Heart failure Tx/Drugs (pt 2) Flashcards
Direct effects of Digoxin
a. Positive inotropic effect – Due to a direct effect to increase the contractile state of the myocardium – Increases stroke volume b. Increases vagal tone – Slows heart rate
Do we see a change in AP when we give pt Digoxin?
NO change in AP but we do see increased Ca+ thus increasd force of contraction
Secondary affects of Digoxin
Decreased heart rate
- Arterial and venous dilation
- Decreased venous pressure
- Normalized arterial baroreceptors
Molecular site of action of Digoxin
• Positive inotropic effect due to inhibition of the Na+,K+ ATPase
– results in increased intracellular [Na+] – decreasing driving force for Ca2+ extrusion by Na+/Ca2+exchanger
– indirectly results in increased intracellular concentration of Ca2+
WHy do we worry about hypokalemia in pts that take Digoxin?
• K+ competes for binding of digoxin to the Na+,K+-ATPase thus end up with low K+ levels
What electrophysiological actions does Digoxin have?
Electrophysiological actions:
• At therapeutic concentrations, mainly related to increased vagal nerve activity
– Reduced firing rate of SA node
– Decreased conduction velocity in AV node
– Heart block can develop
Main effect of Digoxin on ECG?
increased PR interval
Key pharmK of Digoxin
1/2life?
absorption and excreation?
when do we see best benefits for contractility vs neurohormonal
1/2 = 36 hrs
oral absorption with renal excreation
best cnx benefits at 1.4ng/ml and best neurohormonal at 0.8 ng/ml
What are the adverse effects/toxicity related to Digoxin
Low therapeutic index (~2)!!!!!
Affects all excitable tissues
a. GI tract (most common)- anorexia,, vomiting, diarrhea
b. Visual disturbances- Blurred vision, photophobia, color disturbances
c. Neurologic- disorientation, hallucinations
d. Muscular- muscle weakness, fatigue
e. Cardiac – arrhythmias (any type)
Toxicity with Digoxin is enhanced when pt is
hypokalemic.. may be related to diuretic use
What effect does Digoxin have on CHF progression?
debated.. some say helps, others say you only see benefit vs placebo when taking pts off because they were on a medince for long period of time, much like you would have withdrawl from other drugs
What effect does Digoxin have on overall mortality in CHF pts?
NONE!!! we see no overall benefit, also this drug has narrow tx window so it’s difficult to monitor.
Better to use in pts with atrial fib or if pts have severe heart fail and this helps reduce symptoms
clincial Uses of Digoxin
Use limited to heart failure patients with LV systolic
dysfunction in atrial fibrillation or in some cases to patients in sinus rhythm who remain symptomatic despite maximal therapy with other therapies
• If used, administer a low doses
dobutamine, dopamine are what type of drugs and when do we use them for heart fail pts?
b adrenergic agonists
– Used i.v. for temporary hemodynamic support for
acutely ill patients (acute decompensated heart
failure)
Milrinone is what type of drug and when do we administer to heart fail pts?
• Phopsphodiesterase inhibitors (
– Use limited to i.v. administration for acutely ill patients
– Positive inotrope and also produce vasodilation
Mainstay of heart failure management
• Reduce fluid volume and preload
• Reduction in heart size improves efficiency and reduces wall stress
• Reduce edema (and its symptoms)
Diuretics!
Diuretics reduce:
fluid volume and preload and edema
Furosemide is what type of dieuretic?
loop diuretic
Widely used – most heart failure patients require chronic
therapy with a loop diuretic to maintain euvolemia
– Promote K+loss - hypokalemia
Chlorothiazide is what type of diuretic?
Thiazide; Rarely used alone
– Combination therapy with loop diuretics in patients refractory to loop diuretics alone
– Promote K+loss - hypokalemia
Issue with loop diuretics and thiazides?
promote K loss–hypokalemia
Amiloride and Triamterene are what kind of diuretic?
K sparing diuretic
Weak diuretic activity but limited K+ and Mg2+ wasting
Benefit provided by VENOdialtors?
Increase venous capacitance and thereby decrease preload
Benefit provided by arterial vasodialtors
Arterial vasodilator
– Reduce systemic vascular resistance
– Results in increased stroke volume
– hydralazine
ACE inhibitors, ARBs, isorbide dinitrate/hydralizine are all examples of
balanced or mixed vasodialators: reduced atrial and venous
The failing heart dt systolic heart fail is very sensitive to
changes in
afterload
Potent arterial constrictor (afterload) that promotes Na and water retnetion through it’s effect on glomerular filtration and aldosterone secreation
Angiotensin II
How does Ang II promote SNS activity
increasing neuronal and adrenal medullary catecholamine release
What effect does Ang II have on heart muscle?
- Arrhythmogenic
- Promotes myocardial hypertrophy and apoptosis
Promotes Na and water retention and K+ secreation
Aldosterone
What effect does Aldosterone have on the heart?
Stimulates fibrosis in the heart and
vasculature as well as Cardiac hypertrophy
Captopil, lisinopril, enalapri are all:
Ace inhibitors
What actions do Ace Inhibitors cause in heart fail pts?
effect on afterload and preload?
– Decrease systemic vascular resistance (afterload)
– Reduce left ventricular filling pressure (preload)
– Reduces Na+retention
ACE inhibitors will _____ survival rate and ______ renal function
Found to increase survival rate
Can decrease renal function particularly in heart failure
patients
_______particularly if you use ACE inhibitors with with aldosterone antagonist
Hyperkalemia may develop
Losartan is an example of an:
Angiotensin Receptor1 Blockers or ARBs
When would we prescribe Lorsartan?
• Actions in heart failure
– similar to ACE inhibitors
• Like ACE inhibitors, beneficial effect on survival
• Alternative for patients that cannot tolerate ACE
inhibitor therapy
What effect does Isosorbide Dinitrate/Hydralazine
Combination have on preload and afterload?
– Decreases preload and afterload
– As a result, increases stroke volume
Does Isosorbide Dinitrate/Hydralazine Combination effect overall survival in heart fail pts?
• Like ACE inhibitors, found to improve survival rate in clinical trials
– Particularly effective in the African American population
When do we prescribe Isosorbide Dinitrate/Hydralazine Combination?
- Used when ACE inhibitors or ARBs not tolerated
* Less development of tolerance with combination
Provides mixed arterial and venous dilation
Isosorbide Dinitrate/Hydralazine Combination
Spironolactone, eplerenone are what types of drugs?
Aldosterone antagonists
What actions do we see from aldosterone antagonists (spironolactone and eplerenone) in heart fail pts?
– Reduce edema
– Decrease fibrosis in myocardium and vessels(counteracts some aspects of adverse remodeling)
• Improve mortality rate and reduce symptoms
– even in the presence of an ACE inhibitor
Negative side effect of aldosterone antagonists?
• Hyperkalemia – necessary to monitor potassium levels
What type of heart fail pts recieve aldosterone antagonists?
• Added with moderately severe to severe symptoms (NYHA III or IV) of heart failure
Action of Beta blockers in heart fail patients:
– Decrease: arrhythmias, oxygen demand, blood pressure
– Prevent disease progression (remodeling)
– Inhibit cardiotoxic actions of catecholamines
– Reduce b1receptor down-regulation
What type of improvements do we see when we put heart fail pts on B blockers?
Improves: Symptoms, ventricular function, mortality rate
What do we need to be cautious of when prescribing B blockers to heart fail pts?
• Can initially worsen cardiac function
– must start at a low dose and gradually increased to a maximum tolerated dose
• Not all b blockers proven useful (genetic variability?)
– metoprolol (succinate; extended release form), carvedilol, and bisoprolol shown to provide benefit
LCZ696 is a _____ and used in comb with:
– neprolysin inhibitor and combine with ARB (valsartan)
a peptidase that degrades endogenous vasoactive peptides including bradykinin, ANPs, and others
– Inhibition increases levels of these substances countering the neurohormonal activation that contributes to
vasoconstriction, sodium retention, and maladaptive
remodeling
• Neprolysin
Non drug therapies for heart fail
Salt restriction • Bi-ventricular pacing • Implantable Cardiodefibrillator Devices (ICD) • Left ventricular assist device (LVAD) • Heart transplant
Treatment of Heart Failure with Preserved Ejection Fraction
Relief of pulmonary and systemic congestion
Address correctable causes of impaired diastolic function
Diuretics to reduce pulmonary congestion and peripheral edema
In pts with heart fail with preserved EF what do we need to be careful of when administering diuretics
– Use cautiously to avoid under filling of LV
– Could reduce stroke volume
ACE inhibitors, b blockers, ARBs in heart fail pts with preserved EF:
have no demonstrated mortality benefit
Role of ionotropic drugs in heart fail with preserved EF
Because contractile function is preserved, inotropic drugs have no role in this condition
