Psychostimulants

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Overview & Classes - Brain's Fast Lane

Psychostimulants: Drugs that ↑ alertness, wakefulness, & locomotor activity.

  • Core MOA: Potentiate catecholamine (Dopamine, Norepinephrine) effects.
  • Key Uses: ADHD, narcolepsy.
  • Major Risk: High abuse potential.

Classification of Psychostimulants:

ClassExamplesMoA (Primary)
AmphetaminesAmphetamine, Methamphetamine↑ DA/NE release & ↓ reuptake
MethylphenidateMethylphenidateBlocks DA/NE reuptake
XanthinesCaffeine, TheophyllineAdenosine antag., PDE inhib.
ModafinilModafinil, ArmodafinilAtypical (?DAT inh.)
CocaineCocaineBlocks DA/NE/5-HT reuptake

MoA & Pharmacokinetics - Neurotransmitter Party

  • Mechanism of Action (MoA): General effect: ↑ synaptic Dopamine (DA), Norepinephrine (NE), & Serotonin (5-HT).
    • 📌 Mnemonic: Stimulants ARE UP (Amphetamines Release Efflux; Uptake blocked by Phenidates/Cocaine).
    • Amphetamines & derivatives: Promote NT release from presynaptic vesicles.
    • Cocaine, Methylphenidate: Inhibit reuptake transporters (DAT, NET, SERT).
  • Pharmacokinetics (PK):
    • Absorption: Rapid (oral, IV, inhalation).
    • Distribution: Highly lipid-soluble, readily cross Blood-Brain Barrier (BBB).
    • Metabolism: Primarily hepatic (e.g., CYP2D6 for amphetamine).
    • Excretion: Renal; urine pH influences amphetamine excretion (acidic pH ↑ excretion). Cocaine's Mechanism of Action at the Synaptic Cleft

⭐ Cocaine is unique among psychostimulants for its additional action as a sodium channel blocker, leading to local anesthetic effects.

Specific Drugs & Indications - Focus & Wakefulness

DrugPrimary MoAKey Use(s)Unique Side Effect/Note
MethylphenidateNET & DAT block; ↑ DA/NEADHD, NarcolepsyInsomnia, ↓Appetite, headache; 📌 MPH: More Productive Hours (less sleep/food)
Amphetamine↑ NE/DA release; NET/DAT blockADHD, Narcolepsy, Binge eating disorderPsychosis risk, Abuse potential, HTN; Growth delay (children)
ModafinilAtypical DAT block; ↑ Histamine, Orexin; ↓ GABANarcolepsy, SWSD, OSA (adjunct)SJS (rare), headache; Less abuse potential than amphetamines
AtomoxetineSelective NET block (SNRI); ↑ NE in PFCADHD (esp. with substance abuse risk/tics)Non-stimulant; Suicidal ideation (BBW); Hepatotoxicity, Somnolence

Adverse Effects & Cautions - Handle With Care

  • Common Adverse Effects:
    • CNS: Insomnia, anxiety, irritability, nervousness, headache.
    • CVS: Tachycardia, palpitations, ↑BP.
    • GI: Anorexia, weight loss, dry mouth, nausea.
  • Serious Adverse Effects:
    • Dependence, tolerance, withdrawal symptoms.
    • Psychotic episodes, hallucinations (especially with abuse).
    • Seizures (may lower threshold).
    • Cardiovascular events (MI, stroke, sudden death in those with pre-existing cardiac conditions).
    • Growth suppression in children (monitor height/weight).
  • Contraindications & Cautions: ⚠️
    • Known hypersensitivity.
    • Symptomatic cardiovascular disease (arrhythmias, severe hypertension).
    • Glaucoma (angle-closure).
    • Hyperthyroidism.
    • Agitated states, severe anxiety.
    • History of drug abuse.
    • Tourette’s syndrome or tics.
    • MAOI use (concurrently or within 14 days).

      ⭐ Concomitant use of psychostimulants (e.g., amphetamine, methylphenidate) with MAOIs is contraindicated. This combination poses a high risk of life-threatening hypertensive crisis due to synergistic increases in synaptic norepinephrine.

High‑Yield Points - ⚡ Biggest Takeaways

  • Psychostimulants primarily ↑ DA & NE; cocaine blocks reuptake, amphetamines also promote release.
  • Key uses: ADHD (methylphenidate, amphetamines), narcolepsy (modafinil, amphetamines).
  • Methylphenidate: Common for ADHD, acts by blocking DAT and NET.
  • Adverse effects: Sympathomimetic (tachycardia, HTN), insomnia, psychosis; risk of dependence & withdrawal.
  • Cocaine uniquely blocks Na+ channels (local anesthetic effect) & causes coronary vasospasm.
  • Modafinil is an atypical stimulant for narcolepsy with lower abuse potential than amphetamines.
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