So, first let’s talk about first line diuretics.
As you can imagine, there have been a lot
of randomized double-blind controlled trials
testing different drugs for control of hypertension.
I’m going to only tell you about the ones
where there’s excellent data that says,
“These drugs really work.” Not only do
they decrease blood pressure, but they also
decrease the risk for stroke and for heart
attack and kidney failure and all the things
we talked about before that are the end result
of uncontrolled high blood pressure.
This little diagram is a diagram of the…
of course, multiple times magnified of the
kidney tubule system that makes urine. It
turns out that diuretics or drugs that increase
urine flow are also anti-hypertensive. And
there are three different categories of diuretic,
but the one that works best for controlling
blood pressure is the one that works in the
proximal tubule of the kidney, the Thiazide
So, Thiazide diuretics have been known for
decades to be very excellent in controlling
blood pressure. They're generic, they're
very inexpensive and they're usually very,
very well tolerated. They increase urine flow
a little bit, not a huge amount, but they
also have effects on the blood vessels so
that they decrease peripheral resistance and
thereby, they drop the blood pressure.
There are a number of Thiazide diuretics,
and again, as I said, doctors will decide,
“Oh, this is the one I like best because
my patients tolerate it best, there’s less
side effects or it’s less expensive, it’s
easier to get.” The one that I use, as you
can see down there, the one that says HCTZ,
that stands for hydrochlorothiazide. And the
pharmacist know when I write a prescription
for HCTZ that that’s what we’re getting.
Chlorthalidone is another one that’s quite
popular. It’s actually a little more effective
at lowering blood pressure compared to hydrochlorothiazide,
but has more side effects. And here’s a
little data from a scientific study in which
patients who are on hydrochlorothiazide with
reasonable control of blood pressure were
switched to chlorthalidone and what you see
from the left to the right is that when they
switch to chlorthalidone, their blood pressure
Unfortunately, the side effects were also
more increased, particularly, low blood potassium.
Potassium is an essential mineral in our blood.
It determines a good muscle function, good
nerve function, a whole variety of important
biochemical functions relate to having a good
potassium level. When your potassium level
is low, you may have cramps and fatigue and
actually, you may even have electrical short
circuits in the heart - arrhythmias. So, we
try not to have people have low potassium
and that’s one of the problems with chlorthalidone.
It lowers potassium more than hydrochlorothiazide.
Hypokalemia or low potassium is one of the
commonest side effects with diuretics. Why?
Because the diuretics cause potassium to be
washed out in the urine. So, for that reason,
I don’t usually use chlorthalidone. I usually
use hydrochlorothiazide and I try and use
the smallest dose possible so I decrease the
risk for high… for hypokalemia and the high
risk kinds of complications that occur with
As you see here, the risk of the problems
with hypokalemia, it’s dose related. So,
I try and give the smallest dose tolerated
that controls the blood pressure and that
gets me good control of the blood pressure
without a lot of side effects.
Another side effect from thiazides is that
they have a tendency to push people towards
diabetes. So, if you are an inherited person
where lots of folks in your family, you have
an inheritance for diabetes, lots of family
members with diabetes, of course, thiazide
diuretic might not be the best choice for
you because it might push you into having
overt or clinical of diabetes. And if you
have a tendency towards gout, thiazide diuretics
can cause gout too.
So, when we talk to the patients, we usually
want to find out, do they have any of these
risks. Have they had problems with hypokalemia
in the past with other drugs, are there a
lot of diabetics in their family, have they
had gout or lots of family members with gout?
Thiazides wouldn’t be the first choice in
somebody who had one of these kinds of complications.
And if there’s kidney damages ahead of time,
we usually don’t use diuretics because they
can worsen the kidney damage.
Now, there’s a complex series of actions
from the different kinds of blood pressure
medicines and what this diagram shows you
is that some of the medicines, on the arrow
on the left hand side, decrease peripheral
vascular resistance. The thiazides do that,
I just mentioned that.
On the other hand, drugs that I’ve mentioned
before in the arena of ischemic heart disease,
Beta Blockers decrease the cardiac output
and decrease the heart rate and they drop
the blood pressure in that fashion. And then,
there are drugs that actually quiet down the
‘oomph’ of the heartbeat, the contractility
of the heartbeat, Beta Blockers can do that
and some calcium blockers do that. And that
also decreases the blood pressure.
And by the way, as you’ll find out later
in this lecture, it usually requires more
than one drug to control blood pressure. Very
few people are controlled with one drug. So,
you often use a combination. You might use
a combination of a thiazide to decrease peripheral
vascular resistance and, for example, a Beta
Blocker in order to decrease the cardiac output
a little bit, or other combinations. And we’ll
talk a little bit about the favorite combinations
in a moment.