Pharmacotherapy for Heart Failure Flashcards
Preload is controlled by?
Ventricular filling
Afterload is controlled by?
Arterial pressure (TPR)
bowditch is?
the subsequent increase in contractility with increased HR
Anrep is?
the subsequent increase in contractility with increased afterload
In long term HF what is the worst causative issue in people?
Sympathetic system activation due to low CO caused by HF
-stimulates more load and more cardiac remodeling
Frank starling relationship to contractile status:
linear - increase preload = increase in contractility up to some point
Stage A HF - patient descritpion:
(HIGH RISK FOR HF)
- HTN
- CAD
- DM
- FMx of cardiomyopathy
Stage B HF - patient descritpion:
(ASYMPTOMATIC HF)
- Previous MI
- LV systolic dysfunction
- Asymptomatic valvular disease
Stage C HF- patient description:
(SYMPTOMATIC HF)
- known structural heart disease
- shortness of breath and fatigue
- reduced exercise tolerance
Stage D HF - patient description:
(REFRACTORY END STAGE HF)
- marked symptoms at rest despite maximal med therapy
- cant safely discharge these people from the hosptial
Cardiac remodeling starts in which stage?
STAGE A - RIGHT AWAY SLOW PROCESS THAT JUST MAKES IT WORSE UNTIL YOU PROGRESS TO SYMPTOMATIC HF
Drugs for Stage A:
ACEI or ARB
Drugs for Stage B
ACEI or ARB
Beta-blocker
Drugs for Stage C:
ACEI or ARB Beta blocker Diuretics aldosterone antagonist hydralazine and nitrates Digoxin
Drugs for Stage D:
ACEI or ARB Beta blocker Diuretics Digoxin Positive inotropes (drugs that inc cAMPs); dobutamine (Beta1 agonist)
Heart failure is when what two types of symptoms converge?
congestive and low output symptoms
Factors controlling intrinsic myocardial contractility:
1) beta receptor agonists binds –> g-protein –> cAMP made
2) activate PKA –> activate calcium channels = more calcium
3a) calcium stimulates release of more calcium from SR
3b) calcium is sequestered
lusitropic and inotropic
**Practical approaches to increase myocardial contractility:
1) increase cytosolic Ca using cardiac glycosides (Digitalis)
2) increased myocardial cAMP concentration using phosphodiesterase inh (amrinone, Milrinone)
3) agonism at beta1 receptors using beta adrenergic agonists (Isuprel, dobutamine, dopamine, epinephrine, NE)
4) increase beta1 receptor density using beta receptor antagonist (metoprolol and carvedilol)
Digoxin -
- type of drug?
- what does it do/MOA?
- glycoside - positive inotrope
- blocks the cardiac Na(out)/K(in) ATPase=accumulation of Na inside cell = reduced activity of Na(in)/Ca(out) exchanger leading to increased influx of Ca from extracellular space = enhanced contraction
Digoxin - cardiac effects:
1) pos inotropic effect=
a) dec EDV and dec ESV
b) dec pulmonary and systemic venous pressure
c) reflex dec SANS = dec preload, afterload and HR)
2) direct pos vagal effect:
a) inc vagal tone = decrease AV conduction (USED FOR ATRIAL FIB)
b) inc PR interval (longer ERP)
c) dec APD ( shorter QT)
3) inc coronary flow (dec hypertrophy)
4) dec renal artery resistance (inc RBF–> Inc GFR –> inc UO)
5) Proarrhythmic - Inc PR and dec QT intervals - more severe arrhythmias (TYPICAL HOCKEY STICK) - ST depression
Digoxin - pharmacokinetics
- *-T1/3 = 36-48hrs
- *-excreted by the kidney-affected by Rx that change renal RBF
- *-near steady state blood level ~7days
- inactivated by eudacterium lentum (intestinal bacteria some people have = less effect)
- plasma concentratin affectd by many drugs - CV Rx= antiarrhythmics class Ia and IV, spironolactone, vasodilators; cimetidine
Digoxin- adverse effects:
- -low margin of safety (lethal dose is 5-10x minimal effective dose
- -electrolyte disturbances (hypokalemia) and acid-base disbalance –> susceptibility to side effects –> monitor plasma K
- -arrhythmias
- poor compliance
- visual and neuro disturbances
- -CTZ stimulation induces anorexia, nausea, vomiting
Especially careful when using digoxin with what kind of drugs?
K-excreting drugs - diuretics - or loop diuretics,
ACEI,spirnonolactone, amiodarone, inc K serum
Digoxin in Tx of HF:
- used frequently** especially CHF with Af
- DOES NOT improve all-cause mortality –> no longer a first line therapy
Correctin of adverse elevations in plasma digoxin (arrhythmias)
- *cholestyramine
- *-digoxin immune Fab (des-IgG):
- – binds to both bound and free cardiac glycoside where it is sequested in extracellular fluid and eliminated thorugh the kidneys
- – administered IV - **immediate onset of action
- –toxicity reversal within minutes
- –**clinical effects also reverse
phosphodiesterase 3 inh -
- Drugs?
- MOA?
- inamrinone and milrinone
- MOA: cyclic AMP-PDE inhibitors decrease cellular cyclic AMP degredation resulting in elevated levels of cyclic AMP in cardiac and smooth muscle myocytes`
phosphodiesterase 3 inhibitors-
-cardiovascular effects:
-directly stimulate myocardial relaxation
-accelerate myocardial relaxation
-balanced arterial and venous dilation
===> dec TPR, PVR,
===> dec LV, RV pressures
========> ALL = increase CO
phosphodiesterase 3 inhibitors:
-therapeutic uses:
- short half lives
* ** -approved for short term circulation support in advanced congestive HF
ACEI
1) Mortality rate?
2) exercise tolerance?
3) quality of life?
1) dec 20%
2) mild improvement
3) mild improvement
Beta-blocker
1) Mortality rate?
2) exercise tolerance?
3) quality of life?
1) dec 35%
2) mild or no improvement
3) mild or no improvement
aldosterone antagonist
1) Mortality rate?
2) exercise tolerance?
3) quality of life?
1) dec 30%
2) mild or no improvement
3) mild improvement
digoxin
1) Mortality rate?
2) exercise tolerance?
3) quality of life?
1) no effect
2) mild improvment
3) unk
diuretic
1) Mortality rate?
2) exercise tolerance?
3) quality of life?
1) unk
2) moderate improvement
3) moderate improvement
