Let's move on to direct vasodilators
for blood pressure control.
There is a lot of different drug types
that we can talk about.
Let's first deal with calcium channel blockers.
Calcium channel blockers are divided into two major groups.
The dihydropyridines and the non-dihydropyridines.
We also have nitrodilators. Now, these are agents
that act somehow through nitric oxide.
We also have potassium channel openers which are perhaps
more interesting from a test or exam point of view
than it is from a clinical point of view.
And then we have the new dopamine or D1 receptor agonists.
These also are going to be interesting from an exam point of
view, but from a real world practice point of view,
they are not used this often.
So, we will go through each of these classes
in a little bit more detail now.
Let's talk about the direct vasodilators,
specifically the calcium channel blockers.
And I want to compare and contrast the dihydropyridine
class with the non-dihydropyridine class.
So, the dihydropyridines refer to nifedipine and amlodipine,
the non-dihydropyridines refer to diltiazem and verapamil.
You do need to know which drugs go in which class.
Now, both of them work on calcium channels.
But the dihydropyridine class of drugs tend to work more
on the blood vessels in the periphery, whereas the
non-dihydropyridine class tend to work on blood vessels
and in the heart. So, if you think about it, there's actually
going to be some advantages to the non-dihydropyridines,
because the dihydropyridines cause reflex tachycardia.
So, let's think about that.
When you cause a relaxation in the periphery,
you drop blood pressure.
The heart thinks through its baroreceptor reflex that the
body is not getting enough blood, and so it tries to pump faster.
That's why you get a reflex tachycardia
with a peripheral vasodilator.
Now, if you also affect the heart with your calcium channel
blocker, you're going to block that reflex tachycardia.
So, non-dihydropyridines don't cause reflex tachycardia.
And in fact, one of the drugs, verapamil is often used
in tachydysrhythmias. So, these are great drugs,
they work quite well for preventing reflex tachycardia.
Side effects of both. Constipation. You will get more
constipation from the dihydropyridines than you will
from the non-dihydropyridines. Fatigue is relatively rare
and peripheral edema is actually quite common.
And the edema is going to be a dose related phenomenon.
So, the higher the dose of your medication,
the higher the risk of edema.
Both classes of drugs are going to interact with grapefruit.
So, you have to tell your patients
don't eat grapefruit anymore when you're on these drugs.
Let's go on to the more exoteric drugs in hypertension
control. Let's first deal with potassium channel openers.
So, there is several of them on the market.
Minoxidil, diazoxide and others.
They dilate arteries by affecting the calcium channel
metabolism. So, they open up potassium channel,
and that causes a reduction in calcium influx.
When you have a reduction in calcium influx,
there's less contraction of that blood vessel.
Like any peripheral vasodilator,
you're going to probably get a reflex tachycardia
because you want to try and increase cardiac output,
or at least the heart does.
You may also have a bit of
renin release with these medications.
Side effects also can include
sodium retention and palpitations.
Let's move on to nitrodilators.
I have them listed here in green.
They usually cause a significant baroreceptor reflex.
Additional agents are often recommended
when you use these medications. So, sometimes
we'll combine them, either with a beta blocker,
or perhaps with a non-dihydropyridine
calcium channel blockers.
The side effects often include headache and flushing.
And in fact, most of the time, patients will complain of
some headache, particularly when they
first start these medications.
It's really important, really really important that we do not
use these medications with erectile dysfunction medications.
Now, I want you to go back and take a look at
our autonomic nervous system lecture,
because I mentioned how combining drugs like Viagra with
drugs like nitroglycerine can be potentially fatal.
Remember, once again, do not use these drugs with
erectile dysfunction medications.
We also have to be very careful using these drugs
in patients who have endothelial dysfunctions.
Okay, what does that mean? So, if you take a look at the
blood vessel, the blood vessel has several layers within it.
And the innermost layer is called the endothelium. When
you release nitric oxide on the inside of the blood vessel,
the nitric oxide works through the endothelium
to cause vasodilation.
If you remove the endothelium, there is a
paradoxical spasm of that part of the blood vessel.
So, in patients who have endothelial dysfunction,
you can actually induce vascular spasm,
and you can actually make things worse. This is important
both from an angina treatment point of view,
and from a blood pressure point of view.
The other problem that we have with this medication
is that tachyphylaxis is very common.
Tachyphylaxis is wearing off of the effect of the drug
or reduced activity after prolonged exposure.
So for example, with our nitro patches,
we only apply them 12 hours a day
because we need the patient to have
an on-off kind of schedule
so that they don't develop resistance or tachyphylaxis.
This is a new class of drug.
The peripheral dopaminergic antihypertensive medication.
It just recently came onto the market in Canada,
it has been in the United States for a couple of years,
and in Europe for several years as well.
It is an intravenous medication
and it acts at the D1 receptor.
It has prompt arteriolar dilatation and the
duration of action is anywhere between 5 and 10 minutes.
It's used in hypertensive emergencies only.