Basic Pharmacology of Heart Failure Management

Question 1

describe the general approach to CHF treatment

Answer 1

1. patients in CHF have one or more of the following
   -excessive PRELOAD due to increased blood volume and systemic vasoconstriction: use diuretics and venodilators

-excessive AFTERLOAD from vasoconstriction: use arteriolar vasodilators

-abnormal cardiac CONTRACTILITY: use positive inotropes

-abnormalities of heart rate and rhythm: use antiarrhythmics

2. therefore, drugs that influence these factors are often used (see above)

Question 2

describe the first line approach to acute left sided CHF (FONSI_

Answer 2

F: furosemide
-goal: reduce blood volume/preload, alleviate congestion

O: supplemental Oxygen
-goal: increase alveolar-capillary O2 gradient, reduce hypoxemia

N: nitroglycerin (topical ventilator)
-goal: reduce preload, alleviate congestion

S: sedation with a cardio friendly drug (butorphenol)
-goal: alleviate anxiety caused by respiratory distress

I: inotropic support
-goal: support contractility, improve cardiac output

additional considerations: mechanical ventilation, further afterload reduction in severe cases

Question 3

describe diuretic agents

Answer 3

Di=through uresis=urination

1. diuretics promote water loss by
   -directly interfering with Na+ reuptake from tubular infiltrate (natriuresis), or
   -modifying the content of renal tubular filtrate (osmotic diuresi)
2. Na+ controls distribution of H2O among fluid compartments (H2O follows Na+)
   -renal glomerulus freely filters Na+ and H2O
   -large amounts of each must be reabsorbed daily to maintain blood volume
   -even small % decreases in reabsorption = large increases in Na+/H2O excretion
3. diuresis: mobilize edema ONLY
   -decreased blood volume (preload)
   -reduced arterial pressure/volume
   -decreases capillary hydrostatic pressure
   -decreases edema formation (congestion)
   -IMPORTANT: diuresis does NOT improve cardiac output!! so ALWAYS use the LOWEST effective dose (could become hypotensive, cardiogenic shock, etc.)

Question 4

which diuretic do you NOT use in CHF?

Answer 4

1. osmotic diuretics work in proximal convoluted tubule
   -do NOT use in CHF!! can only give IV, cause massive fluid shifts where interstitial fluids all over body are shifted into vascular space and worsen preload
   -only used to neuro stuff
   -main one is mannitol

Question 5

describe loop diuretics

Answer 5

1. used extensively in first-line CHF treatment
2. renal effects:
   -actively secreted into tubular fluid by proximal tubule and BLOCK Na+/K+/2Cl- co-transporter in loop of Henle
   –so water stays in tubule with Na+ (and K+ and Cl-)
   –greater Na+ delivery downstream causes K+ and H+ loss in collecting duct
   –driving force for Mg2+ and Ca2+ reabsorption decreases
   -net reusult: increase H2O, Na+, K+, Cl+, H+, Mg2+, and Ca2+ LOSS
   -because LOH has a large capacity for Na+ absorption, LD have profound high ceiling diuretic action (most powerful diuretic available)

-the Na+/K+/2Cl- transporter is VITAL to the macula densa
–MD turns on RAAS in response to decreased Na+ in distal tubular
–transporter blockade inhibits MD’s ability to detect tubular [Na+], result is ACTIVATION of RAAS

-use of LD as sole agent WORSENS outcomes in CHF versus when given with a RAAS blocking agent!!
-ALWAYS co-administer RAAS blocker (ACE inhibitors or angiotensin receptor blocker) in patients treated chronically with a loop diuretic

Question 6

describe loop diuretic examples

Answer 6

1. furosemide/lasix: most commonly prescribed
   -wide dose rangeL IV, SQ, PO
   -IV: rapid onset of action (5 min), time to peak effect (30 min), duration of effect (2-3 hr)
2. torsemide: frequency of clinical use is increasing, 10x more potent and more bioavailable than furosemide

clinical indications:
1. acute and chronic management of CONGESTIVE heart failure
2. tissue edema due to hypoalbuminemia
3. hypercalcemia
4. oliguric renal failure

Question 7

describe inotropic agents

Answer 7

1. affect cardiac contractility
2. positive vs. negative
   -positive inotropes are prescribed in conditions/situations associated with compromised ventricular systolic function

–most act by increasing cytosolic Ca2+

–potential costs = pro-arrhythmia, increased myocardial energy demand and O2 consumption

–newer agents (pimobendan) increase sarcomere sensitivity to Ca2+, avoiding these costs

3. positive inotropic agents:
   -B-adrenergic agonists (sympathomimetics)
   -phosphpdiesterase inhibitors
   -calcium-sensitizing agents
   -cardiac glycosides
4. negative inotropic agents:
   -B-adrenergic blockers
   -calciu channel blockers