Withdrawal Reactions Research Articles

Psychosomatic reactions and hypertension in stress conditions

Introduction: Psychosomatic diseases are diseases of organs, partialy induced by mental and somatic reactions to prolonged stress. Emotional factors probably play the key role in origin of psychosomatic diseases. Objective: The aim is to establish whether there is a difference in the behavior and the expression of psychosomatic reactions to stress in healthy and hypertensive population, and to prove or reject hypothesis that hypertension is associated with psychosomatic diseases. Method: The respondents were given the original questionnaire with closed questions about ways of reaction in stressful situations. Majority of emotions included fear and withdrawal. Results: Statistical analysis was conducted on a sample of 100 patients who were divided into two groups: patients with hypertension (HTA)and control group. Research hypothesis were formed: H0:NTA is not related to psychosomatic diseases; HI: HTA is related to psychosomatic diseases. As the achieved χ2 value of 44.72 is higher than critical value of χ2=24.996, with 15 degrees of freedom and level of confidence p=0.05, the zero hypothesis must be rejected and alternative hypothesis must be accepted with p>0,05 confidence value, which leads to conclusion that there is connection between HTA and psychosomatic diseases. Secondary hipothesis is also tested: H0:HTA and withdrawal reactions are not connected; H1:HTA and withdrawal reactions are connected. As the achieved χ2 value equals 29.99 is higher than critical value χ2=3.841, with 1 degree of freedom and level of confidence p=0.05, the zero hypothesis must be excluded and alternative hypothesis must be accepted with p<0.05 margin of error and certainty of p>95% which leads to conclusion that there is connection between HTA and withdrawal reactions. Conclusion: Modern science of psychosomatic diseases suggests one of the integrative models to explain psyshophysiological mechanisms causing HTA: this model includes all findings of classic and psychosomatic medical science, in attempt to explain the dynamic chain of changes that leads to final result: high blood pressure.

Effect of Nimodipine on Morphine-related Withdrawal Syndrome in Rat Model: An Observational Study.

Objective:To observe the effect of L-type calcium channel blocker like nimodipine on morphine's withdrawal when it was administered continuously along with morphine versus a single bolus dose of nimodipine, which was administered at the end of the experiment before the precipitation of withdrawal reaction in morphine-dependent rats.Materials and Methods:Four groups of adult male Wistar rats were rendered morphine dependent by subcutaneous injections of morphine at a dose of 10 mg/kg for 10 days. Nimodipine 10 mg/kg intraperitoneally (ip) administered to one group once daily before morphine administration in the entire experimental period, and another group received nimodipine only once at the end of the experiment as a single bolus dose 2 mg/kg before the administration of naloxone. Naloxone 3 mg/kg was administered ip to all the groups to precipitate withdrawal reactions. The withdrawal reactions were evaluated and scored as per the Gellert and Holtzman global withdrawal rating scale.Results:Nimodipine when administered as a single bolus dose before naloxone administration in morphine-dependant rats reduced the features of withdrawal reactions more effectively than continuous administration of nimodipine along with morphine throughout the experimental period.Conclusion:We discovered that nimodipine helps in attenuating the severity of morphine withdrawal having potential role encountered during pharmacotherapy with morphine management of opioid dependence, well memory, impairement, cell signaling and phosphorylation of neuron.

Modified Suanzaorentang Had the Treatment Effect for Generalized Anxiety Disorder for the First 4 Weeks of Paroxetine Medication: A Pragmatic Randomized Controlled Study.

Background. Paroxetine does not show satisfactory therapeutic effect for generalized anxiety disorder (GAD) patients for the first 2–4 weeks of medication. Diazepam is always concurrently used although it has some shortcomings such as physical dependence and withdrawal reactions. In this study, we aimed to identify whether modified Suanzaorentang (MSZRT), a combined Chinese formula including Suanzaorentang (SZRT) and Zhizichitang (ZZCT), could control the anxiety of GAD for the first 4 weeks of paroxetine medication. Methods. 156 GAD patients were randomized to the treatment of paroxetine, paroxetine-diazepam, or paroxetine-MSZRT for 4 weeks. Hamilton Anxiety Scale (HAMA) Test and Self-Rating Anxiety Scale (SAS) Test were determined each week as the evaluation of clinical efficacy. Adverse events (AEs) were also closely observed by performing the Treatment Emergent Symptom Scale (TESS) Test. Results. Both paroxetine-MSZRT and paroxetine-diazepam decreased more HAMA and SAS total scores than paroxetine from weeks 1 to 3. Paroxetine-MSZRT as well as paroxetine-diazepam had an obviously higher onset rate than paroxetine in each week. After 4 weeks' treatment, the overall effectiveness rate in the paroxetine-MSZRT group (90.00%) was obviously higher than those of the paroxetine group (74.42%) but did not significantly differ from the paroxetine-diazepam group (93.88%). Conclusion. MSZRT had the treatment effect for GAD when paroxetine was used for the first 4 weeks.

Injection of Toll-like receptor 4 siRNA into the ventrolateral periaqueductal gray attenuates withdrawal syndrome in morphine-dependent rats.

We assessed the role of the Toll-like receptor 4 (TLR4) gene in the ventrolateral periaqueductal gray (vlPAG) region of morphine-dependent rats on attenuating withdrawal syndrome, and regulating glutamic acid decarboxylase (GAD67), glutamic acid (Glu), and gamma-aminobutyric acid (GABA). After siRNA-mediated downregulation of TLR4, changes were observed in withdrawal behavior and downstream signaling molecules. Rats were injected into the vlPAG with TLR4 siRNA, followed by intraperitoneal injection of morphine for 5 consecutive days, and then naloxone, and the behavioral indices of morphine withdrawal were observed. 'Wet-dog' shakes, teeth chattering, and the total scores of withdrawal reactions were reduced. TLR4 expression and Glu levels were reduced, whereas GAD67 and GABA levels were increased. Overall, these findings indicate that modifying TLR4 gene expression in the vlPAG stimulates expression of the downstream signaling molecule, GAD67, which decreases Glu levels and increases GABA levels. This mechanism may explain the inhibition of withdrawal syndrome in morphine-dependent rats.

Development and Validation of a Self-reported Questionnaire for Measuring Internet Search Dependence.

Internet search has become the most common way that people deal with issues and problems in everyday life. The wide use of Internet search has largely changed the way people search for and store information. There is a growing interest in the impact of Internet search on users’ affect, cognition, and behavior. Thus, it is essential to develop a tool to measure the changes in psychological characteristics as a result of long-term use of Internet search. The aim of this study is to develop a Questionnaire on Internet Search Dependence (QISD) and test its reliability and validity. We first proposed a preliminary structure and items of the QISD based on literature review, supplemental investigations, and interviews. And then, we assessed the psychometric properties and explored the factor structure of the initial version via exploratory factor analysis (EFA). The EFA results indicated that four dimensions of the QISD were very reliable, i.e., habitual use of Internet search, withdrawal reaction, Internet search trust, and external storage under Internet search. Finally, we tested the factor solution obtained from EFA through confirmatory factor analysis (CFA). The results of CFA confirmed that the four dimensions model fits the data well. In all, this study suggests that the 12-item QISD is of high reliability and validity and can serve as a preliminary tool to measure the features of Internet search dependence.

Smoking environment cues reduce ability to resist smoking as measured by a delay to smoking task

Introduction: Environments associated with smoking may promote lapse and relapse in smokers attempting to quit. Here we examined the effects of exposure to visual smoking environment cues on smoking urge and the ability to resist smoking, as measured with a delay-to-smoking task in which monetary contingencies are provided for resisting smoking. Methods: Adult daily smokers (n=22) completed two experimental sessions, each following 6h smoking abstinence. Sessions differed only in the type of cue participants were exposed to (smoking environments vs. nonsmoking environments). Participants completed subjective ratings of smoking urge, withdrawal and other reactions (i.e. craving, affect). Behavioral outcomes on the delay-to-smoking task included latency to first cigarette, number of cigarettes smoked and average number of puffs per cigarette. Results: Across cue exposure sessions, 64% of participants initiated smoking (no effect of condition was observed). However, exposure to smoking environments as compared to the nonsmoking environments resulted in greater craving, faster initiation of smoking, and more smoked cigarettes. Greater craving was associated with a shorter time to initiate smoking, but this effect did not differ across sessions. In contrast, withdrawal was more strongly associated with number of cigarettes smoked during smoking environment sessions. Conclusion: Together, these results suggest smoking environments increase smoking urge and promote smoking behavior. Further research is necessary to examine the specific and interactive effects of smoking-related environments on real-world smoking lapse and relapse.

Influence of emotional stimulus valence on inhibitory control in adults with and without ADHD.

Human behavior is influenced both by approach and avoidance automatic reactions to positive and negative stimulus, respectively, but these reactions have not been well studied in attention-deficit/hyperactivity disorder (ADHD) patients. Moreover, studies employing spatial stimulus-response compatibility tasks in ADHD and healthy control (HC) subjects are scarce and inconclusive. The present study investigated inhibitory control and emotional processing in ADHD adults with a modified stimulus-response compatibility task in which spatial and emotional features of affective stimuli had to be processed together to select the correct response. Manual responses to figures of Favorite and Rival soccer team players were measured, and compatible or incompatible responses were chosen according to the soccer team figure. Eighteen HC participants and sixteen ADHD adults performed the task. We found an ordinary spatial compatibility effect for the Favorite soccer team and a reversed one for the Rival team in the ADHD group but not in the HC group. The effects may be due to stronger approach and withdrawal reactions toward the Favorite soccer team and away from the Rival one, respectively, indicating poor inhibitory control for the ADHD group. These results show that differences between ADHD and HC subjects become prominent when response selection involves both emotional and spatial features of the stimulus.

Letter: interruption of beta‐blockers in patients with cirrhosis – hasten slowly!

Payancé et al.'s conclusion ‘interruption of beta-blockers in patients with cirrhosis may not require particular dosing or surveillance’ is a slippery slope.1 Indeed, findings should have been more robust. First, this prospective clinical trial was restricted to patients with cirrhosis undergoing right heart catheterisation, this means patients hospitalised, probably also receiving premedication or at least reassurance, and resting quietly at the time of the investigation. In such instances without stressful events causing adrenergic discharge, it is unlikely to observe consequences of receptors’ upregulation. Similarly, rebound propranolol withdrawal reaction was not obvious in patients with angina pectoris having propranolol abruptly discontinued prior to elective coronary arteriography.2 Rebound events after withdrawal of beta blockade are related to the specific clinical setting and easily observed by measuring heart rate under simple conditions of increased sympathetic drive - such as standing or the Valsalva manoeuvure.3 Second, the lack of rebound after withdrawal may also be due to the lack of effective beta-adrenergic blockade (inadequate dosage or poor compliance). Third, claims of safety need a real-life setting during a longer period of time in a larger series. Last, the concern for safety should have not been restricted to gastro-intestinal bleeding considering these 25 patients with probably specific risk factors for coronary artery disease.4 Indeed, the test is far from routine and is only considered when there are relevant risk factors among transplantation candidates.5, 6 Could Payancé et al. provide the risk factors of the 25 patients justifying the myocardial stress testing vs. the others groups? Despite being 40 years old, the advice ‘chronically administered propranolol should be gradually reduced, and activity restricted during its withdrawal’ is still topical.4, 5 Declaration of personal and funding interests: None.

Application of artificial dermis in repair of fingertip defects in children

Objective To investigate the surgical techniques of repairing fingertip defects in children with artificial dermis and its clinical efficacy. Methods A total of 20 fingers in 15 children with fingertip defects accompanied with bone or tendon exposure that were treated from June 2013 to March 2015 were included in the study. After thorough debridement, a template of the defect was made on to a piece of fabric. The artificial dermis was tailored according to the size and shape of the template and sewed to the fingertip to cover the wound. Three weeks postoperatively, the artificial dermis was removed. Results Postoperative granulation tissue growth was satisfactory. The surface of the wound was naturally epithelialized. Good appearance of the affected fingers was observed after 4 to 24 months′ follow-up. Withdrawal reaction was observed in patients younger than 5 years when their fingertips were pricked with a needle. Two-point discrimination of the fingertips in patients older than 5 years (including 5 years) was 4 to 6 mm. According to the functional evaluation criteria of the upper extremity issued by the Hand Surgery Society of the Chinese Medical Association, the results were excellent in 17 fingers and good in 3 fingers. Conclusion Repairing fingertip defects in children with artificial dermis is an ideal technique that is easy to handle without donor site morbidity. It alleviates pain and produces reliable outcomes. Key words: Child; Finger injuries; Artificial dermis; Repair

Mesoporous Silica Particles as a Multifunctional Delivery System for Pain Relief in Experimental Neuropathy.

The long-term use of potent analgesics is often needed to treat chronic pain. However, it has been greatly hindered by their side effects such as addiction and withdrawal reactions. The study seeks to circumvent these drawbacks by taking advantage of a multifunctional delivery system based on nanoparticles to target on pathological neuroinflammation. A drug delivery system is designed and generated using mesoporous silica nanoparticles (MSNs) that are loaded with Δ9-THC (Δ9-tetrahydrocannabinol, a cannabinoid) and ARA290 (an erythropoietin-derived polypeptide), both of which possess analgesic and anti-inflammatory functions. The actions of such THC-MSN-ARA290 nanocomplexes depend on the enhanced permeability and retention of THC through nanosized carriers, and a redox-sensitive release of conjugated ARA290 peptide into the local inflammatory milieu. The biosafety and anti-inflammatory effects of the nanocomplexes are first evaluated in primary microglia in vitro, and further in a mouse model of chronic constriction injury. It is found that the nanocomplexes attenuate in vitro and in vivo inflammation, and achieve a sustained relief of neuropathic pain in injured animals induced by both thermal hyperalgesia and mechanical allodynia. Thus, a nanoparticle-based carrier system can be useful for the amelioration of chronic neuropathic pain through combinatorial drug delivery.

ID 253 – Good functional outcome after prolonged postanoxic coma and myoclonic status epilepsy

Objective Present the possibility of a reasonable neurological recovery in early onset myoclonic status epilepsy (MSE) and prolonged postanoxic coma (PC). Methods A 43-year-old woman suffered a severe respiratory failure due to an anaphylactic reaction during anaesthetic induction before surgery. She required an urgent tracheostomy and remained in PC with reactive pupils and corneal reflexes, but with no withdrawal reaction to painful stimuli. Over the next hour she showed diffuse myoclonic jerks refractory to different antiepileptic drugs, midazolam and propofol. The EEG pattern revealed diffuse epileptiform discharges suggestive of MSE. Therapeutic hypothermia was induced, as was a barbituric coma using tiopental. Results PC and MSE persisted after suppression of the barbituric coma. The MRI was normal and repeated EEG confirmed MSE with stimulus-induced discharges. Cortical somatosensory evoked potentials (CSEP) were preserved and a second barbituric coma was induced. 48 days later the patient regained consciousness and was able to interact, being discharged on day 90. Conclusions Even in the event of an unfavourable initial prognosis, preserved brainstem reflexes, CSEP and EEG reactivity indicate the requirement for an intensive treatment of postanoxic status epilepsy. Key message Despite early onset of MSE and prolonged PC a global evaluation is necessary before establishing an accurate prognosis.

Somatosensory and auditory startle reaction in patients with movement disorders

Background Startle reflex (SR) is a generalized defense reaction which is elicited by unexpected stimuli. To elicit SR, auditory and electrical stimulations are used in electrophysiological investigations. Somatosensory startle reflex (SS-SR) is recently described in healthy volunteers after median and tibial stimulation. Studies in patients with brainstem lesions showed importance of upper brainstem in development of SS-SR. Here, we aim to investigate SS-SR systematically in various movement disorders to address its characteristics in comparison to ASR. Methods We have examined ASR and SS-SR in patients with dystonia ( n = 12), multiple system atrophy ( n = 8), corticobasal degeneration ( n = 5), restless legs syndrome ( n = 14), progressive supranuclear palsy ( n = 11), essential tremor ( n = 18) and idiopathic PD (n = 16) and healthy volunteers ( n = 35) under the same conditions. ASR and SS-SR were recorded over orbicularis oculi (o.oc), sternocleidomastoid (SCM), and biceps brachii (BB) after bilateral auditory and median nerve electrical stimulations, respectively. Results The pattern and probability rates over each three muscle of ASR were similar in MSA, RLS, ET, PD and healthy individuals. Probability rates of responses over each muscle and total ASR probability were the highest in dystonia group whereas they were the lowest in CBD and PSP ( p o.oc = 0.016, p scm = 0.036, p bb = 0.000, p total = 0.009). Onset latencies of O.oc responses were also longer in CBD and PSP groups ( p = 0.001). Presence of SSR was also the highest in dystonia and lowest in PSP group similar to ASR. Latency of O.oc response was longest in CBD group. Pattern of SS-SR was similar to healthy individuals in all disease groups except dystonia and MSA in which BB responses were more common than SCM responses. Conclusions The findings of ASR parallel the previous findings. Dystonia patients are known to have exaggerated ASRs. The decreased response in PSP was previously suggested as a support to show extent of pathology. Findings regarding SS-SR also parallel ASR. SS-SR is also exaggerated in dystonia. Different pattern of response appears to be a reflection of overflow phenomenon. However, development of withdrawal reaction is a possibility. Shorter onset latencies in dystonia group probably also reflect increased excitability. Absence of SS-SR or longer latencies in PSP reflects impairment of its pathway which supports the opinion that it may share pathway with ASR and its generator is possibly in the upper brainstem.

The model of the Nociceptive Withdrawal Reflex in horses

In equine pain research, the Nociceptive Withdrawal Reflex (NWR) model has been proposed as an alternative to classical thermal, mechanical and electrical models to investigate the physiology of nociception. This model does not only allow a more reliable definition of the nociceptive threshold through neurophysiological characterization of the elicited response , but also consents plotting a stimulus-response curve as well as the evaluation of temporal summation mechanisms. Aim of this report is to summarize the experience and results obtained using the NWR model in horses over the last 15 years, firstly with the purpose of describing its physiological characteristics and secondly with the aim of evaluating its pharmacological modulation through analgesic and anaesthetic compounds. The NWR can be elicited in horses through electrical transcutaneous stimulation of a peripheral sensory nerve and is recorded through electromyographic electrodes from the muscles involved in the withdrawal reaction. As the non-nociceptive fibres have lower threshold to electrical stimuli than the nociceptive one, it is impossible to differentiate between the two groups on the stimulus side. So, the only guidance to assess the quality of the stimulus and the recruitment of nociceptive afferents should rely on the characteristics of the electromyographic response, most of all on the timing of its various components. A reflex response can be considered to be a true NWR only if it appears within a time epoch compatible with the conduction velocity of the Aδ fibers. Furthermore a clearly recognizable EMG burst in the epoch of interest has to be accompanied by a consistent aversive behavioural reaction, thus allowing the definition of a reliable NWR threshold. Responses to stimulation intensities below and above thresholds can be quantified to draw a stimulus response curve. Furthermore, through repeated stimulation at subthreshold intensities, it is possible to elicit the phenomenon of temporal summation, considered to be the early phase of the wind up phenomenon and of relevant interest to study central integrative mechanisms of pain processing. Alpha-2 agonists, opioids, systemic lidocaine, ketamine and inhalation anaesthetics have been investigated using the NWR model in horses. Drug-specific modulation of NWR threshold, stimulus-response curves and temporal summation are summarized for each tested compound.

Statins attenuate hyperalgesia and inflammation in experimentally induced acute and neuropathic pain in rats

Background Available medications for the treatment of neuropathic pain, such as steroidal anti-inflammatory drugs and NSAIDs, were shown to be of limited therapeutic benefit. Objectives This study aimed to evaluate the analgesic and anti-inflammatory effects of atorvastatin and pravastatin in acute and neuropathic pain in rats. Materials and methods Acute and neuropathic pains were induced in rat models by means of subplantar carrageenan injection and partial sciatic nerve ligation (PSNL), respectively. The anti-inflammatory effect of statins was assessed by the reduction in plantar edema (at 0, 1, 2, and 3 h) and prolongation of paw withdrawal reaction time in response to thermal stimulation (at 0, 0.5, 1, 2, 3, and 4 h) after carrageenan injection. Atorvastatin (2, 4, or 8 mg/kg) and pravastatin (4, 8, or 12 mg/kg) were administered intraperitoneally 30 min before carrageenan injection. The effect of statins on neuropathic pain was assessed by prolongation of paw withdrawal reaction time in response to thermal stimulation evaluated at 0, 3, 6, 9, 12, 15, and 18 days after PSNL. Atorvastatin (2, 4, or 8 mg/kg) and pravastatin (4, 8, or 12 mg/kg) were administered orally for 18 consecutive days after PSNL. In addition, the effect of atorvastatin and pravastatin on total cholesterol and tumor necrosis factor-α levels was also assessed. Results Both atorvastatin and pravastatin ameliorated carrageenan-induced rat paw edema and prolonged withdrawal time in response to thermal-induced pain. Both statins were also effective in ameliorating neuropathic pain induced by PSNL. These effects were independent of statin-induced hypolipidemic action but were concomitant with reduction of serum tumor necrosis factor-α levels. Conclusion Atorvastatin and pravastatin demonstrated effective therapeutic potentials to reduce acute and chronic pain together with the associated inflammation and hyperalgesia independent of their hypolipidemic effect.

Contributions to drug abuse research of Steven R. Goldberg's behavioral analysis of stimulus-stimulus contingencies.

By the mid-1960s, the concept that drugs can function as reinforcing stimuli through response-reinforcer contingencies had created a paradigm shift in drug abuse science. Steve Goldberg's first several publications focused instead on stimulus-stimulus contingencies (respondent conditioning) in examining Abraham Wikler's two-factor hypothesis of relapse involving conditioned withdrawal and reinforcing effects of drugs. Goldberg provided a compelling demonstration that histories of contingencies among stimuli could produce lasting withdrawal reactions in primates formerly dependent on opioids. Other studies conducted by Goldberg extended the analysis of effects of stimulus-stimulus contingencies on behavior maintained by opioid reinforcing effects and showed that withdrawal-inducing antagonist administration can produce conditioned increases in self-administration. Subsequent studies of the effects of stimuli associated with cocaine injection under second-order schedules showed that the maintenance of behavior with drug injections was in most important aspects similar to the maintenance of behavior with more conventional reinforcers when the behavior-disrupting pharmacological effects of the drugs were minimized. Studies on second-order schedules demonstrated a wide array of conditions under which behavior could be maintained by drug injection and further influenced by stimulus-stimulus contingencies. These schedules present opportunities to produce in the laboratory complex situations involving response- and stimulus-stimulus contingencies, which go beyond simplistic pairings of stimuli and more closely approximate those found with human drug abusers. A focus on the response- and stimulus-stimulus contingencies, and resulting quantifiable changes in objective and quantifiable behavioral endpoints exemplified by the studies by Steve Goldberg, remains the most promising way forward for studying problems of drug dependence.

Reducing inappropriate polypharmacy: the process of deprescribing.

Inappropriate polypharmacy, especially in older people, imposes a substantial burden of adverse drug events, ill health, disability, hospitalization, and even death. The single most important predictor of inappropriate prescribing and risk of adverse drug events in older patients is the number of prescribed drugs. Deprescribing is the process of tapering or stopping drugs, aimed at minimizing polypharmacy and improving patient outcomes. Evidence of efficacy for deprescribing is emerging from randomized trials and observational studies. A deprescribing protocol is proposed comprising 5 steps: (1) ascertain all drugs the patient is currently taking and the reasons for each one; (2) consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention; (3) assess each drug in regard to its current or future benefit potential compared with current or future harm or burden potential; (4) prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes; and (5) implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects. Whereas patient and prescriber barriers to deprescribing exist, resources and strategies are available that facilitate deliberate yet judicious deprescribing and deserve wider application.

Alcohol Use Disorders: Implications for the Clinical Toxicologist

Alcohol use disorders (AUDs) are a health problem of high prevalence in most communities and such problems account for 5% of the total burden of disease worldwide. Clinical toxicologists are commonly required to treat patients having AUDs and associated drug/alcohol-related harm. There have been recent changes to some of the diagnostic criteria (notably in DSM V) relevant to AUDs, with older terms “alcohol abuse” and “alcohol dependence” no longer being classified. AUDs may sometimes not be clearly recognizable and use of evidence-based screening interventions can help identify such conditions and lead to effective brief interventions (e.g. SBIRT programs in emergency departments). AUDs are viewed as chronic disorders of alcohol consumption occurring across a spectrum of severity. While most AUDs are mild to moderate in severity and usually self-limiting conditions, more severe presentations are more commonly encountered by physicians in emergency settings. Hence, clinical toxicologists are more likely to see patients within the more severe form of disorder, at end of the spectrum of AUDs. Among this group of patients, multi-morbidity and particularly high mortality risk exists, and thus they usually require management collaboration with specialist services. Patients with AUDs are most likely to be recognized by a clinical toxicologist in the following scenarios: following acute heavy alcohol ingestion and subsequently developing acute alcohol intoxication (ethanol toxidrome), following accidental or intentional drug overdosage where alcohol has also been consumed, following acute alcohol consumption that has been associated with behavioral risk-taking and/or self-harming (e.g. poisoning, envenomation, etc.), when alcohol withdrawal reactions are severe requiring hospitalization and possibly following an adverse drug reaction.

Repeated electrical stimulations as a tool to evoke temporal summation of nociceptive inputs in healthy, non-medicated experimental sheep

The nociceptive withdrawal reflex (NWR) model is used in animal pain research to quantify nociception. The aim of this study was to evaluate the NWR evoked by repeated stimulations in healthy, non-medicated standing sheep.Repeated electrical stimulations were applied at 5Hz for 2s to the digital nerves of the right thoracic and the pelvic limbs of 25 standing sheep. The stimulation intensities applied were fractions (0.5, 0.6, 0.7, 0.8, 0.9 and 1) of the individual previously determined nociceptive threshold (It) after single stimulation. Surface-electromyographic activity (EMG) was recorded from the deltoid, the femoral biceps or the peroneus tertius muscles. The repeated stimulation threshold (RS It) was reached if at least one stimulus in the train was followed by a reflex with a minimal root-mean-square-amplitude (RMSA) of 20μV. The behavioural reaction following each series of stimulations was scored on a scale from 0 (no reaction) to 5 (vigorous whole-body reaction).For the deltoid muscle, RS It was 2.3mA (1.6–3mA) with a reaction score of 2 (1–2) and at a fraction of 0.6 (0.5–0.8)×It. For the biceps femoris muscle, RS It was 2.9mA (2.6–4mA) with a reaction score of 1 (1–2) at a fraction of and 0.55 (0.4–0.7)×It while for the peroneus tertius muscle RS It was 3mA (2.8–3.5mA) with a reaction score of 1 (1–2) and at a fraction of 0.8 (0.8–0.95)×It. Both, RMSA and reaction scores increased significantly with increasing stimulation intensities in all muscles (p<0.001).The repeated application of electrical stimuli led to temporal summation of nociceptive inputs and therefore a reduction of the stimulus intensity evoking a withdrawal reaction in healthy, standing sheep. Data achieved in this study can now serve as reference for further clinical or experimental applications of the model in this species.

The benefits and harms of deprescribing.

Deprescribing is the process of trial withdrawal of inappropriate medications. Currently, the strongest evidence for benefit of deprescribing is from cohort and observational studies of withdrawal of specific medication classes that have shown better patient outcomes, mainly through resolution of adverse drug reactions. Additional potential benefits of deprescribing include reduced financial costs and improved adherence with other medications. The harms of ceasing medication use include adverse drug withdrawal reactions, pharmacokinetic and pharmacodynamic changes and return of the medical condition. These can be minimised with proper planning (ie, tapering), monitoring after withdrawal, and reinitiation of the medication if the condition returns. More evidence is needed regarding negative, non-reversible effects of ceasing use of certain classes of medication, such as acetylcholinesterase inhibitors. Cessation of use has not been studied for many medication classes, and large-scale randomised controlled trials of systematic deprescribing are required before the true benefits and harms can be known.

P820: Withdrawal reaction in response to a single nociceptive stimulus in myelopathy

P820: Withdrawal reaction in response to a single nociceptive stimulus in myelopathy