia Care for Rat Models of Stroke: A Meta-Analysis Comparing the Years 2005 and 2015.

Numerous studies using rats in stroke models have failed to translate into successful clinical trials in humans. The Stroke Therapy Academic Industry Roundtable (STAIR) has produced guidelines on the rodent stroke model for preclinical trials in order to promote the successful translation of animal to human studies. These guidelines also underline the importance of anaesthetic and monitoring techniques. The aim of this literature review is to document whether anaesthesia protocols (i.e., choice of agents, mode of ventilation, physiological support and monitoring) have been amended since the publication of the STAIR guidelines in 2009. A number of articles describing the use of a stroke model in adult rats from the years 2005 and 2015 were randomly selected from the PubMed database and analysed for the following parameters: country where the study was performed, strain of rats used, technique of stroke induction, anaesthetic agent for induction and maintenance, mode of intubation and ventilation, monitoring techniques, control of body temperature, vascular accesses, and administration of intravenous fluids and analgesics. For each parameter (stroke, induction, maintenance, monitoring), exact chi-square tests were used to determine whether or not proportions were significantly different across year and p values were corrected for multiple comparisons. An exact p-test was used for each parameter to compare the frequency distribution of each value followed by a Bonferroni test. The level of significant set at < 0.05. Results show that there were very few differences in the anaesthetic and monitoring techniques used between 2005 and 2015. In 2015, significantly more studies were performed in China and significantly fewer studies used isoflurane and nitrous oxide. The most striking finding is that the vast majority of all the studies from both 2005 and 2015 did not report the use of ventilation; measurement of blood gases, end-tidal carbon dioxide concentration, or blood pressure; or administration of intravenous fluids or analgesics. The review of articles published in 2015 showed that the STAIR guidelines appear to have had no effect on the anaesthetic and monitoring techniques in rats undergoing experimental stroke induction, despite the publication of said guidelines in 2009.

Recipes for obstetric spinal hypotension: The clinical context counts.

Hypotension following obstetric spinal anaesthesia remains a common and important problem. While recent research advances have brought us closer to the perfect recipe for the obstetric spinal anaesthetic, these advances have not been translated into practical guidelines able to reduce the unacceptable number of fatalities that occur in environments where resources are limited. In South Africa, more than half of anaesthetic deaths are still related to spinal hypotension. A gap exists between the 'perfect recipe', developed from a clinical context rooted in resource-rich research environments, and its application and performance in real-world resource-poor environments - conditions experienced by more than 75% of the world's population. This review attempts to define this knowledge gap and proposes a research agenda to address the deficiencies.

Genotoxicity of Anesthetics Evaluated In Vivo (Animals).

The anesthesia has been improved all over the years. However, it can have impact on health, in both patients and animals anesthetized, as well as professionals exposed to inhaled anesthetics. There is continuing effort to understand the possible effects of anesthetics at molecular levels. Knowing the effects of anesthetic agents on genetic material could be a valuable basic support to better understand the possible mechanisms of these agents. Thus, the purpose of this review is to provide an overview on the genotoxic potential, evaluated in animal models, of many anesthetics that have already been used and those currently used in anesthesia.

Impact of anesthesia on cancer recurrence.

Surgery remains the mainstay treatment in the majority of solid cancers. Anesthetics and analgesics used during the perioperative period may modulate the innate and adaptive immune system, inflammation and angiogenesis, and have a direct effect on cancer cells that could ultimately modify oncological outcomes. For instance, volatile anesthetics and opioid analgesics have shown predominantly pro-tumor effects, while propofol, non-steroid anti-inflammatory drugs have mostly anticancer effects. Researchers have been especially interested in investigating the association between the use of regional anesthesia techniques and the postoperative survival of patients with cancers. Since the results of the current retrospective studies are conflicting, several researchers are conducting prospective randomized trials.

Parenterally administered moderate sedation and paracervical block versus general anesthesia for hysteroscopic polypectomy: a pilot study comparing postoperative outcomes.

STUDY OBJECTIVE: To compare parenterally administered moderate sedation and paracervical block versus general anesthesia during day-case operative hysteroscopy for polypectomy in terms of patients' postoperative pain perception, operating time, and postoperative drug administration. DESIGN: A pilot study (Canadian Task Force classification I). SETTING: A university hospital. PATIENTS: Women undergoing hysteroscopic polypectomy procedures (N = 56). INTERVENTIONS: Hysteroscopic polypectomy with general anesthesia or moderate parenteral sedation and paracervical block. MEASUREMENTS AND MAIN RESULTS: The patients were divided into 2 groups: 26 underwent general anesthesia (group 1), and 30 were submitted to moderate parenteral sedation and a paracervical block (group 2). General anesthesia was induced with the laryngeal mask airway with propofol (1% 1-2.5 mg/kg) and fentanyl (1-2 µg/kg) and maintained with an infusion of propofol (2% 3-5 mg/kg/h). After the procedure, patients in the general anesthesia group received postoperative analgesic medication with paracetamol (20 mg/kg) and ketorolac (0.6 mg/kg) or tramadol (2-3 mg/kg). The group receiving moderate parenterally sedation and a paracervical block received a paracervical block with mepivacaine (1% 10 mL) and lidocaine (2% 10 mL) and received fentanyl (1 µg/kg) and propofol (1% 1-3 mg/kg/h) maintaining spontaneous breathing. A blind observer recorded the operative time and the discomfort of patients using a 4-step scale (0-3). The postoperative pain assessment was performed 3 hours after the procedure with a self-administered validated tool, the Brief Pain Inventory. We found that women receiving moderate parenteral sedation and a paracervical block perceived significantly less pain in daily activity (p < .001), walking (p < .001), daily work (p < .001), relations with others (p = .007), sleep (p < .001), and pain contrasting enjoyment of life (p < .001). The total amount of time spent in the operating room in group 2 was significantly lower than in group 1 (p < .014). CONCLUSION: Moderate sedation plus a paracervical block for operative hysteroscopy is associated with reduced pain perception and a shorter operative time.

International online survey to assess current practice in equine anaesthesia.

REASONS FOR PERFORMING STUDY: Multicentre Confidential Enquiries into Perioperative Equine Fatalities (CEPEF) have not been conducted since the initial CEPEF Phases 1-3, 20 years ago. OBJECTIVES: To collect data on current practice in equine anaesthesia and to recruit participants for CEPEF-4. STUDY DESIGN: Online questionnaire survey. METHODS: An online questionnaire was prepared and the link distributed internationally to veterinarians possibly performing equine anaesthesia, using emails, posters, flyers and an editorial. The questionnaire included 52 closed, semiclosed and open questions divided into 8 subgroups: demographic data, anaesthetist, anaesthesia management (preoperative, technical equipment, monitoring, drugs, recovery), areas of improvements and risks and motivation for participation in CEPEF-4. Descriptive statistics and Chi-squared tests for comparison of categorical variables were performed. RESULTS: A total of 199 questionnaires were completed by veterinarians from 14 different countries. Of the respondents, 43% worked in private hospitals, 36% in private practices and 21% in university teaching hospitals. In 40 institutions (23%) there was at least one diplomate of the European or American colleges of veterinary anaesthesia and analgesia on staff. Individual respondents reported routinely employ the following anaesthesia monitoring modalities: electrocardiography (80%), invasive arterial blood pressures (70%), pulse oximetry (60%), capnography (55%), arterial blood gases (47%), composition of inspired and expired gases (45%) and body temperature (35%). Drugs administered frequently or routinely as part of a standard protocol were: acepromazine (44%), xylazine (68%), butorphanol (59%), ketamine (96%), diazepam (83%), isoflurane (76%), dobutamine (46%), and, as a nonsteroidal anti-inflammatory drug, phenylbutazone (73%) or flunixin meglumine (66%). Recovery was routinely assisted by 40%. The main factors perceived by the respondents to affect outcome of equine anaesthesia were the preoperative health status of the animal and training of the anaesthetist. CONCLUSIONS: Current practice in equine anaesthesia varies widely, and the study has highlighted important topics relevant for designing a future prospective multicentre cohort study (CEPEF-4). The Summary is available in Chinese - see Supporting information.

Prescription of addictive and non-addictive drugs to home-dwelling elderly.

BACKGROUND: Complex medical conditions are frequent among seniors, and their medical treatment represents a challenge. Older patients have a high rate of consumption of prescription drugs, greater risks of medication interactions, and a higher likelihood of side effects. Many common drugs used by the elderly also have addictive potential. Prescription patterns involving general practitioners (GPs) are not sufficiently known. OBJECTIVE: Our objective was to examine the regular GP role in the prescription of addictive and non-addictive drugs to home-dwelling older people in Norway. DESIGN: The study was designed as a panel data study. SETTING: Data on all prescription drugs dispensed at pharmacies to patients 70 years and older from the Norwegian Prescription Database were merged with data on GPs and GPs' patient lists from the Regular General Practitioner Database. The dataset included 624,308 patients and 4,520 GPs in the period from 2004 to 2007. OUTCOME MEASURES: Outcome measures included quantities of addictive and non-addictive drugs prescribed and dispensed per patient by the regular GP, other GPs, non-GP specialists, and hospital doctors; the number of prescribers per patient; and time trend over the observation period. RESULTS: On average, 319 defined daily doses of medication were prescribed per quarter to an older patient, 6 % of which were classified as possibly addictive medications. Of all drugs, 72 % were prescribed by the patients' regular GP, 77 % of addictives and 71 % of non-addictives. Drug quantities prescribed increased with multiple prescribers and did so to a greater extent for addictives than for non-addictives. Time trends show an increasing number of prescribers and increasing drug quantities over the observation period. CONCLUSION: The regular GP prescribes the major portion of non-addictive and, especially, addictive medications to older patients and thus holds a key role in the coordination of prescriptions to this group. Focusing on the role of the GP is important in view of the increasing time trends.

Undiagnosed myopathy before surgery and safe anaesthesia table.

Patients with muscle pathology are a challenge for anaesthesiologists because of possible life-threatening general anaesthesia complications. A review of the current medical literature on the issue clearly indicates that increasing awareness by anaesthesiologists in recent years has led to a reduction in the occurrence of adverse events in patients with diagnostically well-defined muscle disease. On the other hand, the current emerging aspect is that the great majority of complications concern subjects with clinically non-overt (silent to mildly symptomatic) and thus undiagnosed myopathy. With a view to improving prevention of possible critical anaesthesia complications in such patients, we present a "Safe Anaesthesia Table", listing both the anaesthetic drugs to be avoided and those considered harmless for myopathic patients, irrespective of age and type of pathology. In addition, a brief outline about the clinical aspects suggestive of a possible muscle pathology is also provided. Using "safe drugs" during routine surgical procedures in subjects with suspected undiagnosed myopathy will enable the anaesthesiologist to avoid delaying surgery, while protecting them from anaesthesia complications. By following this approach the presumed myopathy can be properly investigated after surgery.

Studies in animal models of the effects of anesthetics on behavior, biochemistry, and neuronal cell death.

Recent clinical studies have suggested that there is an increased risk of Alzheimer's disease (AD) in patients undergoing surgical interventions, but it is unknown whether this effect is related to anesthesia, cardiovascular complications of surgery, or associated conditions such as hypothermia. In addition, many patients, especially the elderly, present persistent post-operative cognitive deterioration after anesthesia, without clear complications during surgery. Experimental studies in animals may be helpful to dissect the pathogenic role of the different factors involved in surgery. Here, we review studies on the effects of anesthesia on neuronal function performed in tissue culture and in experimental animals. Several studies have shown that a small inhalation of anesthetics induces activation of caspases and cell toxicity on glioma and pheochromocitoma cells in culture, which is prevented by treatment with the metal chelating agent clioquinol. Exposure of old rodents to anesthesia produced memory deficits and increased levels of amyloid-ß (Aß) peptide and phosphorylated tau in brain. The effects of long term or short term repetitive exposure to small molecular weight anesthetics are more severe in transgenic AßPPswe than in wild type mice. In the former, low molecular weight increased the number of TUNEL(+) apoptotic cells and the ratio of pro-apoptotic proteins in hippocampus; reduced astroglial and increased microglial responses; increased Aß aggregates and high molecular weight peptides; abnormal chaperone responses and reduced autophagy. In conclusion, anesthetic gases induce changes which may reproduce AD pathology in mice with mutations which produced AD. It would be interesting to know whether anesthetics are risky for subjects with special genetic risk factors.

Top 60 medications used for orofacial pain treatment.

This article introduces the 60 top pharmacologic treatments provided for chronic orofacial pain patients. It explains that the majority of "chronic" orofacial pain patients will not find a "cure" to their pain with medications but may find a way to manage their pain. The medications in this article are the most commonly utilized "pain" medications and where it exists. This article reviews some of the current evidence supporting their use on chronic orofacial pain disorders.

Brain protection: current and future options.

The ability to reduce brain injury before, during or after an ischaemic injury, irrespective of the cause, remains an exciting prospect. In this article, we will discuss some of the current research behind cerebral protection, which will include the use of anaesthetic agents, as well as therapies targeted specifically at the complex cascades following brain injury.

Anaesthesia of small rodents during magnetic resonance imaging.

The use of experimental animals for magnetic resonance studies requires anaesthesia to provide immobility and acquire signals with minimal stress and maximal reproducibility. However, the conduct of anaesthesia within a magnetic resonance imaging (MRI) suite implicates many problems, because most of the anaesthetic and monitoring equipment contains ferromagnetic substances. To decrease disturbances during anaesthesia and make data interpretation more accurate, it is mandatory that investigators become familiar with methods and physiologic effects of anaesthesia under these special conditions. This article is intended to give an overview of anaesthetic medication, administration routes and practical instructions for anaesthesia in small rodents during MRI.