Narcolepsy in the context of Modafinil


Narcolepsy in the context of Modafinil

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⭐ Core Definition: Narcolepsy

Narcolepsy is a chronic neurological disorder that impairs the ability to regulate sleep–wake cycles, and specifically impacts REM (rapid eye movement) sleep. The symptoms of narcolepsy include excessive daytime sleepiness (EDS), sleep-related hallucinations, sleep paralysis, disturbed nocturnal sleep (DNS), and cataplexy. People with narcolepsy typically have poor quality of sleep.

There are two recognized forms of narcolepsy, narcolepsy type 1 and type 2. Narcolepsy type 1 (NT1) can be clinically characterized by symptoms of EDS and cataplexy, and/or will have cerebrospinal fluid (CSF) orexin levels of less than 110 pg/ml. Cataplexy are transient episodes of aberrant tone, most typically loss of tone, that can be associated with strong emotion. In pediatric-onset narcolepsy, active motor phenomena are not uncommon. Cataplexy may be mistaken for syncope, tics, or seizures. Narcolepsy type 2 (NT2) does not have features of cataplexy, and CSF orexin levels are normal. Sleep-related hallucinations, also known as hypnagogic (going to sleep) and hypnopompic (on awakening), are vivid hallucinations that can be auditory, visual, or tactile and may occur independent of or in combination with an inability to move (sleep paralysis). Narcolepsy is a clinical syndrome of hypothalamic disorder, but the exact cause of narcolepsy is unknown, with potentially several causes. A leading consideration for the cause of narcolepsy type 1 is that it is an autoimmune disorder. Proposed pathophysiology as an autoimmune disease suggest antigen presentation by DQ0602 to specific CD4+ T cells resulting in CD8+ T-cell activation and consequent injury to orexin producing neurons. Familial trends of narcolepsy are suggested to be higher than previously appreciated. Familial risk of narcolepsy among first-degree relatives is high. Relative risk for narcolepsy in a first-degree relative has been reported to be 361.8. However, there is a spectrum of symptoms found in this study, from asymptomatic abnormal sleep test findings to significantly symptomatic.

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👉 Narcolepsy in the context of Modafinil

Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant and eugeroic (wakefulness promoter) medication used primarily to treat narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and sudden sleep attacks. Modafinil is also approved for stimulating wakefulness in people with sleep apnea and shift work sleep disorder. It is taken by mouth. Modafinil is not approved by the US Food and Drug Administration (FDA) for use in people under 18 years old.

Common side effects of modafinil include anxiety, insomnia, dizziness, and headache. Modafinil has potential for causing severe allergic reactions, psychiatric effects, hypersensitivity, adverse interactions with prescription drugs, and misuse or abuse. Modafinil may harm the fetus if taken during or two months prior to pregnancy.

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Narcolepsy in the context of Sleep disorder

A sleep disorder, or somnipathy, is a medical disorder that disrupts an individual's sleep patterns and quality. This can cause serious health issues and affect physical, mental, and emotional well-being. Polysomnography and actigraphy are tests commonly ordered for diagnosing sleep disorders.

Sleep disorders are broadly classified into dyssomnias, parasomnias, circadian rhythm sleep disorders, and other disorders (including those caused by medical or psychological conditions). When a person struggles to fall or stay asleep without an obvious cause, it is referred to as insomnia, which is the most common sleep disorder. Other sleep disorders include sleep apnea, narcolepsy, hypersomnia (excessive sleepiness at inappropriate times), sleeping sickness (disruption of the sleep cycle due to infection), sleepwalking, and night terrors.

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Narcolepsy in the context of Automatic behavior

Automatism is a set of brief unconscious or automatic behaviors, typically at least several seconds or minutes, while the subject is unaware of actions. This type of automatic behavior often occurs in certain types of epilepsy, such as complex partial seizures in those with temporal lobe epilepsy, or as a side effect of particular medications such as zolpidem.

Automatic behaviors involve the spontaneous production of purposeless verbal or motor behavior without conscious self-control or self-censorship. This condition can be observed in a variety of contexts, including schizophrenia, dissociative fugue, Tourette syndrome, epilepsy (in complex partial seizures and Jacksonian seizures), narcolepsy, or in response to a traumatic event.

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Narcolepsy in the context of Hypnotic

A hypnotic (from Greek Hypnos, sleep), also known as a somnifacient or soporific, and commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to induce sleep and to treat insomnia (sleeplessness). Some hypnotics are also used to treat narcolepsy and hypersomnia by improving sleep at night and thereby reducing daytime sleepiness. Certain hypnotics can be used to treat non-restorative sleep and associated symptoms in conditions like fibromyalgia as well.

This group of drugs is related to sedatives. Whereas the term sedative describes drugs that serve to calm or relieve anxiety, the term hypnotic generally describes drugs whose main purpose is to initiate, sustain, or lengthen sleep. Because these two functions frequently overlap, and because drugs in this class generally produce dose-dependent effects (ranging from anxiolysis to loss of consciousness), they are often referred to collectively as sedative–hypnotic drugs.

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Narcolepsy in the context of Methylphenidate

Methylphenidate, sold under the brand name Ritalin and Concerta, among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It may be taken by mouth or applied to the skin, and different formulations have varying durations of effect. For ADHD, the effectiveness of methylphenidate is comparable to atomoxetine but modestly lower than amphetamine. Methylphenidate reduces core ADHD symptoms and may do so in part by enhancing cognitive control of behavior (i.e., working memory and inhibitory control).

At therapeutic doses, methylphenidate increases alertness and concentration and reduces hyperactivity and impulsive behavior in individuals with ADHD. Common side effects include loss of appetite, weight loss, trouble sleeping, and small increases in heart rate and blood pressure. Long-term treatment in children has been associated with slightly slower growth. Methylphenidate can be misused; dependence and withdrawal are mainly reported with high-dose or non-medical use and are uncommon at therapeutic doses.

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Narcolepsy in the context of Amphetamine

Amphetamine is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity; it is also used to treat binge eating disorder in the form of its inactive prodrug lisdexamfetamine. Amphetamine was discovered as a chemical in 1887 by Lazăr Edeleanu, and then as a drug in the late 1920s. It exists as two enantiomers: levoamphetamine and dextroamphetamine. Amphetamine properly refers to a specific chemical, the racemic free base, which is equal parts of the two enantiomers in their pure amine forms. The term is frequently used informally to refer to any combination of the enantiomers, or to either of them alone. Historically, it has been used to treat nasal congestion and depression. Amphetamine is also used as an athletic performance enhancer and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. It is a prescription drug in many countries, and unauthorized possession and distribution of amphetamine are often tightly controlled due to the significant health risks associated with recreational use.

The first amphetamine pharmaceutical was Benzedrine, a brand which was used to treat a variety of conditions. Pharmaceutical amphetamine is prescribed as racemic amphetamine, Adderall, dextroamphetamine, or the inactive prodrug lisdexamfetamine. Amphetamine increases monoamine and excitatory neurotransmission in the brain, with its most pronounced effects targeting the norepinephrine and dopamine neurotransmitter systems.

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Narcolepsy in the context of Alertness

Alertness is a state of active attention characterized by high sensory awareness. Someone who is alert is vigilant and promptly meets danger or emergency, or is quick to perceive and act. Alertness is a psychological and physiological state.

Lack of alertness is a symptom of a number of conditions, including narcolepsy, attention deficit hyperactivity disorder, chronic fatigue syndrome, depression, Addison's disease, and sleep deprivation. Pronounced lack of alertness is an altered level of consciousness. States with low levels of alertness include drowsiness.

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Narcolepsy in the context of Ephedrine

Ephedrine is a central nervous system (CNS) stimulant and sympathomimetic agent that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in nasal congestion. It can be taken by mouth or by injection into a muscle, vein, or just under the skin. Onset with intravenous use is fast, while injection into a muscle can take 20 minutes, and by mouth can take an hour for effect. When given by injection, it lasts about an hour, and when taken by mouth, it can last up to four hours.

Common side effects include trouble sleeping, anxiety, headache, hallucinations, high blood pressure, fast heart rate, loss of appetite, and urinary retention. Serious side effects include stroke and heart attack. While probably safe in pregnancy, its use in this population is poorly studied. Use during breastfeeding is not recommended. Ephedrine works by inducing the release of norepinephrine and hence indirectly activating the α- and β-adrenergic receptors. Chemically, ephedrine is a substituted amphetamine and is the (1R,2S)-enantiomer of β-hydroxy-N-methylamphetamine.

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Narcolepsy in the context of Excessive daytime sleepiness

Excessive daytime sleepiness (EDS) is characterized by persistent sleepiness and often a general lack of energy, even during the day after apparently adequate or even prolonged nighttime sleep. EDS can be considered as a broad condition encompassing several sleep disorders where increased sleep is a symptom, or as a symptom of another underlying disorder like narcolepsy, circadian rhythm sleep disorder, sleep apnea or idiopathic hypersomnia.

Some persons with EDS, including those with hypersomnias like narcolepsy and idiopathic hypersomnia, are compelled to nap repeatedly during the day, fighting off increasingly strong urges to sleep during inappropriate times such as while driving, while at work, during a meal, or in conversations. As the compulsion to sleep intensifies, the ability to complete tasks sharply diminishes, often mimicking the appearance of intoxication. During occasional unique and/or stimulating circumstances, a person with EDS can sometimes remain animated, awake and alert, for brief or extended periods of time. EDS can affect the ability to function in family, social, occupational, or other settings. A proper diagnosis of the underlying cause and ultimately treatment of symptoms and/or the underlying cause can help mitigate such complications. According to the National Sleep Foundation, around 20 percent of people experience EDS.

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Narcolepsy in the context of Onset of sleep

Sleep onset is the transition from wakefulness into sleep. Sleep onset usually transits into non-rapid eye movement sleep (NREM sleep) but under certain circumstances (e.g. narcolepsy) it is possible to transit from wakefulness directly into rapid eye movement sleep (REM sleep).

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Narcolepsy in the context of Sleep paralysis

Sleep paralysis is a state, during waking up or falling asleep, in which a person is conscious but in a complete state of full-body paralysis. During an episode, the person may hallucinate (hear, feel, or see things that are not there), which often results in fear. Episodes generally last no more than a few minutes. It can recur multiple times or occur as a single episode.

The condition may occur in those who are otherwise healthy or those with narcolepsy, or it may run in families as a result of specific genetic changes. The condition can be triggered by sleep deprivation, psychological stress, or abnormal sleep cycles. The underlying mechanism is believed to involve a dysfunction in REM sleep. Diagnosis is based on a person's description. Other conditions that can present similarly include narcolepsy, atonic seizure, and hypokalemic periodic paralysis.

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Narcolepsy in the context of Eugeroic

A eugeroic, or eugregoric, is a type of drug that increases wakefulness. The term has been used inconsistently and in multiple ways in the scientific literature, either to refer specifically to modafinil-type wakefulness-promoting agents or to refer to wakefulness-promoting agents generally. It was first introduced in the French literature in 1987 as a descriptor for modafinil-like wakefulness-promoting drugs and for purposes of distinguishing such drugs from psychostimulants. However, the term "eugeroic" has not been widely adopted in the literature, and instead the term "wakefulness-promoting agent" (and variations thereof) has been more widely used, both for modafinil-type drugs and other agents.

Eugeroics, in the sense of modafinil-type wakefulness promoting agents, include modafinil itself, armodafinil, and adrafinil, among others. They are medically indicated for the treatment of certain sleep disorders, including excessive daytime sleepiness (EDS) in narcolepsy or obstructive sleep apnea (OSA). Eugeroics are also often prescribed off-label for the treatment of EDS in idiopathic hypersomnia. In contrast to classical psychostimulants, such as amphetamine and methylphenidate, which are also used in the treatment of these disorders, eugeroics typically do not produce euphoria, and, consequently, have lower misuse potential.

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