Chapter 26: GERD & Peptic Ulcer Disease Treatment

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Welcome to the Deep Dive.

We take complex source material.

And pull out what you really need, right?

Exactly.

The essential high -value stuff.

Today, it's GI Pharmacology.

Yep.

Focusing on the heavy hitters, G, R, D, and P, U.

Vascular esophageal reflux disease and pyptic ulcer disease.

And our mission,

well, it's to give you that structured review.

Focusing on the mechanisms, the clinical pearls, the key warnings for advanced practice students.

It's definitely a vital area.

These conditions are, I mean, they're everywhere.

They really are.

You're looking at, what, maybe 18 to 28 % of US adults having GRD symptoms every week.

Wow.

And that's symptoms, sometimes with erosion, sometimes without PUD.

Pyptic ulcer disease is also super common, often comes back again and again.

Damage to the lining from acid.

So the goal with the drugs is pretty clear then.

Yeah.

Three main things.

Relieve the symptoms, obviously.

Help the mucosa heal.

And crucially prevent the really bad stuff.

Like GI bleeds.

GI bleeding.

Barrett's esophagus.

Things you really want to avoid.

Okay.

That sets the stage perfectly.

So before we jump into the drugs, let's talk about what's actually going wrong.

What are we trying to fix?

Starting with GERD.

Right.

GERD.

The main problem is the lower esophageal sphincter, the LES.

The valve at the bottom of the esophagus.

Exactly.

It's either just weak all the time or more typically it has these moments where it just relaxes when it shouldn't.

Transient relaxations.

And that lets stomach acid.

Flash back up.

Reflex.

And anything that increases pressure in your abdomen makes this way worse.

Like obesity or pregnancy.

Perfect examples.

Obesity, pregnancy.

Even tight clothing sometimes.

And you mentioned common triggers in the chapter.

Things people eat or drink.

Oh yeah.

Table 26 .1 lays it out.

Fatty foods are a big one.

Chocolate, caffeine, peppermint, spearmint.

Things that taste good.

Unfortunately, yes.

They're known to decrease that LES tone.

Make it looser.

And medications too, right?

Definitely can't forget those.

Calcium channel blockers for instance.

Nicotine's a big one.

Some nitrates.

They all can weaken that barrier.

So it's the LES relaxing.

It's mostly that, but it's also a failure of the body's defenses.

You know, the LES is one defense.

But you also have esophageal clearance peristalsis pushing stuff down bicarbonate in your saliva neutralizing acid.

And then there's the nucosal protection itself.

Bicarbonate from glands in the esophagus.

If gastric emptying is slow maybe from smoking or a high fat meal, that backup just adds to the problem.

That really clarifies G -E -R -D.

Okay, let's switch gears to peptic ulcer disease.

P -U -D.

You mentioned stress ulcers, but mostly it's H.

pylori or NSAIDs.

That's right.

Those are the two main culprits by far.

H.

pylori infection and NSAID use.

So how do they actually damage the stomach or duodenal lining?

Let's start with H.

pylori.

Okay, H.

pylori is this little gram -negative spiral rod.

And it's got this amazing survival trick.

Which is?

It produces an enzyme called urease.

Urease breaks down urea, which is around, into ammonia and carbon dioxide.

Ammonia.

That's basic.

Exactly.

It creates this little non -acidic cloud around itself, neutralizing the stomach acid right there.

So it can survive where it shouldn't.

Survive and thrive.

It burrows into the mucus layer, actually increases acid production nearby,

releases enzymes that damage the cells, and that leads to an ulcer.

Nasty little bug.

And NSAIDs, how do they cause ulcers?

It's different, right?

Totally different mechanism.

Well, two mechanisms, really.

First, NSAIDs themselves are weak acids, so they can cause some direct irritation just by being there.

Okay, direct damage.

But the bigger issue, the indirect harm, is that they block the KeOX1 enzyme.

KeOX1.

That's important for?

Prostaglandins.

Specifically, the protective prostaglandins in the stomach.

These prostaglandins normally tell the stomach to produce protective mucus and bicarbonate.

So NSAIDs shut down the stomach's own defense system.

You got it.

Block KeOX1, you block those protective signals, and the lining is left vulnerable to acid damage.

Okay, so we understand the why.

Before we even get to prescriptions, there's a foundation of lifestyle changes for both GOD and POD.

Absolutely critical.

Can't skip this step.

We're talking weight loss, if needed.

Definitely quitting smoking, cutting back on alcohol.

Avoiding those trigger foods we mentioned.

Yes.

Identifying and avoiding personal triggers.

And some simple behaviors make a huge difference.

Elevating the head of the bed for GRD.

Right, using gravity.

And avoiding lying down too soon after eating.

Give it like three hours between your last meal and hitting the sack.

These seem basic, but they really work.

They significantly help with mild symptoms, and honestly, they help the medications work better even in severe cases.

It's foundational.

Okay, foundation laid.

Let's get into the drugs.

The main acid suppressing classes.

Antacids, H2RAs, and PPIs.

Where do antacids fit in?

Antacids are your quick fix.

Think Tums, Rolades, Melanta.

Their job is simple.

Neutralize the hydrochloric acid that's already there.

Just direct chemical neutralization.

Pretty much.

Raising the pH also indirectly stops pepsin, another stomach enzyme, from working.

But the key things are immediate relief, but it doesn't last long.

So when do you use them?

Only for mild, infrequent symptoms, like heartburn less than twice a week.

Or maybe as a rescue dose if symptoms break through other therapies.

And we need to warn patients about side effects, depending on what's in them.

Definitely.

It's classic pharmacology.

Aluminum causes constipation.

Magnesium causes diarrhea.

Often they're combined to try and balance that out.

Old Malox or Melanta.

Exactly.

And a crucial point for advanced practice.

Both aluminum and magnesium build up if the kidneys aren't working well.

So real caution in renal impairment.

Okay.

And the big one with antacids interactions.

Huge clinical significance.

Because they change the stomach pH and combine to drugs, they mess with the absorption of tons of other medications.

Like iron, tetracyclines.

Iron, tetracyclines, some antifungals, floroquinolones.

The list is long, the rule is separation.

Take other meds either one hour or four, or wait a full four hours after taking the antacid.

Got it.

Okay, stepping up the ladder.

H2Rase.

Histamine 2 receptor antagonists.

Right.

Think Femotidine, which is pepstid.

These work differently.

They block the H2 receptors on the parietal cells in the stomach.

Carietal cells make the acid.

Correct.

Histamine normally signals these cells to make acid.

H2Rase block that signal so you get less acid secretion.

It also reduces pepsin activation.

So more sustained effect than antacids.

Definitely.

Onset is maybe one to two hours, last longer.

Good for mild GERD, healing some ulcers and preventing certain NSAID -related ulcers, specifically duodenal ones.

But there's a catch with using them long term.

Yeah.

So tachyphylaxis, tolerance.

The body adapts and they become less effective over time with continuous use.

So better for intermittent or as needed use, perhaps.

Often, yes.

Or for shorter courses.

Also remember cimetidine, the older one.

Tag them out.

Yeah.

It's a potent inhibitor of the CYP450 enzyme system in the liver.

Ah, the drug metabolism pathway.

Exactly.

It could really boost levels of other drugs metabolized that way, like warfarin, phenytoin.

Dangerous interactions are possible.

Newer H2Rase like Femotidine don't really have this issue.

Good distinction.

Any other key H2Rase points?

Um, generally well tolerated, but in older adults, especially with kidney issues, you can sometimes see CNS side effects like confusion or dizziness.

Okay.

Now, the top tier for acid suppression.

PPIs.

Proton pump inhibitors.

The powerhouse class, absolutely.

Think omeprazole, pentaprazole, lancoprazole.

Pralasec, Protonics, Prevacid.

Right.

These are the strongest because they irreversibly block the final step in acid production.

The proton pump itself.

The H plus K plus the ET paste pump.

Yeah.

They shut it down directly.

And because it's irreversible, the effect lasts much longer until the body makes new pumps.

So significantly more acid reduction.

Oh yeah.

We're talking like a 66 % reduction in acid secretion by day five.

That's why they're superior for moderate to severe GERD, erosive esophagitis, and they're essential in H.

pylori treatment regimens.

There's a specific way to take them for best effect, isn't there?

Super important dosing pearl, often missed.

Most PPIs work best when you take them 30 to 60 minutes before your first meal of the day.

Why is that?

They need an acidic environment to be activated, and they work best on pumps that are actively trying to secrete acid, which happens when you anticipate eating.

So take it before breakfast, let it get absorbed, then eat, and it nails the pumps as they turn on.

Takes it for one.

Right.

Dexalensiprazole.

It has a dual delayed release thing, so you can actually take that one anytime with or without food.

Okay.

Now, because they're so potent and often used long term, there are some significant FDA warnings.

Yes, absolutely.

We need to counsel patients about these, especially with chronic use, meaning over a year.

What are the main categories of risk?

I think of them in two buckets.

First, issues potentially related to reduced nutrient absorption because of the low acid.

That includes increased risk of fractures linked to possible calcium malabsorption or effects on bone cells,

so osteoporosis concerns.

Also, hypomagnesemia, low magnesium levels,

and vitamin B12 deficiency.

Okay.

Nutrient issues.

What's the second bucket?

Increased risk of infections.

With less acid, bacteria might overgrow.

So there's a higher risk of clostridioids, diphysephal colitis C.

diff.

A nasty diarrheal infection.

Very nasty.

And possibly other bacterial gastroenteritis infections too.

It's a definite risk benefit conversation for long term users.

And there's that one really critical drug interaction people debate.

Ah, the clopidogrel interaction.

Yes.

Clopidogrel, or platix, is an antiplatelet drug.

It's a prodrug, meaning it needs to be activated in the body.

By which enzyme?

CYP2C19.

The problem is, some PPIs, particularly omrazole and its twin esoprazole and lanciprazole, also inhibit that same enzyme.

So the PPI might stop clopidogrel from working properly.

That's the concern.

Less active clopidogrel could mean higher risk of clots, heart attack, or stroke in patients who need that drug.

It's still debated how clinically significant this is for everyone, but the potential is there.

Is there a safer PPI choice in that situation?

Panoprazole seems to have the least interaction with CYP2C19, so it's often preferred if a patient absolutely needs both a PPI and clopizor.

Okay, that covers the acid suppressors really well.

Let's shift now to the specialized agents, particularly for PUD.

When it's H.

pylori, acid suppression isn't enough, right?

Not at all.

You have to kill the bacteria.

Antibiotics are essential, but they never work alone for H.

pylori.

Always combined with?

Always combined with strong acid suppression, usually a PPI.

You need the PPI to raise the pH so the antibiotics can work better and to help the ulcer heal.

It's typically triple or quadruple therapy for 10 to 14 days.

Let's run through the main antibiotics used and their key warnings.

Amoxicillin.

Standard penicillin class antibiotic works on the cell wall.

Main thing.

Obviously, don't use it if someone has a penicillin allergy.

Clarithromycin.

Macrolide antibiotic inhibits protein synthesis.

Very effective, but bacterial resistance is a growing problem.

A key point.

If someone fails a regimen containing clarithromycin, you generally shouldn't use it again in their next treatment attempt.

Okay.

Metronidazole.

Metronidazole messes with bacterial DNA.

The absolute must -know warning.

And no alcohol.

None.

Not even a little bit in cough syrup.

Why not?

It causes a disulfiram -like reaction.

Think violent nausea, vomiting, flushing, headache, palpitations.

It's miserable and potentially dangerous.

Patients have to avoid alcohol during treatment and for a few days after.

Got it.

And tetracycline?

Also inhibits protein synthesis.

Big warning.

Avoid in children under 8 years old.

It can permanently stain developing teeth and affect bone growth.

And like antacids, it has absorption issues.

Major ones.

Dairy products, iron supplements, calcium supplements, antacids.

They all bind to tetracycline and prevent it from being absorbed.

You have to take tetracycline at least two hours apart from any of those things.

That's a lot to juggle for patients.

It really is.

Adherence is tough with these complex regimens.

Okay.

Beyond antibiotics, we sometimes need mucosal protectants, especially maybe for preventing NSA ulcers.

Tell us about misoprostol.

Misoprostol is basically a synthetic version of pastaglandin E1.

So it replaces what the NSA block.

Exactly.

It does two things.

Slightly inhibits acid secretion, but more importantly, it boosts the natural mucosal defenses, increases mucus and bicarbonate secretion.

It's effective for preventing NSAID -induced ulcers.

But it has a huge contraindication.

Massive.

It absolutely cannot be used in pregnancy.

It stimulates uterine contractions and can cause miscarriage or induced labor.

It's an abortifacient.

You must confirm non -pregnancy and ensure contraception in anyone who could become pregnant.

Okay.

Crystal clear on that.

What about sucral fate?

You described it like a band -aid earlier.

That's a good way to think about it.

Sucral fate is aluminum sucrose sulfate.

In the acidic stomach environment, it forms this thick, sticky paste that binds to the ulcer crater, forming a physical barrier against acid and pepsin.

So it coats and protects the ulcer?

Precisely.

It's used sometimes for active ulcers or stress ulcer prophylaxis.

Important notes.

It's not really for GERD or H.

pylori, and it needs an empty stomach to work properly.

And it has to be taken frequently.

Yeah, the effect doesn't last that long, so it's often dosed like four times a day before meals and at bedtime.

And it needs to be separated from other drugs like antacids by at least 30 minutes, and from others like fluoroquinolones or dioxin by a couple of hours, because it can bind them up.

Constipation is a common side effect too.

Okay.

Lastly, bismuth, subcellous salad like Pepto -Bismol.

It plays a role in PUD too.

Yes, but usually as part of a quadruple therapy regimen for H.

pylori, combined with a PPI and two other antibiotics.

The bismuth part seems to have some direct antimicrobial effects against H.

pylori and might stop it from sticking to the stomach wall.

Any specific warnings for bismuth?

Patients need to know it predictably causes harmless blackening of the stool and sometimes a tongue.

It can look alarming if they're not expecting it.

Also, the subcellous salicylate part is related to aspirin, so there's a small theoretical risk of increased bleeding, especially if someone's already on anticoagulants.

All right, we've covered the major drug classes.

Let's talk clinical strategy for GAD when you step up versus step down.

Good question.

Step up means starting with lifestyle changes, maybe adding an antacid or H2RA for mild infrequent symptoms and only moving to a PPI if needed.

Starting low, going high.

Right.

Step down is the opposite.

Usually preferred for moderate to severe symptoms or if there's actual esophageal erosion seen on endoscopy.

You start strong with a standard dose PPI to get rapid relief and healing.

Get control quickly.

Exactly.

Then, once symptoms are controlled, you might try to decrease the PPI dose, switch to an H2RA, or even stop therapy if possible, stepping down the intensity.

For moderate to severe G or A, step down often works better and faster.

And for P -Day, let's say it's H.

pylori.

What's the first line approach?

First line for H.

pylori is typically PPI -based triple therapy for 10 -14 days.

That's usually a PPI plus clarithromycin plus amoxicillin.

But didn't you mention resistance?

Huge factor now.

If local clarithromycin resistance rates are high, say over 15%, or if the patient had prior macrolide exposure, then triple therapy might fail.

In that case, bismuth quadruple therapy is often recommended first line.

Which is?

PPI, bismuth subsalicylate, tetracycline, and metronidazole.

More complex but overcomes clarithromycin resistance.

Okay.

And what if the ulcer is caused by NSAIDs?

First choice is always stop the NSAID if possible.

The ulcer will usually heal with just a PPI or H2RA then.

But if they have to stay on the NSAID, like for severe arthritis.

Then you absolutely need ongoing therapy to protect the stomach.

And this is critical.

You need a PPI or mesoprostol.

Why not an H2RA?

They reduce acid.

They do.

But studies show H2RAs are much less effective at healing or preventing gastric ulcers, ulcers in the stomach itself, when the NSAID is still being taken.

They work okay for duodenal ulcers, but not gastric.

PPIs work for both.

That's a really important clinical distinction.

Okay, what about special populations?

Older adults?

Yeah, geriatrics.

Higher risk for complications from GARE and PIORI.

They're more sensitive to those CNS side effects from H2RA as we talk about confusion, dizziness.

Right.

Got to be careful with aluminum antacids if kidney function is down.

And that long -term PPI risk of main pediatric point is avoiding tetracyclines under age 8.

For pregnancy, antacids are generally okay, but avoid sodium bicarbonate ones.

Mesoprostol is absolutely contraindicated.

PPIs and H2RAs are used sometimes as necessary, but lifestyle first.

Okay, last section, monitoring.

How do we know if the treatment is working or if it failed?

Primarily by symptoms.

For non -erosive GERD, you expect improvement within a few weeks on a PPI.

If symptoms aren't better after, say, four weeks of PPI or maybe six to eight weeks of H2RA, you might need to extend therapy, increase the dose, or rethink the diagnosis.

Maybe it's not acid reflux.

And for erosive disease?

Healing takes longer.

PPI therapy often needs eight, maybe even 16 wins.

If symptoms keep coming back quickly after stopping, or if there are alarm symptoms, difficulty swallowing, weight loss, bleeding, then endoscopy and specialist referral are needed.

What about confirming H.

pylori is gone?

Crucial for high -risk patients, like those with complicated ulcers or gastric cancer risk.

You need to confirm eradication.

But you have to wait.

Wait for what?

Wait until at least four weeks after finishing the antibiotics, and ideally off PPIs, for one to two weeks before testing.

Testing too soon can give a false negative, because the drugs might just suppress the bacteria, not kill them all.

What tests are used?

Usually a urea breath test or a stool antigen test.

Blood antibody tests aren't useful for confirming eradication, because the antibodies stick around for a long time, even after the infection is gone.

And bringing it all together, what's often the biggest reason for treatment failure?

Honestly, non -adherence.

Patients start feeling better after a few days on a PPI or antibiotics.

And they stop taking the meds.

Especially with those complex antibiotic regimens.

They stop early, the bug isn't fully eradicated, symptoms come back, or resistance develops.

Counseling on the importance of finishing the entire course is absolutely key.

That makes total sense.

Patient education is paramount here.

It really is.

So maybe a final thought to leave everyone with tying this together.

Think about that really tricky patient.

Someone with high cardiovascular risk, maybe already on clopidogrel, who also has bad arthritis and needs an NSAI long -term.

Okay, complex case.

You know they need ulcer projection, right?

Because of the NSAID.

But we just said PPIs are best for that, especially for gastric ulcers.

Right, better than H2RAs if the NSAID continues.

But wait, this patient is on clopidogrel.

And we talked about that potential interaction risk, with some PPIs potentially reducing clopidogrel's effectiveness.

So you need the PPI for the stomach, but it might pose a small risk related to the heart medication.

Exactly.

It highlights that clinical balancing act.

You might choose pantoprazole to minimize the interaction risk, or have a serious discussion about risks versus benefits.

It shows that even with clear guidelines, managing these conditions often involves weighing competing risks and tailoring therapy.

It's rarely simple.

That's a perfect illustration of the challenge in the art of advanced practice pharmacology.

Balancing risks, benefits, and individual patient needs.

Thank you so much for walking us through all of that.

My pleasure.

It's crucial information.

And thank you all for joining us on this deep dive into GI pharmacology.

Keep exploring, keep learning, and we'll see you on the next deep dive.