Let's go on to heart failure.
Heart failure is kind of a sister disease to angina treatment
because we use many of the similar kinds of treatments.
Now, how we treat heart failure is a little bit different.
We can use inotropes and those inotropes include
cardiac glycosides, beta agonists, and PDE inhibitors.
We can use vasodilators like the PDE inhibitors,
nitrates, and the loop diuretics. And we can use
classic cardiac remodelling agents like loop diuretics,
ACE inhibitors, ARBs, spironolactone,
and the new nesiritide.
Let's move on to the cardiac glycosides.
The prototypical agent in this drug class is digoxin.
There are other cardiac glycosides out there. Digoxin is derived
from the digitalis plant, it's also called the foxglove plant.
It inhibits the sodium-potassium-ATPase pump.
This results in an increased in sodium levels in the cell.
This results in less excretion of calcium through the
cotransporter and higher levels of calcium within the cell.
With higher levels of calcium within the cell, you have
increased calcium release from the sarcoplasmic reticulum.
Now, the strength of contraction is going to be increased
because you have more calcium.
So, strength of contraction is proportional to
you'll also have a reduction in heart rate.
Digoxin reduces symptoms of heart failure,
and it reduces hospitalization due to heart failure,
but it does not prolong life.
This is based on major studies looking at
this particular agent in heart failure.
Dosing. It has a very narrow therapeutic window.
So, we actually have to monitor digoxin levels in patients.
The drug can accumulate in the body, so that's why
we monitor the serum levels. You can get digoxin toxicity.
This beautiful picture here is just a picture of the
foxglove plant, which actually grows as a weed where I grew up.
Interactions of digoxin. It interacts with quinidine,
which is also derived from a similar plant.
The toxicity is increased with low potassium levels,
and low magnesium levels, and low serum calcium levels.
So, when you're going to administer digoxin to a patient,
make sure you check the electrolytes.
Toxicity can also result in arrhythmia,
nausea, vomiting, and diarrhoea.
The arrhythmia is occuring due to
intercellular calcium overload.
How do you treat it? Number 1, correct your electrolyte
abnormality. Number 2, we can give antiarrhytmic drugs.
Lidocaine, phenytoin and propranolol
are some of the agents that we use.
There is actually a product called digibind,
which is fragments of binding material that bind the product
or bind the digoxin in the serum and bring it out of activity.
We do not use antiarrhythmics in patients who have heart block,
because the antiarrhytmics are not gonna help them.
Consider pacemaker therapy. Now, at one time,
we used to use a ton of digoxin, and at that time,
we used to see a lot of patients coming in
with significant heart block from digoxin toxicity.
We used to get maybe one or two a night in our hospital,
and so we used to use temporary pace in quite a bit.
With the reduction of use of digoxin over the years,
we are doing less and less of this.
Let's move on to beta 1 agonists. These drugs are mostly used
in the intensive care unit or in the coronary care unit.
These are IV drugs. Dobutamine and dopamine.
They are not appropriate for chronic long term failure,
because these drugs are subject to tolerance. They can also cause
arrhythmia so we don't like to use them if we don't have to.
There is no oral version of this medication. So, taking a pill
of this particular drug is just not an option.
Milrinone is a phosphodiesterase inhibitor that is
now being used in heart failure.
Once again, this is an ICU or CCU drug.
It has positive inotropic effects
because it releases cyclic AMP by
inhibiting the PDE3 molecule.
This increases intracellular levels of calcium.
And by increasing intracellular levels of calcium,
you have an increased strength of contraction or inotropy.
Now, remember the word inotropy comes from
the Greek God Inos who is the god of strength.
So, whenever you hear inotropy,
your ino, that's strength of contraction.
That is a vasodilatory action that milrinone has as well,
and we think that it's having a direct action right at the level
of vascular smooth muscle. It can be arrhythmogenic, and so
we tend to avoid it in long term chronic heart failure patients.
It can actually increase mortality in chronic heart failure.
So, it's really not a great choice in those patients.