Narcolepsy, treatment

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GABA-A receptor thereby enhancing the action of GABA. Sodium oxybate is the sodium salt of Y-hydrox)rbutyrat commonly referred to as GHB. This dmg has a very specific indication which is the treatment of cataplexy in narcolepsy. Narcolepsy is a chronic sleep disorder and the narcoleptic patient will often present as having severe insomnia. Cataplexy is a sudden loss of muscle tone and strength, usually caused by an extreme emotional stimulus. This occurs regularly (approximately 75% of cases) in patients with narcolepsy. Treatment with sodium oxybate is reported to improve the symptoms of narcolepsy and also to reduce the number of occurrences of cataplexy. 

Pemoline [2152-34-3] (24), stmcturally dissimilar to amphetamine or methylphenidate, appears to share the CNS-stimulating properties. As a consequence, pemoline is employed in the treatment of ADHD and of narcolepsy. There are several other compounds that are stmcturally related to amphetamines, although not as potent and, presumably, without as much abuse potential. These compounds also have anorexic effects and are used to treat obesity. Some of the compounds available are phentermine [122-09-8] fenfluramine [458-24-2] and an agent that is available over-the-counter, phenylpropanolamine [1483815-4] (26). 

The mode of action of modafinil, a new arousal-promoting compound used in the treatment of sleepiness associated with narcolepsy, is not fully understood. 

Amphetamines (speed sulph, sulphate, uppers, wake-ups, billy whizz, whizz, whites, base) are synthetic stimulants which as medicines have been formed into a variety of tablets. Their current medical use is very limited and in fact only dexamphetamine sulphate, Dexedrine, is now available for use solely in the treatment of narcolepsy. The only other amphetamine available for medical use is methylphenidate (Ritalin) for the treatment of attention deficit syndrome in children. As a street drug, amphetamine usually comes as a white, grey, yellowish or pinky powder. The purity rate of street powders is less than 10%, the rest being made up of milder stimulants such as caffeine, other drugs such as paracetamol or substances like glucose, dried baby milk, flour or talcum powder. 

Treatment of excessive daytime sleepiness in narcolepsy and other sleep disorders may require the use of sustained- and immediate-release stimulants to effectively promote wakefulness throughout the day and at key times that require alertness. 

Littner M, Johnson SF, McCall WV, et al. Practice parameters for the treatment of narcolepsy An update for 2000. Sleep 2001 24 451M55. 

Scammell TE. The neurobiology, diagnosis, and treatment of narcolepsy. Ann Neurol 2003 53 154-166. 

Soldatos CR, Kales A and Cadieux R (1979). Narcolepsy Evaluation and treatment. In DE Smith, ME Wessen et al. (eds), Amphetamine Use, Misuse and Abuse. Prentice Hall, Boston. 

The answer is a. (Hardman, p 22L Katzang, p L3L) Methylphenidate is similar to amphetamine and acts as a CN5 stimulant, with more pronounced effects on mental than on motor activities. It is effective in the treatment of narcolepsy and attention-deficit hyperactivity disorders. 

Compiled from US. Modafinil in Narcolepsy Multicenter Study Group and Standard of Practice Committee of the American Sleep Disorders Association. Pradice parameters for the use of stimulants in the treatment of narcolepsy. Seep 1994 17 348-351. 

ACT-078573 (20) is the first oral orexin receptor antagonist that penetrates the blood-brain barrier and is capable of inducing a transient and reversible blockade of the two receptors, 0X1 and 0X2 [61]. In animal models, the administration of 20 resulted in a dose-dependent decrease in alertness and increased non-REM and REM sleep. The compound, administered at oral doses ranging from 10 to 300 mg/kg, dose-dependently decreased alertness in rats and exhibited increased duration of REM and non-REM sleep, indicating no intrusive REM sleep that is characteristic of narcolepsy. In dogs, treatment with 20 (10-100 mg/kg p.o.) resulted in dose-dependent reductions in mobility and also induced signs of clinical somnolence. 

In 1970, the U.S. government passed the original Controlled Substances Act, and under this law methamphetamine was classified as a Schedule II drug in its injectable form and a Schedule III in its noninjectable (pill) form. However, a year later, both forms of methamphetamine were reclassified as Schedule II drugs. Today, it is still sold under the name Des-oxyn for a few medical uses, such as for the treatment of atten-tion-deficit/hyperactivity disorder (ADHD) and narcolepsy. 

Substance-Induced Anxiety Disorder. Numerous medicines and drugs of abuse can produce panic attacks. Panic attacks can be triggered by central nervous system stimulants such as cocaine, methamphetamine, caffeine, over-the-counter herbal stimulants such as ephedra, or any of the medications commonly used to treat narcolepsy and ADHD, including psychostimulants and modafinil. Thyroid supplementation with thyroxine (Synthroid) or triiodothyronine (Cytomel) can rarely produce panic attacks. Abrupt withdrawal from central nervous system depressants such as alcohol, barbiturates, and benzodiazepines can cause panic attacks as well. This can be especially problematic with short-acting benzodiazepines such as alprazolam (Xanax), which is an effective treatment for panic disorder but which has been associated with between dose withdrawal symptoms. 

Methylphenidate (Ritalin). Methylphenidate was developed in the late 1950s and its first use was the treatment of what we now call ADHD. Since that time, it has also been approved for the treatment of narcolepsy. Its only other use is the treatment of severe refractory depression either in medically ill patients who need rapid clinical improvement or as an augmentation agent when added to other antidepressants. In the treatment of ADHD, methylphenidate not only improves attention but also reduces hyperactivity and impulsivity. Verbal and physical aggression typically decreases as well. 

Modafinil (Provigil). The newest stimulant, modafinil, is not, pharmacologically, a true stimulant. Nevertheless, it is an effective treatment for narcolepsy at doses from 200 to 400mg/day. Several studies indicate that modahnil has little potential for abuse and is easier to tolerate than other stimulants. Modafinil has been studied in the treatment of ADHD. Though not approved for marketing by the FDA at the time of this writing, it may gain the indication in the near future. 

The discussion that follows will be limited to those sleep disorders that are common in adults and that frequently require medication as part of the usual treatment. Specifically, we will discuss insomnia and narcolepsy (the most common hypersomnia). We will briefly mention treatments for the nighttime limb movement disorders. 

Whereas insomnia consists of too little sleep or poor quality sleep, hypersomnia is just the opposite. Hypersomnia is literally too much sleep. This may mean either persistent drowsiness or an irresistible urge to sleep despite a good night s sleep. There are several variants of hypersomnia, but most are extremely rare with the notable exception of narcolepsy. For this reason, we will coniine our discussion to the treatment of narcolepsy, by far the most common of the hypersomnias. 

The main risk factor appears to be a genetic susceptibility to the illness. The majority of narcolepsy patients, particularly those with cataplexy, have a genetic marker known as HLA-DQB1 0602. Recent evidence indicates that the key dysfunction in narcolepsy is diminished activity of a newly discovered neurotransmitter known as hypocretin. This new evidence has led to the development of a new diagnostic test for narcolepsy and may ultimately lead to new treatments that act directly on hypocretin systems in the brain. 

Other Hypersomnias. Narcolepsy is not the only hypersomnia, but it is by far the most common. Primary hypersomnia shares sleep attacks and excessive daytime sleepiness with narcolepsy but does not feature cataplexy or REM-associated abnormalities. Another rare hypersomnia is Kleine-Levin syndrome (KLS), which most often occurs in teenage boys. KLS consists of intermittent bouts of hypersomnia and bizarre behaviors including compulsive eating and sexual inappropriateness. Distinguishing these hypersomnias from narcolepsy may help clarify the patient s prognosis, but the treatment alternatives are very similar. 

Stimulants. Treatment for narcolepsy has focused on its most disabling symptoms namely, sleep attacks and daytime drowsiness. The mainstay of treatment has... 

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