Let’s start off with the diuretics. And let’s start with the
most simple of diuretic mechanisms, the osmotic diuretics. The most commonly used osmotic diuretic is mannitol.
It literally pulls water into the collecting tubules. It also works very very well in intracranial hypertension. Now, as a high blood pressure pill,
it doesn’t work that well, in particular and in clinical use,
we don’t use it much at all. We use it a lot in people who have had
some kind of a head injury, and we are trying to reduce the intracranial pressures. It is an important medication and it will be on your exams,
just remember clinically we don’t use it that much. The next class of drugs
are the carbonic anhydrase inhibitors. The prototypical drug in this drug class is acetozolamide.
We don’t use it that much in hypertension, but we do use it in other areas. Now, what it does,
is it inhibits carbonic anhydrase, leaving more sodium, bicarbonate, and chloride
in the collecting tubules. Now, this results in a metabolic acidosis.
So, it is used in altitude sickness. It can cause low potassium or hypokalemia,
and it can cause low sodium or hyponatremia. And finally, it can also cause
low chloride levels or hypochloremia. In terms of using it for altitude sickness,
how it works, is by causing a metabolic acidosis. You are automatically protected from the hypocapnia and
respiratory alkalosis that you would develop at high altitude. So, it tends to help quite a bit and I personally
have used it when I was climbing mountains in Peru. So, certainly it’s a very good drug for altitude sickness, not so much for hypertension,
so we don’t use it that much in high blood pressure. The loop diuretics are very powerful diuretics.
The prototypical drug is furosemide, sold as Lasix all over the world. One of the
newer loop diuretics is ethacrynic acid or Edecrin. Ethacrynic acid is often used
when people have an allergy to furosemide. Finally, there is another loop diuretic called bumetanide. It’s not particularly used, but if you have
allergies to the other two medications, we can resort to it. How it works, is by reducing sodium
reabsorption in the thick ascending loop of Henle. That’s a good exam question by the way,
so I want you to remember that loop diuretics work in the
thick ascending loop of Henle. And so it’s going to be very powerful because it alters
the countercurrent mechanism that you see in the kidney. Now, if you just review your
physiology lectures by Lecturio, on the kidney, you’ll see how powerful
the countercurrent mechanism is in the kidney, and when you disrupt that countercurrent mechanism,
and you disrupt the way that it works with the loop diuretic, you get quite a massive diuretic effect.
So, it is the most powerful of the diuretic class. Of course, there’s downsides and that includes low potassium.
And in some cases, you may also get low sodium, although that’s a lot less common. Furosemide is a very effective drug in renal failure as well,
so you’ll often see nephrologist prescibe it in certain circumstances. The next class that I want to discuss
are the thiazide diuretics. Now, these diruetics are a little bit weaker than the
loop diuretics, but they are used more often. And in fact, we sometimes combine the diuretics
right inside the pill with ACE inhibitors and ARBs. The most commonly used in North America is hydrochlorothiazide.
The most commonly used in the UK and Europe is indapamide. Both are used in both places. Indapamide is purported to be
better tolerated, and that’s what a lot of people believe. I personally haven’t found that to be the case. But remember
that there are people who are going to have allergies to hydrochlorothiazide, and that’s why we use indapamide. For your perspective, you need to know both.
So, just remember that they are both thiazide diuretics. There is a third diuretic that I want to mention
which is called metolazone. And we’re going to mention it later in the lecture
when we talk about heart failure. The next class of diuretics are quite interesting
because they are potassium sparing diuretics. Now, up until this point, every single one of the
diuretics that we talked about cause low potassium. This is unique because of the way it works.
It does not cause low potassium. And when you have poeple who are prone to having
low potassium on diuretics, you get quite concerned. Now, what happens with amiloride is that it inhibits
sodium reabsorption in the collecting tubule. Now, sodium and free water are still excreted,
but the potassium stays in the body. There are three channels that we want to talk about
where amiloride could have an effect. There is the ENAC or the epithelial sodium channel.
There is the NHE1 which is the sodium-hydrogen antiporter that works in the heart in heart failure,
and it also works in the kidney. The ASIC or acid sensing ion channel inhibition is also
another potential action that amiloride works through. There is a low risk of hypokalemia for obvious reasons,
and it does cause a metabolic acidosis. The other potassium sparing diuretics
are spironolactone, which is sold as Aldactone. And it’s a very powerful aldosterone blocker.
It inhibits sodium reabsorption. And it actually is the only diuretic to have been shown
to reduce mortality in heart failure. So, it’s a very very good drug, and it’s one of our
main drugs that we use in high blood pressure control. Now, one of the downsides of a drug like spironolactone
is that it does potentially raise your potassium level. And one of the most commonly used antihypertensive
medications are either ACE inhibitors or ARBs which also raise the potassium level. So, although it’s a great drug, we don’t use it that much because the patient is already on a drug that raises
potassium, and we don’t want to raise potassium too much. The interesting thing two is that
it has antiandrogen effect. So, in women who have hirsutism or you know,
when they grow a moustache and have male characteristics, you can actually give them low doses of aldosterone,
and that helps with those musculin kind of characteristics. The testosterone is very active in the skin
in those patients. So, you can either use an antitestosterone treatment,
which has lots of problems, or you can use something simple like Aldactone. Triamterene is another potassium sparing diuretic.
It inhibits sodium reabsorption as well. It acts in the collecting tubule,
and it also works through the ENAC channel. It has got a low risk for potassium or hypokalemia,
it can cause hyperkalemia in some patients. Once again, this drug causes also a metabolic acidosis. One of the things that you have to be
particularly aware of with triamterene, is it can cause renal stones or nephrolithiasis.
And those stones are going to be calcium oxalate stones. So, that’s another good exam question.
What kind of renal stones can you get from triamterene? And the answer is calcium oxalate.