An 11-year-old girl is brought to the office due to disruptive behavior at home and at school. Her parents report that she gets in trouble for talking during class and not following instructions. Although the patient is of above-average intelligence, her grades are poor. Teachers note that she makes careless mistakes while rushing through tests and frequently forgets to hand in assignments. At home, she is easily distracted while trying to focus on her homework. The patient has frequent conflicts with her mother, who says, "Getting her ready for school in the morning is impossible. We're frequently late because she always misplaces her cell phone and books." The patient has no other medical history, and developmental milestones are within normal range. Physical examination shows no abnormalities. The girl and her parents are willing to consider medication if it will help. A drug with which of the following mechanisms of action is most appropriate for this patient?

Question

An 11-year-old girl is brought to the office due to disruptive behavior at home and at school.  Her parents report that she gets in trouble for talking during class and not following instructions.  Although the patient is of above-average intelligence, her grades are poor.  Teachers note that she makes careless mistakes while rushing through tests and frequently forgets to hand in assignments.  At home, she is easily distracted while trying to focus on her homework.  The patient has frequent conflicts with her mother, who says, "Getting her ready for school in the morning is impossible.  We're frequently late because she always misplaces her cell phone and books."  The patient has no other medical history, and developmental milestones are within normal range.  Physical examination shows no abnormalities.  The girl and her parents are willing to consider medication if it will help.  A drug with which of the following mechanisms of action is most appropriate for this patient?

Quizplus · Accepted Answer

This patient's inattention, distractibility, disorganization, and forgetfulness are characteristic of attention-deficit hyperactivity disorder (ADHD). Norepinephrine and dopamine are the key neurotransmitters involved in the pathophysiology of ADHD symptoms. Symptoms of hyperactivity, impulsivity, and inattention have been linked to reduced levels of norepinephrine and dopamine in the prefrontal cortex. Stimulant drugs, including methylphenidate and amphetamines, are first-line drug treatments for school-age children with ADHD. They work by blocking norepinephrine and dopamine reuptake at synapses in the prefrontal cortex. In addition, amphetamines increase the release of norepinephrine and dopamine from presynaptic storage vesicles and inhibit monoamine oxidase. (Choice A) Alpha-2 adrenergic agonists (not antagonists) are used in the treatment of ADHD but do not have the same evidence for efficacy as stimulants. Examples include clonidine and guanfacine. (Choice B) Antagonism of dopamine D2 receptors is the mechanism of action of antipsychotic medications. These drugs do not specifically treat ADHD. (Choices D and E) Selective serotonin reuptake inhibitor antidepressants increase availability of serotonin by blocking serotonin reuptake from the synapse. Serotonin-norepinephrine reuptake inhibitors block the reuptake of both serotonin and norepinephrine. These agents are commonly used to treat depressive and anxiety disorders, not ADHD. (Choice F) Benzodiazepines work as positive allosteric modulators of GABA, facilitating the increased frequency of chloride-channel opening in the GABA receptor. Benzodiazepines have sedative, hypnotic, anxiolytic, anticonvulsant, and muscle-relaxant properties. Educational objective: Stimulant medications are a first-line treatment for attention-deficit hyperactivity disorder. They work by increasing the availability of norepinephrine and dopamine in the prefrontal cortex. __________ References: The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder. (http://www.ncbi.nlm.nih.gov/pubmed/21550021) The pharmacology of amphetamine and methylphenidate: relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities. (http://www.ncbi.nlm.nih.gov/pubmed/29428394)

An 11-Year-Old Girl Is Brought to the Office Due to Disruptive