Central Nervous System Stimulants and Related Drugs

Central Nervous System (CNS) Stimulants – General Concepts

• Very broad class of agents that increase the activity of specific regions of the brain and/or spinal cord.
• Primary pharmacodynamic action: direct stimulation of excitatory neurons ➔ effects look like heightened sympathetic tone.
  • Neurotransmitter mimicry: norepinephrine (NE), dopamine (DA), serotonin (5-HT).
  • Hence many stimulants are also called adrenergic / sympathomimetic drugs.
• Clinical relevance: large share of therapeutics either produce desired effects in the CNS or evoke adverse effects there.

Three Parallel Classification Systems

• 1️⃣ Chemical structure
  • Amphetamines
  • Serotonin agonists ("triptans")
  • Sympathomimetics
  • Xanthines
• 2️⃣ Anatomic / functional site of action (e.g., cerebral cortex vs. medulla)
• 3️⃣ Therapeutic indication – 5 major groups
  • Anti-attention-deficit (ADHD)
  • Antinarcoleptic
  • Anorexiant
  • Antimigraine
  • Analeptic (respiratory stimulants)

Key Disorders Treated With Stimulants

Attention-Deficit/Hyperactivity Disorder (ADHD)

• Prevalence: 10.8\% of U.S. children.
• Cardinal symptoms: impaired sustained attention, hyperactivity, impulsivity (developmentally inappropriate).

Narcolepsy

• Incurable neurologic condition ➔ sudden "sleep attacks" during normal activities.
  • Up to \ge 70\% of patients report car accidents or near misses.
  • Also causes dysfunctional REM sleep.

Obesity / Overweight

• Definitions by body-mass index (BMI):
  • Overweight: 25 \le \text{BMI} \le 29.9
  • Obesity: \text{BMI} \ge 30

Migraine Headache

• Recurrent headache lasting 4{-}72\text{ h}.
  • Qualities: pulsatile, unilateral > bilateral, worsens with each pulse.
  • Associated: nausea, vomiting, photophobia, phonophobia.
• Epidemiology: 12\% of U.S. population; female:male ≈ 3 : 1.
  • Pediatric: 10\% of school-age, 28\% of adolescents.

Neonatal Apnea

• Periodic breathing cessation in preterm infants.
  • Incidence ≈ 70\% when gestational age <34\text{ weeks}.

ADHD & Narcolepsy Pharmacotherapy

• First-line = CNS stimulants (Schedule II, high tolerance / dependence potential).
• Major families: amphetamines, non-amphetamine analeptics, certain anorexiants.
• Representative pro-drug: lisdexamfetamine (Vyvanse) ➔ dextroamphetamine after hepatic activation.

Mechanisms & Desired CNS Effects

• Stimulate cerebral cortex + thalamus ➔ ↑ mental alertness, euphoria, wakefulness; ↓ fatigue.
• Respiratory stimulation is prominent (↑ RR, depth).

Adverse Effects (Dose-dependent, appear sooner at high doses)

• CNS: mood swings, irritability, insomnia, seizures, psychosis, mania.
• CV: tachycardia, ↑BP, palpitations, angina.
• GI/Other: ↓ appetite, nausea, dry mouth, blurred vision, tremor, ↑ metabolic rate.

Contraindications

• Known allergy.
• Structural heart disease, severe HTN.
• Marked anxiety, agitation, Tourette’s / tics.
• Glaucoma.

Atomoxetine (non-stimulant ADHD option)

• Adverse: headache, abdominal pain, vomiting, anorexia, cough.

Anorexiants (Anti-Obesity)

• MOA (multi-factorial, partly theoretical):
  • Suppress hypothalamic appetite centers.
  • ↑ basal metabolic rate, mobilize adipose, enhance cellular glucose uptake.
  • Some agents ↓ intestinal fat absorption.
• NOT recommended as monotherapy – require diet + exercise.

Major Agents & Unique Facts

• Orlistat – not a stimulant; lipase inhibitor ➔ fat malabsorption ☞ ↑ fecal fat elimination.
• Lorcaserin (Belviq) – 5-HT$_{2C}$ agonist.
• Qsymia = phentermine + topiramate.
• Contrave = naltrexone + bupropion (synergy via reward pathways).
• Saxenda (liraglutide) – GLP-1 analogue for diabetes & weight loss.

Contraindications / Cautions

• Drug allergy.
• Severe CV disease, uncontrolled HTN, hyperthyroidism, glaucoma.
• Psychiatric agitation, drug abuse history, eating disorders.
• Seizure disorders, hepatic dysfunction.

Adverse Effects

• ↑ BP, palpitations, dysrhythmias at high doses (except diethylpropion).
• Paradoxical reflex bradycardia at therapeutic doses.
• GI: oily spotting, fecal urgency (mainly orlistat). ➔ Monitor fat-soluble vitamins A, D, E, K.
• CNS: insomnia, mood change, seizures.

Antimigraine Drugs

Triptans (Selective Serotonin Receptor Agonists – SSRAs)

• Abortive therapy ONLY; can be taken during aura but not preventive.
• Forms: PO, intranasal, SC injection.
• Contraindicated in coronary artery disease & serious CV disorders (vasoconstriction risk).
• Adverse: chest tightness, flushing, tingling, local injection irritation, ↑BP, congested head feeling.

Ergot Alkaloids (older class)

• Contraindications: uncontrolled HTN, vascular diseases, dysrhythmias, glaucoma, CAD/IHD.
• Adverse: N/V, cold/clammy extremities, muscle pain, dizziness, bitter taste, anxiety.

CGRP Inhibitors (newest, preventive & abortive)

• Block calcitonin gene-related peptide mediated cerebral & dural vasodilation.

Analeptics (Respiratory Stimulants)

• Agents: doxapram (Dopram), methylxanthines – aminophylline, theophylline, caffeine.
• MOA: Stimulate medullary respiratory center & spinal cord.
  • High doses ➔ activate vagal, vasomotor, respiratory centers + ↑ skeletal muscle blood flow.

Indications

• Neonatal apnea / bronchopulmonary dysplasia.
• Hypercapnic COPD.
• Post-anesthesia or drug-induced respiratory depression.

Pediatric Note

• Caffeine preferred in neonates ➔ fewer tachyarrhythmias & feeding intolerance vs. theophylline.

Contraindications

• Allergy.
• Peptic ulcer disease (especially caffeine).
• Serious CV conditions.

Nursing Process & Patient-Centered Care

Assessment Priorities (All Stimulants)

1. Comprehensive medical history – special focus: CV, cerebrovascular, neuro, renal, hepatic diseases.
2. Substance misuse history (alcohol, nicotine, illicit, OTC, herbal).
3. Complete medication reconciliation – avoid interactions (e.g., MAOIs, other sympathomimetics).
4. Nutritional & dietary baseline (weight, BMI, growth charts in children).

Monitoring & Evaluation

• Vital signs: HR, BP (watch for hypertension or reflex bradycardia).
• Neurologic: mental status, seizure threshold, insomnia, irritability.
• Growth charts in pediatrics – stimulants can stunt weight gain / height.
• Cardiac rhythm if high-dose or pre-existing disease.
• Respiratory status when using analeptics.
• Liver & renal labs for prolonged therapy.

Therapeutic Goals & Indicators

• ADHD: ↓ hyperactivity, ↑ attention span, improved school/work performance.
• Narcolepsy: fewer daytime sleep attacks.
• Obesity: sustained weight loss, appetite control.
• Migraine: abort attacks, ↓ frequency with preventive agents, ↑ daily functioning.
• Neonatal apnea: regular respirations, adequate oxygenation.

Patient / Family Education

• Risk of tolerance & psychological dependence; medications are Schedule II (except some anorexiants).
• Timed dosing to minimize insomnia (e.g., last ADHD dose \ge 6\text{ h} before bedtime).
• Emphasize adjunct lifestyle modifications: diet, exercise, behavioral therapy.
• Instruct to journal symptoms, triggers, therapeutic responses, adverse events – valuable for dose titration.
• Report immediately: chest pain, palpitations, severe headache, vision changes, worsening psychiatric symptoms.
• For triptans: use at first migraine sign; do NOT exceed recommended dosing frequency (vasospasm risk).
• Orlistat: anticipate oily stools; take with meals & multivitamin \ge 2\text{ h} apart.

Inter-professional Collaboration / Ethical Points

• School coordination for pediatric ADHD (teachers, nurses, parents) ≈ key to adherence.
• Drug abuse surveillance in adolescents & adults (diversion potential).
• Counsel reproductive-age women on migraine drugs ➔ some are pregnancy category X (ergot derivatives).

High-Yield Numerical & Statistical References

• ADHD prevalence: 10.8\% of U.S. children.
• Narcolepsy traffic incident rate: \ge 70\%.
• Migraine prevalence: 12\% overall, female ≈ 3\times male.
• Pediatric migraine: 10\% (school-age) & 28\% (adolescents).
• Neonatal apnea: 70\% if <34\text{ weeks} gestation.
• Overweight BMI: 25{-}29.9; Obesity: \ge 30.

Quick Drug–Adverse Effect Pairs (Mnemonic Aid)

• Amphetamines ➔ Arrythmia, Mood swings, Psychosis, Hypertension.
• Orlistat ➔ Oily stool, Reduced fat-soluble vitamins.
• Triptans ➔ Tight chest, Rising BP, Injection pain.
• Caffeine neonatal ➔ Central (mild), fewer Arrhythmias than theophylline.