Narcolepsy side effects

Tricyclic Antidepressants (TCAs). TCAs were introduced in the 1950s and over the years have become the mainstay of treatment for cataplexy and the other REM-related symptoms. The doses used are usually less than the doses required in the treatment of depression. Imipramine (Tofranil) is the most widely used TCA for narcolepsy and is usually effective at doses from 10 to 75 mg given once a day. Some doctors prefer the TCA protriptyline (Vivactil) because it has mild stimulant effects, but it has not been as widely used or as thoroughly studied in narcolepsy. The common side effects of TCAs are drowsiness, dry mouth, and constipation, but these are usually not a problem at the lower doses used for narcolepsy. Patients should receive a baseline electrocardiograph (EKG) before starting a TCA and should have blood levels of the medication checked periodically. 

Psychiatrists most often use these medications to treat ADHD, narcolepsy, and refractory depression. Conservative measures are often sufficient to counteract the side effects of increased dopamine. When insomnia or nausea is a problem, changing the dose schedule can be helpful. Avoiding or reducing evening doses can alleviate insomnia taking the medications after meals can lessen nausea and upset... 

GHB was hrst synthesized in the laboratory by the French biochemist Henri Lahorit (1914-1995) in 1961. In the succeeding four decades, extensive research has been conducted on the pharmacological uses and effects of GHB. In general, those studies appear to suggest that GHB has some valuable applications in the medical sciences. It functions well as an anesthetic with apparently few or no serious side effects. Based on this research, the drug has been adopted in many parts of the world for use as a general anesthetic, a treatment for narcolepsy and insomnia, a treatment for alcoholism, and an aid in childbirth. 

Figure 25-8 Baseline separation of enantiomers of the drug Ritalin by HPLC with a chiral stationary phase. One enantiomer is pharmacologically active for treating attention deficit disorder and narcolepsy. The other enantiomer has little activity but could contribute to undesired side effects. Pharmaceutical companies are moving toward providing enantiomerically pure drugs, which could be safer than mixtures of optical isomers. [From R. Bakhtiar, L Ramos, and F. L. S. Tse, "Quantification of Methylphenidate in Plasma Using Chiral Uquid-Chromatography/Tandem Mass Spectrometry Application to Taxicokinetic Studies," Anal. Chim. Acta 2002, 469.261.]...

The primary drug therapies are psychostimulants which are indicated for both emotional based sleep disorders (i.e., narcolepsy) as well as ADHD. The drugs of choice are Ritalin (methylphenidate), dextroamphetamine or Cylert (pemoline), all CNS stimulants that effect the monoamine systems. The current therapies provide symptomatic relief but the current medications are not without side effects, including abuse potential, cardiovascular effects, insomnia, appetite suppression, head and stomach aches, crying and nervous mannerisms. 

GHB (gamma hydroxybutyrate) was originally developed as an anesthetic, but was withdrawn due to unwanted side effects. GHB holds several U.S. patents for use in the treatment of sleep disorders such as narcolepsy and insomnia, and as a muscle relaxant. GHB is used as a fast-acting anesthetic in small animals. The compounds and compositions made from GHB are useful in the treatment of Parkinson s disease, schizophrenia, and other dopamine-related disorders. 

The recommended dose of modafinil is 200 mg/day for the treatment of excessive daytime sleepiness associated with narcolepsy however, doses of 400 mg/day are FDA-approved. While there is evidence that the higher dose is well tolerated, it has not been established that it confers additional therapeutic benefit (196). In sleep-deprived subjects, doses of 600 mg/day have been administered, but the preponderance of evidence suggests that 300M00 mg/day is probably sufficient and less likely to produce unwanted side effects. 

Modafinil another wakefulness promoting agent with an unknown mechanism of action used for narcolepsy in adults and being studied for use in children at present dose range is 1 Of MOO mg/day divided bid. Side effects include headaches, anxiety, nausea and nervousness. 

GHB was investigated as an anesthetic agent but was discontinued because of its lack of analgesia and because of adverse side effects including seizures. It is used outside the United States to treat alcohol and opioid withdrawal and was recently approved in the United States under the name Xyrem for the treatment of narcolepsy. 

Fenetylline is an interesting example where the molecule consists of a combination of sympathomimetic-like entities. In this compound the caffeine derivative theophylline is fused to amfetamine and it has been used for the treatment of ADHD and narcolepsy. It has been claimed that fenetylline showed fewer amfetamine-type side effects such as elevated blood pressure, tremor and fine motor activity, but became ill al due to increased numbers of abusers. A typical adult dose of fenetylline hydrochloride is 25-50 mg once or twice a day. Fenetylline abuse has been reported to be particularly prominent in the Middle East and a large number of counterfeit products are circulating. 

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