277.3 🏥 內科專科考前版

277.3.1 Mechanistic Deep Dive

277.3.1.1 Pharmacogenomics

  • ACE I/D polymorphism affects BP response (modest)
  • CYP3A5 affects calcineurin inhibitors → HTN risk in transplant
  • Genetic testing not routine

277.3.1.2 Mechanisms of Resistance

  • Volume overload (high Na, missed diuretic)
  • Sympathetic overactivity
  • RAAS escape
  • Aldosterone breakthrough
  • OSA
  • Drug-induced

277.3.1.3 Endothelin Pathway

  • ET-1 potent vasoconstrictor
  • Receptors: ETA (vasoconstriction), ETB (vasodilation)
  • Aprocitentan = dual ETA/ETB antagonist
  • Side effects: edema, hepatotoxicity, anemia

277.3.2 Recent Trials & Updates

277.3.2.1 SPRINT-Senior (2016)

  • Subgroup of SPRINT in ≥ 75 yo
  • Intensive < 120 still better, even in frail
  • Watch orthostasis

277.3.2.2 STEP (2021)

  • Chinese 60-80 yo
  • < 130 vs < 150 (note: not < 140)
  • ↓ stroke + CV events
  • Confirms benefit in Asian elderly

277.3.2.3 CLICK (2021)

  • Chlorthalidone vs HCTZ in resistant HTN with CKD
  • Chlorthalidone superior in BP reduction
  • Mostly elderly with eGFR < 45

277.3.2.4 TIME (2022)

  • Timing of antihypertensives (AM vs PM)
  • No clear MACE benefit; chronotherapy controversial
  • Vs MAPEC (2010, +ve) — methodology debates
  • Current: take meds whenever consistent

277.3.2.5 PRECISION (2023) / Aprocitentan

  • Resistant HTN
  • Aprocitentan + 3 antihypertensives
  • ↓ SBP 4-7 mmHg
  • 2024 FDA approval

277.3.2.6 Renal Denervation Trials (Reborn)

  • SPYRAL HTN-OFF MED (2018): positive
  • RADIANCE-HTN SOLO (2018): positive (ultrasound)
  • SPYRAL HTN-ON MED (2020): positive on meds
  • RADIANCE II Pivotal (2023): positive
  • TARGET BP I (2023): positive
  • 2024 FDA approval for resistant HTN

277.3.2.7 ENDURANCE (2024)

  • Long-term efficacy of RDN
  • Maintained BP effect at 5 years
  • Re-treatment possible

277.3.2.8 Sodium Substitutes (SSaSS 2021)

  • 75% NaCl + 25% KCl
  • 21,000 rural Chinese
  • ↓ Stroke 14%, ↓ CV mortality 13%, ↓ all-cause 12%
  • Simple, cheap intervention

277.3.3 High-Yield Specialist Points

277.3.3.1 Drug-Drug Interactions

  • ACEi/ARB + K-sparing diuretic → hyperkalemia
  • ACEi/ARB + NSAIDs → AKI, ↓ efficacy
  • β-blocker + non-DHP CCB → heart block
  • MAOI + sympathomimetic → hypertensive crisis
  • Statin + amlodipine (especially simvastatin > 20 mg) → myopathy

277.3.3.2 Hypertensive Urgency Management

  • BP > 180/120 without acute end-organ damage
  • Oral agents, gradual reduction (over 24-48h)
  • Avoid IV / rapid drop (can cause stroke)
  • Restart home meds, identify cause
  • F/U within 1-7 days

277.3.3.3 Hyperaldosteronism After Confirmed Adenoma

  • Adrenalectomy curative in 30-50%
  • Pre-op: MRA + K+ correction
  • Adrenal vein sampling > CT for lateralization
  • Post-op: BP may not normalize completely

277.3.3.4 Pheochromocytoma Treatment

  • α-blockade (phenoxybenzamine 10 mg BID, titrate up)
  • Add β-blocker after α (NEVER first — unopposed α causes crisis)
  • Volume expansion
  • Surgery (laparoscopic preferred)
  • Genetic testing (MEN2, VHL, NF1, SDHB/C/D)

277.3.3.5 Beta-Blocker Withdrawal

  • Avoid abrupt — rebound HTN, MI, arrhythmia
  • Taper over 1-2 weeks

277.3.3.6 Pregnancy-Specific

  • Chronic HTN: methyldopa, labetalol, nifedipine
  • Gestational HTN / Preeclampsia: same agents; IV labetalol/hydralazine for severe
  • Magnesium sulfate for seizure prophylaxis (preeclampsia → eclampsia)
  • Delivery definitive treatment for severe disease at term

277.3.4 Pearls

  • 2017 ACC/AHA + 2024 update: SBP < 130 for most
  • Lifestyle first, then drugs; SPC for adherence
  • ACEi/ARB + CCB + thiazide = “Big 3” core regimen
  • β-blocker only for specific indications (HF, post-MI, angina, AF, migraine)
  • Resistant HTN 4th drug = spironolactone (PATHWAY-2)
  • Renal denervation + aprocitentan are 2024 game-changers
  • Pregnancy first-line: methyldopa, labetalol, nifedipine — avoid ACEi/ARB/MRA
  • SSaSS 2021 salt substitute: cheap public health intervention with BP benefit