Kay Brune

Friedrich-Alexander-University of Erlangen-Nürnberg | FAU · Department of Experimental and Clinical Pharmacology and Toxicology

The voltage-gated sodium channel subtype NaV1.8 is expressed in the peripheral nervous system in primary afferent nociceptive C-fibers and is essential for noxious cold signaling. We utilized functional magnetic resonance imaging on NaV1.8-deficient (NaV1.8−/−) compared with wildtype (WT) mice to identify brain structures decoding noxious cold and/...

Vor 130 Jahren wurde durch einen Zufall die antipyretische Wirkung des Acetanilids, eines direkten Abkömmlings des Anilins entdeckt. Trotz gefährlicher Methämoglobinbildung fand Acetanilid und das daraus entwickelte Phenacetin weltweit Anwendung. Phenacetin kam nach 50 Jahren intensiven Gebrauchs in Verdacht, Nierenschäden auszulösen. Dieses Proble...

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the action of many traditional NSAIDs, diclofenac inhibits cyclooxygenase (COX)-2 enzyme with greater potency than it does COX-1. Similar to other NSAIDs, diclofenac is associated with...

Non-steroidal anti-inflammatory drugs (NSAIDs), which act via inhibition of the cyclooxygenase (COX) isozymes, were discovered more than 100 years ago. They remain a key component of the pharmacological management of acute and chronic pain. The COX-1 and COX-2 isozymes have different biological functions; analgesic activity is primarily (although n...

Acetaminophen/paracetamol is the most widely used drug of the world. At the same time, it is probably one of the most dangerous compounds in medical use, causing hundreds of deaths in all industrialized countries due to acute liver failure (ALF). Publications of the last 130 years found in the usual databases were analyzed. Personal contacts existe...

A series of cases of postoperative bleeding were reported to the Drug Commission of the German Medical Association (Arzneimittelkommission der deutschen Ärzteschaft, AkdÄ) within the spontaneous reporting system after the regimen for postoperative pain treatment was changed from diclofenac (150 mg per day) to celecoxib (400 mg per day). All patient...

Acetaminophen (APAP)/paracetamol is one of the most commonly used over-the-counter drugs taken worldwide for treatment of pain and fever. Although considered as safe when taken in recommended doses not higher than 4 g/day, APAP overdose is currently the most important cause of acute liver failure (ALF). ALF may require liver transplantation and can...

Cyclooxygenase (COX) inhibitors are widely used to relieve musculoskeletal pain. COX inhibitors are a group of heterogenous substances including non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen). Moreover, various selective cyclooxygenase-2 (COX-2) inhibitors with improved gastrointestinal tolerability as compared with...

Aims Computer-assisted signal generation is an important issue for the prevention of adverse drug reactions (ADRs). However, due to poor standardization of patients' medical data and a lack of computable medical drug knowledge the specificity of computerized decision support systems for early ADR detection is too low and thus those systems are not...

To prevent pain inhibiting their performance, many athletes ingest over-the-counter (OTC) analgesics before competing. We aimed at defining the use of analgesics and the relation between OTC analgesic use/dose and adverse events (AEs) during and after the race, a relation that has not been investigated to date. Prospective (non-interventional) coho...

Administering cyclooxygenase-2 inhibitors preoperatively appears attractive since these drugs reduce post-operative pain, but do not increase the risk of post-operative bleeds, asthmatic attacks and stress-related gastrointestinal ulcers. In a former investigation, we could show that post-operative administration of etoricoxib reduces prostaglandin...

Nicht-steroidale Antiphlogistika sind als Schmerzmittel unverzichtbar. Sie stehen wegen unerwunschter Arzneimittelwirkungen (zuletzt: Herz-Kreislauf-Erkrankungen) in der offentlichen Kritik. Gerade altere Menschen konnen ohne diese Wirkstoffe kaum auskommen. Da es an Alternativen mangelt, geht es darum, diejenigen Patienten zu erkennen, die ein bes...

Paracetamol is recommended as first-line therapy for pain associated with osteoarthrosis and is one of the most widely used over-the-counter analgesic drugs worldwide. Despite its extensive use, its mode of action is still unclear. Although it is commonly stated that paracetamol acts centrally, recent data imply an inhibitory effect on the activity...

At first glance, the title of the article published by Doherty et al 1 (see page 1534) does not promise much. Who would be interested in reading an investigation comparing two old well-known analgesics with each other or combinations of both? At a second glance, however, this cautious and excellent long-term study reveals many new and important fin...

Patients with arthritis frequently are at increased risk for future cardiovascular (CV) events. We investigated the performance of the cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP) for predicting CV events in patients with arthritis taking chronic nonsteroidal antiinflammato...

There has been a consistent gap in understanding how TNF-alpha neutralization affects the disease state of arthritis patients so rapidly, considering that joint inflammation in rheumatoid arthritis is a chronic condition with structural changes. We thus hypothesized that neutralization of TNF-alpha acts through the CNS before directly affecting joi...

There has been a consistent gap in understanding how TNF-α neutralization affects the disease state of arthritis patients so rapidly, considering that joint inflammation in rheumatoid arthritis is a chronic condition with structural changes. We thus hypothesized that neutralization of TNF-α acts through the CNS before directly affecting joint infla...

Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the alpha2delta family calcium c...

Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the α2δ family calcium channel s...

In den letzten 10 Jahren beschäftigten sich fast 10.000 Publikationen mit dem kardiovaskulären Risiko der so genannten Zyklooygenase-2-Hemmer. Dabei zeigte sich, dass alle Inhibitoren der Zyklooxygenasen (COX), selektive genauso wie nichtselektive, mit einem erhöhten kardiovaskulären Risiko einhergehen. Da diese Pharmaka inklusive des Paracetamols...

Cyclo-oxygenase (COX) inhibitors are widely used to relieve musculoskeletal pain. These agents block the production of prostaglandins (PGs) at sites of inflammation by inhibiting the activity of two COX enzymes necessary for PG production and normal organ homeostasis. Inhibition of PG production at sites unrelated to pain is associated with adverse...

During the last decade there have been nearly 10,000 publications dealing with the cardiovascular risk of cyclooxygenase inhibitors and it can be concluded that the use of both selective and non-selective inhibitors is accompanied by a substantial cardiovascular risk (e.g. infarction, thromboembolic events, cardiac insufficiency and possibly stroke...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Die Anwendung von Komplementär- und Alternativmethoden, wie Homöopathie, anthroposophische Arzneimittel, Bachblütentherapie, und andere besondere Heilweisen entziehen sich der wissenschaftlichen Bewertung. Auf sie sind die üblichen Kriterien der wissenschaftlichen Beweisführung für evidenzbasierte Empfehlungen nicht anwendbar, oder die Anwendung de...

The perioperative administration of selective cyclooxygenase-2 (COX-2)-inhibitors to avoid postoperative pain is an attractive option: they show favorable gastro-intestinal tolerability, lack inhibition of blood coagulation, and carry a low risk of asthmatic attacks. The purpose of this study was to determine the cerebrospinal fluid (CSF), plasma,...

Seit Juni 2006 haben Fachvertreter aus 33 medizinischen und nicht-medizinischen Fachgesellschaften in einer Arbeitsgruppe begonnen, die Nationalen Versorgungsleitlinien Kreuzschmerz zu erarbeiten (S3-Niveau). Die Arbeiten wurden von der Ärztlichen Zentralstelle für Qualitätssicherung in der Medizin (ÄZQ, als Institut der Bundesärztekammer) und der...

This functional magnetic imaging study investigated the functional implications of genetic modification and pharmacological intervention on cerebral processing of heat-induced nociception in mice. Comparing dynorphin-overexpressing dream(-/-) with wild-type mice, smaller activated cortical and limbic brain structure sizes could be observed. Moreove...

Non-steroidal, anti-inflammatory drugs are the most widely used remedies worldwide. Drug interactions are frequent, life threatening ones are rare: Bleeds on the basis of inhibition of platelet aggregation and loss of organ protection (GI-tract), thrombotic events due to loss of vasoprotection and increased propensity for blood coagulation (stroke)...

The human organic anion-transporting polypeptide 2A1 (OATP2A1) is a prostaglandin transporter expressed in several tissues and plays an important role for local distribution of prostaglandins, which contribute to the integrity of gastric mucosa. Blockade of prostaglandin pathways by cyclooxygenase (COX) inhibitors has been associated with serious s...

The female gender appears to suffer from more adverse drug reactions (ADRs) than the male gender. So far, there has been no epidemiologic study analyzing gender-based differences in drug prescribing and its ADR risks. The aim of the present study was to establish a drug risk stratification adjusted to age, number of prescriptions and drug classes w...

Zyklooxygenasehemmer (NSAR, Coxibe) gehören zu den meist verwendeten Arzneimitteln. Interaktionen sind daher häufig und meist unvermeidlich. Wenige von davon sind allerdings akut lebensgefährlich. Dazu gehören Blutungen aufgrund gehemmter Plättchenaggregationsfähigkeit, thromboembolische Ereignisse aufgrund der Hemmung vaskulärer Schutzfunktionen,...

This study aims to describe the drug use on a Neonatal Intensive Care Unit (NICU) at a University Children's Hospital in Germany, to investigate the licensing status of the drugs used and to conclude critical areas in neonatal intensive care to support prioritisation of future research. An 11-month, prospective cohort study was conducted on the NIC...

The discovery of the mode of action of all non-opioid analgesics (inhibitors of cyclooxygenases; COX) has led to a better understanding of traditional drugs, in particular acetaminophen and aspirin. It also led to the discovery of the so-called COX-2 selective inhibitors or coxibs which - after having been enthusiastically welcomed - were partly wi...

The discovery of the mode of action of all non-opioid analgesics (inhibitors of cyclooxygenases; COX) has led to a better understanding of traditional drugs, in particular acetaminophen and aspirin. It also led to the discovery of the so-called COX-2 selective inhibitors or coxibs which - after having been enthusiastically welcomed - were partly wi...

The discovery of the mode of action of all non-opioid analgesics (inhibitors of cyclooxygenases; COX) has led to a better understanding of traditional drugs, in particular acetaminophen and aspirin. It also led to the discovery of the so-called COX-2 selective inhibitors or coxibs which - after having been enthusiastically welcomed - were partly wi...

The discovery of the mode of action of all non-opioid analgesics (inhibitors of cyclo-oxygenases; COX) has led to a better understanding of traditional drugs, in particular acetaminophen and aspirin. It also led to the discovery of the so-called COX-2 selective inhibitors or coxibs which - after having been enthusiastically welcomed - were partly w...

This report describes a young woman who developed dysmenorrhoea at the age of 12. She received a levonorgestrel (LNg)-releasing intrauterine device at the age of 21, and this was replaced twice within 8 years. At the age of 28, she started to have multiple bone and joint pain (predominantly low back pain), which, after intensive diagnostic of blood...

Lumiracoxib is a selective cyclo-oxygenase 2 (COX-2) inhibitor used for symptomatic treatment of osteoarthritis and acute pain. Among the available COX-2 inhibitors, lumiracoxib is the only compound with gastrointestinal benefit in patients with osteoarthritis that has been demonstrated in a large outcome study.1 Several countries have approved lu...

Traditional nonsteroidal anti-inflammatory drugs block cyclooxygenase (COX). They are the most widely used drugs for pain relief. They are indispensable for their effects but are condemned for their adverse drug reactions. Two COX inhibitors, acetaminophen and aspirin, are the most widely used over-the-counter drugs. They have low (but useful) ther...

Introduction, Antipyretic (or nonopioid) analgesics are a group of heterogenous substances including acidic (nonsteroidal anti-inflammatory drugs [NSAIDs]) and nonacidic (acetaminophen, pyrazolinones) drugs. Moreover, various selective cyclooxygenase-2 (COX-2) inhibitors with improved gastrointestinal tolerability compared with conventional NSAIDs...

Within the past 20 years many cyclooxygenase (COX) inhibitors were removed for unwanted drug effects shortly after entering the drug market (e.g. benoxaprofen and isoxicam), whereas others (e.g. diclofenac and ibuprofen) were not. This has continued with the suspension of the sale of the COX-2 inhibitors rofecoxib, valdecoxib and lumiracoxib, where...

Several publications indicate that the female gender experiences a higher incidence of adverse drug reactions (ADRs) than does the male gender. The reasons, however, remain unclear. Gender-specific differences in the pharmacokinetic and pharmacodynamic behaviour of drugs could not be identified as an explanation. The aim of this study was to analys...

we investigated whether higher concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts cardiovascular adverse events (CV-AEs) in patients with osteoarthritis treated with antiinflammatory drugs. NT-proBNP was measured in baseline samples from 433 patients enrolled in a prospective randomized study designed to test the thera...

Over the last few years, there has been concern regarding the cardiovascular safety of selective cyclooxygenase (COX)-2 inhibitors and high-dose regimens of nonsteroidal anti-inflammatory drugs (NSAIDs). On the other hand, those compounds which elicit an almost complete (> 95%) and continuous suppression of platelet COX-1 may represent an exception...

For more than three decades, acetaminophen (INN, paracetamol) has been claimed to be devoid of significant inhibition of peripheral prostanoids. Meanwhile, attempts to explain its action by inhibition of a central cyclooxygenase (COX)-3 have been rejected. The fact that acetaminophen acts functionally as a selective COX-2 inhibitor led us to invest...

Attempts to substitute animal experiments with in vitro or in silico methods were of limited success when complex (regulatory) processes, e.g. of the cardiovascular, metabolic or neuronal system, were to be analysed. Consequently, strategies to reduce the number of and the burden placed on experimental animals in these fields of research are requir...

Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment. A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology. Facilitation of spinal gamma-aminobut...

The arteriovenous loop (AV loop) model is gaining importance as a means of initiating and sustaining perfusion in tissue engineering constructs in vivo. This study represents an attempt to dissect the morphology of early arterialization and angiogenesis in the AV loop in a fibrin matrix with special focus on the interpositional venous graft (IVG) s...

Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment. A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology. Facilitation of spinal gamma-aminobut...

In recent studies one serine residue (Ser-346) within the protein-kinase-A (R-E-S-R) consensus sequence of the GlyRalpha3 intracellular loop has proven to be an essential target for prostaglandin-E(2)-mediated phosphorylation, which further modulates spinal nociceptive transmission and central inflammatory pain sensitization. In the present study w...

Non-steroidal, anti-inflammatory drugs (NSAIDs) are still the most widely used drugs worldwide. The introduction of selective cyclooxygenase (COX)-2 inhibitors has led to compounds which appear less damaging to the gastrointestinal tract, but possibly more risky to the cardiovascular system than older drugs. None has as yet reached OTC-status. This...

We determined in vitro the potency of macrolides as P-glycoprotein inhibitors and tested in hospitalised patients whether coadministration of P-glycoprotein inhibitors leads to increased serum concentrations of the P-glycoprotein substrates digoxin and digitoxin. In vitro, the effect of macrolides on polarised P-glycoprotein-mediated digoxin transp...

Following the withdrawal of rofecoxib and valdecoxib, the discussion concerning selective cyclo-oxygenase (COX)-2 inhibitors was often characterized more by emotions than scientific evidence. In fact, the original rationale of these substances is still valid, in that selective COX2 inhibitors cause significantly fewer severe side effects in the gas...

Antiphlogistic analgesics comprise the most widely used class of drugs worldwide. These compounds derive more or less directly from three prototypes which were discovered about 130 years ago in Central Europe: acetylsalicylic acid (aspirin), acetanilide (the forerunner of acetaminophen), and phenazone. All of them are still available. Attempts to i...

Dipyrone (INN, metamizol) is a common analgesic used worldwide. Its widespread prescription or over-the-counter use in many countries (e.g., Brazil, Israel, Mexico, Russia, Spain) requires insight into its mode of action. This study therefore addressed the impact of its metabolites 4-methyl-amino-antipyrine (MAA) and 4-amino-antipyrine (AA) on peri...

Antiphlogistische Analgetika sind die weltweit am meisten gebrauchten Arzneistoffe. Sie haben sich in den vergangenen 130 Jahren aus den Salicylaten, den Inhaltsstoffen zahlreicher Pflanzen, aus dem auf der Suche nach einem Ersatzstoff für das Chinidin in Erlangen synthetisierten Phenazons und aus dem zufällig in Straßburg entdeckten Acetanylid (Vo...

The aim of this study was to determine the analgesic effect of acetaminophen compared to a combination of both caffeine and acetaminophen or caffeine alone using tonic and phasic pain stimulation. Twenty-four subjects were treated orally with 1000 mg acetaminophen, 130 mg caffeine, and a combination of both in a 4-way crossover, double-blind, place...

Inhibitors of cyclooxygenases (COXs) are the most widely used drugs. They reduce discomfort and fever, inhibit peri-operative and inflammatory pain. These effects are largely mediated by inhibition of cyclooxygenase-1 and -2 (COX-1 and COX-2)-enzymes found throughout the body producing prostaglandins, which are important mediators of pain and fever...

Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the pathogenesis of acute and chronic lung disease as a major regulator governing the functions of granulocyte and macrophage lineage populations. Chronic obstructive pulmonary disease (COPD) is a disease characterized by lung inflammation with accumulation of neut...

Unter dem Begriff der rheumatischen Erkrankungen werden schmerzhafte, entzündliche und degenerative Struktur- und Funktionsstörungen des muskuloskelettalen Systems zusammengefasst. Bei Chronifizierung können sie zu Destruktionen und Bewegungsunfähigkeit führen. Leitsymptom der rheumatischen Erkrankungsformen ist der „wandernde“ (griech. rhein = fli...