Pharmacology
Summary
Psychostimulants such as amphetamine, dexamphetamine, lisdexamfetamine, and methylphenidate predominantly revolves around their influence on neurotransmission of dopamine and norepinephrine. These medications primarily treat attention deficit hyperactivity disorder (ADHD); however, lisdexamfetamine also treating moderate to severe binge eating disorders, and methylphenidate can be used to treat narcolepsy. Amphetamines facilitate the release of monoamines from presynaptic neurons, serve as full agonists of TAAR1, inhibit the vesicular monoamine transporter two (VMAT2), and reverse the uptake at monoamine transporters (DAT & NAT), ultimately elevating synaptic concentrations of dopamine and norepinephrine. In contrast, methylphenidate mainly acts by obstructing dopamine and norepinephrine transporters.
A notable feature of lisdexamfetamine is its status as a prodrug, undergoing enzymatic hydrolysis to yield dexamphetamine and L-lysine, providing sustained action and a diminished risk of abuse due to its attenuated euphoric effects. Administering psychostimulants alongside or within 14 days of MAO inhibitors is contraindicated due to risks of sympathetic overactivation. They are also inadvisable for those with hyperthyroidism or pheochromocytoma, also due to the risk of sympathetic overactivation. Precaution is essential for individuals with pre-existing psychiatric or cardiac conditions, given potential exacerbations. Common side effects include insomnia, weight loss, headaches, and nausea. To minimize sleep disturbances, dosing should be early in the day.
Lesson Outline
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FAQs
Amphetamine and dexamphetamine promote the release of monoamines, specifically dopamine and norepinephrine, into the synaptic cleft. This is facilitated by their roles as full agonists of the trace amine-associated receptor 1 (TAAR1) and by inhibiting the vesicular monoamine transporter 2 (VMAT2). Lisdexamfetamine, a prodrug of dexamphetamine, has a more gradual onset and prolonged duration of action, which decreases its potential for abuse. Methylphenidate, on the other hand, hampers the function of monoamine transporters, especially dopamine (DAT) and norepinephrine transporters (NAT), causing an upsurge of these neurotransmitters in the synaptic cleft.
The primary therapeutic use of these medications is for the management of attention-deficit/hyperactivity disorder (ADHD). Additionally, they can be prescribed to treat moderate to severe binge eating disorders. Methylphenidate, in particular, is also recognized for its efficacy in addressing narcolepsy.
These medications should not be administered to individuals who are currently on MAO inhibitors or have discontinued their use within the past 14 days due to the heightened risk of sympathetic overactivation. Furthermore, they are not recommended for individuals with hyperthyroidism or pheochromocytoma due to analogous risks. Careful consideration should be given when prescribing these medications to patients with a documented history of substance abuse or those diagnosed with psychiatric or cardiovascular conditions.
Users of these medications may experience side effects such as insomnia, weight loss, nausea, and headaches. To mitigate the risk of insomnia, it's advisable to avoid consumption of these medications in the early afternoon or evening. Periodic monitoring of weight, cardiovascular activity, and height may be warranted.
Lisdexamfetamine is classified as a prodrug, implying that it remains inactive until metabolized within the body. This metabolic conversion leads to a gradual onset and sustained release of the active compound. Consequently, there's a moderated spike in dopamine levels, which reduces the euphoric sensation often linked with drug misuse. This characteristic results in a diminished potential for abuse and diversion in comparison to immediate-release counterparts.
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