Cv Pharm - Lv Failure Part 1

Front 1

What is the cause of systolic HF?

Back 1

Decreased contractility

Front 2

What are the four fundamental pathophysiological mechanism involved in HF?

Back 2

1. Decrease in performance (contractility ) of the heart associated with LV enlargement
2. Salt and water retention by kidney
3. Vasoconstriction of peripheral blood vessels
4. Activation of neurohormonal mechanisms (sympathetics, renin-angiotensin system, endothelin, etc.)

Front 3

What are the initial important compensatory mechanisms in acute heart failure?

Back 3

-Salt and water retention by kidney
-Vasoconstriction of peripheral blood vessels
-Activation of neurohormonal mechanisms (sympathetics, renin-angiotensin system, endothelin)

Front 4

What is the purpose of the initial compensatory mechanisms in acute heart failure?

Back 4

-To maintain cardiac output and organ perfusion
-To keep the organism alive

Front 5

Describe the therapeutic strategy for acute heart failure

Back 5

-Stabilize the hemodynamics
-Stimulate heart contractility with a positive inotropic drug
-Eliminate fluid retention with a loop diuretic drug
-Dilate peripheral blood vessels with a direct acting vasodilating drug

Front 6

What drugs are used to stimulate heart contractility in acute heart failure?

Back 6

Beta receptor agonists such as dopamine or dobutamine, amrinone, and milrinon that inhibit phosphodiesterase (PDE) to increase cAMP

Front 7

What drugs are used to dilate peripheral blood vessels in acute heart failure?

Back 7

-Nitrates
-Hydralazine
-Nitroprusside

Front 8

Describe how to give IV administration of drugs in acute heart failure

Back 8

Start with a low dose and titrate upward

Front 9

What is contraindicated in acute heart failure?

Back 9

-The neurohormonal blocking drugs used in therapy of chronic heart failure
-Activation of neurohormonal systems enables the heart to continue to supply organs with an adequate blood supply

Front 10

Describe what occurs if compensatory mechanisms for acute HF are activated for a prolonged period f time

Back 10

They become maladaptive and cause progressive worsening of heart failure by stimulating remodeling

Front 11

Describe the compensatory mechanisms that occur when there is decrease performance of the heart due to damage of the ventricular muscle through infarction, cardiomyopathy, and ischemia

Back 11

-The compensatory mechanisms are salt and water tension by kidney, vasoconstriction of peripheral blood vessels, and activation of neurohormonal mechanisms
-These are initially adaptive in acute failure to maintain CO
-Prolonged activation of these mechanisms lead to deterioration of heart function with evokes further compensatory mechanisms which causes further degradation

Front 12

Contrast the use of diuretics in heart failure vs hypertension

Back 12

Heart failure: Used to decrease fluid retention (edema)

Hypertension: Used to reduce BP

Front 13

How do diuretics improve ventricular performance?

Back 13

Reduction of fluid retention and edema can improve ventricular performance by reducing the end diastolic pressure and volume of the heart which in turn can decrease the size of the ventricles and stress on the wall

Front 14

What are the three types of diuretics?

Back 14

-Thiazide diuretics
-Loop diuretics
-Potassium sparing diuretics

Front 15

Describe thiazides (use, site of action, mechanism)

Back 15

-Used for hypertension, not usually used for heart failure
-Site of action is early distal convoluted tubule
-Inhibits Na/Cl cotransporter that transports Na from the tubular lumen into the interstitial space
-Decreased Na reabsoprtion leads to decreased water reabsorption and increased water retention
-Does not affect renal medullary Na+ concentration

Front 16

Give an example of a loop diuretics

Back 16

Furosemide

Front 17

Describe Loop diuretics (effectiveness, site of action

Back 17

-More powerful than thiazides
-Site of action is at the loop of Henle
-Inhibits TALH Na, K, Cl cotransporter, which transports Na out of tubular lumen into the interstitium
-Accesses this receptor site from inside the tubular lumen (must be secreted into the lumen to exert its effects)
-Distal tubules cannot reabsorb increased Na in the lumen, leads to increased Na excretion along with obligated water-Decreased medullary interstitial Na concentration results in decreased water reabsorption in collecting duct where water is reabsorbed because of osmotic gradient

Front 18

Describe the use of Loop diuretics

Back 18

Used widely in treatment of HF since they are much more powerful than the thiazides

Front 19

Compare Thiazides vs Loop diuretics

Back 19

-Loop diuretics can achieve an effect when thiazines have reduced or no activity-Thiazines block 5-10% of Na reabsoprtion while loop diuretics block about 25%
-Thiazide stops working at creatinine clearance less than 30 while loop diuretics are still effective when creatinine clearance is as low as 5
-There is a decrease in renal blood flow in HF and a reduced creatinine clearance to between 20-70
-Thiazides are not effective under these conditions of impaired renal function but loop diuretics are effective

Front 20

Describe how diuretics work

Back 20

-Work from within the renal tubules and enters the tubules in the renal filtrate
-Impairment of renal perfusion may not deliver enough diuretic into tubular lumen. This means that dose of diuretic must be increased as renal function decreases to get enough diuretic into the tubular lumen

Front 21

Describe the use of diuretics in mild heart failure

Back 21

-Small doses of loop diuretic are effective
-Increased dose is necessary to deliver same concentration into tubular lumen as heart failure worsens

Front 22

Describe fluid retention with diuretics

Back 22

-Occurs in the guy
-Slows absorption from GI tract which may retard efficacy of diuretic
-A dose of drug that is not effective orally, must be effective IV

Front 23

Describe diuretic titration in HF

Back 23

Titrated to achieve an adequate diuretic effect
-Adequate effect is considered to be the absence of physical signs of fluid retention (JVD, pulmonary rales, and peripheral edema)
-The goal is to bring the patient back to Na and water balance which is characterized by low venous pressure and absence of physical signs of fluid retention

Front 24

What do you do when a single diuretic drug doesnt work?

Back 24

Adding a second drug that acts at a different site (more distally) in renal tubule gives an added effect on blocking Na reabsorption) such as a potassium sparing diuretic that blocks aldosterone

Front 25

What are the adverse effects of diuretic in the treatment of HF?

Back 25

a. If diuresis is too great, a decrease in blood volume may lead to a decreased BP. This in turn may further worsen renal function
b. Increased neurohormonal activation (sympathetics, renin angiotensin system) because of volume reduction, decreased CO, and decreased BP. Chronic effects of further neurohormonal activation are deleterious to HF and accelerate disease progression. Diuretics alone do not prevent disease progression and do not decrease mortality. Diuretics must be used in combination with drugs that block neurohormonal activation.
c. K wasting and Mg wasting are a consequence of delivery of increased Na to the distal tubules and activation of RAS system.

Front 26

What does aldosterone do?

Back 26

Increased Na+ channel formation on the tubular lumenal membrane in the distal tubule. Increased reabsorption of Na+ is accompanied by an increased secretion of K into the tubular lumen and therefore a loss of K (wasting).

Front 27

How do you overcome Potassium and Magnesium wasting?

Back 27

Administering oral potassium and magnesium salts, by giving another drug to block activation of RAS and/or by giving a K sparing diuretic concomitantly (spironolactone which blocks aldosterone receptors)