371.3 🏥 內科專科考前版

371.3.1 Mechanistic Deep Dive

371.3.1.1 Orexin/Hypocretin System

  • Lateral hypothalamus
  • Promotes wakefulness
  • Cell loss in narcolepsy type 1 (autoimmune)
  • HLA-DQB1*06:02 association
  • Anti-streptococcal trigger possible

371.3.1.2 Sleep-Wake Regulation

  • Two-process model:
    • Process S (sleep homeostatic — adenosine)
    • Process C (circadian — SCN, melatonin)
  • Neurotransmitters:
    • Wake: orexin, histamine, NE, DA, 5HT, acetylcholine (cortical)
    • Sleep: GABA (VLPO), galanin, adenosine
    • REM: acetylcholine (brainstem), glycine

371.3.1.3 OSA Pathophysiology

  • Upper airway collapse during sleep
  • Anatomic + functional factors
  • Loss of tone
  • ↑ negative pressure
  • Resultant arousals + desats
  • Sympathetic activation
  • Metabolic dysregulation

371.3.2 Recent Trials & Updates

371.3.2.1 Daridorexant (Quviviq)

  • DORA
  • FDA 2022
  • Insomnia
  • Improves sleep + daytime function

371.3.2.2 Solriamfetol (Sunosi)

  • DNRI
  • FDA 2019
  • Narcolepsy + OSA residual sleepiness

371.3.2.3 Pitolisant (Wakix)

  • H3 antagonist
  • FDA 2019
  • Narcolepsy + cataplexy

371.3.2.4 Mixed-Salt Oxybate (Xywav)

  • Lower sodium content
  • Narcolepsy + idiopathic hypersomnia (FDA expanded 2021)

371.3.2.5 Tirzepatide for OSA + Obesity

  • SURMOUNT-OSA trial 2024
  • Significant AHI reduction with weight loss
  • FDA approved for OSA + obesity 2024

371.3.2.6 Orexin Receptor 2 Agonists

  • TAK-994, TAK-861 (Takeda)
  • Direct replacement for narcolepsy type 1
  • Phase 2-3 trials
  • Promising

371.3.2.7 Suvorexant for Alzheimer Sleep

  • May modestly help
  • Concerns about safety in cognitive impairment

371.3.2.8 SERVE-HF (2015)

  • ASV worsened mortality in HFrEF
  • Contraindicated EF < 45%

371.3.2.9 CPAP and CV Outcomes

  • SAVE trial (2016) — neutral for CV events
  • Adherence issues
  • Despite physiological benefits

371.3.3 High-Yield Specialist Points

371.3.3.1 Cheyne-Stokes Respiration

  • Crescendo-decrescendo
  • Central apneas
  • HF, stroke
  • ASV beneficial except in HFrEF EF < 45%

371.3.3.2 Opioid-Induced Central Apnea

  • Increasingly recognized
  • Methadone and others
  • Can persist after discontinuation

371.3.3.3 Idiopathic Hypersomnia

  • Long sleep times (> 10 hr/24)
  • Difficulty awakening (sleep drunkenness)
  • Excessive daytime sleepiness
  • Not narcolepsy
  • Treatment: modafinil, methylphenidate, mixed-salt oxybate

371.3.3.4 Kleine-Levin Syndrome

  • Recurrent hypersomnia
  • Hyperphagia
  • Hypersexuality
  • Cognitive
  • Episodes lasting days-weeks
  • Adolescents typically

371.3.3.5 Klein-Levin = Sleeping Beauty Syndrome

  • Rare
  • Limited treatment
  • Lithium for prevention

371.3.3.6 Narcolepsy in Children

  • Often misdiagnosed as ADHD
  • Modafinil + behavioral

371.3.3.7 Restless Sleep Disorder

  • Newly recognized
  • Children
  • Iron supplementation

371.3.3.8 Tirzepatide for OSA

  • GLP-1/GIP dual agonist
  • FDA 2024 for OSA + obesity
  • Effective weight loss
  • AHI reduction

371.3.3.9 Adaptive Servo-Ventilation (ASV)

  • For CSA, complex SDB
  • AVOID in HFrEF (SERVE-HF)
  • Otherwise effective

371.3.3.10 Hypoglossal Nerve Stimulation (Inspire)

  • For moderate-severe OSA + PAP intolerance
  • BMI < 32-35
  • No concentric collapse on DISE
  • Significant AHI reduction
  • Adoption increasing

371.3.3.11 CPAP Adherence

  • ~ 50-70%
  • Education + interface optimization + humidification + APAP
  • Telemonitoring

371.3.4 Pearls

  • Sleep stages: NREM N1-N3 + REM; cycles 90 min
  • OSA: AHI ≥ 5 + symptoms or ≥ 15; CPAP mainstay
  • Tirzepatide for OSA + obesity (FDA 2024)
  • Narcolepsy type 1: ↓ orexin, cataplexy, HLA-DQB1*06:02
  • Oxybate for narcolepsy + cataplexy
  • Pitolisant + solriamfetol newer for sleepiness
  • RBD: prodrome of synucleinopathy
  • Insomnia: CBT-I first-line; daridorexant newer DORA
  • Tasimelteon for non-24 in blind
  • ASV contraindicated in HFrEF EF < 45%