Methylphenidate narcolepsy

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). 

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. 

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. 

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. 

Methylphenidate (Ritalin, Concerta, Focalin). Methylphenidate was introduced in the late 1950s and is now the most widely used prescription stimulant. It was first used to treat ADHD in children but is also effective for narcolepsy. Like dextroamphetamine, methylphenidate should be started at 5 mg per dose given two to three times each day with meals. The average effective dose is 20-30 mg/day, but some patients require as much as 60 mg/day. The benefit of methylphenidate should also be apparent on the first day or so, and the dose can be increased every 5-7 days as needed. Focalin dosing is approximately half that of methylphenidate. 

Pemoline is a less potent stimulant than methylphenidate or dextroamphetamine. It should be initiated at 18.75 mg taken each morning with breakfast and can be increased in increments of 18.75mg every week or so. Typical dosing for pemoline ranges from 60 to 200mg/day in treating narcolepsy. Because pemoline is less potent than other stimulants, it is more likely to be ineffective, even at its higher doses. When pemoline does not relieve daytime sleepiness or sleep attacks, then the patient should be switched to a different stimulant. 

There is no place anymore for the amphetamines in our therapeutic armamentarium. The only indications for the other stimulants, modaflnil and methylphenidate, are respectively narcolepsy and the attention deflcit disorders (ADHD) and hyperactivity syndromes in children. Their mechanisms of action include enhanced release of dopamine and norepinephrine, re-uptake inhibition of dopamine and norepinephrine and to some extend monoamine oxidase inhibition. 

Comparisons of modafinil with agents that have proven effective in narcolepsy, including methylphenidate, pemoline, and dextroamphetamine, are needed to clarify its relative safety and efficacy, and place in therapy... 

The best-known products come from the amphetamine group (see Table 1.12) Dexedrine1 1 (generic name d-amphetamine) and Pervitin 1 (methamphetamine) were particularly used in the 1950s and 1960s as stimulants and also as appetite suppressants, but today play hardly any role in medical practice. Ritalin (methylphenidate) has some relevance its psychostimulant action is said to be weaker than that of amphetamines and it is apparent ) less abused than the latter. Because methylphenidate also possesses mild antidepressant activity, in some countries it is used to combat not only narcolepsy and ADHD but also mild depressions without suicide risk (Satel and Nelson, 1989). 

Stimulants (amphetamines [Adderall, Dexedrine] and methylphenidate [Concerta, Ritalin]) increase alertness, attention, and energy. They also increase blood pressure and heart rate, constrict blood vessels, increase blood glucose, and open up the pathways of the respiratory system. Historically, stimulants were prescribed to treat asthma and other respiratory problems, obesity, neurological disorders, and a variety of other ailments. As their potential for abuse and addiction became apparent, the prescribing of stimulants by physicians began to wane. Now, stimulants are prescribed for treating only a few health conditions, most notably ADHD, narcolepsy, and, in some instances, depression that has not responded to other treatments. 

Ritalin and related generic methylphenidate drugs are available by prescription for individuals six years and older. Ritalin is distributed in 5, 10, and 20 mg tablets. In addition to ADHD, methylphenidate is used for several other medical conditions. It continues to be used for narcolepsy. It has also been used in treating depression, especially in elderly populations. Methylphenidate has been suggested for use in the treatment of brain injury from stroke or brain trauma it has also been suggested to improve appetite and the mood of cancer and HIV patients. Another use is for pain control and/or sedation for patients using opiates. 

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. 

Children with ADHD are inattentive, impulsive, and hyperactive. The areas of their brains that control attention and restraint do not function properly. Stimulant drugs, specifically amphetamines, have been used in the United States to treat children with inattention and hyperactivity disorders since the 1930s. MPH was also discovered to have a calming effect on hyperactive children and a focusing effect on those with attention deficit disorder (ADD). However, it was not until the 1960s that the U.S. Food and Drug Administration (FDA) approved methylphenidate for the treatment of ADHD. At the turn of the twenty-first century, approximately 90% of all methylphenidate was prescribed for ADHD children. Most of the rest was prescribed to treat adults with a sleeping sickness known as narcolepsy. 

Besides attention deficit hyperactivity disorder (ADHD), methylphenidate is used to treat narcolepsy, a... 

Methylphenidate is considered a mild central nervous system stimulant that affects the brain and nerves, relieving fatigue, and inducing clearer thoughts for relatively short periods. According to the DEA, possible effects experienced by those who do not have ADHD or narcolepsy include increased alertness, excitation, and euphoria. Increased energy and increased mental clarity may be experienced for a short period. 

Methylphenidate is marketed in the United States under the prescription names Concerta, Metadate, Methylin, and Ritalin (26). It is available in immediate and sustained-release formulations for the treatment of attention deficit/hyperactivity disorder (ADHD) and the symptomatic management of narcolepsy (a disorder characterized by excessive daytime sleepiness). 

Clinically, methylphenidate also is used for the treatment of daytime sleepiness associated with narcolepsy. It is a mainstay treatment for this problem and has a long record of efficacy in alleviating the sleepiness symptoms (31) and maintaining alertness and performance in narcoleptic patients (32,33). 

Pemoline, an oxizolidine compound, acts similarly to methylphenidate—through catecholamine uptake inhibition in the CNS (27) with minimal sympathomimetic effects (57). Although pemoline is not the first-line stimulant for the treatment of ADHD, it has been successfully used for the treatment of this disorder in both children and adults (28,30). Pemoline has also been used for the treatment of daytime sleepiness associated with narcolepsy (31), and although it is somewhat effective for this purpose (33), it is not a first-line choice owing to its potentially lethal liver toxicity. 

Pemoline is a mild psychostimulant with CNS effects that are not clearly understood the exact mechanism and site of action of the drag are not known. While it is structurally different from amphetamine and methylphenidate, its actions are similar to those of the other stimulants (56). The typical use of pemoline is for the treatment of the symptoms of distractibility, hyperactivity, and impulsivity in ADHD. It has not been approved for the treatment of narcolepsy, but it does have alerting effects in adults (31,33). Researchers have examined the use of pemoline... 

Mitler MM, Shafor R, Hajdukovich R, Timms RM, Browman CP. Treatment of narcolepsy objective studies on methylphenidate, pemoline, and protriptyline. Sleep 1986 9(l) 260-264. 

Methylphenidate was synthesized in 1944 in Europe in an unsuccessful attempt to create a stimulant that would not produce addiction or tolerance (Figure 1.1). Introduced in the United States in 1955, it was first approved by the FDA for the treatment of drug-induced lethargy, mild depression, and narcolepsy. In the early 1960s, the drug was first marketed under the name Ritalin to improve memory in elderly patients and to treat several behavioral problems in children. 

The treatment of narcolepsy with psychostimulants such as amphetamine 2 (Adderall), and methylphenidate 3 (Ritalin) has been reported.3 However, these are schedule 2 DEA-controlled substances and have a potential risk of abuse, overdose, and dependence, which present substantial barriers to widespread use.4 As a result, there has been a significant effort to identify novel therapeutic agents for the... 

ANAESTHETICS-GENERAL INDIRECTLY ACTING SYMPATHOMIMETICS (e.g. methylphenidate) 1. Risk of arrhythmias when inhalational anaesthetics are co-administered with methylphenidate 2. Case report of 1 sedative effect of midazolam and ketamine by methylphenidate 1. Uncertain attributed by some to sensitization of the myocardium to sympathomimetics by inhalational anaesthetics 2. Uncertain at present possibly due to CNS stimulation caused by methylphenidate (hence its use in narcolepsy) Avoid giving methylphenidate on the day of elective surgery... 

Structurally-related drugs include dexamfet-amine (used for narcolepsy and in attention deficit hyperactivity disorder (ADHD) see p. 387), methylphenidate (used for ADHD), tenamfetamine (Ecstasy, see p. 189), phentermine, diethylpropion, and pemoline. 

---