Jul 12, 2021
Acid Reducer Drug Suffix PRAZOLE Pharmacology (Proton Pump Inhibitor Suffix)
Find the Memorizing Pharmacology book here: https://adbl.co/3wAZEmN
The body system we continue to cover is gastrointestinal and omeprazole, esomeprazole, lansoprazole, pantoprazole are all proton pump inhibitors PPIs.
TonyPharmD YouTube Channel here: https://www.youtube.com/c/tonypharmd
Here is the Link to my Pharmacy Residency Courses: residency.teachable.com
Suffixes
Omeprazole (Prilosec) with the -prazole suffix, p-r-a-z-o-l-e suffix is a true proton pump inhibitor, abbreviated PPI. We want to watch out for aripiprazole (Abilify) and brexpiprazole (Rexulti) which are antipsychotics, not PPIs but have the -piprazole ending, p-i-p-r-a-z-o-l-e. Also, some drug cards say the ending is -azole, but that is not an actual suffix, that is a chemical group, using that ending might have you confuse antifungals like fluconazole (Diflucan) for PPIs, so again, the PPI suffix is -prazole.
You will notice that omeprazole (Prilosec) and esomeprazole (Nexium) are very similar and it’s that omeprazole contains two molecules, a left and right mirror image and esomeprazole only contains the left-handed image. In Latin, left is sinister, so the “es, e-s” represents that only left-handed side. Why does that matter? That left-handed molecule is the active molecule.
Mechanism of Action (MOA)
PPIs or “prazoles” work by blocking your stomach’s parietal cells which normally release hydrogen ions contributing to the stomachs’ acidity. This, without the proton pump inhibitor, could lead to heartburn or possible GI ulceration. The proton pump inhibitor blocks the hydrogen/potassium ATPase pump preventing protons from going in the stomach. This raises the pH, making it more basic, and removes the excessive acid.
Indications
We then use proton pump inhibitors to manage heartburn, gastroesophageal reflux disease (GERD), peptic ulcer disease, and Barrett's esophagus. Barrett’s esophagus is a condition where the acid reflux damages the esophagus causes it to redden. Many times patients who are on chronic NSAIDs or anticoagulants have a higher GI bleed risk and a proton pump inhibitor is for prophylaxis rather than active treatment.
Dosing
Traditional dosing is to give the PPI 30 to 60 minutes before breakfast. A concern comes when the medication does not seem to work, but it is not the medication, rather, the patient is taking with or even after breakfast. Make sure you know which is which. Also, H2 blockers work a bit more quickly, so the patient might expect a similar timetable with a PPI, let them know that it will take a bit longer.
Clinical Considerations
Acute use for a few weeks, especially with over-the-counter lengths of time, usually 2 weeks, tends to cause few side effects. Long term, however, we have concerns of B-12 deficiency, increased fracture risk, C. Diff, an opportunistic infection. Again, B-12 deficiency comes because the now less acidic stomach does not do as good a job at absorbing B-12.
Before we start this section, here’s a reminder contrasting enzyme inhibition and enzyme induction. A drug that inhibits and enzyme blocks the enzyme somewhat increasing drug levels making the patient toxic. A drug that induces and enzyme, makes the enzyme work better reducing drug levels and making the patient subtherapeutic.
CYP2C19 inhibition can happen with citalopram (Celexa) and escitalopram (Lexapro), so in this case the antidepressant drug levels can go up leading to QTc prolongation. That’s why we have dosing maximums on citalopram of 20 milligrams daily with someone on omeprazole.
CYP2C19 induction with omeprazole and clopidogrel (Plavix) is one class example as clopidogrel is a pro-drug and by inducing the enzyme to break down more clopidogrel, the enzyme lowers clopidogrel levels. A pro-drug is one that is not quite the drug yet, the liver may have to metabolize it into a drug. Clopidogrel itself is an antiplatelet drug, so reducing the effectiveness of an antiplatelet drug while trying to prevent myocardial infarction (heart attacks) and strokes.
Note, prescribers can use cilostazol (Pletal) for intermittent claudication, a problem with blood flow in the legs where they might be in pain for short distances and the drug allows them to walk further is also a concern. Using lansoprazole or a similar PPI might create a favorable effect.
Some drugs need an acidic environment for absorption like iron supplements and lowering the acidity runs counter to the best situation for iron. Adding ascorbic acid, vitamin C can help.
Cefuroxime (Ceftin) is a second-generation cephalosporin antibiotic with good gram-positive coverage, but one might change to another antibiotic if they see omeprazole in the chart.
Mesalamine (Pentasa) for ulcerative colitis and itraconazole (Sporanox) and antifungal both both benefit from an acidic stomach.
Auto Generated Transcript:
Okay, welcome to the Memorizing Pharmacology Podcast. Today, we're going to talk about 'prazole,' P-R-A-Z-O-L-E. I'm Tony Guerra, a pharmacist and pharmacology and chemistry instructor, and I wanted to talk a little bit about why I use this Word document. Many of these names are very difficult to spell and certainly difficult to pronounce, and I want to make sure that it's clear for you. I did have someone ask, 'Could you just zoom in a little bit?' and that's what I've done. So, from now on, you should see me zoom in. As I'm talking, what I'll do is I'll make sure to underline the errors or these red marks are Microsoft Word trying to correct partial pieces. Because what unfortunately happens with this is that it's looking at a stem or a portion and saying, 'Well, that's spelled wrong,' and it's like, 'No, that's exactly what I want.' So, it's not spelled wrong as much as it's just the way that Word works.
Well, let's look at the suffix 'omeprazole' or 'prazole' of 'omeprazole,' which is brand 'Prilosec,' with the 'prazole' suffix. 'P-R-A-Z-O-L-E,' which is a true proton pump inhibitor, abbreviated 'PPI.' We want to watch out for 'aripiprazole,' brand 'Abilify,' and 'brexpiprazole,' brand 'Rexulti,' which are antipsychotics, not PPIs, but have the 'piprazole' ending, 'P-I-P-R-A-Z-O-L-E.' Also, some electronic drug cards say the ending is 'azole,' but that is not an actual suffix; that is a chemical group. So using that ending might confuse antifungals like 'fluconazole,' where 'conazole' is the stem, brand 'Diflucan' for PPIs. So again, the PPI (proton pump inhibitor) suffix is 'prazole.'
You will notice that 'omeprazole' (Prilosec) and 'esomeprazole' (Nexium) are very similar, and it's that 'omeprazole' contains two molecules, a left and right mirror image, and 'esomeprazole' only contains the left-handed image. In Latin, 'left' is 'sinister,' so the 'E' in 'ES' represents that only the left-handed side. Why does that matter in practice? The left-handed molecule is the active molecule; the right-handed molecule is inactive. So in 'omeprazole,' you have this mixture of something inactive and active, and it doesn't hurt anything; it just doesn't have the active part or it doesn't take out the inactive part. But in 'esomeprazole,' it is only the active part.
The mechanism of action will be our next step. The PPIs or 'prazoles' work by blocking parietal cells in the stomach, which release hydrogen ions, contributing to the stomach's acidity. This, in turn, leads to heartburn or possible GI ulceration. The proton pump inhibitor blocks the hydrogen-potassium ATPase pump, preventing protons from going into the stomach. This raises the pH, making it more basic and removes the excessive acid. Now, a lot of what I said is really clear if you had chemistry. If you do not have chemistry, just the kind of takeaways that you need are one, hydrogen, which is the very first 'H' on the periodic table, can form into ions that make the stomach very acidic. The way we measure that acidity is through the pH scale. Now, pH is the negative logarithm of the hydronium concentration, which is probably more than most need to know. But what the pH scale, you do need to know, is that the lower on the pH scale you are (1, 2, and 3, for example), the very acidic, and the higher on the pH scale (which goes to 14, 12, 13, 14), is alkaline or basic. So when you hear 'alkalosis,' then we're talking about something basic, or if you see 'here basicity,' we're talking about the upper end. The middle is 7, which is neutral. So let's give a couple of examples just to clarify this. Seven is neutral; your blood is a little basic at around 7.35, and milk is a little acidic at a pH of like 6. So why do some people give milk if they've got a stomach acid problem or something like that? Well, the stomach acid is around 2, from 1 to 14, so very, very acidic, and milk is at 6. So you're still bringing it up and making it less acidic, and that's really what matters. So in this case, what a proton pump inhibitor would do is, if there are fewer protons, then we would see that pH creeping up from the traditional 2 in the stomach, and
we'll see that that can kind of cause some problems later. But again, if you haven't had chemistry, the big thing to know is hydrogen ions represent acidity. You might hear them as hydronium, which is H3O+. So you're taking the 'H' and adding it to H2O, which makes H3O+. And again, this is, and again, getting into the weeds, but it's going into the Brønsted-Lowry theory of acid-base if you want to review that in chemistry.
So, what do we use these for? We use proton pump inhibitors to manage heartburn, gastroesophageal reflux disease or GERD, peptic ulcer disease, and Barrett's esophagus, which is where the acid reflux damages the esophagus, causing it to redden. Many times, patients who are on chronic NSAIDs, so again, examples of NSAIDs are like 'ibuprofen' in the U.S., brand 'Advil' and 'Motrin,' or 'naproxen,' which is brand 'Aleve' in the U.S., or anticoagulants, they have a higher GI bleed risk because of those medicines, and 'omeprazole' is for prophylaxis. We're trying to prevent damage to the stomach, and hopefully, that works.
Pharmacokinetics: So standard dosing is to give the PPI 30 to 60 minutes before breakfast. A concern that comes when the medication does not seem to work, but it is not the medication; rather, the patient is taking it with or even after breakfast. And I understand this; I'm busy, I've got three kids, and if I want to remember something, I attach it to something I already do. It's tough to attach something to 30 minutes before breakfast or 60 minutes before breakfast; it's easy to say, 'Oh, I'm eating breakfast; I want to make sure to take my medicine; I'll put those both at the same time.' So that's why it becomes a problem because the patient's just trying to remember it, and their way of remembering it is with meals.
Also, H2 blockers like 'famotidine' (brand 'Pepcid'), and maybe I should put something like that in there, 'F-O-F-A-M-O-T-I-D-I-N-E,' which is brand 'Pepcid.' These work a bit more quickly, so the patient might expect a similar timetable with the proton pump inhibitor.
Adverse effects: Well, if you use it acutely for a few weeks, especially with over-the-counter protocols of just 14 days, it tends to cause a few side effects, no problem. Well, hopefully long-term, however, we have concerns of B12 deficiency, increased fracture risk, C. diff, which is an opportunistic infection. Where does that come from? Where's the B12 deficiency issue come from? Well, when you lower acidity, it's tougher for the body to absorb B12. And then when you take away that acid, which is a barrier to most bacteria, it's very difficult for bacteria to survive in that kind of environment. Then it also makes it easier for other infections to come in.
Interactions: Before we start this section, let's remember or here's a reminder contrasting enzyme induction and enzyme inhibition. So a drug that induces an enzyme makes the enzyme work better, but that can be a problem because if you make the enzyme work better, it reduces drug levels and makes the patient subtherapeutic. So again, just like a submarine is below the ocean, a subordinate is below a superior. Subtherapeutic means that we are below the therapy where we want to be. So again, an inducer makes the enzyme work better at breaking down the drug, and so our drug levels go down, and then the patient doesn't get as much medicine as they need. A drug that inhibits an enzyme blocks the enzyme and somewhat increases drug levels, making the patient toxic. So again, if we inhibit the enzyme, we block it, and we increase those drug levels. And unfortunately, the patient becomes toxic. Induction: The enzyme works better, but we have less drug. Inhibition: The enzyme doesn't work as well, and we have more drug. In either case, we don't have the right amount of drug. But induction and inhibition are very important terms to remember.
Let's use a good example here where we can talk about the SIP enzymes, and I get it, many of you may not have to have SIP enzymes in the level of pharmacology that you're in, but what I want to do is I want to kind of go into this because there's a great contrast between induction and inhibition. So I'll read this to you and maybe make a couple of comments. So SIP 2C19 induction with 'omeprazole' and 'clopidogrel.' 'Clopidogrel' is brand 'Plavix' if you're not familiar with it, is one class example. 'Clopidogrel' is a prodrug, and by inducing the enzyme to break down more 'clopidogrel,' the enzyme lowers 'clopidogrel' levels. Okay, so a prodrug is one that is not quite the drug yet; the liver may have to metabolize it into a drug. 'Clopidogrel' itself is an antiplatelet drug, so reducing the effectiveness of an antiplatelet drug while trying to prevent myocardial infarction (heart attacks) and strokes, obviously not a very good thing.
If you want to kind of look at the brand name 'Plavix,' you can see 'platelet' or the beginning of the word 'platelet,' and then 'Vix' is very similar to the word 'vex.' So kind of vexing platelets, not making them work quite as well as they should, which prevents that clotting from happening in the first place. But I think that's where that name came from. 'Prilosec,' just to kind of let you know, the name was supposed to be 'Losec,' but it was too much like 'Lasix,' so they had to actually change the name. But you can think of 'Prilosec' as 'protons' and 'low secretion.' So a low secretion of protons is a good way to think of 'Prilosec' as a mnemonic.
So let's look at the other side of it. That's induction; you're making an enzyme work better, and the 'clopidogrel' levels go down quicker than we expect, which is not good for the patient. CYP2C19 inhibition can happen with 'citalopram,' which is 'Celexa,' and 'escitalopram,' which is 'Lexapro.' And this is where we kind of get into the weeds with the stems. 'Pram' is not actually a stem. If we go into the long, long list, it's not in there. But we can take a look and see, wait a minute, I remember seeing 'esomeprazole' and 'omeprazole,' and there's that 'S' he was talking about. And again, what's happening here is that 'citalopram' was the first drug to come out, and what that was was the 'R' and the 'S,'
and sometimes you might see it represented as a capital 'R' 'S' like that with a hyphen in front of it. So 'RS citalopram.' But that just becomes confusing for a lot of people, so they just put 'citalopram.' But this is just the 'S,' so instead of putting 'S' hyphen or an 'S' in front of it, which makes it like 'sketalopram,' you know, the Skittles of antidepressants, it they put in 'S-citalopram' to let someone know that that's the 'S' or sinister mirror image side of 'Lexapro.' So 'Lexapro' is the left-handed side only, just like 'S-omeprazole' is the left-handed sided only side of that molecule. So in this case, the antidepressant drug levels can go up because if you're going to inhibit the enzyme, it doesn't break down these drugs as well as we like. Then we can have QTC prolongation. So again, QTC prolongation is that real concern with arrhythmias and things like that. So that's why we have dosing maximums on 'citalopram' of 20 milligrams daily with someone on 'omeprazole' or something like that. So why are these interactions so important? Because we have a patient that is with the induction we have a patient who's trying to prevent a heart attack and with the inhibition, where we have a patient on an antidepressant that just happens to have some kind of acidic condition and all of a sudden we're making them toxic because we're trying to treat their GERD. And so that's why so important if somebody's on over-the-counter medicines to let the prescriber know.
No 'Cilostazol,' which is 'Pletal,' that's used occasionally for intermittent claudication, which is a problem with blood flow in the legs where they might be in pain for short distances, and this drug allows them to walk further. So 'Pletal,' so you can see the word kind of 'platelet' in there to kind of remind you of what that's for. And intermittent claudication again, that problem with the blood flow to the legs. You may know something that's called Raynaud's syndrome where you get the really, really cold extremities, especially the fingertips and things like that. This is quite a bit different than that one. Okay, so again, that's the real concern there. So some drugs also require an acidic environment for absorption. And I talked about the B12 above, but 'cefuroxime,' which is brand 'Ceftin,' and this is the first prefix we've looked at. So 'ceph' in the first generation cephalosporin, it's actually 'C-E-P-H.' But 'Cepheuroxime' or 'Cefuroxime' 'Ceftin' is a second-generation cephalosporin antibiotic. It's got great gram-positive coverage. But again, gram-positive is you can divide bacteria into gram-positive and gram-negative. Gram-positive means that it takes the gram stain because it doesn't have that kind of third layer, and gram-negative, where it doesn't take the gram stain. Just a way to separate out bacteria. 'Mesalamine' and here's one that is a little more important when we get to something like 'bismuth subsalicylate,' but that 'cell' is a root meaning an acetyl cell. There's some kind of salicylic component to it. So acetylsalicylic acid, which is aspirin, would have that 'cell' stem. 'Bismuth subsalicylate' is another concern, but 'that cell' is a concern because you're not supposed to give children aspirin or aspirin-like products. And so that's what makes it like aspirin; it's that 'cell.' But 'misalamine,' which is 'Pentasa,' that's good for ulcerative colitis. And you can see the abbreviation in here for 'ASA,' which is 'aspirin' (acetylsalicylic acid) for ulcerative colitis. And then 'iron supplements,' they all need a good acid environment to work well.
So many different ways that we can have drug interactions and concerns with the 'prazoles,' 'omeprazole,' and so forth. But again, knowing that stem is really going to help you identify it at the most basic level, which is, 'What is this?' It's a proton pump inhibitor that reduces acid.
Like to learn more?
Find my book here: https://geni.us/iA22iZ
and subscribe to my YouTube Channel TonyPharmD here: https://www.youtube.com/c/tonypharmd
Here is the Link to my Pharmacy Residency Courses: residency.teachable.com