Recommended
More Related Content
What's hot
What's hot (20)
Similar to How to Wake Up Safely and Effectively
Similar to How to Wake Up Safely and Effectively (20)
Recently uploaded
Recently uploaded (20)
How to Wake Up Safely and Effectively
- 1. How to wake up?Dr.Jaidaa Mekky A.Prof of Neuropsychiatry Sleep Medicine Consultant ESRS,AAN , AASM member
- 3. Neurobiology
- 5. Interconnected brain areas involved in sleep control and EEG sleep waves generation that present T- typedependentactivity.Exampleof LTCPs evoked from hyperpolarized membrane potentials in response to depolarizing current injections in layer V/VI cortical neuron (1), TC (2) and NRT (3) neurons, ventrolateral preoptic neuron (VLPO, 4) and hypocretin-orexin expressing neurons (hcrt/orx, 5) of the lateral hypothalamus.Both tonic firing and LTCParepresentedin1,4,and5. https://www.researchgate.net/figure/nterconnected-brain-areas-involved-in-sleep-control-and- EEG-sleep-waves-generation-that_fig2_260754936
- 7. The ascending arousal system sends projections from the brainstem and posterior hypothalamus diffusely to the forebrain. Neurons of the laterodorsal tegmental nuclei and pedunculopontine nuclei (LDT and PPT, blue circles ) send cholinergic fibers (Ach) to many forebrain targets, including the thalamus, which then regulate cortical activity. Aminergic nuclei ( green circles ) project diffusely throughout the forebrain, regulating the activity of cortical and hypothalamic targets directly. Neurons of the tuberomammillary nucleus (TMN) contain histamine (HA), neurons of the raphe nuclei contain 5-HT, and neurons of the locus coeruleus (LC) contain noradrenaline (NA). Sleep-promoting neurons of the ventrolateral preoptic nucleus (VLPO, red circle ) containGABA and galanin (Gal). From Saper CB, ChouTC, ScammellTE.The sleep switch: hypothalamic control of sleep and wakefulness
- 8. Hypothalamic and brainstem sleep/wake regulation systems (a) Distinct roles of the brainstem, thalamus, hypothalamus and cortex for vigilance control. (b) Recent discoveries of the sleep-promoting GABAergic/galanininergic (Gal) neurons in the ventrolateral preoptic area (VLPO) and the wake- promoting hypocretin/orexin neurons in the lateral hypothalamus focus attention on the hypothalamus. Destruction of these systems induces insomnia and narcolepsy, respectively, mirroring the pioneering clinical observations during the encephalitis lethargica epidemic.
- 10. Homeostasisof Synapses: Expansion DuringWakefulness, Contraction During Sleep During sleep, synaptic sizes shrink and glutamate receptor levels decrease. This is driven by theHomer1a-induced remodeling of the mGluR5 signaling complex. Dashed lines (right) indicate the profile of the synapse in the awake state . Received: 22 February 2017 / Accepted: 8 March 2017 Shanghai Institutes for Biological Sciences,CAS and Springer Science+Business Media Singapore 2017
- 11. Modulation of glutamate receptor function has therefore been proposed as a promising target for antidepressant, anxiolytic, and antipsychotic drug development (Popoli et al, 2012). Positive and negative modulators of mGluR subtype 5 (mGluR5), in particular, have been suggested as novel agents for the treatment of depression file:///C:/Users/MC/Downloads/Stefan%20Leber%20Thesis%20(17.09.15).pdf
- 16. CAUSESOF EDS The sleep disorders narcolepsy (daytime sleepiness) and sleep apnea (interruptions of breathing during sleep) Not getting enough sleep at night (sleep deprivation) Being overweight Drug or alcohol abuse A head injury or a neurological disease, such as multiple sclerosis or Parkinson's disease Prescription drugs, such as tranquilizers or antihistamines Genetics (having a relative with hypersomnia) Depression RLS
- 17. NARCOLEPSY
- 22. Symptoms
- 24. Management
- 25. StimulantTherapy
- 26. Narcolepsy Tricyclic Antidepressants Selective serotonin reuptake inhibitors Selective noradrenergic reuptake inhibitors Stimulants Modafinil or Armodafinil
- 27. FDAApproval FDA approval of armodafinil was based on the results of four clinical trials. In each trial a p-value of less than 0.05 was required for statistical significance. Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS) Narcolepsy Shift Work Sleep Disorder (SWSD)
- 29. Its mechanisms of action are complex acting on serotonin, norepinephrine, dopamine, histamine, orexin, glutamate, and GABA receptors. https://www.psychiatry.cam.ac.uk/blog/2012/10/15/modafinil-effects-on-schizophrenia-a-systematic-review/
- 33. FATIGUE They improved attention in well-rested individuals, while maintaining wakefulness, memory, and executive functions in sleep-deprived individuals compared to placebo. However, repeated doses of armodafinil were unable to prevent deterioration of cognitive performance over a longer period of sleep deprivation . In a trial with 41 participants under conditions of 64-hour sleep deprivation, 300 mg armodafinil significantly improved cognitive capabilities compared to placebo, while amphetamine (20 mg) and modafinil scored similarly in mood, fatigue level, and cognitive tests. Also, this study showed that even after 64 hours of sleep deprivation, participants under the influence of modafinil reported almost the same fatigue and mood levels as the participants had when they were well rested
- 35. Modafinil vs. Amphetamines Armodafinil and d-amphetamine produced similar results in improving cognitive function, fatigue, and mood during a 64-hour sleep deprivation . Armodafinil produced overconfidence and overestimation of one’s own cognitive abilities. While armodafinil disrupted one’s self- monitoring cognitive performance, participants given amphetamine performed accurate self-monitoring throughout the study . However, amphetamines are capable of increasing anxiety levels, while armodafinil is not, as shown by both animal and human studies . While armodafinil has much lower abuse potential, amphetamines, on the other hand, increase dopamine levels across the brain to a greater extent.
- 36. Armodafinil vs. Methylphenidate Methylphenidate, is similar to modafinil regarding its cognitive enhancing properties Although therapeutic doses of methylphenidate no not produce addiction, higher doses could cause euphoria and dependence if used often An Overview of the Clinical Uses, Pharmacology, and Safety of Modafinil ACS Chem Neurosci. 2018 Feb 21;9(2):151-158. doi: 10.1021/acschemneuro.7b00374. Epub 2017 Dec 4.
- 37. Modafinil vs. Methylphenidate Methylphenidate, is similar to modafinil regarding its cognitive enhancing properties Although therapeutic doses of methylphenidate no not produce addiction, higher doses could cause euphoria and dependence if used often
- 38. APPROVAL BOTH have not been studied in pediatric patients in any setting and is not approved for use in pediatric patients for any indication. Use in pregnancy and lactaion is not approved yet Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-.
- 39. Side Effects Adverse events associated with the use of STIMULANTTHERAPY may include: Headache Nausea Dizziness Insomnia Dry mouth Anxiety Diarrhea Rash
- 40. Adverse Effects Serious Dermatologic Reactions, including Stevens-Johnson Syndrome And Toxic Epidermal Necrosis There are no factors, including duration of therapy, that are known to predict the risk of occurrence or the severity of rash associated with modafinil or armodafinil. In cases where the time of onset was reported, serious rash occurred 1 day to 2 months after initiation of treatment, but isolated cases of serious dermatologic reactions have been reported with symptoms beginning after prolonged treatment (e.g., 3 months).
- 41. J Clin Sleep Med. 2018 May 15;14(5) Stevens-JohnsonSyndrome After Armodafinil Use. Holfinger S1, Roy A2, Schmidt M2,3. Abstract We present the case of a 21-year-old woman in whom Stevens- Johnson syndrome (SJS) developed after initiation of armodafinil. Although this rare and life-threatening reaction is listed on armodafinil's label, no cases have been reported in the literature. This case, in addition to an update of the drug's label after post- marketing research, both support the link between armodafinil and SJS. Providers should maintain a high clinical suspicion for SJS when starting therapy to minimize associated morbidity and mortality by discontinuing armodafinil at the onset of first symptoms. Mucocutaneous ulcerations with irregular purpuric macules, 13 days after initiation of armodafinil.
- 42. DRESS (DrugRash with Eosinophilia and SystemicSymptoms) PRESENTS with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. One fatal case of DRESS that occurred in close temporal association (3 weeks) with the initiation of NUVIGIL treatment has been reported in the postmarketing setting.