Flashcards in Drugs for CHF Deck (39):
What are the hemodynamic effects involved in heart failure?
(describe the process from low CO to romodelling, hypertrophy and apoptosis)
Decreased CO leads to:
1. decreased carotid firing- increased SNS- increased preload, HR and contractility
2. decreased RBF- renin release- increased AngII--increased afterload (volume and PVR)
3. Combo of RAAS and SNS effects leads to remodeling which weakens the walls of the heart and can lead to more problems
Why is there increased afterload in a failing heart?
Why is this a downward spiral?
The decreased CO activates SNS and RAAS which both increase SVR to maintain adequate blood flow.
Long term this is bad because the heart has to work harder to pump against the increased afterload. If there is already heart failure, the CO is decreased more.
What increases preload in a failing heart?
Preload is dependent on intraventricular pressure and volume. It will increase in situations of low perfusion to maintain tissue blood flow.
This is good short term, but long term, the heart cannot respond to increased filling with increased SV (frank-starling)
What 3 things are chronically elevated in chronic heart failure? What long-term changes in the heart occur as a result?
3. ang II
This leads to remodeling, fibrosis and hypertrophy
What are the 3 main goals for acute heart failure? What drugs can accomplish this?
What are the risks?
1. maintain BP
2. improve stroke volume
3. decrease congestion
1. ionotropic agents
5. PDE inhibitors
(you want to decrease afterload, increase CO)
What are the 3 main goals for chronic heart failure?
What drugs are used?
What are risks?
1. alleviate symptoms
2. prevent arrhythmias
3. inhibit remodeling
1. ACEI, ARB
What drugs are used for acute HF?
1. beta-agonists (ionotropic)
5. PDE inhibitors (milrinone)
What drugs are used for chronic HF?
1. ACEI and ARB
What are the 3 major effects of digoxin?
1. increase ionotropic effects directly
2. indirectly decrease sympathetic tone
3. indirectly increase vagal tone
What is the mechanism of action of digoxin?
What is the overall effect?
1. It binds Na/K ATPase inhibiting Na from pumping out and K from pumping in.
2. Na builds up in the myocyte reducing the gradient for Na/Ca exchanger which increases intracellular Ca
3. Increased Ca is taken up by the SR and is available for subsequent contractions
Overall effect: increased contractility
What does digoxin do to the AP duration in atria and ventricles?
It shortens it due to the increased resting potential and increased extracellular K.
It can induced delayed afterdepolarizations due to increased Ca leakage from SR
How does digoxin decrease sympathetic tone? What are the overall results?
1. reflex is withdrawn after increased CO
2. additional withdrawal of elevated sympathetic tone due to increased baroreceptor sensitivity.
vasodilation and, electrophysiological effect
What are the 2 main pharmacological effects of digoxin on the heart?
1. increased contractility--> increased CO, decreased EDP due to increased velocity of shortening
2. decreases automaticity of SA and AV nodes due to increased vagal tone and decreased sympathetic activity.
How is digoxin absorbed and excreted?
What is the half life?
Taken IV in emergencies or oral.
Excreted renally as unchanged drug.
Half life is 36-48 hours if there is normal kidney function.
The principal reservoir for digoxin is _________ not _____ so dosing should be based on _______.
skeletal muscle and not fat so dosing should be based on lean body mass.
What is digitalis intoxication? What are common signs?
Who is likely to get digitalis intoxication?
What is the treatment?
1. arrhythmias (specifically fast atrial with AV block)
2. nausea, vomiting, anorexia, diarrhea
3. disturbances of cognitive function (vision problems, see yellow)
Usually in older patients with decreased renal function.
Treat with anti-dig antibody treatment
What are the serious electrophysiological consequences of digitalis intoxication?
What are the cause of many of these?
1. Ectopic beats of AV junction/ ventricle
2. first degree AV block
3. slow ventricular rate with A. fib
4. accelerated AV junctional pacemaker
Caused by delayed afterdepolarization due to Ca leakage from SR sufficient to reach threshold
What are the major drug interactions with digoxin?
1. quinidine (Na channel blocker)- elevates serum digoxin by decreasing renal clearance and volume of distribution
2. verapamil, diltiazem, amiodarone, flecainide, spironolactone
3. drugs that cause hypokalemia because this will potentiate the arrhythmia potential of dig (diuretics, ampho B, steroids)
What are the 2 main therapeutic uses for digoxin?
1. chronic CHF- reduces symptoms but no mortality improvement
2. Terminate reentrant arrhythmias of the AV node
What diuretics are indicated in the treatment of most patients with heart failure?
What diuretics are useful as single drugs only in patients with mild heart failure?
What is the purpose of prescribing a K sparing diuretic for someone in heart failure?
This is done if they are on a K wasting diuretic (loop, thiazide) and there is fear that they will be hypokalemic.
What diuretic drug has been shown to decrease mortality for chronic heart failure (not just relieve symptoms)?
Spironolactone- it is an aldosterone inhibitor that can block long-term maladaptive remodeling
Who are the recommended patients for digoxin?
1. HF and atrial fibrillation
2. symptomatic despite ACEI and BB
What are the potential adverse effects of spironolactone?
1. Hyperkalemia (esp. if also on ACEI) which can contribute to arrhythmias
2. GI ulcers, gastric bleeding
3. gynecomastia in men
What drug should be given to all patients with LV systolic dysfunction HF if they can tolerate it?
ACEI- for mild, moderate and severe HF
Frequently combined with:
What are adverse effects of ACEI?
2. hyperkalemia (leads to arrhythmia)
3. worsening of renal function
4 .cough and angioedema
What drug should you be sure to give at a very low dose (specifically on the first administration) due to abrupt BP drops?
What 4 precautions should be taken when administering ACEI?
1. Start with a low dose and work up (patients can experience extreme drop in BP especially on the first dose)
2. decrease dose if there is decreased renal function (like bilateral renal artery stenosis)
3. be aware of small rise in serum K+
4. substitute with ARB if there is a cough
Do ACEI reduce venous or arterial tone?
Both due to the inhibition of Ang II. This is what makes them beneficial short-term to restore cardiac function (decrease afterload, preload)
What are the major actions of Ang II that get blocked by ACEI?
1. bradykinin doesn't get cleaved--> vasodilation
2. decrease SNS to decrease PVR
3. decrease aldosterone - reduced Na/H20 retention
4. reduce intrarenal vasoconstriction
5. decrease AngII generation in the heart where it plays a role in remodeling and ventricular hypertrophy
Why might you have to convince patients to continue the course with BB?
At first BB will reduce EF. You need to encourage them to "stay the course" because eventually EF improves (about an month) and there is a mortality benefit.
Do nitrates dilate arteries or veins?
Are they used in acute or chronic CHF?
Both but more effective with veins. This allows them to decrease preload and afterload.
The effect on arteries is modest so there is little sympathetic reflex effect on the heart.
They are used in both acute and chronic CHF
Why is hydralazine used to treat heart failure?
Does it work on arteries or veins?
Does it treat acute or chronic?
It is used in the treatment of acute heart failure to reduce the afterload by reducing vascular resistance.
It has minimal effect on veins so it is useful to combine with nitrate.
If you have an AA patient with heart failure and they are not responding to ACEI, BB, digoxin or diuretics, what should you try?
BiDil- hydralazine and isosorbide dinitrate
The combination has mortality benefits**
What class of drug is dobutamine?
What is the mechanism of action of dobutamine?
What receptor does it bind to?
What are the effects in cardiac muscle and smooth muscle?
B1 and B2 agonist
It binds a Gs receptor which increases cAMP--> increases PKA-->
1. increased calcium and contractility in cardiac muscle
2. myosin light chain kinase relaxation of smooth muscle
What scenario would encourage the use of dobutamine?
in acute heart failure you would use IV infusion for a short term treatment
What is the mechanism of action of dopamine when treating heart failure?
It acts on D1 receptors, B1 receptors and at large enough doses A1 receptors as an agonist.
It has little effect in treating systolic LV dysfunction.