drugs used in heart failure Flashcards
equation for CO
SV*HR = CO
equation for bp
BP= CO*TPR
response to decreased cardiac output
increase sympathetic nervous tone -> Increase HR, Stroke volume and renin release -> vasoconstriction
-Frank -starling compensation-> increased filling to increase wall tension and thus force results in increased preload
-
three interventions for chronic HF
increase inotropy (inotropes)
- reduce afterload ( ace inhibitors, vasodilators)
- reduce preload ( diuretics and vasodilators)
inotropic agents - MOA
increase contractility
- increasing resting Ca++ levels
- increase Ca++ entry during an action potential
- increasing Ca++ sensitivity of the contractile apparatus
Digoxin ( digitalis drugs)
MOA: inhibits Na/K ATPase -> which reduces the Na/Ca transporter and this increase the resting Ca++ levels and thus have a stronger condtraction when the AP is induced- strong CO
- increase parasympathetic effects on the heart
- reduces HR - better filling
- blocks sympathetic effects on the heart - some vasodilation
- no decrease in mortality
digoxin - toxicity
TOXICTIY: blocks Na/K ATpase is found in all tissues! so it gets blocked everywhere
30% show toxicity
cardiac: depressed AV function-> Premature ventricular depolarization
- av blockade
extras :
anorexia, nausea, diarrhea, color vision abnormality, disorientation, yellow vision, gynecomastia ( in males)
long half life( 40 hr for digoxin and 170 digitoxin)
digoxin- drug interactions
metabolized in the kidney and kidney function decreases with age -> increase of toxicity
- agents that alter renal clearance can lead to elevation- quinidine
- diuretics-> induce hypokalemia( thiazides and loop diuretics) and increase risk for toxicity
sympathomimetic inotropes
increase Ca++ entry
- not used for Chronic HF
diuretics
reduction in salt and water retention
- reduce ventricular preload -> reduces edema and reduction in cardiac size which increases pumping efficiency
- thiazides -low ceiling ( med edema)
-loop diuretics - high ceiling (bad edema)
both can induce K+ loss -> exacerbate digoxin - **( reduce mortality) - spironolactone/ eplerenone -> aldosterone antagonist - K sparing diuretics
- blocks aldosterone effects ( so we will reduce myocardial fibrosis,increase NO)
vasodilators
reduce afterload ( hydralazine )
reduce preload ( nitrates)
verapamil and diltiazem DHP -> NO - inotropes
B.Dil - hydralazine/ isosnbide dinitrate - in African Americans
Beta Blockers
LOW DOSES - reduce mortality MOA? : better filling - protects against arrhythmias -antiapoptotic -reducing renin release
carvedilol, metoprolol, bisprolol
M+B= beta 1 selective
C= non selective B1,B2 A1
ACE inhibitors and angiotensin receptor blockers
DECREASE MORTALITY
reduce peripheral resistance -> afterload
by reducing aldosterone secretion -> reduce preload via reduction of salt and water retention.
- reduce long-term remodeling of the heart
Dobutamine
- Beta 1 selective agonist with high inotropic and low chronotropic activity
- MOA - increase cAMP levels -> B1-> heart B2- > periperharl vasodilation
ACUTE USE
Amrinone and Milrinone
phosphodiesterase (PDE) inhibitor -> elevation of cAMP
- orally active agents -> selective for cardiac isoform PDE3
- decrease mortality
- ACUTE IV treatment
Dopamine
low doses -> release NE at the heart-> leads to B1 adrenergic stim
- activation of dopamine receptors in periphery leads to inhibiition of NE release and vasodilation and enhanced renal and cerebral perfusion.
Higher doses-> direct alpha 1 adrenergic activit-> vasoconstrition.
ACUTE IV
norepinephrince
ACUTE HF - when systolic pressure needs to be increased due to cardiogenic shock
Nesiritide
recombinant version of the human B-type natriuretic peptide. Activates guanylate cyclase and leads to vasodilation, especially reducing right atrial pressure and pulmonary capillary wedge pressure. maybe a short-term mortality increase with it-> usefulness not proven yet
standard step therapy for chronic HF
- reduce workload of the heart thru weight reduction, limiting activity
- restrict NA intake to help reduce fluid retention
- diuretics to reduce blood volume
- ace inhibitors
- b-blockers
- digitalis compounds
- vasodilators
ACE inhibitors
MOA
hemodynamic effect
clinical notes
MORTALITY REDUCTION
inhibits AT II generation
-> decrease AT1 receptor activation
decrease afterload and preload
may cause hyperkalemia
B-antagonist
MOA
hemodynamic effect
clinical notes
MORTALITY REDUCTION
competitive antagonist at B-adrenergic receptor -> decrease renin release
decrease afterload and preload
may be relatively contraindicated in severely decompensated heart failure
spironolactone
MOA
hemodynamic effect
clinical notes
MORTALITY REDUCTION
competitive antagonist at aldosterone receptor
decrease preload
mortality benefit may be independent of hemodynamic effects ; may cause hyperkalemia
Na+/ H20 resitriction
MOA
hemodynamic effect
clinical notes
decrease intravascular volume
decrease preload
may help limit edema formation
diuretics
MOA
hemodynamic effect
clinical notes
inhibit renal Na+ reabsorption
decrease preload
furosemide most effective
aquaretics
MOA
hemodynamic effect
clinical notes
competitive antagonist at vasopressin
->V2 receptor- decrease renal aquaporin expression and membrane trafficking , decrease free water reabsorption
decrease preload
increase solute-free urine output; increased serum sodium
digoxin
MOA
hemodynamic effect
clinical notes
inhibits Na/K aTPAse - increase intracellular Ca2+ and contractility
increased contractility
delays atrioventricular nodal conduction
organic nitrates
MOA
hemodynamic effect
clinical notes
increase NO -> venous smooth muscle relaxation
-> increase venous capacitance
decreased preload
reduces myocardial 02 demand
dobutamine
MOA
hemodynamic effect
clinical notes
stimulates B- adrenergic receptors
increased contractility (b1) decreased afterload (b2)
ACUTE setting only
inamrinone , milrinone
MOA
hemodynamic effect
clinical notes
inhibit phosphodiesterase
-> increase B-adrenergic effect
increase contractility
decreased afterload
decrease preload
used in the acute setting only
increase contractility
inotropes; digoxin and beta agonist
reduce afterload
Ace inhibitors and arterio vasodilators
reduce preload
diuretics, ace inhibitors venodilators
