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Explain the mechanism of action amphetamine.

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1. Explain the mechanism of action amphetamine.
According to Stahl (2021) the mechanism of action for amphetamine vs methylphenidate differ and the way amphetamine works it can have abuse potential when taken at higher doses. Amphetamine works by being a competitive inhibitor at the dopamine transporter (DAT), it will displace the dopamine and the amphetamine will be transported back into the cell. Once inside it will also act upon the VMAT also displacing the dopamine to be transported into storage. When these occur it leads to excess amounts of dopamine free intracelluraly at which point it will spill out of the cell via DA channels or by reversing DAT leaving more DA available in the synapse (Stahl, 2021). When this medication is taken at high doses the amount of DA in the synapse increases which will then lead to the sence of euphoria which can lead to abuse.
Alpha-2 agonists are also used in the treatment of ADHD. For which symptoms are the most effective? Who might be an ideal candidate for monotherapy?
Alpha-2 agonists (a2) such as guanfacine and clonidine are two a2 agonists used in psychiatry to treat ADHD. The symptoms they are helpful in treating are inattention, hyperactivity, impulsivity, and oppositional behaviors (Stahl, 2021). There are recommendations for both monotherapy and adjunctive therapy to a stimulant. According to Stahl (2021) these medications used in patients with inattention, hyperactivity and impulsivity can be tried o on monotherapy. For patients with behavioral concerns the recommendation would be to use is adjunctively with a stimulant.
Read the following scenario. There is no “right answer.” Please support your answer with evidence
A college student presents to your clinic reporting issues with school, and, recently at work too. They have a history of ADHD and were treated for it in high school. However, they felt “like a zombie” all the time and didn’t want to be on medication. Now, they are struggling to maintain their grades and making mistakes at their job. What would you suggest?
For this patient scenario first I would want to find out what medication it was they were taking that made them feel that way. If they had been on a stimulant prior I would recommend using one of the two norandrenegic medications atomoxetine or bupropion. These medications are often used for patient who experienced side effects from stimulants (Stahl, 2021). If the medication they had been on before was an norandrenergic medication, because according to Cerrillo-Urbina et al. (2018) these can cause the side effect of somnolence I would recommend attempting methylphenidate since this has a lower abuse potential (Stahl, 2021).
Cerrillo-Urbina, A., García-Hermoso, A., Pardo-Guijarro, M., Sánchez-López, M., Santos-Gómez, J., & Martínez-Vizcaíno, V. (2018).The effects of long-acting stimulant and nonstimulant medications in children and adolescents with attention-deficit/hyperactivity disorder: A meta-analysis of randomized controlled trials. Journal of Child and Adolescent Psychopharmacology, 28(8), 494-507. (Links to an external site.)
Stahl, S. M. (2021). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (5th ed.). Cambridge University Press.
2. Explain the mechanism of action of lisdexamfetamine. Why is this agent more difficult to abuse?
Drugs that have a high potential for abuse interact with the dopamine transporter (DAT) for too long, too fast, and too much. Lisdexamfetamine is the prodrug of the D-isomer of amphetamine bound to lysine. Lysine is cleaved slowly in the stomach and converted into active D-amphetamine, which causes slow absorption into the bloodstream. This optimizes the length of time, rate, and amount of DAT inhibition for therapeutic use but below what is typically known for abuse potential (Stahl, 2021).
As we have learned in previous modules, many medications are used “off label.” Which medications are used “off label” to treat ADHD or to augment first line treatment?
There are several medications used off-label for the treatment of ADHD. Below are a few drugs that are not indicated for ADHD but have shown various degrees of effectiveness. The NDRI, bupropion indicated for depression, has been shown to decrease symptoms of ADHD (Verbeeck et al., 2017). Alpha-2-adrenergic agonists used for hypertension, immediate-release clonidine (Catapres), and immediate-release guanfacine (Tenex) are prescribed. The extended-release versions of these drugs are FDA approved for ADHD; however, the immediate release drugs are prescribed off-label (Panther et al.,2017). Modafinil is indicated for sleep disorders but is helpful for ADHD because it enhances cognitive performance (Wang et al., 2016). SNRIs venlafaxine and dasotraline are used off-label for ADHD and are effective because they increase norepinephrine and serotonin, leading to improved concentration. NMDA receptor antagonists, amantadine and memantine, are helpful for ADHD because they stimulate dopamine production. Amantadine is indicated to treat Parkinson’s disease, and memantine is used for dementia (Pozzi et al., 2020).
Read the following scenario. There is no “right answer.” Please support your answer with evidence.
A five year old male presents to the clinic with his parent. He is impulsive, hyperactive, and has been “kicked out” of three day cares. After your assessment, you believe he does show s/s of ADHD and plan on prescribing medication. What would you suggest?
First-line therapy for children under six years old is behavioral therapy (Centers for Disease Control and Prevention, 2021), specifically parent training in behavior management (Wolraich et al., 2019). However, some children have cases where there is still significant disruption after behavioral therapy. In these cases, medication management and behavioral therapy are recommended; however, there are no medications that are FDA approved for children under six. A study by Boston Children’s Hospital suggests alpha-2-adrenergic agonists for reducing ADHD symptoms. There are fewer side effects of drugs than stimulants like methylphenidate (Harstad et al., 2021). However, according to trusted sources like UpToDate, methylphenidate is the first choice for children under six (Krull, 2022). Methylphenidate has been studied and shown efficacy for ADHD symptom reduction in preschoolers and safety in seven of ten concurrent studies (Wolraich, 2022), while the one study for alpha-2-adrenergic agonists was retrospective (Harstad et al., 2021). Due to the limited studies on alpha-2-adrenergic drugs in treating ADHD for preschoolers, my recommendation for this child would be methylphenidate. The risk of delaying treatment and starting methylphenidate must be made.

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