Blood Pressure & CHF Medicines — Study Notes

Foundational HF therapy (HFrEF)

• Quadruple therapy = RAAS inhibitor (ACEi/ARB/ARNI) + β-blocker + MRA + SGLT2 inhibitor.

• Proven to ↓ mortality & hospitalizations.

Drug Classes

1. Diuretics

• Thiazides: block Na⁺–Cl⁻ in DCT → mild diuresis, ↓BP.

  • Ex: HCTZ, chlorthalidone.

  • ADRs: ↓K⁺, ↓Na⁺, ↑uric acid, ↑glucose, ↑lipids.

• Loops: block Na⁺–K⁺–2Cl⁻ in thick ascending limb → potent diuresis.

  • Ex: furosemide, bumetanide.

  • ADRs: ↓K⁺, ↓Mg²⁺, alkalosis, ototoxicity.

• K⁺-sparing (ENaC blockers): block Na⁺ in collecting duct.

  • Ex: amiloride, triamterene.

  • ADRs: ↑K⁺, acidosis.

• MRAs: block aldosterone receptor → ↓remodeling.

  • Ex: spironolactone, eplerenone.

  • Use: HFrEF mortality benefit.

  • ADRs: ↑K⁺, gynecomastia (spironolactone).

2. ACE inhibitors

• MOA: block Ang I → Ang II + ↑bradykinin → vasodilation, ↓remodeling.

• Ex: lisinopril, enalapril.

• Use: HTN, HFrEF, post-MI, diabetic nephropathy.

• ADRs: cough, angioedema, ↑K⁺, ↑Cr (esp. renal artery stenosis). Contra: pregnancy.

3. ARBs

• MOA: block AT₁ receptor → ↓vasoconstriction/aldosterone.

• Ex: losartan, valsartan.

• Use: HTN, HFrEF (if ACEi not tolerated).

• ADRs: ↑K⁺, ↑Cr. Contra: pregnancy.

4. ARNI--Angiotensin Receptor-Neprilysin Inhibitor (ARNI) Drugs

• Sacubitril/valsartan.

• MOA: sacubitril (↑natriuretic peptides) + valsartan (ARB).

• Use: replaces ACEi/ARB in HFrEF → stronger mortality benefit.

• ADRs: hypotension, ↑K⁺, renal dysfunction, angioedema. Don’t combine with ACEi.

5. β-blockers

• MOA: block β₁ (±β₂/α₁) → ↓HR, ↓remodeling.

• Ex: metoprolol succinate, carvedilol, bisoprolol.

• Use: HFrEF (specific agents), HTN, ischemic heart disease, AF rate control.

• ADRs: bradycardia, fatigue, bronchospasm (non-selective), mask hypoglycemia.

6. SGLT2 inhibitors

• MOA: block SGLT2 in proximal tubule → glucosuria, natriuresis, ↓preload/afterload.

• Ex: dapagliflozin, empagliflozin.

• Use: HFrEF & HFpEF, even without diabetes.

• ADRs: genital infections, volume depletion, rare euglycemic DKA.

7. Calcium channel blockers

• DHPs (amlodipine): vasodilation → ↓BP.

• Non-DHPs (verapamil, diltiazem): ↓HR, ↓contractility.

• Use: HTN, angina, AF (non-DHP). Avoid non-DHP in HFrEF.

• ADRs: edema, constipation (verapamil), bradycardia.

8. Vasodilators & nitrates

• Hydralazine: arteriolar dilator → ↓afterload.

  • Use: HFrEF in ACEi/ARB intolerance; with nitrates in Black patients.

  • ADR: reflex tachy, lupus-like syndrome.

• Nitrates: NO donor → venodilation → ↓preload.

  • Ex: nitroglycerin, isosorbide dinitrate.

  • ADR: headache, hypotension, tolerance.

9. Central α₂ agonists & sympatholytics

• Clonidine, methyldopa: central α₂ agonists → ↓sympathetic outflow.

  • Use: resistant HTN; methyldopa in pregnancy.

  • ADRs: sedation, rebound HTN.

• α₁ blockers (prazosin): vasodilation.

  • Use: HTN + BPH.

  • ADR: orthostatic hypotension.

10. Direct renin inhibitor

• Aliskiren: blocks renin → ↓Ang I/II.

• Use: HTN (rare).

• ADR: ↑K⁺, ↑Cr; avoid with ACEi/ARB in DM/renal disease.

11. Digoxin

• MOA: Na⁺/K⁺ ATPase inhibitor → ↑Ca²⁺ → ↑inotropy; ↑vagal tone.

• Use: symptom relief in HFrEF, AF rate control.

• ADRs: arrhythmias, GI upset, visual halos; toxicity ↑ with ↓K⁺. Monitor drug levels.

12. Inotropes (acute only)

• Dobutamine: β₁ agonist → ↑contractility.

• Milrinone: PDE3 inhibitor → ↑cAMP → ↑inotropy + vasodilation.

• Use: acute decompensated HF/cardiogenic shock.

• ADRs: arrhythmias, hypotension, ↑mortality long-term.

13. Ivabradine

• MOA: blocks funny current (I_f) in SA node → ↓HR without ↓contractility.

• Use: HFrEF with sinus rhythm HR ≥70 despite β-blocker.

• ADRs: bradycardia, visual phosphenes.

14. Vasopressin (V2) antagonists

• Tolvaptan: block V2 → aquaresis.

• Use: severe hyponatremia in HF.

• ADR: thirst, risk of rapid Na⁺ correction.

Cross-cutting monitoring

• Always check: BP, HR, K⁺, Na⁺, renal function.

• Pregnancy: avoid ACEi/ARB/ARNI/Aliskiren.

• HF pearls: start guideline meds early; diuretics only for symptom relief.

Key distinction:

• HTN meds = focus on lowering BP & reducing long-term CV risk.

• HF meds = target remodeling, mortality, and symptoms (quadruple therapy is cornerstone).