Category Archives: Antihypertensives

ACE Inhibitors: The No-Thrill -Prils

Never heard of angiotensin converting enzyme (ACE)?  Check out the post on the Renin-Angiotensin-Aldosterone System (RAAS) for a quick rundown.

ACE Inhibitors (prototype: captopril (Capoten)) are actually very thrilling.  However, the title of this little piece is referring to the other kind of thrill (scratch that, there are too many and some are quite disturbing), vascular thrills, which are palpable vibrations felt over arteries.  You get these when there is turbulent blood flow. Lots of things can cause this, but one of the more common is a sclerotic plaque. Chronic high blood pressure, among other things, increases your risk for developing these buildups, which can lead to arterial blockage and heart attacks.  Avoid the thrills, take the -prils!  Some drug company really needs to hire me for advertising.

As you may have already guessed, ACE Inhibitors like captopril stop the action of ACE (duh). This inhibits the formation of angiotensin II, the protein that responds to a decreased glomerular filtration rate(in the kidneys) and in turn signals the brain and kidneys to release aldosterone (among other things) and constrict the blood vessels. In other words, if the kidneys aren’t sensing the right amount of blood flow coming into them, renin and aldosterone will be released to boost up blood pressure via vascular constriction.   The RAAS is a homeostatic mechanism–it keeps your blood pressure balanced–so this process of constriction and relaxation in the blood vessels is a normal occurence.  But what if your blood pressure is running high?  Inhibiting part of the RAAS will reduce the vasoconstriction, limiting further pressure damage to the vessel walls.  Right on!

I recently attended a lecture on antihypertensives (blood pressure medication) that was led by three (yes, three) pharmacists.  According to them,  ACE inhibitors are the #1 choice for high blood pressure in most patients. Of course, since no drug is entirely safe or selective, there are some patients for which ACE inhibitors are not the best choice.  Other commonly-used drug classes, like beta blockers, are often used as well.

Here are some important highlights of the ACE inhibitors.

1.  Most of their generic names end in -pril.  Enalopril, captopril, lisinopril…you get the idea. Prils for thrills.  ‘Lil -pril pill.

2. Like any antihypertensive, a common adverse effect is hypotension, especially orthostatic hypotension, which is a sudden drop in blood pressure when you sit up or stand up.  As you can imagine, this can be dangerous, so don’t forget to assess BP and educate your patient (or yourself!) before you give a -pril!

3. There are at least two kind of weird things that can happen while taking an ACE-inhibitor:

1) A very small percentage of people have a life-threatening hypersensitivity reaction to ACEIs.  It manifests itself as angioedema, a very quick and scary swelling of the eyelids, mouth, and airways.  This can occur even after the drug has been taken for quite some time, and it is a major deal breaker.  No more ACEIs for you, ever again!  Here, have some [other appropriate drug].

2) Some people, and this is more common, develop a dry, hacking cough.  Turns out that angiotensin II, which actually resides in the lungs, has this other responsibility.  When activated, it regulates the release of bradykinin in the bronchioles.  So if it is inhibited, a lot of bradykinin starts building up and irritating the heck out of your airways. Since there are so many options around, this symptom is generally a good reason to switch to another class of drug.




Prazosin: Cut the Corset!

Ladies, and some Gentlemen, you know what I mean:  Although corsets and bustiers are incredibly sexy, very little can compare to the feeling of utter freedom when they are finally taken off.  Corsets constrict your poor expanding rib cage*, giving you a teensy tiny waist, much like alpha-1 constricts the heck out of your blood vessels!

Well, as you can tell by the title, prazosin (Minipress) cuts the constriction.  It is our prototype for the very carefully-prescribed alpha blockers.  You might remember from an earlier post that blocking alpha results in vasorelaxation, dropping the blood pressure by reducing resistance of the arterial walls.  This is very useful when your blood pressure is way too high.  Unfortunately, because it directly affects the blood vessels (instead of the heart, like beta blockers), it has the serious side effect of rebound hypotension and rebound tachycardia.

But wait, there’s more!

There are also alpha-1 receptors near your bladder.  These work in conjunction with muscarinic receptors to control the flow of urine and prevent urinary retention.

Some disease processes interfere with these systems, however, and one of the more common in men over 50 is Benign Prostatic Hyperplasia, or BPH.

Deutsch: Harnverhalt mit riesiger Blase in der...
Deutsch: Harnverhalt mit riesiger Blase in der Computertomographie. (Photo credit: Wikipedia)

Alpha-1 receptors line the internal urethral sphincter–a smooth muscle that tenses to prevent urine outflow.  In BPH, patients suffer urinary retention as a result of the swollen prostate.  Some other alpha blockers, like doxazosin, help relax the sphincter and restore some urine flow.  Save the kidneys!

See that HUGE grey blob in the picture?  That is a BLADDER.  A hugely distended, probably very uncomfortable, urine-filled bladder.  OUCH.  Thank you, alpha-1 blockers, thank you.

To summarize, alpha-1 blockers:

1) Stop vasoconstriction and relax the arterial walls

2) Relax the internal urethral sphincter

3) Can cause rebound hypotension

4) Can cause rebound tachycardia, because now the heart has to make up for the drop in resistance!

*I know there are many people out there who LOVE corsets, so by all means, do not let me dissuade you!  I don’t want any nerdy (because you are reading this post, which implicates you by association) hate mail (because you love corsets and are feeling militant).  Please.  🙂

Loop Diuretics: Someone Build Me an Ark…

…’cause there’s gonna be a FLOOD!

As you may have guessed, loop diuretics REALLY do their job.  Actually, they tend to do their job a little too well, so they are used only when other attempts have failed or in dire cases.

Their main target is the thick ascending Loop of Henle.  I think that sounds kind of gross, so let’s just call it the ascending loop.  If you remember anything about this target, remember reabsorption.  Loop diuretics inhibit the reabsorption (so promote the excretion) of sodium, potassium, calcium, magnesium, and good old H2O.  Look at all of those precious ions being excreted!!

The prototype for loop diuretics is furosemide (Lasix).  I remember this by thinking how furiously furosemide kicks out all of those cute little ions.

What are the therapeutic effects of furosemide?  Well…

1.  Effectively and quickly lowers blood pressure by reducing blood volume

2.  Gets rid of excess fluid in interstitial spaces

And the adverse effects should be rather easy to guess…

1.  Hypokalemia (this is a big one, and really the main problem with loop diuretics)

2.  Dehydration

3. Hypotension

There are other pros and cons, but these are the main ones.  The most common use for furosemide and other loop diuretics is in heart failure, and you will often see them used in conjunction with another cool drug called digoxin!



Metoprolol: Go For the Beta-1!

Metoprolol (Lopressor*) is the prototype for second-generation, or what I like to call souped-up, beta blockers.  Although propanolol is widely used as well, metoprolol has a feature that makes it a safer choice as an antihypertensive.  Right now (and I do mean 12:00 pm on Saturday, May 25, 2013) it is considered the first line drug for hypertension.

Remember the features of an “ideal drug”?  The one that can never exist?  Well, metoprolol is the more ideal answer to some of propanolol’s shortcomings.  The biggest problem with propanolol is that it’s not selective.  Remember, it is a beta-1 and beta-2 antagonist, so it can cause bronchoconstriction by blocking beta-2!

Metoprolol is selective-ish** for the beta-1 receptors.  Woot!  So it’s safer for more patients.

Let’s have a brief overview of the features of a beta-1 antagonist.  For reference, check out the adrenergic receptors section (and don’t forget we are talking about antagonists!).

Negative Chronotropic:  Beta blockers slow down the heart rate

Negative Inotropic:  Beta blockers make the heart a better pump by easing the strength of contractions, thus conserving it’s oxygen supply and energy.

Negative Dromotropic:  Beta blockers slow the rate of conduction so the heart doesn’t spaz out as much. They are actually classified as antidysrhythmics as well, which we will get to later.

All of these things culminate in Reduced Cardiac Output.  Remember that when you have hypertension, there is a lot of resistance in the blood vessels that the heart has to overcome!  So reducing the cardiac output reduces the pressure against the arterial walls, thus reducing blood pressure.  Yeehaw!

*Metoprolol is actually one of the few drugs with a useful (this may be harsh, but some of them are seriously confusing) trade name.  Drugs that constrict blood vessels or cause a rise in blood pressure are called pressors.  I think of the “pressing in” of the arterial walls.  So, Lopressor reminds me that there is low pressor activity, or low pressure.  So you know it’s an antihypertensive!  I still don’t like using trade names, but this one is handy. That, and people use them all the time in clinical settings.  Sigh.

**Yes, selective-ish.  Don’t forget that NO drug is ever entirely selective.  It always affects something else.  But pretty selective is as good as we can get!

Propanolol: LOL!

Get it?  LOL?  Bahahahaha!  Sigh.  Fine.  Well that’s a great way to remember beta blockers, because every last one of them has a generic name that ends in -lol.  This is a great example of why memorizing the generic names of things, instead of the trade names (these are the capitalized ones I put in parentheses), helps you immensely with categorizing drugs like lightning!

Propanolol (Inderal) is the prototype of 1st Generation Beta Blockers.  Propanolol is still prescribed for many things, including hypertension, angina pectoris, and stage fright.  Although it is very effective, it is not the number one drug of choice.  This is because, bless its heart, propanolol is non-selective. It likes both beta-1 and beta-2 just the same!  Can you think of a reason why this might be a problem?

Let’s start with the main therapeutic features of propanolol:

You already know it’s effects on the heart, because you know what the beta-1 receptors do:

1.  Negative Chronotropic (slows the heart rate)

2.  Negative Inotropic (eases the force of contraction)

3.  Negative Dromotropic (slows the rate of conduction)

And the effect of beta blockade on the blood vessels:

4.  Secondary Vasorelaxation (or reducing the amount of resistance from the blood vessels)

You may also remember that there are beta-1 receptors on the kidneys, so:

5. Renin inhibition (stop kidney/heart-controlled vasoconstriction)

But, propanolol also inhibits beta-2!

6.  Bronchoconstriction (anti-bronchodilation, to be more exact)

7.  Uterine relaxation (For our current purposes, just keep this one somewhere in your mind where you store those “fun facts”.  In general, no one gives much of a hoot about beta blockers’ effects on the uterus.  Sigh.)

Those are all the main effects of propanolol on your body!  In summary, they help relieve high blood pressure by loosening the blood vessel walls and stopping renin release, AND help make your heart a better pump by slowing it, letting it relax, and stopping its “go” signal.  All of this adds up to two main therapeutic uses:

1.  Reduced Cardiac Output, which with a little help, leads to…

2.  Antihypertension

But wait, what about the side effects?  For now, just think about that question.  See if you can come up with four possible adverse effects of propanolol, just by looking at what it does!

Beta Blockers: Take a Chill Pill

Beta antagonists, which pretty much everyone just calls beta blockers (and which one of my favorite teachers calls “The Wall”), reduce cardiac output by affecting the heart.  Some of the newest ones, like carvedilol, actually cause vasodilation (can you guess how?), but our prototypes, propanolol and metoprolol, do not.  They are more correctly secondary vasorelaxers (which is a phrase I just made up).  Remember, beta-1 receptors increase cardiac output by making the heart work harder. This also forces more blood through the blood vessels and causes them to resist.  When they are blocked, the heart doesn’t pump blood quite as forcefully.  So, a pure beta blocker, among other things, prevents the smooth muscle from feeling the need to squeeze the heck out of your arteries.  This allows blood to flow more freely!

You may also remember that beta blockers are negative dromotropic, that is, they block some of the electrical conductivity of the heart at the sinoatrial (SA) and atrioventricular (AV) nodes.

Don’t forget that beta-2 is really important for the lungs!  So beta blockers that are non-selective, that is, block both beta-1 and beta-2 receptors, can bronchoconstrict.  We have to be very careful that no one with breathing problems gets these by mistake!

In this section is your overview of three of the various sympatholytics:  the three generations of beta blockers.