Intranasal therapies for acute seizures

Kälviäinen, Reetta

doi:10.1016/j.yebeh.2015.04.027

Cited by 46 publications

(45 citation statements)

References 31 publications

(46 reference statements)

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“…Nevertheless, the pharmacokinetics profile of diazepam and lorazepam following intranasal delivering has been assessed [57][58][59]60 & ,61] with promising results. Intranasal lorazepam was noninferior to intravenous lorazepam for controlling acute convulsive seizures in children [62], and has been proposed as a valid alternative to intramuscular paraldehyde for prolonged convulsive seizures in children [63].…”

Section: Intranasal Rectal Buccal and Intramuscular Routes Of Adminmentioning

confidence: 99%

Recent advances in status epilepticus

Trinka

Brigo

Shorvon

2016

Current Opinion in Neurology

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Section: Intranasal Rectal Buccal and Intramuscular Routes Of Adminmentioning

confidence: 99%

Recent advances in status epilepticus

Trinka

Brigo

Shorvon

2016

Current Opinion in Neurology

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“…Patients with SE are at risk of neurologic complications. Early intervention is frequently needed to shorten seizure duration [3]. The sooner seizures are treated, the more likely they will be controlled [4].…”

Section: Introductionmentioning

confidence: 99%

Alleviation of Oxidative Damage and Involvement of Nrf2‐ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline

Kang

Yan

Fang

et al. 2017

Oxidative Medicine and Cellular Longevity

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The current studies were aimed at evaluating the efficacy of intranasal pentoxifylline (Ptx) pretreatment in protecting mesodopaminergic system and hippocampus from oxidative damage of lithium-pilocarpine induced status epilepticus (SE) and the involvement of nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response elements pathway. Pentoxifylline was administered to rats intranasally or intraperitoneally 30 minutes before inducing SE. Our results showed the impaired visuospatial memory, the defected mesodopaminergic system, and the oxidative damage and the transient activation of Nrf2 in SE rats. The transient activation of Nrf2 in SE rats was enhanced by Ptx pretreatment, which was followed by the upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Ptx pretreatment to SE rats significantly suppressed the epileptic seizures, decreased the levels of lipid peroxide and malondialdehyde, and elevated the ratio of reduced glutathione/oxidized glutathione. Compared with intraperitoneal injection, intranasal Ptx delivery completely restored the visuospatial memory and the activity of mesodopaminergic system in SE rats. Intranasal administration of Ptx may hopefully become a noninvasive, painless, and easily administered option for epileptic patients.

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“…Due to the rich vascularization, the olfactory and in particular the respiratory zone, with a total surface of approximately 145 cm2, may serve as an efficient absorption surface for topically applied drugs [9]. The intranasal administration of BDZs became rapidly attractive because the nasal cavity is easily accessible and the nasal absorption is not subjected to the hepatic first-pass effect [10] [11]. In addition, the absorption through the cribriform plate can lead to a rapid increase in drug concentrations in the CSF as compared to other delivery methods and this is obviously crucial for a brain disorder like epilepsy [12].…”

Section: Intranasal Deliverymentioning

confidence: 99%

“…In particular, there are two intranasal DZP formulations currently under development by Neurelis (10 mg) and Acorda Therapeutics (20 mg) and a MDZ intranasal formulation by Upsher-Smith Laboratories (2.5 mg, 5 mg, 7.5 mg) [10]. Intranasal MDZ is the one at the more advanced stage as it is already under Phase III while DZP studies are still in Phase I for Neurelis and Phase II for Acorda [10]. Pharmacokinetic data showed that absorption is more reliable and efficient than using the injectable solution but data in patients with epilepsy in "real life" settings are still lacking.…”

Section: Intranasal Deliverymentioning

confidence: 99%

“…Available data suggests that intranasal MDZ is effective, safe and more efficient that rectal DZP in controlling seizure activity [7] (Table 3). In general terms, as compared to DZP, MDZ has the advantage of a faster absorption but the lower bioavailability and the shorter half-life may be potentially associated with an increased risk of recurrence [10]. Future studies comparing purpose-developed intranasal formulations of MDZ will be of interest.…”

Section: Intranasal Deliverymentioning

confidence: 99%

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New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective

Mula

2016

CNS Drugs

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Benzodiazepines (BDZs) represent first line treatment for the acute management of epileptic seizures and status epilepticus. The emergency use of BDZs requires timely administration and considering that most seizures occur outside of the hospital, there is a significant need for easy to use delivery methods that can be given quickly and safely by nonclinical caregivers. In addition, the ideal route of administration should be reliable in terms of absorption. In the US, rectal diazepam is the only licensed formulation, while in the EU rectal diazepam and buccal midazolam are currently licensed. However, both the rectal and buccal administration are not ideal as the absorption can be sometimes unpredictable. Several alternative routes are being explored and are currently under investigation. This is a narrative review of available data about delivery methods for BDZs alternative to the intravenous and oral routes for the acute treatment of seizures. Unconventional delivery options such as the direct delivery in the central nervous system or inhalers are reported. Available data shows that intranasal diazepam or midazolam and the intramuscular auto-injector for midazolam are as effective as rectal or intravenous diazepam. Head to head comparisons with buccal midazolam are urgently needed. In addition, the majority of trials focused on children and adolescents and further trials in adults are warranted.

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Intranasal therapies for acute seizures

Cited by 46 publications

References 31 publications

Recent advances in status epilepticus

Recent advances in status epilepticus

Alleviation of Oxidative Damage and Involvement of Nrf2‐ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline

New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective

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