Exam 7: CHF Flashcards Preview

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Flashcards in Exam 7: CHF Deck (30):

Digoxin immune Fab

Antibody that binds Digoxin
Antidote for digoxin toxicity


Digoxin vs digitoxin pharmacokinetics

Absorption, plasma protein binding, onset, half life, therapeutic plasma levels, toxic levels are all higher with digitoxin than with digoxin.
Toxic level is much closer to therapeutic level with digitoxin.
Digitoxin is metabolized by the liver, while digoxin is excreted by the kidneys.


Digitalis glycoside toxicity

Due to the inhibition of the Na/K exchanger (ATPase) in places other than the heart, or too much in the heart
Often first symptoms are in the GI tract.
Can cause bradycardia or tachycardias
CNS effects, digitalis delirium, vision problems
Treatment by Increasing serum K can help by increasing activity of the inhibited Na/K ATPase
Anything that raises Ca or lowers K plasma levels will make it worse.
Another treatment is digoxin immune Fab


Digoxin dosing

Usually given orally, can be given IV
Can give a loading dose to get concentration up quickly, then follow with maintenance dose.
You can also start with maintenance dose and slowly let the concentration rise. This is the safer method.


Digoxin mechanism

Digitalis glycoside
Inhibits Na/K exchanger In cardiac cell membrane (mostly) which decrease ability of cells to pump Na out of the cell. This compromises the gradient used to pump out calcium in exchange for sodium. This leads to increased intracellular Ca concentration, which increases contractility.
Result is an immediate increased stroke volume and cardiac output, this leads to better perfusion of kidneys, which helps relieve edema and congestion of CHF (preload).
Also results in reversal of compensatory sympathetic activity, decreasing rate.
Also decrease HR in standard doses due to sensitization of receptors associated with vagus nerve (Muscarinic receptors in SA node).


What happens to cardiac myocytes as a result of CHF?

Beta receptors in the cell membrane become desensitized
This results in less cAMP production in response to Beta adrenergic stimulation
This reduces Calcium uptake by the sarcoplasmic reticulum, which impairs the ability of the myocardium to contract and to relax
This is the reason that beta blockers can be helpful in CHF. They can prevent this beta receptor desensitization.


Name 4 Non-glycoside inotropic agents. Who receives them?

They are help unreserve for patients refractory to other treatments


Dopamine, dobutamine

non glycoside inotropic agents
They are Beta 1 agonists
Action in the myocytes increases cAMP, increasing contractility.
Also increase HR by stimulating B1 receptors in the SA node


Problems with Dopamine, dobutamine

Increase cardiac O2 demand by increasing contractility and HR
Tolerance is a problem due to down regulation of Beta 1 receptors


Inamrinone, Milrinone

Non glycoside inotropic agents
Inhibit degradation of cAMP by phosphodiesterase, leading to more intracellular Calcium and better calcium exchange in and out of the sarcoplasmic reticulum during contraction/relaxation
Often used once patient is tolerant to dopamine/dobutamine
They also have peripheral vasodilator properties which help relieve CHF symptoms
Like dopamine and dobutamine, they can raise O2 demand


Name 4 ACE inhibitors. Which is not a prodrug?

Captopril, Enalapril, Fosinopril, Quinapril
Captopril is not a prodrug


ACE inhibitors in tx of CHF

Can be used in CHF from early/mild to late/severe
Vasodilation decreases after load, while less retention of Na/water decreases preload/congestion
Aldosterone inhibition can help prevent dangerously low K levels
Actions directly prevent cardiac hypertrophy/stiffening that can be caused by aldosterone and angiotensin


ACE Inhibitors Adverse Effects

Non productive cough due to build up of bradykinin. this is especially bad in CHF because they may already have a cough. ARBs don't have this effect.
They can quickly decrease BP, which can be dangerous if the BP is super high to start with.


Angiotensin II receptor blockers in CHF treatment

Exert many benefits of ACE inhibitors without buildup of bradykinin, cough.
Even better at preventing cardiac hypertrophy, stiffening than ACE inhibitors


Name 3 ARBs

Losartan, Valsartan, Candesartan


Name 4 Diuretics and their classes that are used in CHF

HCTZ (thiazide)
Furosemide (loop)
Spironolactone and Epleronone (mineralocorticoid receptor blockers, spare K)
They help with congestion symptoms, but don't decrease exercise intolerance


What is a special benefit of Spironolactone, Epleronone in CHF?

Inhibition of aldosterone receptors in the HEART helps prevent hypertrophy, stiffening.
They also spare K, which is especially useful with Digoxin on board.


What diuretic would you use if the GFR is very low in a CHF patient?

Loop diuretic (furosemide)


Name 5 direct acting vasodilators

Isosorbide Dinitrate



Treats CHF by dilating arterioles, decreasing after load.



CHF treatment.
Venous and arteriolar dilator, decreasing preload and after load.
Helps combat edema
too much can cause cyanide toxicity
Reflex tachycardia and tolerance are problems



Mostly venous dilator, decreases preload, combats edema
Activates guanylate cyclase, increasing cGMP, causing vasodilation
Reflex tachycardia and tolerance are problems


Isosorbide dinitrate

Mostly venous dilator, decreases preload, combats edema
Activates guanylate cyclase, increasing cGMP, causing vasodilation
More for continued use than nitroglycerine
Reflex tachycardia and tolerance are problems



Recombinant form of the body's own B-type natriuretic peptide
CHF treatment with two effects.
Causes arteriolar and venous dilation, increasing pre and after load.
Also causes diuresis through the increased excretion of Na.
Reflex tachycardia and tolerance are problems


Name 3 Beta blocker examples used in CHF



How can beta blockers help with CHF? (3)

Prevent down-regulation of Beta receptors in the ventricles. That's why it's important to start them early in CHF. If you give it too late, it'll just make things worse.
Also prevent tachycardia, which can paradoxically decrease Cardiac Output (decreased filling)
Decrease release of renin from renal JG cells



Slows HR by inhibiting the so-called “funny” channel current in the SA node
Used in high HR subjects intolerant of beta blockers or as add-on to beta blockers
Used to prevent paradoxical decrease in CO that occurs when HR gets too high.



Beta blocker
Also Alpha blocker
Also an antioxidant


Inamrinone, Milrinone Additional Benefit, potential problem

Vasodilation property is beneficial
May increase O2 demand in the heart, which is not good.


4 effects of digoxin

Increased stroke volume/CO
Increased renal perfusion reducing edema
Decreased sympathetic response
Sensitization to vagus nerve reduces HR