China
Africa
Explore chapters and articles related to this topic
Sleep–Wake Disorders
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Margaret Kay-Stacey, Eunice Torres-Rivera, Phyllis C. Zee
Agents for suppression of cataplexy. These drugs act as REM suppressants and enhance mostly the norepinephrine and serotonin systems. One exception is sodium oxybate, whose exact mechanism of action is unknown. Sodium oxybate appears to consolidate the fragmented sleep of narcoleptics and can treat both cataplexy and EDS in these patients.
Physiology of Sleep and Sleep Disorders
Published in John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford, Head & Neck Surgery Plastic Surgery, 2018
Management of narcolepsy includes planned napping, sleep hygiene and psychosocial support. Sleepiness may respond to stimulants including modafinil, dexamphetamine or methylphenidate. Cataplexy may respond to REM sleep-suppressing medications including tricyclic and SSRI antidepressants. Sodium oxybate or pitolisant may control cataplexy as well as sleep fragmentation and excessive daytime sleepiness.
Common sleep disorders
Published in Ravi Gupta, S. R. Pandi Perumal, Ahmed S. BaHammam, Clinical Atlas of Polysomnography, 2018
Ravi Gupta, S. R. Pandi Perumal, Ahmed S. BaHammam
BaHammam, A. S., Pandi-Perumal, S. R., & Neubauer, D. N., (2015). Sodium Oxybate (Xyrem®): A New and Effective Treatment for Narcolepsy with Cataplexy. In: Guglietta A, editor. Drug Treatment of Sleep Disorders: Milestones in Drug Therapy. Switzerland: Springer International Publishing. p, 231-248.
Narcolepsy Treatment: Voices of Adolescents
Published in Behavioral Sleep Medicine, 2022
Lena Xiao, Anna Chen, Arpita Parmar, Lucy Frankel, Alene Toulany, Brian J. Murray, Indra Narang
The main treatment for narcolepsy is pharmacotherapy addressing excessive daytime sleepiness and cataplexy. Excessive daytime sleepiness is often treated with stimulants such as amphetamine, dextroamphetamine, and methylphenidate, as well as wake-promoting agents including modafinil (Thorpy & Bogan, 2020). However, these medications may cause common side effects such as palpitations, anorexia, headache, nervousness, nausea, and insomnia (Black & Hirshkowitz, 2005; Clavenna & Bonati, 2017; Kingshott et al., 2001; Rammohan, 2002). Cataplexy is treated with sodium oxybate, selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, and tricyclic antidepressants (Wise et al., 2007). Common adverse effects include headache, nausea, epigastric discomfort, weight gain, and dry mouth (Babiker & Prasad, 2015; Kotagal, 2018). Specifically, sodium oxybate is a powerful sedative with the potential for misuse and has an inconvenient dosing regimen requiring a dose in the middle of the night. Tricyclic antidepressants may also cause serious adverse events such as arrhythmias, parkinsonism, neuroleptic malignant syndrome or seizures (Houghton et al., 2004). Overall, the disadvantages of pharmacotherapy in narcolepsy are inconsistent efficacy, development of tolerance, dependence, and nonadherence (Houghton et al., 2004; Pérez-Carbonell et al., 2020). Although there are medications or combinations of medications that are efficacious for narcolepsy, these have to be balanced with side effects, which may negatively impact the adherence with daily treatment over the long-term (Taddeo et al., 2008).
Development of a lower-sodium oxybate formulation for the treatment of patients with narcolepsy and idiopathic hypersomnia
Published in Expert Opinion on Drug Discovery, 2022
Gunjan Junnarkar, Clark Allphin, Judi Profant, Teresa L. Steininger, Cuiping Chen, Katie Zomorodi, Roman Skowronski, Jed Black
In the rat PK study, the oral exposure of oxybate was evaluated following administration of individual-cation formulations (sodium oxybate, potassium oxybate, calcium oxybate, or magnesium oxybate) or a mixed-cation formulation to understand the influence of cations on absorption of oxybate. Each formulation was prepared at 16.5 mg/mL (free base equivalents) of oxybate in water. Rats were fasted for a minimum of 12 hours prior to formulation administration. Each rat (n = 6 per formulation) received a single dose administered by oral gavage. Blood samples were collected from the jugular vein up to 3 hours post-dose and oxybate plasma concentrations were determined. All individual formulations had different PK profiles compared with SXB. Based on the average area under the plasma concentration-time curve (AUC) values, exposure to oxybate was greatest for sodium oxybate and least for magnesium oxybate and the mixed-cations oxybate formulation (53.4, 24.4, and 24.4 µg∙h/mL, respectively).
Emerging therapeutic targets for narcolepsy
Published in Expert Opinion on Therapeutic Targets, 2021
Marieke Vringer, Birgitte Rahbek Kornum
Sodium oxybate (the sodium salt of gamma-hydroxybuturate (GHB)) is efficacious against both cataplexy and EDS [10,96]. The mechanism is not well established, but it has been proposed that the improvement in daytime symptoms is a downstream effect of the acute GHB state, where a sleep-like increase in slow wave activity is seen [97]. This acute sedating effect of GHB is mediated by low-affinity binding to GABAB receptors [98]. Despite the immediate activation of GABAB receptors by GHB, the therapeutic efficacy in NT1 gradually improve over 2–8 weeks [99,100]. This has led people to question whether the GHB-induced slow wave activity is at all relevant for the treatment effect [97]. The effect might also be mediated by other pathways or even via the high-affinity target of GHB, recently reported to be the calcium/calmodulin-dependent protein kinase II (CaMK2) [38]. While sodium oxybate is generally well tolerated, its short half-life causes the administration to be cumbersome. For this reason, recent drug development efforts have also included slow-release formulations and GHB prodrugs [101,102]