Diuretics and RAAS Antagonists Use in Heart Failure Flashcards
HF Pharmacotherapy Goals
1) Reduction of Congestion- Diuretics
2) Modulate Neurohormonal activation- RAAS antagonists and B-Blockers- Positive Remodeling
3) Improve flow- Vasodilators (difficult to obtain pharmacotherapeutically)
Chronic HFrEF Treatments
BB ACEI/ARB Aldosterone antagonist Hydralazine / ISDN \+/- Digoxin ICD/CRT
Chronic HFpEF Treatments
Unknown
Control Risk Factors (DM, HTN, obesity)
Control volume status
Acute HFrEF Treatments
No standard treatment IV Diuresis Nitrates (if BP allows) CPAP (if SOB) Pressors (if very depressed cardiac output/shock)
Acute HFpEF Treatments
No standard treatment
IV diuresis
Nitrates (if BP allows)
CPAP/BiPAP
Preferred Type of Diuretics. Reason. Specific Drugs.
Loop Diuretics are preferred because of EFFICACY. Can be augmented with a thiazide diuretic. Used Chronically and acutely. Furosemide (lasix) is the most common. Torsemide and bumetanide have more reliable absorption.
ACEIs.
Produce vasodilation and decreased aldosterone activation
Plus antiremodeling effect
ARBs. Use?
Used in patients intolerant to ACEIs (most often cough due to Bradykinin breakdown product)
NO apparent benefit from dual therapy with ACEI and ARB
Aldosterone Antagonists. Use and functions?
Added to therapy for LVEF < 30-35%, optimized on ACEI/ARB and β-blocker therapy. Blocks aldosterone effect on kidney. Antiremodeling action plus produces additional Na+ loss at the kidney.
Diuretics (we need to know).
Hydrocholothiazide
Furosemide (Lasix)
Spironolactone (Aldactone)
Diuretic general location of action and mechanisms.
Exert effects at lumenal (urine) surface of renal tubule cells.
Work by:
1) Interactions with membrane transport proteins (thiazides, furosemide)
2) Interactions with enzymes (acetazolamide) or hormone receptors (spironolactone)
3) Osmotic effects preventing water reabsorption (mannitol)
Na+ movement is controlled by?
Na+-K+ ATPase activity at the interstitial (blood) surface. In the kidney, Na+-K+-ATPase produces gradient necessary for Na+ reabsorption from the urine back into the blood. No diuretics work against the Na-K-ATPase.
Loop Diuretic Example(s)
Furosemide (variable bioavailability)
Potassium Wasting Agent(s)
Loop Agents
Thiazides
Potassium Sparing Agent(s)
Aldosterone Antagonists
Furosemide Blocks…? Causes increased excretion of…?
NKCC2. Na-K-Cl Cotransporter. Decreases Sodium transport across membrane (Urine to Blood). Also, decreases potassium transport back into Urine (decreased membrane potential) which blocks magnesium and calcium transport. Leads to increased H20 excretion as well.
TAL
Thick Ascending Limb of Loop of Henle
Loop Diuretics effect on blood flow and diuretic effects on patients with decreased renal function.
Increase renal blood flow via effect on renin-angiotensin and prostaglandin systems
Retain substantial diuretic effect even if renal function is compromised (CrCl < 50 ml/min)
Handled by glomerular filtration and renal secretion
Loop Diuretics Use? Enhanced by?
- Used in HF patients with volume overload to eliminate symptoms of fluid retention
- Efficacy is enhanced with salt restriction (< 2 g/day)
Pt’s with HF have reduced…..
Diuretic Response! Decreased drug delivery to kidney via decreased RBF. Hypoperfusion activates of RAAS and SNS.
Most common use of a thiazide
Refractory Edema! Synergistic effect with Loop Diuretics.
Thiazide Purpose
Block distal tubule sodium reabsorption
Aldosterone Antagonist Improves? Functions?
Improves survival of some patients with HF. Enhances diuresis and ameliorates the potassium wasting at the collecting tubule (CT)
Most efficacious diuretic in HF?
LOOP DIURETICS!! (High-ceiling dose drug)
