Flashcards in Pharmacotherapy of Heart Failure Deck (34)
Definition of heart failure
heart is unable to pump blood in quantities sufficient to support the body's oxygenation needs
Types of heart failure
Systolic- dysfunction in LV contractility
Diastolic- LV stiffness and delayed filling
Signs of heart failure
left sided CHF: pulmonary congestion
right sided CHF: limb edema, ascites, weight gain
cardiac enlargement, myocardial ischemia, tachycardia, atrial fib\
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
Treatment for Class I CHF
exercise restrictions, decreased Na+ intake
Treatment for Class II CHF
exercise restrictions, decreased Na+ intake, thiazide diuretics and spironolactone
Treatment for Class III CHF
exercise restrictions, decreased Na+ intake, thiazide diuretics and spironolactone, positive inotropes (digitalis) OR vasodialators OR beta-AR blockers (carvedilol)
Treatment for Class IV CHF
exercise restrictions, decreased Na+ intake, thiazide diuretics and spironolactone, positive inotropes (digitalis) AND vasodialators OR beta-AR blockers (carvedilol)
Goal of diuretics
decrease blood volume (preload) by increasing Na excretion and decreasing blood volume
Goal of vasodilators
decreasing outflow resistance and venous return
decrease blood pressure, increase tissues perfusion, increase Na and H2O excretion
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
Examples of drugs used as vasodilators in CHF
ACE inhibitors like enalapril, Ca++ blockers like amlodipine
Examples of drugs used as vasodilators in AHF (acute heart failure)
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)
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)
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.
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.
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.
What is the goal of beta blocker treatment?
decrease sympathetic hyperdrive to the heart, increase ejection fraction over time
What are the majority of beta-adrenergic receptors in the heart?
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.
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
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
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)
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
Examples of catecholamines used for ACF
DOBUTAMINE, FENOLDOPAM, dopamine
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.
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
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
What are the effects of digitalis on the cardiac nodes?
Slow heart rate and decrease AV nodal conduction, preventing ventricular responses to supraventricular arrhythmias.
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
What are the effects of cardiac glycosides on the GI tract?
anorexia, vomiting, diarrhea, effects on GI smooth muscle and brain centers
What are the effects of cardiac glycosides on the CNS?
ataxia, depression, convulsions, visual disturbances