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1

Definition of heart failure

heart is unable to pump blood in quantities sufficient to support the body's oxygenation needs

2

Types of heart failure

Systolic- dysfunction in LV contractility
Diastolic- LV stiffness and delayed filling

3

Signs of heart failure

left sided CHF: pulmonary congestion
right sided CHF: limb edema, ascites, weight gain
cardiac enlargement, myocardial ischemia, tachycardia, atrial fib\

4

Classes of Heart Failure

Class I: cardiac lesion, patient shows no signs
Class II: signs of CHF during exercise
Class III: signs of CHF normally
Class IV: signs of CHF at rest

5

Treatment for Class I CHF

exercise restrictions, decreased Na+ intake

6

Treatment for Class II CHF

exercise restrictions, decreased Na+ intake, thiazide diuretics and spironolactone

7

Treatment for Class III CHF

exercise restrictions, decreased Na+ intake, thiazide diuretics and spironolactone, positive inotropes (digitalis) OR vasodialators OR beta-AR blockers (carvedilol)

8

Treatment for Class IV CHF

exercise restrictions, decreased Na+ intake, thiazide diuretics and spironolactone, positive inotropes (digitalis) AND vasodialators OR beta-AR blockers (carvedilol)

9

Goal of diuretics

decrease blood volume (preload) by increasing Na excretion and decreasing blood volume

10

Goal of vasodilators

decreasing outflow resistance and venous return
decrease blood pressure, increase tissues perfusion, increase Na and H2O excretion

11

Diuretic treatment in CHF: which ones?

loop more effective, but lose lots of K+
thiazide are less effective, useful in mild CHF and can be used in combo with loop
aldosterone antagonists like spironolactone can be used with thiazide and loop, may increase survival time

12

Examples of drugs used as vasodilators in CHF

ACE inhibitors like enalapril, Ca++ blockers like amlodipine

13

Examples of drugs used as vasodilators in AHF (acute heart failure)

sodium nitroprusside

14

How can the renin-angiotensin system be regulated to benefit CHF patients?

inhibit renin activity, inhibit angiotensin-convering enzyme and decrease angiotensin II production (enalapril), block angiotensin II receptors, reduce effects of aldosterone (spironolactone)

15

What is the effect of treating with NSAIDs and ACE inhibitors?

GFR is compromised because of the downregulation of PGE and PGI (vasodilator of afferent arteriole) and the downregulation of angiotensin (vasocontriction of efferent venules)

16

Effects of ACE inhibitors

Inhibit angiotensin- converting enzyme to reduce conversion to angiotensin II, a vasocontrictor. Also inhibits breakdown of kinins (vasodilatory effect)
Can produce hypotension in patients with concurrent diuretic therapy, can decrease GFR.

17

Enalapril

ACE inhibitor. Pro-drug, absorbed in the intestines and hydrolyzed in the liver to active form. Dosing is complex due to slow dissociation from ACE. Renal clearance.

18

Amlodipine

Calcium channel blocker. Blocks L-type Ca++ channels on vascular smooth muscle, decreases Ca++ availibility, results in vasorelaxation. Can also be used for cats in hypertension due to renal disease or hypertension in dogs.

19

What is the goal of beta blocker treatment?

decrease sympathetic hyperdrive to the heart, increase ejection fraction over time

20

What are the majority of beta-adrenergic receptors in the heart?

Beta1-AR (70-80%)

21

What are the effects of CHF on B1-AR?

Chronic sympathetic stimulation results in downregulation of receptors, downregulation of positive inotropic effects. Less downregulation of B2-AR.

22

Carvedilol

B-AR antagonist (preference for B1-AR), but also blocks alpha1-AR resulting in decreasing effects of effects of chronic NE stimulation and afterload. Regarding beta2-AR, it blocks g protein-mediated functions but is an agonist to beta-arristin signaling through b2-ARs. Prevents B2-AR upregulation. Tkaes a few months to take effect

23

What is the goal of the use of positive inotropic drugs in CHF?

Improve cardiac performance/pumping efficiency by increasing Ca++ availability to contractile apparatus, increasing velocity of fiber shortening and relaxation and increasing cardiac output

24

How do positive inotropic drugs increase Ca++ availability to contractile apparatus?

Increase myocardial cAMP concentration by increasing beta1-AR (catecholamines, AHF) or inhibiting cAMP breakdown (pimobendan, CHF) or increasing intracellular Na+ concentration by decreasing Na+/Ca++ exchange (digitalis)

25

Catecholamines in heart failure

Increase cardiac output and support blood pressure, agonist at cardiac beta1-AR or dopamine receptors, some produce tachycardia, also dilate the renal blood flow at low doses

26

Examples of catecholamines used for ACF

DOBUTAMINE, FENOLDOPAM, dopamine

27

Pimobendan

Phosphdiesterase inhibitors, Positive inotropic drugs. increases cyclic AMP concentrations by inhibiting breakdown, enhances cardiac myofilament sensitivity to Ca++, produces vasodilation and decreased preload/afterload. Extensive plasma protein binding, hepatic biotransofrmation to active metabolite, lasts for ~8 hours.

28

What are the differences between digoxin and digitoxin?

both have oral administration. Digoxin (digitalis) is used for small animals, t1/2 is >24 hours for dogs, >30 hours for cats, 20% bound to plasma protein, excreted unchanged in the urine
Digitoxin is 90% plasma protein bound, has hepatic metabolism, and the t1/2 is 8-12 hrs for dogs and >100 hours for cats

29

What is the role of cardiac glycosides in the heart?

Blocks activity of Na,K-ATPase, increases intracellular Na+ concentration, decreases Ca++ exchange, results in increased intracellular Ca++ available to contractile apparatus. Increase contraction amplitude and speed

30

What are the effects of digitalis on the cardiac nodes?

Slow heart rate and decrease AV nodal conduction, preventing ventricular responses to supraventricular arrhythmias.

31

What happens if digitalis is given at toxic doses?

greatly increase calcium and increase sympathetic outflow, results in delayed afterdepolarizations, leading to ectopic pacemakers, and ventricular fibrilation

32

What are the effects of cardiac glycosides on the GI tract?

anorexia, vomiting, diarrhea, effects on GI smooth muscle and brain centers

33

What are the effects of cardiac glycosides on the CNS?

ataxia, depression, convulsions, visual disturbances

34

What are the concerns associated with cardiac glycoside treatments?

Narrow therapudic index, hypokalemia or hypercalcemia increase activity