Annunziata Hospital

Cosenza, Italy

Annunziata Hospital

Cosenza, Italy
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De Sarro G.,University of Catanzaro | Paola E.D.D.,University of Catanzaro | Gratteri S.,University of Catanzaro | Gareri P.,University of Catanzaro | And 6 more authors.
Pharmacological Research | Year: 2012

The renin-angiotensin system (RAS) exists in the brain and it may be involved in pathogenesis of neurological and psychiatric disorders including seizures. The aim of the present research was to evaluate the effects of some angiotensin-converting enzyme inhibitors (ACEi; captopril, enalapril, fosinopril and zofenopril), commonly used as antihypertensive agents, in the DBA/2 mice animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive interactions in the same model. All ACEi were able to decrease the severity of audiogenic seizures with the exception of enalapril up to the dose of 100 mg/kg, the rank order of activity was as follows: fosinopril > zofenopril > captopril. The co-administration of ineffective doses of all ACE inhibitors with AEDs, generally increased the potency of the latter. Fosinopril was the most active in potentiating the activity of AEDs and the combination of ACEi with lamotrigine and valproate was the most favorable, whereas, the co-administrations with diazepam and phenobarbital seemed to be neutral. The increase in potency was generally associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of AEDs with ACEi was predominantly more favorable than control. ACEi administration did not influence plasma and brain concentrations of the AEDs studied excluding pharmacokinetic interactions and concluding that it is of pharmacodynamic nature. In conclusion, fosinopril, zofenopril, enalapril and captopril showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations. © 2011 Elsevier Ltd. All rights reserved.


Siniscalchi A.,Annunziata Hospital | Gallelli L.,University of Catanzaro | De Sarro G.,University of Catanzaro | Malferrari G.,Santa Maria Nuova Hospital | Santangelo E.,University of Catanzaro
Pharmacological Research | Year: 2012

Antiepileptic drugs (AEDs) are commonly prescribed for a wide range of disorders other than epilepsy, including both neurological and psychiatric disorders. AEDs play also a role in pharmacological management of neuropathic pain. Central post-stroke pain (CPSP) is a disabling morbidity occurring in 35% of patients with stroke. The pathophysiology of CPSP is not well known but central disinhibition with increased neuronal excitability has been suggested. AEDs include many different drugs acting on pain through several mechanisms, such as reduction of neuronal hyperexcitability. To our knowledge conclusive evidence has not been published yet. The aim of this review is to delineate efficacy and safety of AEDs in CPSP. © 2011 Elsevier Ltd. All rights reserved.


Siniscalchi A.,Annunziata Hospital | Gallelli L.,University of Catanzaro | Russo E.,University of Catanzaro | De Sarro G.,University of Catanzaro
European Journal of Pharmacology | Year: 2013

Fatigue represents a common side effect of several drugs, however, the underlying mechanisms have not been well identified. A depression of the central nervous system (CNS) and/or changes in peripheral processes have been associated with the development of fatigue. Antiepileptic drugs (AEDs), generally decreasing CNS excitability, are used in the treatment of seizures as well as other neurological and psychiatric diseases. Fatigue is certainly a common AEDs' side effect, although a high degree of variability exists depending on both patients' characteristics and the drug used. Here, we delineate the pathophysiological central and peripheral mechanisms by which AEDs may cause fatigue also reviewing the available clinical data in order to assess a possible AEDs rank and highlight each AEDs related risk. It appears that drugs acting on the GABAergic system have the highest incidence (with tiagabine exception) of fatigue followed by Gabapentin and Levetiracetam whereas drugs mainly inhibiting sodium channels (Carbamazepine, Eslicarbazepine, Lamotrigine, Phenytoin and Valproate) have the lowest. However, the dose used, AEDs related side effects and patients' characteristics might influence the degree of fatigue observed. © 2013 Elsevier B.V.


Russo E.,University of Catanzaro | Donato Di Paola E.,University of Catanzaro | Gareri P.,University of Catanzaro | Siniscalchi A.,Annunziata Hospital | And 4 more authors.
Pharmacological Research | Year: 2013

It is known that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in both the primary and the secondary prevention of ischemic heart disease. Increasing evidence indicates that statins have protective effects in several neurological diseases including stroke, cerebral ischemia, Parkinson disease, multiple sclerosis, traumatic brain injury and epilepsy. The aim of the present research was to evaluate the effects of some HMG-CoA reductase inhibitors (i.e. lovastatin, simvastatin, atorvastatin, fluvastatin and pravastatin) commonly used for the treatment of hypercholesterolemia in the DBA/2 mice, an animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; i.e. carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive pharmacological interactions. Simvastatin only was active against both the tonic and clonic phase of audiogenic seizures, whereas the other statins tested were only partially effective against the tonic phase with the following order of potency: lovastatin > fluvastatin > atorvastatin; pravastatin was completely ineffective up to the dose of 150 mg/kg. The co-administration of ineffective doses of all statins with AEDs generally increased the potency of the latter reducing their ED50 values. In particular, simvastatin was the most active in potentiating the activity of AEDs and the combinations of statins with carbamazepine, diazepam, felbamate, lamotrigine, topiramate and valproate were the most favorable, whereas, the co-administrations with the other AEDs studied was in most cases neutral. The increase in potency was generally associated with an enhancement of motor impairment (TD50); however, the therapeutic index (TD50/ED50) of combined treatment of AEDs with statins was predominantly more favorable than control. Statins administration did not significantly affect the total plasma but, in some cases, it increased the free plasma levels and the brain concentrations of some of the AEDs studied (i.e. carbamazepine, diazepam, phenytoin and valproate); however, these alterations where not statistically significant. Therefore, with the exception of the latter compounds, we might exclude pharmacokinetic interactions and conclude that for the most of AEDs, potentiation was of pharmacodynamic nature. In conclusion, simvastatin, fluvastatin, lovastatin and atorvastatin showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, diazepam, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations. The present results suggest that statins, besides the beneficial cardiovascular effects, might be able to affect brain areas, which might participate in the regulation of seizure susceptibility.


Siniscalchi A.,Annunziata Hospital | Gallelli L.,University of Catanzaro | Giofre C.,University of Catanzaro | De Sarro G.,University of Catanzaro
Pharmacological Reports | Year: 2012

Topiramate (TPM) is an O-alkyl sulfamate derivative of the naturally occurring monosaccharide D-fructose with an epileptic activity. However, it has been suggested that, in addition to its use in epilepsy, TPM could also be used in the treatment of neurological disorders, psychiatric conditions and hyperkinetic movement disorders. The clinical applications of TPM in hyperkinetic movement disorders is consistent with the multiple pharmacodynamic mechanisms e.g., the modulation of both γ-aminobutyric acidergic or glutamatergic neurotransmission and the modulation of voltage-gated ion channels or intracellular signalling pathways. The purpose of the present review is to describe the mechanisms of action of TPM and its clinical efficacy in patients with hyperkinetic movement disorders. Copyright © 2012 by Institute of Pharmacology Polish Academy of Sciences.


Siniscalchi A.,Annunziata Hospital | Gallelli L.,University of Catanzaro | Malferrari G.,Santa Maria Nuova Hospital | Pirritano D.,San Giovanni Of Dio Hospital | And 3 more authors.
Journal of Basic and Clinical Physiology and Pharmacology | Year: 2014

Stroke represents the most frequent cause of permanent disability in adults worldwide. Cerebral ischemia triggers the pathological pathways of the ischemic cascade and causes irreversible neuronal injury in the ischemic core within minutes of the onset. Elements of the immune system are involved in all stages of ischemic cascade from acute intravascular events triggered by the interruption of blood supply, to the parenchymal processes leading to brain damage and to the ensuing tissue repair. In this review, we will provide a brief overview of current understanding of the role of cytokines and brain inflammation during acute ischemic stroke. © 2014 by Walter de Gruyter Berlin/Boston.


Corsonello A.,Research Hospital of Cosenza | Abbatecola A.M.,Italian National Research Center on Aging | Fusco S.,Messina University | Luciani F.,Annunziata Hospital | And 4 more authors.
Clinical Microbiology and Infection | Year: 2015

Infectious diseases are more prevalent in older people than in younger adults, and represent a major healthcare issue in older populations. Indeed, infections in the elderly are often associated with higher morbidity and mortality, and may present atypically. Additionally, older patients are generally treated with polypharmacy regimens, which increase the likelihood of drug-drug interactions when the prescription of an antimicrobial agent is needed. A progressive impairment in the functional reserve of multiple organs may affect either pharmacokinetics or pharmacodynamics during aging. Changes in body composition occurring with advancing age, reduced liver mass and perfusion, and reduced renal excretion may affect either pharmacokinetics or pharmacodynamics. These issues need to be taken into account when prescribing antimicrobial agents to older complex patients taking multiple drugs. Interventions aimed at improving the appropriateness and safety of antimicrobial prescriptions have been proposed. Educational interventions targeting physicians may improve antimicrobial prescriptions. Antimicrobial stewardship programmes have been found to reduce the length of hospital stay and improve safety in hospitalized patients, and their use in long-term care facilities is worth testing. Computerized prescription and decision support systems, as well as interventions aimed at improving antimicrobial agents dosage in relation to kidney function, may also help to reduce the burden of interactions and inherent costs. © 2014 European Society of Clinical Microbiology and Infectious Diseases.


Siniscalchi A.,Annunziata Hospital | Gallelli L.,University of Catanzaro | De Sarro G.,University of Catanzaro
Current Neuropharmacology | Year: 2010

Many studies investigated the use of antiepileptic drugs (AEDs) in several neurological diseases other than epilepsy. These neurological disorders, usually, involve neuronal excitability through the modulating of ion channels, receptors and intracellular signaling pathways, and are the targets of the AEDs. This article provides a review of the clinical efficacy of both conventional and newer AEDs in hyperkinetic movement disorders. Some of these indications for AEDs have been established, while others are under investigation. The modulation of GABAergic transmission may explain the neuronal hyper-excitability that underlies some forms of hyperkinetic movement disorders. So, AEDs able to increase GABAergic neurotransmission may play a role in hyperkinetic movement disorders treatment. Therefore, AEDs could represent a useful therapeutic option in the management of hyperkinetic movement disorders where the available treatments are ineffective. ©2010 Bentham Science Publishers Ltd.


Siniscalchi A.,Annunziata Hospital | Gallelli L.,University of Catanzaro | Avenoso T.,University of Catanzaro | Squillace A.,University of Catanzaro | de Sarro G.,University of Catanzaro
Annals of Pharmacotherapy | Year: 2011

OBJECTIVE: To report on a patient with trigeminal neuralgia who responded positively to combined carbamazepine/oxycodone treatment. CASE SUMMARY: A 48-year-old woman with a 4-month history of left facial pain consisting of episodes lasting less than 5 minutes was brought to our institution for clinical evaluation. Clinical, laboratory, and neuroradiologic findings led to a diagnosis of idiopathic trigeminal neuralgia. Carbamazepine treatment was started at 200 mg every 12 hours and increased at discharge to 300 mg every 8 hours. Two weeks later the patient was readmitted with trigeminal neuralgia symptoms that had persisted since the previous admission, although they had decreased in intensity. Carbamazepine was reduced to 200 mg every 8 hours and oxycodone 5 mg every 12 hours was added to the treatment regimen, with a complete resolution of pain within 7 days. DISCUSSION: Pathophysiological mechanisms involved in both the genesis and the maintenance of trigeminal neuralgia have not yet been defined. Several hypotheses could explain this disorder, ranging from peripheral neural ectopic pacemaker to central disinhibition. Both the interruption of the sodium channel and the modulation of both k- and μ-opioid receptors contributed to antinociceptive effects in trigeminal neuralgia. CONCLUSIONS: Treatment with a combination of carbamazepine, a sodium channel blocker, and oxycodone, a mixed k- and μ-opioid receptor agonist, may be useful in alleviating symptoms of trigeminal neuralgia.


Siniscalchi A.,Annunziata Hospital
Current drug safety | Year: 2013

Some papers reported the development of adverse drug reactions in patients with Down's syndrome during the treatment with antiepileptic drugs. However, at this time, no data have been published concerning the development of tremor in patients with Down's syndrome treated with sodium valproate. We report a 17-year-old man with epilepsy and Down's syndrome who experienced tremor during the treatment with a low dosage of sodium valproate. The Naranjo probability scale documented a possible association between tremor and sodium valproate. Sodium valproate was changed to lamotrigine with both a rapid improvement of tremor and an optimal control of symptoms. In conclusion we documented that sodium valproate is able to induce in a patient with epilepsy and Down's syndrome, the development of tremor probably through the decreased activity of GABAergic neurotrasmission; however, further studies may be performed in order to validate this observation.

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