Death following acute poisoning by moclobemide

A fatality due to ingestion of a reversible inhibitor of monoamine-oxidase A (MAO-A) is reported. Moclobemide is generally considered as a safe drug far less toxic than tricyclic anti-depressants. However, severe intoxications may result from interactions with other drugs and food such as selective serotonin reuptake inhibitors (SSRIs), anti-Parkinsonians of the MAOI-type (e.g. selegiline) or tyramine from ripe cheese or other sources. In the present case, high levels of moclobemide were measured in peripheral blood exceeding toxic values reported so far in the scientific literature. The body fluid concentrations of moclobemide were of 498 mg/l in peripheral whole blood, 96.3 mg/l in urine while an amount of approximately 33 g could be recovered from gastric contents. The other xenobiotics were considered of little toxicological relevance. The victim (male, 48-year-old) had a past history of depression and committed one suicide attempt 2 years before death. Autopsy revealed no evidence of significant natural disease or injury. It was concluded that the manner of death was suicide and that the unique cause of death was massive ingestion of moclobemide.

Treatment Options in the Management of Status Epilepticus

Status epilepticus treatment involves the use of several pharmacologic compounds, which are conceptually divided into three successive and additional lines of action. Because of their rapid onset of action, benzodiazepines represent the first approach; these are followed by classic antiepileptic drugs that are administered intravenously. In refractory episodes, pharmacologic coma induction with an appropriate anesthetic is advocated. Apart from first-line compounds, the level of evidence for medications used in status epilepticus is extremely limited. It is important to specifically address etiology in order to maximize the impact of the antiepileptic therapy. Fine-tuning of the treatment strategy, mainly regarding the choice of whether to induce coma, should be approached by balancing the benefits of rapid control of the status epilepticus with the risks of adverse effects. Although each status epilepticus episode should be treated as rapidly as possible, it appears advisable to reserve coma induction for those forms, such as generalized convulsive status, that have been shown to present a consistent risk of neurologic sequelae.

Expositions médicamenteuses pendant la grossesse: une approche différenciée [Drug exposure during pregnancy: a differentiated approach].

Numerous drug exposures do occur unintentionally at the beginning of pregnancy. On the other hand, pursuing drug treatment may be necessary in women who wish to be pregnant. In these situations risk evaluation has to be done in a precise and differentiated manner, taking into account at the same time the risk for the fetus and maternal health. Teratovigilance services are able to give a thorough information enabling to avoid unwarranted drug arrests or pregnancy terminations. In return, physician's catamnesis about the outcome of the pregnancy exposed to one or several therapeutic agents will increase the bulk of knowledge health professionals and pregnant women have at their disposal.

Tobacco and cannabis smoking cessation can lead to intoxication with clozapine or olanzapine

Plasma levels of clozapine and olanzapine are lower in smokers than in nonsmokers, which is mainly due to induction of cytochrome P4501A2 (CYP1A2) by some smoke constituents. Smoking cessation in patients treated with antipsychotic drugs that are CYP1A2 substrates may result in increased plasma levels of the drug and, consequently, in adverse drug effects. Two cases of patients who smoked tobacco and cannabis are reported. The first patient, who was receiving clozapine treatment, developed confusion after tobacco and cannabis smoking cessation, which was related to increased clozapine plasma levels. The second patient, who was receiving olanzapine treatment, showed important extrapyramidal motor symptoms after reducing his tobacco consumption. The clinical implication of these observations is that smoking patients treated with CYP1A2 substrate antipsychotics should regularly be monitored with regard to their smoking consumption in order to adjust doses in cases of a reduction or increase in smoking.

Second-line status epilepticus treatment: comparison of phenytoin, valproate, and levetiracetam.

Purpose:  Phenytoin (PHT), valproic acid (VPA), or levetiracetam (LEV) are commonly used as second-line treatment of status epilepticus (SE), but comparative studies are not available. Methods:  Among 279 adult SE episodes identified prospectively in our tertiary care hospital over 4 years, we retrospectively identified 187 episodes in which PHT, VPA, or LEV were given after benzodiazepines. Patients with postanoxic SE were not included. Demographics, clinical SE features, failure of second-line treatment to control SE, new handicap, and mortality at hospital discharge were assessed. Uni- and multivariable statistical analyses were applied to compare the three agents. Key Findings:  Each compound was used in about one third of SE episodes. VPA failed to control SE in 25.4%, PHT in 41.4%, and LEV in 48.3% of episodes in which these were prescribed. A deadly etiology was more frequent in the VPA group, whereas SE episodes tended to be more severe in the PHT group. After adjustment for these known SE outcome predictors, LEV failed more often than VPA [odds ratio (OR) 2.69; 95% confidence interval (CI) 1.19-6.08]; 16.8% (95% CI: 6.0-31.4%) of second-line treatment failures could be attributed to LEV. PHT was not statistically different from the other two compounds. Second-line treatment did not seem to influence new handicap and mortality, whereas etiology and the SE Severity Score (STESS) were robust independent predictors. Significance:  Even without significant differences on outcome at discharge, LEV seems less efficient than VPA to control SE after benzodiazepines. A prospective comparative trial is needed to address this potentially concerning finding.

Sedación consciente mediante benzodiacepinas en cirugía bucal

La sedación consciente durante el tratamiento odontológico y, en especial, durante el quirúrgico proporciona una mayor comodidad al paciente y al profesional contribuyendo a una mejor calidad de trabajo. Los fármacos más usados son las benzodiacepinas y entre ellos el midazolam está ganando gran aceptación por su rápido inicio de acción y rápida recuperación del paciente. Se dispone además del Dumazenil, un antagonista que puede revertir rápidamente una sobresedación. Otra alternativa es el uso del propofol al que se le atribuye la ventaja sobre el midazolam de tener una recuperación más rápida. Será necesario una adecuada monitorización durante todo el tratamiento y en el postoperatorio.

Neurophysiological effects of vasopressin and oxytocin in the central amygdala of the rat : a potential mechanism for the opposite modulation of anxiety and fear behavior

Abstract The amygdala is a group of nuclei in the temporal lobe of the brain that plays a crucial role in anxiety and fear behavior. Sensory information converges in the basolateral and lateral nuclei of the amygdala, which have been the first regions in the brain where the acquisition of new (fear) memories has been associated with long term changes in synaptic transmission. These nuclei, in turn, project to the central nucleus of the amygdala. The central amygdala, through its extensive projections to numerous nuclei in the midbrain and brainstem, plays a pivotal role in the orchestration of the rapid autonomic and endocrine fear responses. In the central amygdala a large number of neuropeptides and receptors is expressed, among which high levels of vasopressin and oxytocin receptors. Local injections of these peptides into the amygdala modulate several aspects of the autonomic fear reaction. Interestingly, their effects are opposing: vasopressin tends to enhance the fear reactions, whereas oxytocin has anxiolytic effects. In order to investigate the neurophysiological mechanisms that could underlie this opposing modulation of the fear behavior, we studied the effects of vasopressin and oxytocin on the neuronal activity in an acute brain slice preparation of the rat central amygdala. We first assessed the effects of vasopressin and oxytocin on the spontaneous activity of central amygdala neurons. Extracellular single unit recordings revealed two major populations of neurons: a majority of neurons was excited by vasopressin and inhibited by oxytocin, whereas other neurons were only excited by oxytocin receptor activation. The inhibitory effect of oxytocin could be reduced by the block of GABAergic transmission, whereas the excitatory effects of vasopressin and oxytocin were not affected. In a second step we identified the cellular mechanisms for the excitatory effects of both peptides as well as the morphological and biochemical mechanisms underlying the opposing effects, by using sharp electrode recordings together with intracellular labelings. We revealed that oxytocin-excited neurons are localized in the lateral part (CeL) whereas vasopressin excited cells are found in the medial part of the central amygdala (CeM). The tracing of the neuronal morphology showed that the axon collaterals of the oxytocin-excited neurons project from the CeL, far into the CeM. Combined immunohistochemical stainings indicated that these projections are GABAergic. In the third set of experiments we investigated the synaptic interactions between the two identified cell populations. Whole-cell patch-clamp recordings in the CeM revealed that the inhibitory effect of oxytocin was caused by the massive increase of inhibitory GABAergic currents, which was induced by the activation of CeL neurons. Finally, the effects of vasopressin and oxytocin on evoked activity were investigated. We found on the one hand, that the probability of evoking action potentials in the CeM by stimulating the basolateral amygdala afferents was enhanced under vasopressin, whereas it decreased under oxytocin. On the other hand, the impact of cortical afferents stimulation on the CeL neurons was enhanced by oxytocin application. Taken together, these findings have allowed us to develop a model, in which the opposing behavioral effects of vasopressin and oxytocin are caused by a selective activation of two distinct populations of neurons in the GABAergic network of the central amygdala. Our model could help to develop new anxiolytic treatments, which modulate simultaneously both receptor systems. By acting on a GABAergic network, such treatments can further be tuned by combinations with classical benzodiazepines. Résumé: L'amygdale est un groupe de noyaux cérébraux localisés dans le lobe temporal. Elle joue un rôle essentiel dans les comportements liés à la peur et l'anxiété. L'information issue des aires sensorielles converge vers les noyaux amygdaliens latéraux et basolatéraux, qui sont les projections vers différents noyaux du tronc cérébral et de l'hypothalamus, joue un rôle clef premières régions dans lesquelles il a été démontré que l'acquisition d'une nouvelle mémoire (de peur) était associée à des changements à long terme de la transmission synaptique. Ces noyaux envoient leurs projections sur l'amygdale centrale, qui à travers ses propres dans l'orchestration des réponses autonomes et endocrines de peur. Le contrôle de l'activité neuronale dans l'amygdale centrale module fortement la réaction de peur. Ainsi, un grand nombre de neuropeptides sont spécifiquement exprimés dans l'amygdale centrale et un bon nombre d'entre eux interfère dans la réaction de peur et d'anxiété. Chez les rats, une forte concentration de récepteurs à l'ocytocine et à la vasopressine est exprimée dans le noyau central, et l'injection de ces peptides dans l'amygdale influence différents aspects de la réaction viscérale associée à la peur. Il est intéressant de constater que ces peptides exercent des effets opposés. Ainsi, la vasopressine augmente la réaction de peur alors que l'ocytocine a un effet anxiolytique. Afin d'investiguer les mécanismes neurophysiologiques responsables de ces effets opposés, nous avons étudié l'effet de la vasopressine et de l'ocytocine sur l'activité neuronale de préparations de tranches de cerveau de rats contenant entre autres de l'amygdale centrale. Tout d'abord, notre intérêt s'est porté sur les effets de ces deux neuropeptides sur l'activité spontanée dans l'amygdale centrale. Des enregistrements extracellulaires ont révélé différentes populations de neurones ; une majorité était excitée par la vasopressine et inhibée par l'ocytocine ; d'autres étaient seulement excités par l'activation du récepteur à l'ocytocine. L'effet inhibiteur de l'ocytocine a pu être réduit par l'inhibition de la transmission GABAergique, alors que ses effets excitateurs n'étaient pas affectés. Dans un deuxième temps, nous avons identifié les mécanismes cellulaires responsables de l'effet excitateur de ces deux peptides et analysé les caractéristiques morphologiques et biochimiques des neurones affectés. Des enregistrements intracellulaires ont permis de localiser les neurones excités par l'ocytocine dans la partie latérale de l'amygdale centrale (CeL), et ceux excités par la vasopressine dans sa partie médiale (CeM). Le traçage morphologique des neurones a révélé que les collatérales axonales des cellules excitées par l'ocytocine projetaient du CeL loin dans le CeM. De plus, des colorations immuno-histochimiques ont révélé que ces projections étaient GABAergiques. Dans un troisième temps, nous avons étudié les interactions synaptiques entre ces deux populations de cellules. Les enregistrements en whole-cell patch-clamp dans le CeM ont démontré que les effets inhibiteurs de l'ocytocine résultaient de l'augmentation massive des courants GABAergique résultant de l'activation des neurones dans le CeL. Finalement, les effets de l'ocytocine et de la vasopressine sur l'activité évoquée ont été étudiés. Nous avons pu montrer que la probabilité d'évoquer un potentiel d'action dans le CeM, par stimulation de l'amygdale basolatérale, était augmentée sous l'effet de la vasopressine et diminuée sous l'action de l'ocytocine. Par contre, l'impact de la stimulation des afférences corticales sur les neurones du CeL était augmenté par l'application de l'ocytocine. L'ensemble de ces résultats nous a permis de développer un modèle dans lequel les effets comportementaux opposés de la vasopressine et de l'ocytocine sont causés par une activation sélective des deux différentes populations de neurones dans un réseau GABAergique. Un tel modèle pourrait mener au développement de nouveaux traitements anxiolytiques en modulant l'activité des deux récepteurs simultanément. En agissant sur un réseau GABAergique, les effets d'un tel traitement pourraient être rendus encore plus sélectifs en association avec des benzodiazépines classiques.

Driving under drugs in Switzerland : a descriptive cross-sectional study

Objectives: Many drugs, both illicit or for medication, are known to influence driving abilities and increase risks of accidents. We explored the prevalence of psychoactive substances in a random sample of drivers in Switzerland. Methods: Saliva samples from 1078 random drivers were collected at 24 different locations in Western Switzerland from October 2006 to April 2008 for complete toxicological analysis using liquid chromatography/tandem mass spectrometry. Results: Provisional results are available for 437 drivers. 6.2% (CI95% 4.1 to 8.9) were under the influence of illicit drugs and 8.7% under psychoactive medication (CI95% 6.2 to 11.7). 37 drivers (8.5%) were under the influence of alcohol of which 14 (3.2%) were above 0.8 mg/L. 21 drivers (4.8%) were under the combined influence of more than one psychoactive substance; however only 4 drivers (0.9%) were under both the influence of medication and alcohol. Looking more specifically at illicit substances, 22 (5.0%) were positive to cocaine, 5 (1.1%) to cannabis, and 2 (0.5%) to amphetamines ; for psychoactive medication, 17 (3.9%) were positive to benzodiazepines, 16 (3.7%) to antidepressors, 7 (1.6%) to opiates, 7 (1.6%) to neuroleptics, and 3 (0.7%) to other substances influencing driving abilities. 17/21 drivers did not self-report their consumption of drugs whereas only 9/35 failed mentioning their medication. Men drivers were 3.2 times (CI95% 1.1 to 9.5) more likely to be under the influence of illicit drugs than women. Full results will be reported when laboratory data will be available in April. Conclusions: Driving under the influence of psychoactive substances is common. In Western Switzerland, prevention messages could focus on men, driving under medication or cocaine.

Médecine d'urgence [Emergency medicine: updates 2012].

We review some of the most influential papers from 2012 in the different aspects of emergency medicine, such as prehospital medicine, resuscitation, early diagnosis and timely ED discharge and treatment. In particular, intramuscular benzodiazepines have been shown to be efficient in prehospital status epilepticus, epinephrines usefulness in cardiopulmonary resuscitation has been challenged, colloids have been shown to be deleterious in the treatment of severe sepsis and septic shock, the time window for thrombolysis in acute stroke will probably be extended, acute pyelonephritis treatment duration can be decreased, new D-dimers thresholds for older patients may prevent further diagnosis tests, and hs-Troponin may allow earlier discharge of low coronary risk patients.

Emerging therapies for gout.

Over the past decade much has been learned about the mechanisms of crystal-induced inflammation and renal excretion of uric acid, which has led to more specific targeting of gout therapies and a more potent approach to future management of gout. This article outlines agents being developed for more aggressive lowering of urate and more specific anti-inflammatory activity. The emerging urate-lowering therapies include lesinurad, arhalofenate, ulodesine, and levotofisopam. Novel gout-specific anti-inflammatories include the interleukin-1β inhibitors anakinra, canakinumab, and rilonacept, the melanocortins, and caspase inhibitors. The historic shortcomings of current gout treatment may, in part, be overcome by these novel approaches.

Prevalence of substance use in a Swiss psychiatric hospital: interview reports and urine screening.

BACKGROUND: Co-morbid substance misuse is common in psychiatric disorders, has potentially severe adverse consequences and may be frequently undetected. AIMS: To measure the prevalence of substance use among patients admitted to a Swiss psychiatric hospital and to examine the potential utility of routine urine drug screening in this setting. METHOD: 266 inpatients were included. 238 patients completed the interview and 240 underwent a urine drug screening. RESULTS: Lifetime prevalence of substance use among psychiatric patients was very high for alcohol (98%; 95% CI: 96-100), benzodiazepines (86%; 95% CI: 82-91) and cannabis (53%; 95% CI: 47-60), but also for "hard drugs" like cocaine (25% ; 95% CI: 19-30) or opiates (20%; 95% CI: 15-25). Regular current use of alcohol (32%; 95% CI: 26-38) or cannabis (17%; 95% CI: 12-22) was the most frequent. Substance use was associated with male sex, younger age, unmarried status and nicotine smoking. Urine screening confirms reports from patients on recent use, and remained positive for cannabis during hospitalisation, but not for cocaine nor for opiates. CONCLUSION: Substance use is frequent among psychiatric patients. Systematic interviewing of patients about their substance use remains essential, and is usually confirmed by urine screening. Urine screening can be useful to provide specific answers about recent use.

Response to topical clonazepam in patients with burning mouth syndrome: a clinical study

Burning Mouth Syndrome (BMS) is a difficult disease for patients and clinicians. Moreover, there is not a general consensus on how to treat the disease. The main objective of this paper is to evaluate BMS patients' response to topical clonazepam treatment. A double blind study was performed. Among a total of 66 patients, 33 were treated with tablets of clonazepam and another 33 were treated with a placebo. Symptoms were evaluated after 1 month and 6 months of treatment and scored on an analogical scale from 0 to 10. Among the 33 patients treated with clonazepam, 23 showed at least a 50% reduction in symptoms after 1 month of treatment. On the contrary, only 4 in the placebo group exhibited significant improvement. After 6 months, significant differences were observed again, as 23 of the 33 patients treated with the drug reported at least a 50% reduction in symptoms, whereas only 2 among those treated with the placebo significantly improved. However, when measured in terms of a complete cure (lack of symptoms), the differences were not significant: 5 drug-treated patients and one belonging to the placebo group were asymptomatic after one month of treatment. In summary, it seems that clonazepam applied topically was effective in treating BMS in a large proportion of patients

Gériatrie [Review in geriatric medicine 2014].

Several studies contributed to improving the diagnostic and prognostic assessment of delirium in hospitalized older patients. Direct patient education proved efficient in benzodiazepines withdrawal. A position statement of the American Geriatrics Society does not recommend tube feeding when eating difficulties arise in older persons suffering from advanced dementia. Several studies emphasized once again the potential importance of preventative interventions (in particular physical activity) to prevent or delay dementia occurrence. Two randomized controlled trials of monoclonal antibodies that bind amyloid did not show benefit in patients with mild-to-moderate Alzheimer's dementia (AD). In contrast, vitamin E reduced functional decline in these patients, and citalopram reduced agitation among AD patients as well as their caregiver's stress.

Age and adverse drug reactions from psychopharmacological treatment: data from the AMSP drug surveillance programme in Switzerland.

QUESTION UNDER STUDY: The frequency of severe adverse drug reactions (ADRs) from psychotropic drugs was investigated in hospitalised psychiatric patients in relation to their age. Specifically, the incidence of ADRs in patients up to 60 years was compared to that of patients older than 60 years. METHODS: Prescription rates of psychotropic drugs and reports of severe ADRs were collected in psychiatric hospitals in Switzerland between 2001 and 2010. The data stem from the drug surveillance programme AMSP. RESULTS: A total of 699 patients exhibited severe ADRs: 517 out of 28,282 patients up to 60 years (1.8%); 182 out of 11,446 elderly patients (1.6%, ns). Logistic regression analyses showed a significantly negative relationship between the incidence of ADRs and patients' age in general and in particular for weight gain, extrapyramidal motor system (EPMS) symptoms, increased liver enzymes and galactorrhoea. A significantly negative relationship was observed for age and the dosages of olanzapine, quetiapine, risperidone, valproic acid and lamotrigine. When comparing age groups, frequency of ADRs was lower in general for antipsychotic drugs and anticonvulsants, in particular for valproic acid in the elderly. Weight gain was found to be lower in the elderly for antipsychotic drugs, in particular for olanzapine. For the group of mood-stabilising anticonvulsants (carbamazepine, lamotrigine and valproic acid) the elderly exhibited a lower incidence of reported allergic skin reactions. CONCLUSION: The results suggest that for psychiatric inpatients the incidence of common severe ADRs (e.g., weight gain or EPMS symptoms) arising from psychotropic medication decreases with the age of patients.