Stimulants and Cognitive Enhancers

Stimulants & Nootropics: Intro - Brain's Pep Squad

• Psychostimulants: Elevate mood, ↑ alertness, attention, energy. E.g., Amphetamines, Methylphenidate.
• Nootropics (Cognitive Enhancers): Aim to improve cognitive functions like memory, learning, focus, often with neuroprotective properties. E.g., Piracetam, Citicoline.
• General Mechanisms:
  • Stimulants: Primarily boost catecholaminergic (Dopamine DA, Norepinephrine NE) activity.
    • Methods: Reuptake inhibition, ↑ release, MAO inhibition (less common).
  • Nootropics: Diverse pathways.
    • Cholinergic system modulation (e.g., ACh).
    • Glutamatergic system effects.
    • ↑ Cerebral blood flow/metabolism.

⭐ Most CNS stimulants achieve their effects by enhancing dopaminergic and/or noradrenergic neurotransmission in the brain.

MPH & Amphetamines - Focus Fuelers

• MoA: Block DA & NE reuptake. Amphetamines also ↑ their release.
• Indications:
  • ADHD (first-line).
  • Narcolepsy.
  • Binge eating disorder (Lisdexamfetamine).
• Types:
  • Methylphenidate (MPH): e.g., Ritalin, Concerta (ER).
  • Amphetamines: Dextroamphetamine, Mixed salts (e.g., Adderall), Lisdexamfetamine (Vyvanse - prodrug, ↓ abuse risk).
• SE (Common):
  • ↓ Appetite, weight loss, insomnia.
  • Headache, irritability.
  • ↑BP, ↑HR.
• SE (Serious)/CIs:
  • ⚠️ CV: Structural heart disease, uncontrolled HTN.
  • ⚠️ Psych: Psychosis, mania. Tourette's.
  • ⚠️ Growth suppression (children).
  • ⚠️ Abuse potential.
  • ⚠️ MAOI use (hypertensive crisis).
• Monitoring: BP, HR, weight/height (children), mood, sleep.

⭐ Lisdexamfetamine, a prodrug of dextroamphetamine, offers gradual release, potentially ↓ abuse liability vs. IR amphetamines.

Modafinil/Armodafinil - Alertness Aces

• Mechanism: Atypical stimulants; ↑ dopamine (DAT inhibition), norepinephrine, histamine. Exact MOA complex.
• Armodafinil: R-enantiomer of modafinil; longer half-life, potentially smoother plasma concentrations.
• Indications:
  • Narcolepsy
  • Shift work sleep disorder (SWSD)
  • Obstructive sleep apnea (OSA) - adjunct for excessive daytime sleepiness.
• Dosing:
  • Modafinil: 100-200 mg daily (max 400 mg)
  • Armodafinil: 150-250 mg daily
• Advantages: Lower abuse potential than amphetamines; less sympathomimetic effects.
• Side Effects: Headache, anxiety, insomnia, nausea. Rare: Stevens-Johnson Syndrome (SJS).

⭐ Modafinil is a CYP3A4 enzyme inducer; can decrease effectiveness of hormonal contraceptives.

Cognitive Enhancers (AChEIs) - Mind Sharpeners

• Mechanism: ↑ Acetylcholine (ACh) by inhibiting acetylcholinesterase (AChE).
• Primary Use: Alzheimer's Disease (mild-moderate), Dementia with Lewy Bodies.
• Key Drugs (AChEIs): 📌 Remember "Don River Gal"
  • Donepezil: Once daily dosing.
  • Rivastigmine: Oral & transdermal patch (↓ GI side effects).
  • Galantamine: Dual mechanism (AChE inhibition & nicotinic receptor modulation).
• Side Effects: Cholinergic (nausea, vomiting, diarrhea, bradycardia, muscle cramps).
• Other Enhancers:
  • Memantine: NMDA antagonist (moderate-severe Alzheimer's).
  • Piracetam: Nootropic, mechanism less defined.

⭐ Rivastigmine transdermal patch significantly reduces gastrointestinal side effects compared to oral formulations. oka

Atomoxetine for ADHD - Steady Focus Aid

• Mechanism: Selective Norepinephrine Reuptake Inhibitor (SNRI).
• Type: Non-stimulant for ADHD.
• Onset: Slower; full effect in 2-4 weeks.
• Benefits:
  • Low abuse risk.
  • 24-hr coverage.
  • Good for co-morbid anxiety/tics.
• Key SEs: Nausea, insomnia, fatigue, ↑HR, ↑BP.
  • ⚠️ Rare: Liver injury.
• Dosing: Start 0.5 mg/kg/d, target 1.2 mg/kg/d (max 100 mg/d or 1.4 mg/kg/d).

⭐ Slower onset than stimulants but offers continuous coverage without abuse potential.

High‑Yield Points - ⚡ Biggest Takeaways

• Methylphenidate (DAT/NET blocker) & Atomoxetine (NET inhibitor) are first-line for ADHD.
• Monitor for insomnia, anorexia, tics, ↑BP/HR, and growth suppression with stimulants.
• Modafinil treats narcolepsy; amphetamines (↑DA/NE) carry high abuse/psychosis risk.
• Cholinesterase inhibitors (e.g., Donepezil) & Memantine (NMDA antagonist) are key for Alzheimer's.
• Contraindications: MAOI use, glaucoma, severe cardiac disease, hyperthyroidism, history of drug abuse.