Stimulants methylphenidate

Methylphenidate Stimulants, such as methylphenidate and amphetamine, are widely used in the management of attention deficit hyperactivity disorder (ADHD). Such drugs have long been known to reduce hunger, but have not been generally recommended for treatment of BN. A few patients who have symptoms of bulimia nervosa plus some co-morbid features of ADHD have noted that the addition of methylphenidate or amphetamine markedly reduced the frequency of binge eating (Drimmer 2003). 

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). 

Methylphenidate like cocaine largely acts by blocking reuptake of monoamines into the presynaptic terminal. Methylphenidate administration produces an increase in the steady-state (tonic) levels of monoamines within the synaptic cleft. Thus, DAT inhibitors, such as methylphenidate, increase extracellular levels of monoamines. In contrast, they decrease the concentrations of the monoamine metabolites that depend upon monoamine oxidase (MAO), that is, HVA, but not catecholamine-o-methyltransferase (COMT), because reuptake by the transporter is required for the formation of these metabolites. By stimulating presynaptic autoreceptors, methylphenidate induced increase in dopamine transmission can also reduce monoamine synthesis, inhibit monoamine neuron firing and reduce subsequent phasic dopamine release. 

Dopaminergic mechanisms within the ventral striatum (i.e., nucleus accumbens) subserve the ability of amphetamine and methylphenidate in low to moderate doses to increase locomotor activity. In contrast, very low dosages in animals seem to cause hypoactivity presumably by stimulation of autoreceptors, a finding that would be compatible with the clinical impression that methylphenidate might be usefiil in some patients with mania. 

At low doses, both psychostimulants could theoretically stimulate tonic, extracellular levels of monoamines, and the small increase in steady state levels would produce feedback inhibition of further release by stimulating presynaptic autoreceptors. While this mechanism is clearly an important one for the normal regulation of monoamine neurotransmission, there is no direct evidence to support the notion that the doses used clinically to treat ADHD are low enough to have primarily presynaptic effects. However, alterations in phasic dopamine release could produce net reductions in dopamine release under putatively altered tonic dopaminergic conditions that might occur in ADHD and that might explain the beneficial effects of methylphenidate in ADHD. 

Psychostimulants. Figure 2 Dopamine molecules have two different possible targets. Both ways are initially increased by DAT inhibition caused by methylphenidate pre- and postsynaptic dopamine receptors. Stimulation of postsynaptic receptors results in inhibition of presynaptic action potential generation. On the other hand, presynaptic receptor stimulation leads to a transmission inhibition of action potentials. Therefore, both mechanisms are responsible for a decrease in vesicular depletion of dopamine into the synaptic cleft (adapted from [2]). 

The development of psychosis is the most striking clinical characteristic of high-dose stimulant abuse. The amphetamines, methylphenidate, and phen-metrazine all produce psychosis (Ellinwood et al. 1973 Harris and Batki 2000 Iversen et al. 1978 Lucas and Weiss 1971 McCormick and McNeil 1962). 

Because chronic cocaine use appears to reduce the efficiency of central dopamine neurotransmission, a number of dopaminergic compounds, including amantadine, bromocriptine, mazindol, and methylphenidate, have been examined as treatments for cocaine abuse. It is thought that these relatively slow-onset dopaminergic agents, with low or relatively low abuse potential, would correct the dopamine dysregulation and alleviate withdrawal symptoms following chronic stimulant use. 

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 proposed mechanism of ADHD pharmacotherapy is to modulate neurotransmitters in order to improve academic and social functioning. Pharmacologic therapy can be divided into two categories stimulants and non-stimulants. Stimulant medications include methylphenidate, dexmethylphenidate, amphetamine salts, and dextroamphetamine, whereas non-stimulant medications include atomoxetine, tricyclic antidepressants (e.g., imipramine), clonidine, guanfacine, and bupropion. 

Psychostimulants (e.g., methylphenidate and dextroamphetamine with or without amphetamine) are the most effective agents in treating ADHD. Once the diagnosis of ADHD has been made, a stimulant medication should be used first line in treating ADHD (Fig. 39-1). Stimulants are safe and effective, with a response rate of 70% to 90% in patients with ADHD.3,13,14 Generally, a trial of at least 3 months on a stimulant is appropriate, and this includes dose titration to response... 

Initial response to short-acting stimulant formulations (e.g., methylphenidate and dextroamphetamine) is seen within 30 minutes and can last for 4 to 6 hours.13,14 This short duration of effect frequently requires that short-acting stimulant formulations be dosed at least twice daily, thus increasing the chance of missed doses and non-compliance. Further, patients using any stimulant formulation but especially shortacting formulations can experience a rebound effect of ADHD symptoms as the stimulant wears off.14... 

Atomoxetine is the most recent addition to the ADHD armamentarium in both children and adults. In clinical studies, atomoxetine has demonstrated superior efficacy over placebo and equivalent efficacy when compared with a suboptimal immediate-release methylphenidate dose.17 20 However, it is not clear whether atomoxetine is superior to typical methylphenidate doses or other stimulant formulations. Atomoxetine may be used as a second- or third-line medication for ADHD. 

Short-Acting Stimulants Methylphenidate Generic 5-, 10-, or 20-mg tab twice daily ... 

Intermediate-Acting Stimulants Methylphenidate Methylin ER 10- or 20-mg ER tab daily ... 

Extended-Acting Stimulants Methylphenidate Concerta c 30-mg tab daily 18-, 27-, 36-, or 54-mg tab daily ... 

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. 

The dopamine transporter has been a target for developing pharmacotherapies for a number of CNS disorders including ADHD, stimulant abuse, depression and Parkinson s disease. Several excellent reviews in this area have been recently published [28-30]. The dopamine reuptake inhibitor methylphenidate has been successfully used for decades in the management of ADHD in children and adolescents. It remains a first-line treatment along with amphetamine for this disorder [31,32]. 

Sellings LHL, Clarke PBS (2003) Segregation of amphetamine reward and locomotor stimulation between nucleus accumbens medial medial shell and core, J Neurosci 23 6295-6303 Sellings EH, McQuade EE, Clarke PB (2006) Characterization of dopamine-dependent rewarding and locomotor stimulant effects of intravenously-administered methylphenidate in rats. Neuroscience 141 1457-1468... 

Dopamine-Stimulating Medications. A variety of drugs that increase the availability of dopamine have been studied in cocaine addicts including L-DOPA, bupropion, amantadine, and methylphenidate. In small uncontrolled trials, these have shown some benefit, but definitive studies have yet to be performed. In addition, some dopamine-stimulating medications (in particular, the stimulants like methylphenidate or the amphetamines) are themselves subject to abuse, though, of note, this is typically not a problem when they are prescribed to patients who do not have a history of substance abuse such as, for example, in the treatment of attention deficit-hyperactivity disorder. 

Methylphenidate is now the most widely used of the stimulants. It has a well-established record of safety and tolerability and has been used in children throughout the school years and in adults as well. In preschool children, the effects of methylphenidate can vary. 

The prescribing physician should be notified immediately if tics or psychosis (usually paranoia) develop. The medication should always be stopped when psychosis occurs. We once said the same about tics, but recent research suggests that stimulants may not worsen tics. Methylphenidate is now available in a controlled-release preparation (Concerta), which can be prescribed once daily. One key advantage to once-daily dosing is not pharmacological, but rather that it avoids the stigma children may experience when they need to go to the school nurse s office to receive their afternoon dose. Focalin is the active isomer of methylphenidate. 

Dextroamphetamine (Dexedrine). Dextroamphetamine is the second most widely used stimulant and the most commonly used amphetamine in the United States. It is about twice as potent as methylphenidate and should be initiated in the treatment of ADHD at 2.5 mg taken twice daily with breakfast and lunch. Like other stimulants, the benefits of dextroamphetamine can be seen almost immediately. With weekly visits while starting treatment, the dose can be increased in 2.5-5 mg increments until the effective dose is found. Because dextroamphetamine is also slightly longer acting than methylphenidate, patients may be less likely to need an evening dose. If an after-school dose is used, then like methylphenidate it should be 25-50% of the daytime dose. 

Pemoline (Cylert). Pemoline was introduced as an alternative stimulant. Its two key advantages are that it can be taken once a day, though with the extended-release versions of methylphenidate and Adderall this is less of an issue, and it may be less prone to abuse. It was generally believed that pemoline has a gradual onset of action, taking several weeks to reach full therapeutic benefit, but some researchers discount this assumption. 

Close to 70% of children with ADHD will respond to a stimulant. When the child is not helped by the first stimulant that is prescribed, there is still a good chance of responding to a different one. If an initial trial of methylphenidate isn t successful, then switching to dextroamphetamine or Adderall is a reasonable strategy. If dextroamphetamine or Adderall was used first and did not work well, then we recommend switching to methylphenidate. Because dextroamphetamine and Adderall are more similar, it makes less sense to switch between these two. We do not recommend pemoline as a first-line treatment. 

Starting Treatment in Adults with ADHD. Beginning treatment of an adult is not significantly different from doing so in a child. The stimulants and atomoxetine remain the most effective medications. Methylphenidate, dextroamphetamine, and Adderall appear to be equally effective in group trials, but individuals may respond preferentially to one medication or the other. 

Monoamine oxidase inhibitors Paroxetine Protriptyline Sertraline Venlafaxine Stimulants Atomoxetine Dextroamphetamine Methylphenidate Modaflnil Pemoline... 

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. 

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