Stimulants and Cognitive Enhancers

Stimulants and Cognitive Enhancers

Stimulants and Cognitive Enhancers

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Stimulants & Nootropics: Intro - Brain's Pep Squad

Stylized brain with enhanced activity

  • 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). Amphetamine effects on monoamine neurotransmission
  • 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. AChE Inhibitor Mechanism of Actionoka

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.
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Practice Questions: Stimulants and Cognitive Enhancers

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Which anti-psychotic drug is associated with exacerbation of psoriasis?_____

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Which anti-psychotic drug is associated with exacerbation of psoriasis?_____

Lithium

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