Focus on headache as an adverse reaction to drugs

There are a large number of drugs inducing headache as an adverse reaction. Nevertheless, headaches as adverse reactions to drugs have received limited attention. Non-serious adverse reactions, such as headache, are not quantified and described as accurately as serious, life threatening ones. However, non-serious reactions can also be extremely troublesome, above all when they are chronic: they can affect patients' quality of life and contribute to non-compliance. It is absolutely possible that the number of patients with headache as an adverse reaction, which is going to increase, considering the growing use of medications. Physicians should, therefore, be aware of this issue. Indeed, it is difficult to attribute the diagnosis of adverse drug reaction to a condition, headache, which is also a very common symptom in general population

Topiramate-associated acute glaucoma in a migraine patient receiving concomitant citalopram therapy: a case-report

We describe the case of a 34 year-old man with diagnosis of migraine with and without aura that developed myopia and acute glaucoma after 7 days of treatment with topiramate. The patient had also been taking citalopram daily for two months. Both topiramate and citalopram have been related to the increase of intraocular pressure and the development of glaucoma. We can't exclude that in this patient citalopram caused an increase of the ocular pressure in dose-dependent manner, facilitating topiramate-induced glaucoma. We recommend to pay particular attention in prescribing of topiramate in migraine patients who are already under treatment with citalopram or other antidepressants with a similar mechanisms of action

Pharmacoepidemiology of triptans in a headache centre

Aims: The aims of this survey were: (i) to examine the pharmacoepidemiology of triptans in a headache centre; (ii) tocompare the characteristics of patients who continued to take triptans with those of patients who had discontinued them.Methods: We enrolled all migraine patients according to ICHD-II criteria, ensuring they were over 18 years of age,consecutively examined during a follow-up visit at the Headache Centre of the University Hospital of Modena fromOctober 2008 to March 2009. Only patients who had used or were using a triptan were included. A specific questionnaireabout the use and tolerability of triptans was created for the study and administered to every patient.Results: On the whole, 343 patients (migraine without aura: 72%; chronic migraine: 26%; migraine with aura: 2%; mean age40.410 years) had used or were using triptans. Most patients (72%) continued to use triptans, above all for their efficacy.The minority (28%) discontinuing them were younger and suffered from less severe migraine; 59% of them had discontinuedtriptans because of adverse effects. Indeed, 92% of these patients versus 57% of patients who were currently usingtriptans reported adverse effects (p<.0001, Fisher’s exact test). The number of patients reporting adverse effectssignificantly decreased with age (r¼0.230, p<.005, simple linear regression analysis). The triptan discontinued by thehighest percentage of patients (84%) was subcutaneous 6 mg sumatriptan. Significantly more patients reported adverseeffects with subcutaneous 6 mg (89%) and tablet 100 mg sumatriptan (67%) than with any other triptan.Conclusions: The increase of the tolerability of triptans with age could partly explain why younger patients suffering from lesssevere migraine tend to discontinue triptans more than older patients suffering from more severe migraine. In the latter, theefficacy and better tolerability (but not necessarily safety) of triptans could foster the overuse of these medications

Effective prophylactic treatments of migraine lower plasma glutamate levels

The role of glutamate in migraine treatment has not been much studied, even if this amino acid seems to be crucial in the pathogenesis of migraine. Our aim was to determine if there were differences in the plasma levels of glutamate between migraine patients and control subjects and if plasma levels of glutamate in migraine patients modified after 8 weeks of prophylactic treatment. We studied 24 patients with diagnosis of migraine without aura according to International Classification of Headache Disorders, 2nd edn criteria, and 24 age- and sex-matched healthy subjects, as controls. In migraineurs the level of glutamate was measured before and after 8 weeks of prophylactic treatment (topiramate 50 mg/day, five patients; amitriptyline 20 mg/day, seven patients; flunarizine 5 mg/day, seven patients; propranolol 80 mg/day, five patients). Venous blood samples were taken in the morning, after overnight fasting, and at least 3 days after the last migraine day. Glutamate levels were measured by means of a fluorimetric detector high-pressure liquid chromatographic method. Plasma levels of glutamate were significantly higher in migraine patients-either before (61.79 +/- 18.75 mu mol/l) or after prophylactic treatment (17.64 +/- 5.08 mu mol/l)-than in controls (9.36 +/- 2.1 mu mol/l) (P < 0.05, anova followed by Newman-Keuls' test). After prophylactic treatment, with headache frequency reduced, plasma glutamate levels were significantly lower in the same patient with respect to the prior baseline level (P < 0.0001, Student's t-test for paired data), without any differences depending on the kind of prophylactic drug. Effective prophylactic treatments reducing high glutamate plasma levels found in migraine patients could act on the underlying mechanism that contributes to cause migraine. Plasma glutamate level monitoring in migraine patients might serve as a biomarker of response to treatments and as an objective measure of disease status

Involvement of the brain histaminergic system in the melanocortin MC4 receptor agonist RO27-3225-induced resuscitating effect in haemorrhage-shocked rats \u2013 haemodynamic studies.

Involvement of the brain histaminergic system in the melanocortin MC4 receptor agonist RO27-3225-induced resuscitating effect in haemorrhage-shocked rats \u2013 haemodynamic studies

Centrally acting leptin induces a resuscitating effect in haemorrhagic shock in rats.

Centrally acting leptin induces the activation of the sympathetic nervous system with a pressor effect in normotensive rats. The purpose of the study was to examine central leptin-evoked action in critical haemorrhagic hypotension. In anaesthetized male Wistar rats subjected for irreversible haemorrhagic shock with mean arterial pressure (MAP) 20-25 mmHg haemodynamic parameters and plasma concentrations of adrenaline and noradrenaline were measured. Leptin given intracerebroventricularly (20 μg) evoked long-lasting rises in MAP and heart rate (HR), with a subsequent increase in renal, mesenteric and hindquarters blood flows and a 100% survival at 2 h. MAP and peripheral blood flow changes were inhibited by a pre-treatment with α(1)- and α(2)-adrenoceptor antagonists prazosin (0.5 mg/kg) and yohimbine (1 mg/kg), while β-adrenoceptor antagonist propranolol (1 mg/kg) blocked leptin-induced HR changes, without influence on MAP, peripheral blood flows and survival. Twenty min after leptin treatment, there were higher plasma concentrations of noradrenaline, but not adrenaline, in comparison with the saline-treated control group. In conclusion, centrally acting leptin induces a long-lasting pressor effect with an improvement in the survival rate in haemorrhage-shocked rats. The effect may be associated with the activation of the sympathetic nervous system

Comparison of Model Predictions and Laboratory Observations of Transgene Frequencies in Continuously-Breeding Mosquito Populations

The persistence of transgenes in the environment is a consideration in risk assessments of transgenic organisms. Combining mathematical models that predict the frequency of transgenes and experimental demonstrations can validate the model predictions, or can detect significant biological deviations that were neither apparent nor included as model parameters. In order to assess the correlation between predictions and observations, models were constructed to estimate the frequency of a transgene causing male sexual sterility in simulated populations of a malaria mosquito Anopheles gambiae that were seeded with transgenic females at various proportions. Concurrently, overlapping-generation laboratory populations similar to those being modeled were initialized with various starting transgene proportions, and the subsequent proportions of transgenic individuals in populations were determined weekly until the transgene disappeared. The specific transgene being tested contained a homing endonuclease gene expressed in testes, I-PpoI, that cleaves the ribosomal DNA and results in complete male sexual sterility with no effect on female fertility. The transgene was observed to disappear more rapidly than the model predicted in all cases. The period before ovipositions that contained no transgenic progeny ranged from as little as three weeks after cage initiation to as long as 11 weeks

Melanocortins counteract inflammatory and apoptotic responses to prolonged myocardial ischemia/reperfusion through a vagus nerve-mediated mechanism

Recently we reported that an efferent vagal fibre-mediated cholinergic protective pathway, activated by melanocortins acting at brain melanocortin MC3 receptors, is operative in a condition of short-term myocardial ischemia/reperfusion associated with a high incidence of severe arrhythmias and death. Here we investigated melanocortin effects, and the role of the vagus nerve-mediated cholinergic protective pathway, in a rat model of prolonged myocardial ischemia/reperfusion associated with marked inflammatory and apoptotic reactions, and a large infarct size. Ischemia was produced in rats by ligature of the left anterior descending coronary artery for 30 min. At the end of the 2-h reperfusion, western blot analysis of the inflammatory and apoptotic markers tumor necrosis factor-α (TNF-α), c-jun N-terminal kinases (JNK) and caspase-3, as well as of the anti-apoptotic extracellular signal-regulated kinases (ERK 1/2), was performed in the left ventricle. In saline-treated ischemic rats there was an increase in TNF-α levels and in the activity of JNK and caspase-3 accompanied, despite an appreciable ERK 1/2 activation, by a large infarct size. Intravenous treatment, during coronary artery occlusion, with the melanocortin analog [Nle4, D-Phe7]α-melanocyte-stimulating hormone (NDP-α-MSH) produced a reduction in TNF-α levels and in the activity of JNK and caspase-3, associated with marked activation of the pro-survival kinases ERK 1/2, and consequent attenuation of infarct size. Bilateral cervical vagotomy blunted the protective effects of NDP-α-MSH. These results indicate that melanocortins modulate the inflammatory and apoptotic cascades triggered by prolonged myocardial ischemia/reperfusion, and reduce infarct size, seemingly by activation of the vagus nerve-mediated cholinergic protective pathway