Chapter 24  ·  Module 6
Natriuretic Peptides, NK1 Antagonists, and Integration
BNP biomarker guide, nesiritide, aprepitant, and vasoactive peptide clinical matrix
BNP and NT-proBNP in Heart Failure Diagnosis
BiomarkerThresholdClinical Notes
BNP >100 pg/mL supports HF; <50 pg/mL makes HF unlikely Falsely HIGH: renal impairment, atrial fibrillation. Falsely LOW: obesity, sacubitril-valsartan use
NT-proBNP >300 pg/mL in acute setting Not a neprilysin substrate — remains interpretable in patients on sacubitril-valsartan. Preferred biomarker in this population
Serial trend Falling = improving Monitor response to diuresis and heart failure therapy; rising level signals inadequate decongestion or deterioration
Nesiritide and NK1 Antagonists
Recombinant BNP  ·  IV Only
Nesiritide (Natrecor)
  • Mechanism: activates natriuretic peptide receptors → vasodilation + natriuresis + renin-angiotensin-aldosterone suppression
  • Use: acute decompensated heart failure (adjunct to diuretics)
  • ASCEND-HF: modest dyspnea improvement; no mortality benefit
  • Not first-line — diuretics preferred
  • Dose-limiting adverse effect: hypotension
  • Contrast with sacubitril-valsartan: blocks BNP degradation (PARADIGM-HF: mortality benefit)
NK1 Receptor Antagonist  ·  Antiemetic
Aprepitant / Fosaprepitant
  • Mechanism: blocks substance P at NK1 receptors in area postrema → prevents delayed nausea
  • Delayed phase (24–120 hrs): substance P / NK1; Acute phase (0–24 hrs): serotonin / 5-HT3
  • Given with: serotonin type 3 antagonist + dexamethasone (3-drug standard regimen)
  • Aprepitant: oral days 1–3; Fosaprepitant: single IV dose day 1
  • CYP3A4 inhibitor: doubles dexamethasone levels — use reduced dexamethasone dose
  • Induces warfarin metabolism — monitor INR after use
Vasoactive Peptide Clinical Decision Matrix — Chapter 24 Summary
IndicationPeptide TargetDrug(s) and Key Rule
HFrEF — chronic RAAS + neprilysin ACE inhibitor or ARB (mortality benefit) → upgrade to sacubitril-valsartan (PARADIGM-HF); 36-hr washout from ACE inhibitor required
HF — acute decompensation Natriuretic peptide receptors Nesiritide (adjunct to diuretics); no mortality benefit; use NT-proBNP to monitor if on sacubitril-valsartan
Hypertension / Diabetic nephropathy RAAS (ACE or AT1) ACE inhibitor first-line (renal protection); ARB if cough/angioedema; do not combine dual RAAS blockade
Pulmonary arterial hypertension Endothelin (ETA/ETB) ERA (bosentan/ambrisentan/macitentan) + PDE5 inhibitor; absolutely contraindicated in pregnancy
SIADH / Hyponatremia Vasopressin V2 Vaptans (tolvaptan oral, conivaptan IV); aquaresis; tolvaptan: 30-day limit, no liver disease; correct ≤10 mEq/L/24 hr
Central diabetes insipidus / vWD / Hemophilia A mild Vasopressin V2 (agonism) Desmopressin; ineffective in nephrogenic diabetes insipidus; tachyphylaxis with repeated hemostatic dosing
Migraine — acute CGRP receptor Gepants (ubrogepant, rimegepant); no vasoconstriction; preferred over triptans in cardiovascular disease
Migraine — preventive CGRP pathway Anti-CGRP monoclonal antibodies (erenumab targets receptor; others target peptide); monthly/quarterly dosing
Chemotherapy-induced nausea — delayed Substance P / NK1 Aprepitant + serotonin type 3 antagonist + dexamethasone; reduce dexamethasone dose (CYP3A4 inhibition); monitor INR on warfarin