A 20-year-old college student presents to the emergency room complaining of insomnia for the past 48 hours. He explains that although his body feels tired, he is "full of energy and focus" after taking a certain drug an hour ago. He now wants to sleep because he is having hallucinations. His vital signs are T 100.0 F, HR 110 bpm, and BP of 150/120 mmHg. The patient states that he was recently diagnosed with "inattentiveness." Which of the following is the mechanism of action of the most likely drug causing the intoxication?

Increases presynaptic dopamine and norepinephrine release from vesicles

Displaces norepinephrine from secretory vesicles leading to norepinephrine depletion

A 25-year-old woman presents to her college campus clinic with the complaint of being unable to get up for her morning classes. She says that, because of this, her grades are being affected. For the past 6 weeks, she says she has been feeling depressed because her boyfriend dumped her. She finds herself very sleepy, sleeping in most mornings, eating more snacks and fast foods, and feeling drained of energy. She is comforted by her friend’s efforts to cheer her up but still feels guarded around any other boy that shows interest in her. The patient says she had similar symptoms 7 years ago for which she was prescribed several selective serotonin reuptake inhibitors (SSRIs) and a tricyclic antidepressant (TCA). However, none of the medications provided any long-term relief. She has prescribed a trial of Phenelzine to treat her symptoms. Past medical history is significant for a long-standing seizure disorder well managed with phenytoin. Which of the following statements would most likely be relevant to this patient’s new medication?

“While taking this medication, you should avoid drinking red wine.”

“This medication is known to cause anorgasmia during treatment.”

“You will have a risk for cardiotoxicity from this medication.”

“A common side effect of this medication is sedation.”

“While on this medication, you may have a decreased seizure threshold.”

A 24-year-old male comes into the psychiatric clinic complaining of consistent sadness. He endorses feelings of worthlessness, anxiety, and anhedonia for the past couple months but denies feeling suicidal. He further denies any past episodes of feeling overly energetic with racing thoughts. Confident of the diagnosis, you recommend frequent talk therapy along with a long-term prescription of a known first-line medication for this disorder. What is the drug and what are some of the most frequently encountered side effects?

Selective serotonin reuptake inhibitor; anorgasmia, insomnia

Selective serotonin reuptake inhibitor; hypomania, suicidal thoughts

Tricyclic antidepressants; hypomania, suicidal thoughts

Monoamine oxidase inhibitors; Orthostatic hypotension, weight gain

Tricyclic antidepressants; Orthostatic hypotension, anticholinergic effects

An 11-year-old boy is brought to a pediatrician by his parents with the complaint of progressive behavioral problems for the last 2 years. His parents report that he always looks restless at home and is never quiet. His school teachers frequently complain that he cannot remain seated for long during class, often leaving his seat to move around the classroom. A detailed history of his symptoms suggests a diagnosis of attention-deficit/hyperactivity disorder. The parents report that he has taken advantage of behavioral counseling several times without improvement. The pediatrician considers pharmacotherapy and plans to start methylphenidate at a low dose, followed by regular follow-up. Based on the side effect profile of the medication, which of the following components of the patient’s medical history should the pediatrician obtain before starting the drug?

Past history of Kawasaki disease

Past history of recurrent wheezing

Past history of idiopathic thrombocytopenic purpura

Past history of recurrent fractures

Past history of Guillain-Barré syndrome

Stimulant medications — USMLE Lesson

Mechanism of Action - Dopa-Norepi Power-Up

Core Effect: Boosts Dopamine (DA) and Norepinephrine (NE) concentrations in the prefrontal cortex synaptic cleft. This enhances executive functions like attention, focus, and impulse control.
Dual Mechanisms:
- Reuptake Blockade: Competitively inhibit Dopamine Transporters (DAT) and Norepinephrine Transporters (NET), leaving more neurotransmitter in the synapse.
- Enhanced Release: Promote release of DA/NE from presynaptic vesicles (VMAT2 reversal).

⭐ Amphetamines vs. Methylphenidate: While both block reuptake, amphetamines are more potent at promoting dopamine/norepinephrine release from vesicles, whereas methylphenidate primarily acts as a reuptake inhibitor.

ADHD Synaptic Mechanisms: Untreated vs. Stimulant-Treated

Stimulant Classes & Agents - The Stimulant Squad

Two major classes act on dopamine (DA) and norepinephrine (NE) pathways.
📌 Mnemonic: My Attention is Directed (Methylphenidates & Amphetamines).

Class	Primary Mechanism	Key Agents
Methylphenidate	Blocks DA & NE reuptake	- Methylphenidate (Ritalin, Concerta) - Dexmethylphenidate (Focalin)
Amphetamine	Blocks reuptake AND ↑ presynaptic release	- Dextroamphetamine (Dexedrine) - Mixed Salts (Adderall) - Lisdexamfetamine (Vyvanse)

Stimulant Mechanisms of Action on Dopamine Transporters

Adverse Effects & CIs - Handle With Care

Common Side Effects:
- CNS: Insomnia, headache, irritability, nervousness.
- GI: ↓ Appetite, weight loss, abdominal pain.
- Monitor: Height & weight in children due to potential for growth suppression.
Cardiovascular ⚠️:
- ↑ BP & HR.
- ECG screening is debated but consider if positive personal/family history of cardiac disease.
Psychiatric:
- New or worsened tics (motor or phonic).
- May unmask or exacerbate psychosis/mania.
Contraindications:
- Absolute:
  - Use with or within 14 days of MAOIs.
  - Symptomatic cardiovascular disease, hyperthyroidism, glaucoma.
  - History of psychosis or Tourette's syndrome.

⭐ Exam Favorite: Before starting stimulants, screen for personal and family history of sudden death, ventricular arrhythmia, and other significant cardiovascular conditions. An ECG is warranted for positive histories.

High‑Yield Points - ⚡ Biggest Takeaways

Stimulants (methylphenidate, amphetamines) are first-line for ADHD, acting by blocking dopamine (DA) and norepinephrine (NE) reuptake.

Most common side effects include insomnia, decreased appetite, and weight loss.

Monitor blood pressure and heart rate due to cardiovascular risk; consider a baseline EKG.

Can cause a temporary slowing of linear growth in children.

High potential for abuse and diversion (Schedule II drugs).

Contraindicated in patients with psychosis or severe cardiovascular disease.

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